Applications of dihydroarenediols to chemoenzymatic synthesis : approaches to total synthesis of morphine alkaloids

The present studies describe, as a primary goal, our recent progess toward the synthesis of morphine alkaloids from aromatic precursors. Model substrates were synthesized which allowed investigation into Diels-Alder, radical cascade, and palladium-catalyzed bond-forming reactions as possible routes to the morphine alkaloid skeleton. As a secondary objective, three separate series of aromatic substrates were subjected to whole-cell oxidation with Escherichia coli JM 109 (pDTG601), a recombinant organism over-expressing the enzyme toluene dioxygenase. Included in this study were bromothioanisoles, dibromobenzenes, and cyclopropylbenzene derivatives. The products of oxidation were characterized by chemical conversion to known intermediates. The synthetic utility of one of these bacterial metabolites, derived from oxidation of o-dibromobenezene, was demonstrated by chemical conversion to (-)conduritol E.

Chemoenzymatic synthesis of amaryllidaceae alkaloids and their C-1 analogues : symmetry based approach to total synthesis of thebaine

Described herein is the chemoenzymatic total synthesis of several Amaryllidaceae constituents and their unnatural C-I analogues. A new approach to pancratistatin and related compounds will be discussed along with the completed total synthesis of 7 -deoxypancratistatin and trans-dihydrolycoricidine. Evaluation of all new C-l analogues as cancer cell growth inhibitory agents is described. The enzymatic oxidation of dibromobenzenes by Escherichia coli 1M 109 (pDTG60 1) is presented along with conversion of their metabolites to (-)-conduritol E. Investigation into the steric and functional factors governing the enzymatic dihydroxylation of various benzoates by the same organism is also discussed. The synthetic utility of these metabolites is demonstrated through their conversion to pseudo-sugars, aminocyclitols, and complex bicyclic ring systems. The current work on the total synthesis of some morphine alkaloids is also presented. Highlighted will be the synthesis of several model systems related to the efficient total synthesis of thebaine.

Un groupe religieux à l’épreuve du parti politique Sécularisation de l’islamisme au Maroc : mouvement de l’unicité et de la réforme-Parti de la justice et du développement (1996-2011)

Thèse présentée en cotutelle en vue de l’obtention des grades de Philosophiae Doctor (Ph.D.) en Sciences des Religions de l’Université de Montréal et de Docteur en Sociologie de l’École Pratique des Hautes Études Paris-Sorbonne

Effects of grassland conversion and tillage intensities on soil microbial biomass, residues and community structure

Agricultural intensification has a strong impact on level of soil organic matter (SOM), microbial biomass stocks and microbial community structure in agro-ecosystems. The size of the microbial necromass C pool could be about 40 times that of the living microbial biomass C pool in soils. Due to the specificity, amino sugar analysis gives more important information on the relative contribution of fungal and bacterial residues to C sequestration potential of soils. Meanwhile, the relationship between microbial biomass and microbial necromass in soil and its ecological significance on SOM are not fully understood and likely to be very complex in grassland soils. This thesis focuses on the effects of tillage, grassland conversion intensities and fertilisation on microbial biomass, residues and community structure. The combined analyses of microbial biomass and residue formation of both fungi and bacteria provided a unique opportunity to study the effect of tillage, grassland conversion and fertilisation on soil microbial dynamics. In top soil at 0-30 cm layer, a reduction in tillage intensity by the GRT and NT treatments increased the accumulation of saprotrophic fungi in comparison with the MBT treatment. In contrast, the GRT and NT treatments promoted AMF at the expense of saprotrophic fungi in the bottom soil layer at 30-40 cm depth. The negative relationship between the ergosterol to microbial biomass C ratio and the fungal C to bacterial C ratio points to the importance of the relationship between saprotrophic fungi and biotrophic AMF for tillage-induced changes in microbial turnover of SOC. One-season cultivation of winter wheat with two tillage events led to a significant loss in SOC and microbial biomass C stocks at 0-40 cm depth in comparison with the permanent grassland, even 5 years after the tillage event. However, the tillage induced loss in microbial biomass C was roughly 40% less in the long-term than in the short-term of the current experiment, indicating a recovery process during grassland restoration. In general, mould board tillage and grassland conversion to maize monoculture promoted saprotrophic fungi at the expense of biotrophic AMF and bacteria compared to undisturbed grassland soils. Slurry application promoted bacterial residues as indicated by the decreases in both, the ergosterol to microbial biomass C ratio and the fungal C to bacterial C ratio. In addition, the lost microbial functional diversity due to tillage and maize monoculture was restored by slurry application both in arable and grassland soils. I conclude that the microbial biomass C/S ratio can be used as an additional indicator for a shift in microbial community. The strong relationships between microbial biomass and necromass indices points to the importance of saprotrophic fungi and biotrophic AMF for agricultural management induced effects on microbial turnover and ecosystem C storage. Quantitative information on exact biomass estimates of these two important fungal groups in soil is inevitably necessary to understand their different roles in SOM dynamics.

Use of remote sensing to measure change in the extent of habitat for the critically endangered Jerdon's Courser Rhinoptilus bitorquatus in India

Jerdon's Courser Rhinoptilus bitorquatus is one of the most endangered and least understood birds in the world. It is endemic to scrub habitats in southeast India which have been lost and degraded because of human land use. We used satellite images from 1991 and 2000 and two methods for classifying land cover to quantify loss of Jerdon's Courser habitat. The scrub habitats on which this species depends decreased in area by 11-15% during this short period (9.6 years), predominantly as a result of scrub clearance and conversion to agriculture. The remaining scrub patches were smaller and further from human settlements in 2000 than in 1991, implying that much of the scrub loss had occurred close to human population centres. We discuss the implications of our results for the conservation of Jerdon's Courser and the use of remote sensing methods in conservation.

Flavanol monomer-induced changes to the human faecal microflora

We have investigated the bacterial-dependent metabolism of (-)-epicatechin and (+)-catechin using a pH-controlled, stirred, batch-culture fermentation system reflective of the distal region of the human large intestine. Incubation of (-)-epicatechin or (+)-catechin (150mg/l or 1000mg/l) with faecal bacteria, led to the generation of 5-(3,4'-dihydroxyphenyl)-gamma-valerolactone, 5-phenyl-gamma-valerolactone and phenylpropionic acid. However, the formation of these metabolites from (+)-catechin required its initial conversion to (+)-epicatechin. The metabolism of both flavanols occurred in the presence of favourable carbon sources, notably sucrose and the prebiotic fructo-oligosaccharides, indicating that bacterial utilisation of flavanols also occurs when preferential energy sources are available. (+)-Catechin incubation affected the growth of select microflora, resulting in a statistically significant increase in the growth of the Clostridium coccoides-Eubacterium rectale group, Bifidobacterium spp. and Escherichia coli, as well as a significant inhibitory effect on the growth of the C. histolyticum group. In contrast, the effect of (-)-epicatechin was less profound, only significantly increasing the growth of the C. coccoides-Eubacterium rectale group. These potential prebiotic effects for both (+)-catechin and (-)-epicatechin were most notable at the lower concentration of 150 mg/l. As both (-)-epicatechin and (+)-catechin were converted to the same metabolites, the more dramatic change in the growth of distinct microfloral populations produced by (+)-catechin incubation may be linked to the bacterial conversion of (+)-catechin to (+)-epicatechin. Together these data suggest that the consumption of flavanol-rich foods may support gut health through their ability to exert prebiotic actions.

Confessionalism and conversion in the Reformation

Recent research on the Reformation has been concerned with the process by which lay people acquired a religious identity, whether it began merely as an act of political obedience or by a sudden ‘conversion’ to new doctrines. Confessional politics made it imperative for rulers to try to control the religious allegiances of their people, but the doctrine of conversion (as a spiritual change) made this theoretically impossible. Instead, a ‘culture of persuasion’ developed by which clerical and secular rulers sought to persuade their people to accept teachings authorized by the state. The possibility of religious dissent, of converting away from the state-sanctioned denomination, made conversion an issue whose importance was far greater than the actual number of converts. The study of confessionalism and conversion emphasises two theses fundamental to Reformation studies: that the era produced radical changes in the ways that people thought about their personal and communal identities, and that it made individuals’ religious choices the urgent concern of their governors.

Ecological traits affect the sensitivity of bees to land-use pressures in European agricultural landscapes

1. Bees are a functionally important and economically valuable group, but are threatened byland-use conversion and intensification. Such pressures are not expected to affect all species identically; rather, they are likely to be mediated by the species’ ecological traits. 2. Understanding which types of species are most vulnerable under which land uses is an important step towards effective conservation planning.3. We collated occurrence and abundance data for 257 bee species at 1584 European sites from surveys reported in 30 published papers (70 056 records) and combined them with species-level ecological trait data. We used mixed-effects models to assess the importance of land use (land-use class, agricultural use-intensity and a remotely-sensed measure of vegetation),traits and trait 9 land-use interactions, in explaining species occurrence and abundance.4. Species’ sensitivity to land use was most strongly influenced by flight season duration and foraging range, but also by niche breadth, reproductive strategy and phenology, with effects that differed among cropland, pastoral and urban habitats.5. Synthesis and applications. Rather than targeting particular species or settings, conservation action s may be more effective if focused on mitigating situations where species’ traits strongly and negatively interact with land-use pressures. We find evidence that low-intensity agriculture can maintain relatively diverse bee communities; in more intensive settings, added floral resources may be beneficial, but will require careful placement with respect to foraging ranges of smaller bee species. Protection of semi-natural habitats is essential, however; in particular, conversion to urban environments could have severe effects on bee diversity and pollination services. Our results highlight the importance of exploring how ecological traits mediate species responses to human impacts, but further research is needed to enhance the predictive ability of such analyses.

Combined solar and pellet heating systems for single-family houses : How to achieve decreased electricity usage, increased system efficiency and increased solar gains

In Sweden, there are about 0.5 million single-family houses that are heated by electricity alone, and rising electricity costs force the conversion to other heating sources such as heat pumps and wood pellet heating systems. Pellet heating systems for single-family houses are currently a strongly growing market. Future lack of wood fuels is possible even in Sweden, and combining wood pellet heating with solar heating will help to save the bio-fuel resources. The objectives of this thesis are to investigate how the electrically heated single-family houses can be converted to pellet and solar heating systems, and how the annual efficiency and solar gains can be increased in such systems. The possible reduction of CO-emissions by combining pellet heating with solar heating has also been investigated. Systems with pellet stoves (both with and without a water jacket), pellet boilers and solar heating have been simulated. Different system concepts have been compared in order to investigate the most promising solutions. Modifications in system design and control strategies have been carried out in order to increase the system efficiency and the solar gains. Possibilities for increasing the solar gains have been limited to investigation of DHW-units for hot water production and the use of hot water for heating of dishwashers and washing machines via a heat exchanger instead of electricity (heat-fed appliances). Computer models of pellet stoves, boilers, DHW-units and heat-fed appliances have been developed and the parameters for the models have been identified from measurements on real components. The conformity between the models and the measurements has been checked. The systems with wood pellet stoves have been simulated in three different multi-zone buildings, simulated in detail with heat distribution through door openings between the zones. For the other simulations, either a single-zone house model or a load file has been used. Simulations were carried out for Stockholm, Sweden, but for the simulations with heat-fed machines also for Miami, USA. The foremost result of this thesis is the increased understanding of the dynamic operation of combined pellet and solar heating systems for single-family houses. The results show that electricity savings and annual system efficiency is strongly affected by the system design and the control strategy. Large reductions in pellet consumption are possible by combining pellet boilers with solar heating (a reduction larger than the solar gains if the system is properly designed). In addition, large reductions in carbon monoxide emissions are possible. To achieve these reductions it is required that the hot water production and the connection of the radiator circuit is moved to a well insulated, solar heated buffer store so that the boiler can be turned off during the periods when the solar collectors cover the heating demand. The amount of electricity replaced using systems with pellet stoves is very dependant on the house plan, the system design, if internal doors are open or closed and the comfort requirements. Proper system design and control strategies are crucial to obtain high electricity savings and high comfort with pellet stove systems. The investigated technologies for increasing the solar gains (DHW-units and heat-fed appliances) significantly increase the solar gains, but for the heat-fed appliances the market introduction is difficult due to the limited financial savings and the need for a new heat distribution system. The applications closest to market introduction could be for communal laundries and for use in sunny climates where the dominating part of the heat can be covered by solar heating. The DHW-unit is economical but competes with the internal finned-tube heat exchanger which is the totally dominating technology for hot water preparation in solar combisystems for single-family houses.

Two sources of Michael Polanyi`s prototypal notion of incommensurability: Evans-Pritchard on Azande witchcraft and St Augustine on conversion

Michael Polanyi argues in Personal Knowledge (1958) that conceptual frameworks involved in major scientific controversies are separated by a `logical gap'. Such frameworks, according to Polanyi (1958: 151), are logically disconnected: their protagonists think differently, use different languages and occupy different worlds. Relinquishing one framework and adopting another, Polanyi's scientist undergoes a `conversion' to a new `faith'. Polanyi, in other words, presaged Kuhn and Feyerabend's concept of incommensurability. To what influences was Polanyi subject as he developed his concept of the logical gap? The answer, as unfolded in this article, is twofold: Evans-Pritchard's Witchcraft, Oracles and Magic among the Azande and the Confessions of St Augustine.

A facile, protic ionic liquid route to N-substituted 5-hydroxy-4-methyl-3- oxoisoindoline-1-carboxamides

Treatment of highly decorated bicyclo[2.2.1]heptadienes with the protic ionic liquid, TfOH:TEA effected quantitative conversion to the corresponding N-substituted 5-hydroxy-4-methyl-3-oxoisoindoline-1-carboxamides. This approach provides rapid access important chemical space for the rapid development of highly functionalised oxoisoindoline and is highly substrate tolerant.

Prospective progression from high-prevalence disorders to bipolar disorder: exploring characteristics of pre-illness stages

BACKGROUND: Identification of risk factors within precursor syndromes, such as depression, anxiety or substance use disorders (SUD), might help to pinpoint high-risk stages where preventive interventions for Bipolar Disorder (BD) could be evaluated.

METHODS: We examined baseline demographic, clinical, quality of life, and temperament measures along with risk clusters among 52 young people seeking help for depression, anxiety or SUDs without psychosis or BD. The risk clusters included Bipolar At-Risk (BAR) and the Bipolarity Index as measures of bipolarity and the Ultra-High Risk assessment for psychosis. The participants were followed up for 12 months to identify conversion to BD. Those who converted and did not convert to BD were compared using Chi-Square and Mann Whitney U tests.

RESULTS: The sample was predominantly female (85%) and a majority had prior treatment (64%). Four participants converted to BD over the 1-year follow up period. Having an alcohol use disorder at baseline (75% vs 8%, χ(2)=14.1, p<0.001) or a family history of SUD (67% vs 12.5%, χ(2)=6.0, p=0.01) were associated with development of BD. The sub-threshold mania subgroup of BAR criteria was also associated with 12-month BD outcomes. The severity of depressive symptoms and cannabis use had high effects sizes of association with BD outcomes, without statistical significance.

CONCLUSIONS AND LIMITATIONS: The small number of conversions limited the power of the study to identify associations with risk factors that have previously been reported to predict BD. However, subthreshold affective symptoms and SUDs might predict the onset of BD among help-seeking young people with high-prevalence disorders.

Application of impedance spectroscopy to evaluate the effect of different setting accelerators on the developed microstructures of calcium phosphate cements

The main goal of the present study was to evaluate the effect of different setting accelerator agents on the developed microstructures of calcium phosphate cements (CPCs) by employing the impedance spectroscopy (IS) technique. Six compositions of CPCs were prepared from mixtures of commercial dicalcium phosphate anhydrous (DCPA) and synthesized tetracalcium phosphate (TTCP) as the solid phases. Two TTCP/DCPA molar ratios (1/1 and 1/2) and three liquid phases (aqueous solutions of Na(2)HPO(4), tartaric acid (TA) and oxalic acid (OA), 5% volume fraction) were employed. Initial (I) and final (F) setting times of the cement pastes were determined with Gillmore needles (ASTM standard C266-99). The hardened samples were characterized by X-ray powder diffraction (XRD), Fourier transformed infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), and apparent density measurements. The IS technique was employed as a non-destructive tool to obtain information related to porosity, tortuosity and homogeneity of the cement microstructures. The formulation prepared from a TTCP/DCPA equimolar mixture and OA as the liquid phase presented the shortest I and F (12 and 20 min, respectively) in comparison to the other studied systems. XRD analyses revealed the formation of low-crystallinity hydroxyapatite (HA) (as the main phase) as well as the presence of little amounts of unreacted DCPA and TTCP after 24 h hardening in 100% relative humidity. This was related to the proposed mechanisms of dissolution of the reactants. The bands observed by FTIR allowed identifying the presence of calcium tartrate and calcium oxalate in the samples prepared from TA and OA, in addition to the characteristic bands of HA. High degree of entanglement of the formed crystals was observed by SEM in samples containing OA. SEM images were also correlated to the apparent densities of the hardened cements. Changes in porosity, tortuosity and microstructural homogeneity were determined in all samples, from IS results, when the TTCP/DCPA ratio was changed from 1/1 to 1/2. The cement formulated from an equimolar mixture of TTCP/DCPA and OA as the liquid phase presented setting times, degree of conversion to low-crystallinity HA and microstructural features suitable to be used as potential bone cement in clinical applications. The IS technique was shown to be a very sensitive and non-destructive tool to relate the paste composition to the developed microstructures. This approach could be very useful to develop calcium phosphate bone cements for specific clinical demands.

Evaluation of a simple alkaline pretreatment for screening of sugarcane hybrids according to their in vitro digestibility

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Evaluation of the Parameters Affecting the Photoelectrocatalytic Reduction of CO2 to CH3OH at Cu/Cu2O Electrode

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)