Enhanced sensitivity of ubiquinone-deficient mutants of Saccharomyces cerevisiae to products of autoxidized polyunsaturated fatty acids.

Coenzyme Q (ubiquinone or Q) plays a well known electron transport function in the respiratory chain, and recent evidence suggests that the reduced form of ubiquinone (QH2) may play a second role as a potent lipid-soluble antioxidant. To probe the function of QH2 as an antioxidant in vivo, we have made use of a Q-deficient strain of Saccharomyces cerevisiae harboring a deletion in the COQ3 gene [Clarke, C. F., Williams, W. & Teruya, J. H. (1991) J. Biol. Chem. 266, 16636-16644]. Q-deficient yeast and the wild-type parental strain were subjected to treatment with polyunsaturated fatty acids, which are prone to autoxidation and breakdown into toxic products. In this study we find that Q-deficient yeast are hypersensitive to the autoxidation products of linolenic acid and other polyunsaturated fatty acids. In contrast, the monounsaturated oleic acid, which is resistant to autoxidative breakdown, has no effect. The hypersensitivity of the coq3delta strains can be prevented by the presence of the COQ3 gene on a single copy plasmid, indicating that the sensitive phenotype results solely from the inability to produce Q. As a result of polyunsaturated fatty acid treatment, there is a marked elevation of lipid hydroperoxides in the coq3 mutant as compared with either wild-type or respiratory-deficient control strains. The hypersensitivity of the Q-deficient mutant can be rescued by the addition of butylated hydroxytoluene, alpha-tocopherol, or trolox, an aqueous soluble vitamin E analog. The results indicate that autoxidation products of polyunsaturated fatty acids mediate the cell killing and that QH2 plays an important role in vivo in protecting eukaryotic cells from these products.

Genetic engineering of vein grafts resistant to atherosclerosis.

Previously, researchers have speculated that genetic engineering can improve the long-term function of vascular grafts which are prone to atherosclerosis and occlusion. In this study, we demonstrated that an intraoperative gene therapy approach using antisense oligodeoxynucleotide blockage of medial smooth muscle cell proliferation can prevent the accelerated atherosclerosis that is responsible for autologous vein graft failure. Selective blockade of the expression of genes for two cell cycle regulatory proteins, proliferating cell nuclear antigen and cell division cycle 2 kinase, was achieved in the smooth muscle cells of rabbit jugular veins grafted into the carotid arteries. This alteration of gene expression successfully redirected vein graft biology away from neointimal hyperplasia and toward medial hypertrophy, yielding conduits that more closely resembled normal arteries. More importantly, these genetically engineered grafts proved resistant to diet-induced atherosclerosis. These findings establish the feasibility of developing genetically engineered bioprostheses that are resistant to failure and better suited to the long-term treatment of occlusive vascular disease.

Applying model-driven engineering to the development of Rich Internet Applications for Business Intelligence

Business Intelligence (BI) applications have been gradually ported to the Web in search of a global platform for the consumption and publication of data and services. On the Internet, apart from techniques for data/knowledge management, BI Web applications need interfaces with a high level of interoperability (similar to the traditional desktop interfaces) for the visualisation of data/knowledge. In some cases, this has been provided by Rich Internet Applications (RIA). The development of these BI RIAs is a process traditionally performed manually and, given the complexity of the final application, it is a process which might be prone to errors. The application of model-driven engineering techniques can reduce the cost of development and maintenance (in terms of time and resources) of these applications, as they demonstrated by other types of Web applications. In the light of these issues, the paper introduces the Sm4RIA-B methodology, i.e., a model-driven methodology for the development of RIA as BI Web applications. In order to overcome the limitations of RIA regarding knowledge management from the Web, this paper also presents a new RIA platform for BI, called RI@BI, which extends the functionalities of traditional RIAs by means of Semantic Web technologies and B2B techniques. Finally, we evaluate the whole approach on a case study—the development of a social network site for an enterprise project manager.

Letter from John Quincy Adams to his brother, Thomas Boylston Adams, 1786 July 2

This letter was written by John Quincy Adams on July 2, 1786 to his younger brother, Thomas Boylston Adams, who was then staying with their uncle, the Reverend John Shaw, in Haverhill, Massachusetts. In the letter, John gives Thomas advice on life as a student at Harvard, instructing him to choose his friends carefully, to favor those who are virtuous and studious over those who are idle and prone to vice, to maintain an "unblemished moral reputation," and to spend as much as six hours each day studying in order to excel as a scholar.

Investigating the Role of cAMP-Signaling in the Regulation of Vascular Endothelial Cell Adaptive Responses to Fluid Shear Stress

The circulating blood exerts a force on the vascular endothelium, termed fluid shear stress (FSS), which directly impacts numerous vascular endothelial cell (VEC) functions. For example, high rates of linear and undisturbed (i.e. laminar) blood flow maintains a protective and quiescent VEC phenotype. Meanwhile, deviations in blood flow, which can occur at vascular branchpoints and large curvatures, create areas of low, and/or oscillatory FSS, and promote a pro-inflammatory, pro-thrombotic and hyperpermeable phenotype. Indeed, it is known that these areas are prone to the development of atherosclerotic lesions. Herein, we show that cyclic nucleotide phosphodiesterase (PDE) 4D (PDE4D) activity is increased by FSS in human arterial endothelial cells (HAECs) and that this activation regulates the activity of cAMP-effector protein, Exchange Protein-activated by cAMP-1 (EPAC1), in these cells. Importantly, we also show that these events directly and critically impact HAEC responses to FSS, especially when FSS levels are low. Both morphological events induced by FSS, as measured by changes in cell alignment and elongation in the direction of FSS, and the expression of critical FSS-regulated genes, including Krüppel-like factor 2 (KLF2), endothelial nitric oxide synthase (eNOS) and thrombomodlin (TM), are mediated by EPAC1/PDE4D signaling. At a mechanistic level, we show that EPAC1/PDE4D acts through the vascular endothelial-cadherin (VECAD)/ platelet-cell adhesion molecule-1 (PECAM1)/vascular endothelial growth factor receptor 2 (VEGFR2) mechanosensor to activate downstream signaling though Akt. Given the critical role of PDE4D in mediating these effects, we also investigated the impact of various patterns of FSS on the expression of individual PDE genes in HAECs. Notably, PDE2A was significantly upregulated in response to high, laminar FSS, while PDE3A was upregulated under low, oscillatory FSS conditions only. These data may provide novel therapeutic targets to limit FSS-dependent endothelial cell dysfunction (ECD) and atherosclerotic development.

Using multiple landscape genetic approaches to test the validity of genetic clusters in a species characterized by an isolation-by-distance pattern

Bayesian clustering methods are typically used to identify barriers to gene flow, but they are prone to deduce artificial subdivisions in a study population characterized by an isolation-by-distance pattern (IbD). Here we analysed the landscape genetic structure of a population of wild boars (Sus scrofa) from south-western Germany. Two clustering methods inferred the presence of the same genetic discontinuity. However, the population in question was characterized by a strong IbD pattern. While landscape-resistance modelling failed to identify landscape features that influenced wild boar movement, partial Mantel tests and multiple regression of distance matrices (MRDMs) suggested that the empirically inferred clusters were separated by a genuine barrier. When simulating random lines bisecting the study area, 60% of the unique barriers represented, according to partial Mantel tests and MRDMs, significant obstacles to gene flow. By contrast, the random-lines simulation showed that the boundaries of the inferred empirical clusters corresponded to the most important genetic discontinuity in the study area. Given the degree of habitat fragmentation separating the two empirical partitions, it is likely that the clustering programs correctly identified a barrier to gene flow. The differing results between the work published here and other studies suggest that it will be very difficult to draw general conclusions about habitat permeability in wild boar from individual studies.

Radical Language, Radical Identity: Korean Writers in Japanese Spaces and the Burden to "Represent"

Thesis (Ph.D.)--University of Washington, 2016-06

Use of X-radiographs to distinguish members of the Montastraea annularis reef-coral species complex

Recent work suggests the Montastraea annularis species complex consists of at least three species, which can be distinguished qualitatively in the field using features related to colony growth (e.g. overall growth form. bumpiness, growth along the colony edge). However, when whole colonies are not available and surfaces are eroded, identification becomes problematic when relying on such characteristics. Characters based on internal skeletal structures are less prone to loss due to taphonomic processes. Previous work has shown that internal corallite architectural features measured in transverse thin sections can be used to distinguish species. To determine whether internal colony-level features measured on X-radiographs can be used. eight characters related to corallite budding and accretionary growth were measured on specimens representing three modern members of the M. annularis species complex (M. annularis, M. flaveolata and M. franksi), as well as two fossil forms (columnar and organ-pipe). All eight characters showed significant differences among species. Discriminant function analysis using seven of these characters resulted in distinct species groupings In canonical scores plots and a 100% classification success for specimens from Panama. These results suggest that measurements made on X-radiographs provide a useful tool for quantitatively distinguishing members of the M. annularis complex as well as between other massive reef corals.

IL10 and IL12B polymorphisms each influence IL-12p70 secretion by dendritic cells in response to LPS

Dendritic cells (DC) are the main producers of the cytokine IL-12p70, through which they play a direct role in the development of IFN-gamma-secreting Th1 cells, costimulation of CTL differentiation and NK-cell activation. In contrast, IL-10, which is also produced by DC, negatively regulates IL-12 production. IL-12p70 production varies widely between individuals, and several polymorphisms in the gene encoding IL-12p40 (IL12B) have been identified that influence susceptibility and severity of infectious, autoimmune and neoplastic disease. Here we show that polymorphisms not only of IL12B, but also in the IL10 promoter, influence IL-12p70 secretion by monocyte-derived DC in response to LPS. Although IL12B promoter homozygotes were prone to making more IL-12p70, presence of the IL10 high genotype restricted IL-12p70 production in these individuals. These observations provide a further genetic control of IL-12p70 regulation and emphasize the complexity of production of this cytokine. They also suggest genotypes that might influence the outcome of DC immunotherapy.

An analysis of fatal accidents in agriculture in Great Britain

The number of fatal accidents in the agricultural, horticultural and forestry industry in Great Britain has declined from an annual rate of about 135 in the 1960's to its current level of about 50. Changes to the size and makeup of the population at risk mean that there has been no real improvement in fatal injury incidence rates for farmers. The Health and Safety Executives' (HSE) current system of accident investigation, recording, and analysis is directed primarily at identifying fault, allocating blame, and punishing wrongdoers. Relatively little information is recorded about the personal and organisational factors that contributed to, or failed to prevent accidents. To develop effective preventive strategies, it is important to establish whether errors by the victims and others, occur at the skills, rules, or knowledge level of functioning: are violations of some rule or procedure; or stem from failures to correctly appraise, or control a hazard. A modified version of the Hale and Glendon accident causation model was used to study 230 fatal accidents. Inspectors' original reports were examined and expert judgement applied to identify and categorise the errors committed by each of the parties involved. The highest proportion of errors that led directly to accidents occurred whilst the victims were operating at the knowledge level. The mix and proportion of errors varied considerably between different classes of victim and kind of accident. Different preventive strategies will be needed to address the problem areas identified.

Measurement of ocular component contributions to residual astigmatism in adult human eyes

The aim of this study was to determine whether an ophthalmophakometric technique could offer a feasible means of investigating ocular component contributions to residual astigmatism in human eyes. Current opinion was gathered on the prevalence, magnitude and source of residual astigmatism. It emerged that a comprehensive evaluation of the astigmatic contributions of the eye's internal ocular surfaces and their respective axial separations (effectivity) had not been carried out to date. An ophthalmophakometric technique was developed to measure astigmatism arising from the internal ocular components. Procedures included the measurement of refractive error (infra-red autorefractometry), anterior corneal surface power (computerised video keratography), axial distances (A-scan ultrasonography) and the powers of the posterior corneal surface in addition to both surfaces of the crystalline lens (multi-meridional still flash ophthalmophakometry). Computing schemes were developed to yield the required biometric data. These included (1) calculation of crystalline lens surface powers in the absence of Purkinje images arising from its anterior surface, (2) application of meridional analysis to derive spherocylindrical surface powers from notional powers calculated along four pre-selected meridians, (3) application of astigmatic decomposition and vergence analysis to calculate contributions to residual astigmatism of ocular components with obliquely related cylinder axes, (4) calculation of the effect of random experimental errors on the calculated ocular component data. A complete set of biometric measurements were taken from both eyes of 66 undergraduate students. Effectivity due to corneal thickness made the smallest cylinder power contribution (up to 0.25DC) to residual astigmatism followed by contributions of the anterior chamber depth (up to 0.50DC) and crystalline lens thickness (up to 1.00DC). In each case astigmatic contributions were predominantly direct. More astigmatism arose from the posterior corneal surface (up to 1.00DC) and both crystalline lens surfaces (up to 2.50DC). The astigmatic contributions of the posterior corneal and lens surfaces were found to be predominantly inverse whilst direct astigmatism arose from the anterior lens surface. Very similar results were found for right versus left eyes and males versus females. Repeatability was assessed on 20 individuals. The ophthalmophakometric method was found to be prone to considerable accumulated experimental errors. However, these errors are random in nature so that group averaged data were found to be reasonably repeatable. A further confirmatory study was carried out on 10 individuals which demonstrated that biometric measurements made with and without cycloplegia did not differ significantly.

Catalyst studies on the ring opening of tetrahydrofuran-dimethanol to 1,2,6-hexanetriol

The metal catalyzed hydrogenolysis of the biomass-derived THF-dimethanol to 1,2,6-hexanetriol using heterogeneous catalysts was investigated. Bimetallic Rh-Re catalysts (4 wt% Rh and a Re/Rh (mol. ratio of 0.5) on a silica support gave the best performance and 1,2,6-hexanetriol was obtained in 84% selectivity at 31% conversion (120 C, 80 bar, 4 h); the selectivity reaches a maximum of 92% at 80 C. The product distribution at prolonged reaction times or higher temperatures or both shows the formation of diols and mono-alcohols, indicating that the 1,2,6-hexanetriol is prone to subsequent hydrodeoxygenation reactions. Different silica supports were investigated and optimal results were obtained with an amorphous silica featuring an intermediate surface area and an average mesopore size of about 6 nm. TPR and XPS surface analysis support the presence of mixed Rh and Re particles. The redox Reδ+/ReTotal surface ratio correlates with the conversion in a volcano type dependency. Both gas phase as well as Rh200Re1OH cluster DFT calculations support an acid-metal bifunctional mechanism and explain the products distribution. © 2013 Elsevier B.V. All rights reserved.

Memory Bias for Anxiety Prior to Academic Achievement Situations: Influences of Time, Mood, Personality and Post-Event-Processing

The current thesis examines memory bias for state anxiety prior to academic achievement situations like writing an exam and giving a speech. The thesis relies on the reconstruction principle, which assumes that memories for past emotions are reconstructed rather than stored permanently and accurately. This makes them prone to memory bias, which is af-fected by several influencing factors. A major aim is to include four important influencing factors simultaneously. Early research on mood and emotional autobiographical memory found evidence for the existence of a propositional associative network (Bower, 1981; Col-lins & Loftus, 1975), leading to mood congruent recall. But empirical findings gave also strong evidence for the existence of mood incongruent recall for one’s own emotions, which was for example linked to mood regulation via mood repair (e.g. Clark & Isen, 1982), which seems to be associated to the personality traits extraversion and neuroticism (Lischetzke & Eid, 2006; Ng & Diener, 2009). Moreover, neuroticism and trait anxiety are related to rumination, which is seen as negative post-event-processing (e.g. Wells & Clark, 1997). Overall, the elapsed time since the emotional event happened should have an impact on recall of emotions. Following the affect infusion model by Robinson and Clore (2002a), the influence of personality on memory bias should increase over time. Therefore, three longitudinal studies were realized, using naturally occurring as well as laboratory settings. The used paradigm was equivalent in all studies. Subjects were asked about their actual state anxiety prior to an academic achievement situation. Directly after the situation, cur-rent mood and recall of former anxiety were assessed. The same procedure was repeated a few weeks later. Personality traits and post-event-processing were also assessed. The results suggest a need to have a differentiated view on predicting memory bias. Study 1 (N = 131) as well as study 3 (N = 53) found evidence for mood incongruent memory in the sense of mood repair and downward regulation as a function of personality. Rumination was found to cause stable overestimation of pre-event anxiety in study 2 (N = 141) as well as in study 3. Although the relevance of the influencing factors changed over time, an increasing relevance of personality could not consistently be observed. The tremendously different effects of the laboratory study 2 indicated that such settings are not appropriate to study current issues. Theoretical and psychotherapeutically relevant conclusions are drawn and several limitations are discussed.

Shortcuts to adiabaticity in the double well

123 p.

Age-Dependent Fragility and Life-Cycle Cost Analysis of Timber and Steel Distribution Poles Subjected to Hurricanes

Power distribution systems are susceptible to extreme damage from natural hazards especially hurricanes. Hurricane winds can knock down distribution poles thereby causing damage to the system and power outages which can result in millions of dollars in lost revenue and restoration costs. Timber has been the dominant material used to support overhead lines in distribution systems. Recently however, utility companies have been searching for a cost-effective alternative to timber poles due to environmental concerns, durability, high cost of maintenance and need for improved aesthetics. Steel has emerged as a viable alternative to timber due to its advantages such as relatively lower maintenance cost, light weight, consistent performance, and invulnerability to wood-pecker attacks. Both timber and steel poles are prone to deterioration over time due to decay in the timber and corrosion of the steel. This research proposes a framework for conducting fragility analysis of timber and steel poles subjected to hurricane winds considering deterioration of the poles over time. Monte Carlo simulation was used to develop the fragility curves considering uncertainties in strength, geometry and wind loads. A framework for life-cycle cost analysis is also proposed to compare the steel and timber poles. The results show that steel poles can have superior reliability and lower life-cycle cost compared to timber poles, which makes them suitable substitutes.