Enantiospecific total synthesis of ent-10, 11-thapsan-10-ol

First enantiospecific total synthesis of optical antipode of the sesquiterpene 10,11-epoxythapsan-10-ol has been described. (R)-Carvone has been employed as the chiral starting material and a combination of intramolecular alkylation and Criegee fragmentation are employed for intramolecular stereospecific transfer of the chirality. An intramolecular diazoketone cyclopropanation and regioselective cyclopropane ring cleavage reactions have been employed for the creation of the three requisite contiguous quaternary carbon atoms.

Nimbolide a limonoid from Azadirachta indica inhibits proliferation and induces apoptosis of human choriocarcinoma (BeWo) cells

We investigated the cytotoxic effects of nimbolide, a limonoid present in leaves and flowers of the neem tree (Azadirachta indica) on human choriocarcinoma (BeWo) cells. Treatment with nimbolide resulted in dose- and time-dependent inhibition of growth of BeWo cells with IC50 values of 2.01 and 1.19 μM for 7 and 24 h respectively, accompanied by downregulation of proliferating cell nuclear antigen. Examination of nuclear morphology revealed fragmentation and condensation indicating apoptosis. Increase in the generation of reactive oxygen species (ROS) that was reversed by addition of reduced glutathione suggested ROS involvement in the cytotoxicity of nimbolide. A decrease in Bcl-2/Bax ratio with increased expression of Apaf-1 and caspase-3, and cleavage of poly(ADP-ribose) polymerase provide compelling evidence that nimbolide-induced apoptosis is mediated by the mitochondrial pathway. The results of the present study suggest that nimbolide has immense potential in cancer prevention and therapy based on its antiproliferative and apoptosis inducing effects.

Nimbolide a limonoid from Azadirachta indica inhibits proliferation and induces apoptosis of human choriocarcinoma (BeWo) cells

We investigated the cytotoxic effects of nimbolide, a limonoid present in leaves and flowers of the neem tree (Azadirachta indica) on human choriocarcinoma (BeWo) cells. Treatment with nimbolide resulted in dose- and time-dependent inhibition of growth of BeWo cells with IC50 values of 2.01 and 1.19 μM for 7 and 24 h respectively, accompanied by downregulation of proliferating cell nuclear antigen. Examination of nuclear morphology revealed fragmentation and condensation indicating apoptosis. Increase in the generation of reactive oxygen species (ROS) that was reversed by addition of reduced glutathione suggested ROS involvement in the cytotoxicity of nimbolide. A decrease in Bcl-2/Bax ratio with increased expression of Apaf-1 and caspase-3, and cleavage of poly(ADP-ribose) polymerase provide compelling evidence that nimbolide-induced apoptosis is mediated by the mitochondrial pathway. The results of the present study suggest that nimbolide has immense potential in cancer prevention and therapy based on its antiproliferative and apoptosis inducing effects.

Subsurface deformation in dry sliding of hypo-eutectic Al-Si alloys

The subsurface deformation during dry sliding of Al-Si alloys is studied by fragmentation of silicon particles. The size of the fragmented particles does not vary with load. The depth of deformation is found to increase with increase in normal load. This experimental observation agrees with load-deformation depth characteristics obtained by a slip line field model.

Changing Lived Worlds of Contemporary Amazonian Native Young People : Manchineri Youths in the Reserve and the City, Brazil-Acre

This thesis discusses the contemporary construction of the lived worlds of indigenous Amazonian youths. Today’s native peoples are considerably affected by the processes of globalization and urbanization, which have led to new ways of relating to their cultural traditions. This work presents a case study of Manchineri youngsters aged between 14 and 24 years old living in Acre state in Brazilian Amazonia. The Arawak-speaking Manchineri number some 1,000 people; their legally demarcated reserve is situated next to the River Yaco. The research is based on ethnographic material collected in the Mamoadate reserve and in the state capital, Rio Branco. By comparing the youth in different physical and social environments (the reserve and the city), my attempt has been to search for the most typical elements maintained, altered and created in the current lived worlds of Manchineri youths. Fieldwork methods included interviews, participant observation, photographs, video recordings, and drawings. The material was analyzed within the multidisciplinary framework of the social and cultural construction of knowledge. The study applies the concepts of social field, symbolic capital, and habitus as they have been used by Pierre Bourdieu; perspective as developed recently in Amazonian ethnology; the sacred as a cultural category as understood in the study of religion; and individual and person as concepts central to anthropology and sociology. Additionally, the study can be contextualized within youth studies, Latin American studies, and urban studies. The results of the study show that the everyday lives of young Amazonian native people are formed by a complex mixture of ‘modernity’ and ‘tradition’, fragmentation, and transitions between different conceptual frameworks. Part II discusses the ethnographic material in depth and shows that indigenous adolescents act from a variety of social perspectives: the native youth’s own ethnic group, divided into sub-groups, especially into urban residents and those living in the reserve; ancestors, super-human agents and spirits; other indigenous groups and non-natives. Consequently, besides the traditional initiation ritual, we find various contemporary rites of passage to adulthood: state-education, learning traditional practices, shamanism, matrimony, and transitions between the reserve and urban areas. According to these results, new social roles, political organization, responsibilities, and in general the desire to be respected, require both ‘modern’ and ‘traditional’ abilities. In Part III, the study shows that the current power relations constituted by new social contacts, ethnic recognition, and cooperation with different institutions have resulted in the formation of new social fields: youth cultures, the ethnic group, shamanic practices, the ethnopolitical movement, and indigenous students. The capacity of young Amazonian Indians to act in contemporary social fields produces them as full persons. The study also argues that the elements of the lived worlds can be divided into these social fields. When focusing on these fields, it became evident that these comprise the strategies adopted by young Indians to break through social and cultural barriers.

Perylene-based profluorescent nitroxides for the rapid monitoring of polyester degradation upon weathering: An assessment

A profluorescent nitroxide possessing an isoindoline nitroxide moiety linked to a perylene fluorophore was developed to monitor radical mediated degradation of melamine-formaldehyde crosslinked polyester coil coatings in an industry standard accelerated weathering tester. Trapping of polyester-derived radicals (most likely C-radicals) that are generated during polymer degradation leads to fluorescent closed-shell alkoxy amines, which was used to obtain time-dependent degradation profiles to assess the relative stability of different polyesters towards weathering. The nitroxide probe couples excellent thermal stability and satisfactory photostability with high sensitivity and enables detection of free radical damage in polyesters under conditions that mimic exposure to the environment on a time scale of hours rather than months or years required by other testing methods. There are indications that the profluorescent nitroxide undergoes partial photo-degradation in the absence of polymer-derived radicals. Unexpectedly, it was also found that UV-induced fragmentation of the NO–C bond in closed-shell alkoxy amines leads to regeneration of the profluorescent nitroxide and the respective C-radical. The maximum fluorescence intensity that could be achieved with a given probe concentration is therefore not only determined by the amount of polyester radicals formed during accelerated weathering, but also by the light-driven side reactions of the profluorescent nitroxide and the corresponding alkoxy amine radical trapping products. Studies to determine the optimum probe concentration in the polymer matrix revealed that aggregation and re-absorption effects lowered the fluorescence intensity at higher concentrations of the profluorescent nitroxide, but too low probe concentrations, where these effects would be avoided, were not sufficient to trap the amount of polyester radicals formed upon weathering. The optimized experimental conditions were used to assess the impact of temperature and UV irradiance on polymer degradation during accelerated weathering.

Gossypol mediated DNA degradation

Gossypol, a polyphenolic compound isolated from cotton plant was found to degrade pBR322 DNA Image in a reaction which required the presence of a metal ion, a reducing agent (2-mercaptoethanol) and oxygen as revealed after agarose gel electrophoresis. Fe3+ and Co2+ showed maximum degradation whereas addition of Ca2+ and Mg2+ prevented the gossypol mediated DNA damage. Gossypol caused degradation of rat liver DNA incubated Image even in the absence of added metal ions and 2-mercaptoethanol. Incubation of intact rat liver nuclei with gossypol reveled DNA degradation and nuclei isolated from rats treated with gossypol Image showed higher succestibility to DNA fragmentation when incubated with gossypol Image than control nuclei. EcoRl and AIuI digestion of DNA isolated from gossypol treated rats gave clear cut evidence for DNA degradation. These observations indicate that gossypol is genotoxic and considereable care has to be exercised in its use. SDS, sodium dodecayl sulphate; TE buffer, Tris-HCL-EDTA buffer.

Laatutyöhön sitoutumisen edellytykset ammattikorkeakoulussa

The goal of this research was to establish the necessary conditions under which individuals are prepared to commit themselves to quality assurance work in the organisation of a Polytechnic. The conditions were studied using four main concepts: awareness of quality, commitment to the organisation, leadership and work welfare. First, individuals were asked to describe these four concepts. Then, relationships between the concepts were analysed in order to establish the conditions for the commitment of an individual towards quality assurance work (QA). The study group comprised the entire personnel of Helsinki Polytechnic, of which 341 (44.5%) individuals participated. Mixed methods were used as the methodological base. A questionnaire and interviews were used as the research methods. The data from the interviews were used for the validation of the results, as well as for completing the analysis. The results of these interviews and analyses were integrated using the concurrent nested design method. In addition, the questionnaire was used to separately analyse the impressions and meanings of the awareness of quality and leadership, because, according to the pre-understanding, impressions of phenomena expressed in terms of reality have an influence on the commitment to QA. In addition to statistical figures, principal component analysis was used as a description method. For comparisons between groups, one way variance analysis and effect size analysis were used. For explaining the analysis methods, forward regression analysis and structural modelling were applied. As a result of the research it was found that 51% of the conditions necessary for a commitment to QA were explained by an individual’s experience/belief that QA was a method of development, that QA was possible to participate in and that the meaning of quality included both product and process qualities. If analysed separately, other main concepts (commitment to the organisation, leadership and work welfare) played only a small part in explaining an individual’s commitment. In the context of this research, a structural path model of the main concepts was built. In the model, the concepts were interconnected by paths created as a result of a literature search covering the main concepts, as well as a result of an analysis of the empirical material of this thesis work. The path model explained 46% of the necessary conditions under which individuals are prepared to commit themselves to QA. The most important path for achieving a commitment stemmed from product and system quality emanating from the new goals of the Polytechnic, moved through the individual’s experience that QA is a method of the total development of quality and ended in a commitment to QA. The second most important path stemmed from the individual’s experience of belonging to a supportive work community, moved through the supportive value of the job and through affective commitment to the organisation and ended in a commitment to QA. The third path stemmed from an individual’s experiences in participating in QA, moved through collective system quality and through these to the supportive value of the job to affective commitment to the organisation and ended in a commitment to QA. The final path in the path model stemmed from leadership by empowerment, moved through collective system quality, the supportive value of the job and an affective commitment to the organisation, and again, ended in a commitment to QA. As a result of the research, it was found that the individual’s functional department was an important factor in explaining the differences between groups. Therefore, it was found that understanding the processing of part cultures in the organisation is important when developing QA. Likewise, learning-teaching paradigms proved to be a differentiating factor. Individuals thinking according to the humanistic-constructivistic paradigm showed more commitment to QA than technological-rational thinkers. Also, it was proved that the QA training program did not increase commitment, as the path model demonstrated that those who participated in training showed 34% commitment, whereas those who did not showed 55% commitment. As a summary of the results it can be said that the necessary conditions under which individuals are prepared to commit themselves to QA cannot be treated in a reductionistic way. Instead, the conditions must be treated as one totality, with all the main concepts interacting simultaneously. Also, the theoretical framework of quality must include its dynamic aspect, which means the development of the work of the individual and learning through auditing. In addition, this dynamism includes the reflection of the paradigm of the functions of the individual as well as that of all parts of the organisation. It is important to understand and manage the various ways of thinking and the cultural differences produced by the fragmentation of the organisation. Finally, it seems possible that the path model can be generalised for use in any organisation development project where the personnel should be committed.

Bats and Emerging Zoonoses: Henipaviruses and SARS.

Nearly 75% of all emerging infectious diseases (EIDs) that impact or threaten human health are zoonotic. The majority have spilled from wildlife reservoirs, either directly to humans or via domestic animals. The emergence of many can be attributed to predisposing factors such as global travel, trade, agricultural expansion, deforestation habitat fragmentation, and urbanization; such factors increase the interface and or the rate of contact between human, domestic animal, and wildlife populations, thereby creating increased opportunities for spillover events to occur. Infectious disease emergence can be regarded as primarily an ecological process. The epidemiological investigation of EIDs associated with wildlife requires a trans-disciplinary approach that includes an understanding of the ecology of the wildlife species, and an understanding of human behaviours that increase risk of exposure. Investigations of the emergence of Nipah virus in Malaysia in 1999 and severe acute respiratory syndrome (SARS) in China in 2003 provide useful case studies. The emergence of Nipah virus was associated with the increased size and density of commercial pig farms and their encroachment into forested areas. The movement of pigs for sale and slaughter in turn led to the rapid spread of infection to southern peninsular Malaysia, where the high-density, largely urban pig populations facilitated transmission to humans. Identifying the factors associated with the emergence of SARS in southern China requires an understanding of the ecology of infection both in the natural reservoir and in secondary market reservoir species. A necessary extension of understanding the ecology of the reservoir is an understanding of the trade, and of the social and cultural context of wildlife consumption. Emerging infectious diseases originating from wildlife populations will continue to threaten public health. Mitigating and managing the risk requires an appreciation of the connectedness between human, livestock and wildlife health, and of the factors and processes that disrupt the balance.

Management of plant invasions mediated by frugivore interactions

1. Some of the most damaging invasive plants are dispersed by frugivores and this is an area of emerging importance in weed management. It highlights the need for practical information on how frugivores affect weed population dynamics and spread, how frugivore populations are affected by weeds and what management recommendations are available. 2. Fruit traits influence frugivore choice. Fruit size, the presence of an inedible peel, defensive chemistry, crop size and phenology may all be useful traits for consideration in screening and eradication programmes. By considering the effect of these traits on the probability, quality and quantity of seed dispersal, it may be possible to rank invasive species by their desirability to frugivores. Fruit traits can also be manipulated with biocontrol agents. 3. Functional groups of frugivores can be assembled according to broad species groupings, and further refined according to size, gape size, pre- and post-ingestion processing techniques and movement patterns, to predict dispersal and establishment patterns for plant introductions. 4. Landscape fragmentation can increase frugivore dispersal of invasives, as many invasive plants and dispersers readily use disturbed matrix environments and fragment edges. Dispersal to particular landscape features, such as perches and edges, can be manipulated to function as seed sinks if control measures are concentrated in these areas. 5. Where invasive plants comprise part of the diet of native frugivores, there may be a conservation conflict between control of the invasive and maintaining populations of the native frugivore, especially where other threats such as habitat destruction have reduced populations of native fruit species. 6. Synthesis and applications. Development of functional groups of frugivore-dispersed invasive plants and dispersers will enable us to develop predictions for novel dispersal interactions at both population and community scales. Increasingly sophisticated mechanistic seed dispersal models combined with spatially explicit simulations show much promise for providing weed managers with the information they need to develop strategies for surveying, eradicating and managing plant invasions. Possible conservation conflicts mean that understanding the nature of the invasive plant-frugivore interaction is essential for determining appropriate management.

Landscape structure influences tree density patterns in fragmented woodlands in semi-arid eastern Australia.

Landscape and local-scale influences are important drivers of plant community structure. However, their relative contribution and the degree to which they interact remain unclear. We quantified the extent to which landscape structure, within-patch habitat and their confounding effects determine post-clearing tree densities and composition in agricultural landscapes in eastern subtropical Australia. Landscape structure (incorporating habitat fragmentation and loss) and within-patch (site) features were quantified for 60 remnant patches of Eucalyptus populnea (Myrtaceae) woodland. Tree density and species for three ecological maturity classes (regeneration, early maturity, late maturity) and local site features were assessed in one 100 × 10 m plot per patch. All but one landscape characteristic was determined within a 1.3-km radius of plots; Euclidean nearest neighbour distance was measured inside a 5-km radius. Variation in tree density and composition for each maturity class was partitioned into independent landscape, independent site and joint effects of landscape and site features using redundancy analysis. Independent site effects explained more variation in regeneration density and composition than pure landscape effects; significant predictors were the proportion of early and late maturity trees at a site, rainfall and the associated interaction. Conversely, landscape structure explained greater variation in early and late maturity tree density and composition than site predictors. Area of remnant native vegetation within a landscape and patch characteristics (area, shape, edge contrast) were significant predictors of early maturity tree density. However, 31% of the explained variation in early mature tree differences represented confounding influences of landscape and local variables. We suggest that within-patch characteristics are important in influencing semi-arid woodland tree regeneration. However, independent and confounding effects of landscape structure resulting from previous vegetation clearing may have exerted a greater historical influence on older cohorts and should be accounted for when examining woodland dynamics across a broader range of environments.

Control techniques and management strategies for the problematic Navua sedge (Cyperus aromaticus)

Navua sedge, a member of the Cyperaceae family, is an aggressive weed of pastures in Fiji, Sri Lanka, Malay Peninsula, Vanuatu, Samoa, Solomons, and Tahiti and is now a weed of pastures and roadsides in north Queensland, Australia. Primarily restricted to areas with an annual rainfall exceeding 2500 mm, Navua sedge is capable of forming dense stands smothering many tropical pasture species. Seventeen herbicides were field tested at three sites in north Queensland, with glyphosate, halosulfuron, hexazinone, imazapic, imazapyr, or MSMA the most effective for Navua sedge control. Environmental problems such as persistence in soil, lack of selectivity and movement off-site may occur using some herbicides at the predicted LC90 control level rates. A seasonality trial using halosulfuron (97.5 g ai/ha) gave better Navua sedge control (84%) spraying March to September than spraying at other times (50%). In a frequency trial, sequential glyphosate applications (2,160 g ae/ha) every two months was more effective for continued Navua sedge control (67%) than a single application of glyphosate (36%), though loss of ground cover would occur. In a management trial, single applications of glyphosate (2,160 to 3,570 g ae/ha) using either a rope wick, ground foliar spraying or a rotary rope wick gave 59 to 73% control, while other treatments (rotary hoe (3%), slashing (-13%) or crushing (-30%)) were less effective. In a second management trial, four monthly rotary wick applications were much more effective (98%) than four monthly crushing applications (42%). An effective management plan must include the application of regular herbicide treatments to eliminate Navua sedge seed being added to the soil seed bank. Treatments that result in seed burial, for example, discing are likely to prolong seed persistence and should be avoided. The sprouting activity of vegetative propagules and root fragmentation needs to also be considered when selecting control options.

Population structure, effective population size and adverse effects of stocking in the endangered Australian eastern freshwater cod Maccullochella ikei

Microsatellite markers were used to examine spatio-temporal genetic variation in the endangered eastern freshwater cod Maccullochella ikei in the Clarence River system, eastern Australia. High levels of population structure were detected. A model-based clustering analysis of multilocus genotypes identified four populations that were highly differentiated by F-statistics (FST = 0· 09 − 0· 49; P < 0· 05), suggesting fragmentation and restricted dispersal particularly among upstream sites. Hatchery breeding programmes were used to re-establish locally extirpated populations and to supplement remnant populations. Bayesian and frequency-based analyses of hatchery fingerling samples provided evidence for population admixture in the hatchery, with the majority of parental stock sourced from distinct upstream sites. Comparison between historical and contemporary wild-caught samples showed a significant loss of heterozygosity (21%) and allelic richness (24%) in the Mann and Nymboida Rivers since the commencement of stocking. Fragmentation may have been a causative factor; however, temporal shifts in allele frequencies suggest swamping with hatchery-produced M. ikei has contributed to the genetic decline in the largest wild population. This study demonstrates the importance of using information on genetic variation and population structure in the management of breeding and stocking programmes, particularly for threatened species.

Preliminary investigation into the induction of reproduction in Ulva spp. in Southeast Queensland for mass cultivation purposes

Ulva is a common component of marine intertidal flora in Australia with many species frequently observed along the Queensland coastline. Three species of Ulva, U. lactuca, U. intestinalis and U. prolifera were found to naturally occur at the Bribie Island Research Centre (BIRC) in Southeast Queensland. Studies were undertaken to establish the most optimal conditions for growing Ulva in the BIRC laboratory. These tests were conducted in order to condition the algal material prior to the sporulation studies, offering more controlled material to assess treatment effects conclusively, and helping eliminate other potentially confounding environmental factors. Results showed that a stocking density of between 5-20 grams of Ulva per litre along with the addition of the soluble fertiliser Aquasol at a rate of 87 mg/L of seawater was ideal for achieving a desired doubling of growth per week. In the wild the formation of Ulva fragments occurs naturally in the ocean through wave and storm action. This breakage can trigger a survival response mechanism which stimulates the algae to form and release gametes. By chopping the tissue, this process could be artificially simulated in the laboratory and creating a simple and easy way to produce new individuals. Studies performed into inducing sporulation in Ulva through a combination of fragmentation and renewal of medium at BIRC showed that sporulation can be successfully induced in all three species of Ulva through these methods, however it was found to be to a degree that would not meet the demands of commercial production with on average a rate of only 33% achieved. While the current study did not find a method suitable for a commercial application the results presented here contribute to increasing our understanding about Ulva reproduction and set a platform for future work in to cultivating Ulva within Southeast Queensland.

Candida proteinases in the degradation of oral mucosal tissue components associated with Candida invasion

The aim of this thesis was to compare the degradation of human oral epithelial proteins by proteinases of different Candida yeast species. We focused on proteins associated with Candida invasion in the cell-to-cell junction, the basement membrane zone, the extracellular matrix, and local tissue inflammatory regulators. Another main objective was to evaluate the effect of the yeast/hyphal transition and pH on the degradative capability of Candida. The enzymatic activity of the Candida proteinases was verified by gelatin zymography. Laminins-332 (Lm-322) and -511(Lm-511) produced by human oral keratinocytes were gathered from the growth media, and E-cadherin (E-Cad) was isolated from the cell membrane of the keratinocytes by immunoprecipitation. The proteins were incubated with Candida cells and cell-free fractions, and degradation was detected by fluorography. Fibronectin degradation was visualised by sodium dodecylsulphate polyacrylamide gel electrophoresis (SDS-PAGE). Matrix metalloproteinase-9 (MMP-9) activation and tissue inhibitor of metalloproteinase-1 (TIMP-1) fragmentation was detected by using the Western blot and enhanced chemoluminescence (ECL) techniques. Residual activity of TIMP-1 was evaluated by a casein degradation assay. A fluorimetric assay was used to detect and compare Candida proteinase activities with MMP-9. These studies showed that the ability of the different Candida yeast species to degrade human Lm-332, fibronectin, and E-Cad vary from strain to strain and that this degradation is pH-dependent. This indicates that local acidic pH in tissue may play a role in tissue destruction by activating Candida proteinases and aid invasion of Candida into deeper tissue. A potential correlation exists between the morphological form of the yeasts and the degradative ability; the C. albicans yeast form seems to be related to superficial infections, and hyphal forms can apparently invade deeper tissues between the epithelial cells by degradation of E-Cad. Basement membrane degradation is possible, especially in the junctional epithelium, which contains only Lm-332 as a structural component. Local tissue host inflammatory mediators, such as MMP-9, were activated, and TIMP-1 was degraded by certain Candida species, thus indicating the possibility of a weakened host tissue defence mechanism in vivo.