Separation of enantiomers of drugs by capillary electrophoresis with permethyl-gamma-cyclodextrin as chiral solvating agent

High-throughput screening is a promising new approach in analytical chemistry. Within the framework of an extended screening program (The German-Chinese Drug Screening Program), the enantioseparation of 86 drugs was investigated by capillary zone electrophoresis in the presence of the chiral solvating agent (CSA) octakis-(2,3,6-tri-O-methyl)-gamma-cyclodextrin (TM-gamma-CD). By this means, 15 drugs could be separated into enantiomeric pairs. Approximate measures for the degree of interaction (migration retardation factor, R-m) and for the degree of enantiomer recognition (migration separation factors, alpha(m)) revealed intriguing patterns that were compared with those found for native gamma-cyclodextrin (gamma-CD). Although there is a distinct influence of the analyte structure on the electrophoretic data, interpretation remains difficult. Most remarkably, permethylation of gamma-CD leads neither to a higher affinity nor to better chiral recognition, in contrast to the findings with alpha-CD.

Sporopollen analysis of Core B10 in the southern Yellow Sea and the reflected characteristics of climate changes

Eight sporopollen zones have been divided based on the results of high-resolution sporopollen analysis of Core B10 in the southern Yellow Sea. Based on the results along with C-14 datings and the subbottom profiling data, climatic and environmental changes since the last stage of late Pleistocene are discussed. The main conclusions are drawn as follows: (1) the vegetation evolved in the process of coniferous forest-grassland containing broad-leaved treesconiferous and broad-leaved mixed forest --> coniferous and broad-leaved mixed forest-grassland prevailed by coniferous trees --> coniferous and broad-leaved mixed forest-grassland containing evergreen broad-leaved trees- coniferous and broad-leaved mixed forest-grassland prevailed by broad-leaved trees-deciduous broad-leaved forest-meadow containing evergreen broad-leaved trees- coniferous and broadleaved mixed forest-grassland prevailed by broad-leaved trees- coniferous and broad-leaved mixed forest containing evergreen broad-leaved trees; (2) eight stages of climate changes are identified as the cold and dry stage, the temperate and wet stage, the cold and dry stage, the warm and dry stage, the temperate and wet stage, the hot and dry stage, the temperate and dry stage, then the warm and dry stage in turn; (3) the sedimentary environment developed from land, to littoral zone, to land again, then to shore-neritic zone; and (4) the Yellow Sea Warm Current formed during early-Holocene rather than Atlantic stage.

Effect of spatial variation on areal evapotranspiration simulation in Haibei, Tibet plateau, China

Quantification of areal evapotranspiration from remote sensing data requires the determination of surface energy balance components with support of field observations. Much attention should be given to spatial resolution sensitivity to the physics of surface heterogeneity. Using the Priestley-Taylor model, we generated evapotranspiration maps at several spatial resolutions for a heterogeneous area at Haibei, and validated the evapotranspiration maps with the flux tower data. The results suggested that the mean values for all evapotranspiration maps were quite similar but their standard deviations decreased with the coarsening of spatial resolution. When the resolution transcended about 480 m, the standard deviations drastically decreased, indicating a loss of spatial structure information of the original resolution evapotranspiration map. The absolute values of relative errors of the points for evapotranspiration maps showed a fluctuant trend as spatial resolution of input parameter data layers coarsening, and the absolute value of relative errors reached minimum when pixel size of map matched up to measuring scale of eddy covariance system. Finally, based on the analyses of the semi-variogram of the original resolution evapotranspiration map and the shapes of spatial autocorrelation indices of Moran and Geary for evapotranspiration maps at different resolutions, an appropriate resolution was suggested for the areal evapotranspiration simulation in this study area.

孤北洼陷沙三-沙四段隐蔽油藏形成机制及其预测

Based on the study of sequence stratigraphy, modern sedimentary, basin analysis, and petroleum system in Gubei depression, this paper builds high resolution sequence stratigraphic structure, sedimentary system, sandbody distribution, the effect of tectonic in sequence and sedimentary system evolution and model of tectonic-lithofacies. The pool formation mechanism of subtle trap is developed. There are some conclusions and views as follows. 1.With the synthetic sequence analysis of drilling, seismic, and well log, the highly resolution sequence structure is build in Gubei depression. They are divided two secondary sequences and seven three-order sequences in Shahejie formation. They are include 4 kinds of system traces and 7 kinds of sedimentary systems which are alluvial fan, under water fan, alluvial fan and fan-delta, fan-delta, lacustrine-fan, fluvial-delta-turbidite, lakeshore beach and bar, and deep lake system. Sandbody distribution is show base on third order sequence. 2.Based on a lot of experiment and well log, it is point out that there are many types of pore in reservoir with the styles of corrosion pore, weak cementing, matrix cementing, impure filling, and 7 kinds of diagenetic facies. These reservoirs are evaluated by lateral and profile characteristics of diagenetic facies and reservoir properties. 3.The effect of simultaneous faulting on sediment process is analyzed from abrupt slope, gentle slope, and hollow zone. The 4 kinds of tectonic lithofacies models are developed in several periods in Gubei depression; the regional distribution of subtle trap is predicted by hydro accumulation characteristics of different tectonic lithofacies. 4.There are 4 types of compacting process, which are normal compaction, abnormal high pressure, abnormal low pressure and complex abnormal pressure. The domain type is normal compaction that locates any area of depression, but normal high pressure is located only deep hollow zone (depth more than 3000m), abnormal low pressures are located gentle slope and faulted abrupt slope (depth between 1200~2500m). 5.Two types dynamic systems of pool formation (enclosed and partly enclosed system) are recognized. They are composed by which source rocks are from Es3 and Es4, cap rocks are deep lacustrine shale of Esl and Es3, and sandstone reservoirs are 7 kinds of sedimentary system in Es3 and Es4. According to theory of petroleum system, two petroleum systems are divided in Es3 and Es4 of Gubei depression, which are high or normal pressure self-source system and normal or low pressure external-source system. 6.There are 3 kinds of combination model of pool formation, the first is litholgical pool of inner depression (high or normal pressure self-source type), the second is fault block or fault nose pool in marginal of depression (normal type), the third is fault block-lithological pool of central low lifted block (high or normal pressure type). The lithological pool is located central of depression, other pool are located gentle or abrupt slope that are controlled by lithological, faulting, unconfirmed. 7.This paper raise a new technique and process of exploration subtle trap which include geological modeling, coring description and logging recognition, and well log constrained inversion. These are composed to method and theory of predicting subtle trap. Application these methods and techniques, 6 hydro objects are predicted in three zone of depression.

An application of a multiple agent system for flexible assemble tasks

C.H. Orgill, N.W. Hardy, M.H. Lee, and K.A.I. Sharpe. An application of a multiple agent system for flexible assemble tasks. In Knowledge based envirnments for industrial applications including cooperating expert systems in control. IEE London, 1989.

Monitoring the vegetation start of season (SOS) across the island of Ireland using the MERIS global vegetation index

The aim of this study was to develop a methodology, based on satellite remote sensing, to estimate the vegetation Start of Season (SOS) across the whole island of Ireland on an annual basis. This growing body of research is known as Land Surface Phenology (LSP) monitoring. The SOS was estimated for each year from a 7-year time series of 10-day composited, 1.2 km reduced resolution MERIS Global Vegetation Index (MGVI) data from 2003 to 2009, using the time series analysis software, TIMESAT. The selection of a 10-day composite period was guided by in-situ observations of leaf unfolding and cloud cover at representative point locations on the island. The MGVI time series was smoothed and the SOS metric extracted at a point corresponding to 20% of the seasonal MGVI amplitude. The SOS metric was extracted on a per pixel basis and gridded for national scale coverage. There were consistent spatial patterns in the SOS grids which were replicated on an annual basis and were qualitatively linked to variation in landcover. Analysis revealed that three statistically separable groups of CORINE Land Cover (CLC) classes could be derived from differences in the SOS, namely agricultural and forest land cover types, peat bogs, and natural and semi-natural vegetation types. These groups demonstrated that managed vegetation, e.g. pastures has a significantly earlier SOS than in unmanaged vegetation e.g. natural grasslands. There was also interannual spatio-temporal variability in the SOS. Such variability was highlighted in a series of anomaly grids showing variation from the 7-year mean SOS. An initial climate analysis indicated that an anomalously cold winter and spring in 2005/2006, linked to a negative North Atlantic Oscillation index value, delayed the 2006 SOS countrywide, while in other years the SOS anomalies showed more complex variation. A correlation study using air temperature as a climate variable revealed the spatial complexity of the air temperature-SOS relationship across the Republic of Ireland as the timing of maximum correlation varied from November to April depending on location. The SOS was found to occur earlier due to warmer winters in the Southeast while it was later with warmer winters in the Northwest. The inverse pattern emerged in the spatial patterns of the spring correlates. This contrasting pattern would appear to be linked to vegetation management as arable cropping is typically practiced in the southeast while there is mixed agriculture and mostly pastures to the west. Therefore, land use as well as air temperature appears to be an important determinant of national scale patterns in the SOS. The TIMESAT tool formed a crucial component of the estimation of SOS across the country in all seven years as it minimised the negative impact of noise and data dropouts in the MGVI time series by applying a smoothing algorithm. The extracted SOS metric was sensitive to temporal and spatial variation in land surface vegetation seasonality while the spatial patterns in the gridded SOS estimates aligned with those in landcover type. The methodology can be extended for a longer time series of FAPAR as MERIS will be replaced by the ESA Sentinel mission in 2013, while the availability of full resolution (300m) MERIS FAPAR and equivalent sensor products holds the possibility of monitoring finer scale seasonality variation. This study has shown the utility of the SOS metric as an indicator of spatiotemporal variability in vegetation phenology, as well as a correlate of other environmental variables such as air temperature. However, the satellite-based method is not seen as a replacement of ground-based observations, but rather as a complementary approach to studying vegetation phenology at the national scale. In future, the method can be extended to extract other metrics of the seasonal cycle in order to gain a more comprehensive view of seasonal vegetation development.

Optimisation of chemoenzymatic processes in asymmetric synthesis

This thesis describes the optimisation of chemoenzymatic methods in asymmetric synthesis. Modern synthetic organic chemistry has experienced an enormous growth in biocatalytic methodologies; enzymatic transformations and whole cell bioconversions have become generally accepted synthetic tools for asymmetric synthesis. Biocatalysts are exceptional catalysts, combining broad substrate scope with high regio-, enantio- and chemoselectivities enabling the resolution of organic substrates with superb efficiency and selectivity. In this study three biocatalytic applications in enantioselective synthesis were explored and perhaps the most significant outcome of this work is the excellent enantioselectivity achieved through optimisation of reaction conditions improving the synthetic utility of the biotransformations. In the first chapter a summary of literature discussing the stereochemical control of baker’s yeast (Saccharomyces Cerevisae) mediated reduction of ketones by the introduction of sulfur moieties is presented, and sets the work of Chapter 2 in context. The focus of the second chapter was the synthesis and biocatalytic resolution of (±)-trans-2-benzenesulfonyl-3-n-butylcyclopentanone. For the first time the practical limitations of this resolution have been addressed providing synthetically useful quantities of enantiopure synthons for application in the total synthesis of both enantiomers of 4-methyloctanoic acid, the aggregation pheromone of the rhinoceros beetles of the genus Oryctes. The unique aspect of this enantioselective synthesis was the overall regio- and enantioselective introduction of the methyl group to the octanoic acid chain. This work is part of an ongoing research programme in our group focussed on baker’s yeast mediated kinetic resolution of 2-keto sulfones. The third chapter describes hydrolase-catalysed kinetic resolutions leading to a series of 3-aryl alkanoic acids. Hydrolysis of the ethyl esters with a series of hydrolases was undertaken to identify biocatalysts that yield the corresponding acids in highly enantioenriched form. Contrary to literature reports where a complete disappearance of efficiency and, accordingly enantioselection, was described upon kinetic resolution of sterically demanding 3-arylalkanoic acids, the highest reported enantiopurities of these acids was achieved (up to >98% ee) in this study through optimisation of reaction conditions. Steric and electronic effects on the efficiency and enantioselectivity of the biocatalytic transformation were also explored. Furthermore, a novel approach to determine the absolute stereochemistry of the enantiopure 3-aryl alkanoic acids was investigated through combination of co-crystallisation and X-ray diffraction linked with chiral HPLC analysis. The fourth chapter was focused on the development of a biocatalytic protocol for the asymmetric Henry reaction. Efficient kinetic resolution in hydrolase-mediated transesterification of cis- and trans- β-nitrocyclohexanol derivatives was achieved. Combination of a base-catalysed intramolecular Henry reaction coupled with the hydrolase-mediated kinetic resolution with the view to selective acetylation of a single stereoisomer was investigated. While dynamic kinetic resolution in the intramolecular Henry was not achieved, significant progress in each of the individual elements was made and significantly the feasibility of this process has been demonstrated. The final chapter contains the full experimental details, including spectroscopic and analytical data of all compounds synthesised in this project, while details of chiral HPLC analysis are included in the appendix. The data for the crystal structures are contained in the attached CD.

Application of mesoporous silica for the oral delivery of poorly water-soluble drugs

The objective of this thesis was to improve the dissolution rate of the poorly waters-soluble drug, fenofibrate by processing it with a high surface area carrier, mesoporous silica. The subsequent properties of the drug – silica composite were studied in terms of drug distribution within the silica matrix, solid state and release properties. Prior to commencing any experimental work, the properties of unprocessed mesoporous silica and fenofibrate were characterised (chapter 3), this allowed for comparison with the processed samples studied in later chapters. Fenofibrate was a highly stable, crystalline drug that did not adsorb moisture, even under long term accelerated storage conditions. It maintained its crystallinity even after SC-CO2 processing. Its dissolution rate was limited and dependent on the characteristics of the particular in vitro media studied. Mesoporous silica had a large surface area and mesopore volume and readily picked up moisture when stored under long term accelerated storage conditions (75% RH, 40 oC). It maintained its mesopore character after SC-CO2 processing. A variety of methods were employed to process fenofibrate with mesoporous silica including physical mixing, melt method, solvent impregnation and novel methods such as liquid and supercritical carbon dioxide (SC-CO2) (chapter 4). It was found that it was important to break down the fenofibrate particulate structure to a molecular state to enable drug molecules enter into the silica mesopores. While all processing methods led to some increase in fenofibrate release properties; the impregnation, liquid and SC-CO2 methods produced the most rapid release rates. SC-CO2 processing was further studied with a view to optimising the processing parameters to achieve the highest drug-loading efficiency possible (chapter 5). In this thesis, it was that SC-CO2 processing pressure had a bearing on drug-loading efficiency. Neither pressure, duration or depressurisation rate affected drug solid state or release properties. The amount of drug that could be loaded onto to the mesoporous silica successfully was also investigated at different ratios of drug mass to silica surface area under constant SC-CO2 conditions; as the drug – silica ratio increased, the drug-loading efficiency decreased, while there was no effect on drug solid state or release properties. The influence of the number of drug-loading steps was investigated (chapter 6) with a view to increasing the drug-loading efficiency. This multiple step approach did not yield an increase in drug-loading efficiency compared to the single step approach. It was also an objective in this chapter to understand how much drug could be loaded into silica mesopores; a method based on the known volume of the mesopores and true density of drug was investigated. However, this approach led to serious repercussions in terms of the subsequent solid state nature of the drug and its release performance; there was significant drug crystallinity and reduced release extent. The impact of in vitro release media on fenofibrate release was also studied (chapter 6). Here it was seen that media containing HCl led to reduced drug release over time compared to equivalent media not containing HCl. The key findings of this thesis are discussed in chapter 7 and included: 1. Drug – silica processing method strongly influenced drug distribution within the silica matrix, drug solid state and release. 2. The silica surface area and mesopore volume also influenced how much drug could be loaded. It was shown that SC-CO2 processing variables such as processing pressure (13.79 – 41.37 MPa), duration time (4 – 24 h) and depressurisation rate (rapid or controlled) did not influence the drug distribution within the SBA- 15 matrix, drug solid state form or release. Possible avenues of research to be considered going forward include the development and application of high resolution imaging techniques to visualise drug molecules within the silica mesopores. Also, the issues surrounding SBA-15 usage in a pharmaceutical manufacturing environment should be addressed.

DISSIMILAR CONTEMPORARIES: SELECTED PIANO MUSIC OF SERGEI RACHMANINOFF AND SERGEI PROKOFIEV

Virtual contemporaries, Sergei Rachmaninoff and Sergei Prokofiev were pianists, steeped in the traditions of Russian pianism; recordings of both pianists-composers playing their own works are available. Although the composers can be perceived as having little in common, in fact both composed in classical forms, both had a strong lyrical sense and both had an unbreakable connection with their Russian heritage. Rachmaninoff was the last great representative of Russian late Romanticism as well as one of the finest pianists of his generation. He cultivated a sweepingly passionate and melodious idiom, with pronounced lyrical quality, expressive breath and structural ingenuity. Prokofiev, on the other hand, tried to push the Russian Romantic traditions to a point of exacerbation and caricature before experimenting with various kinds of modernism. Stressing simplicity, he helped invent Neo-Classicism. His melodies are essentially tonal with wide skips and sweeping long lines. Harmonically, he used triadic harmony full of dissonances, strange inversions, unusual spacings, and jarring juxtapositions. Writing in classical forms, he incorporated rhythmic vitality and lyrical elements into his music. I have chosen to perform five works by each composer, written in a variety of genres, including the sonata, the toccata, variations, the concerto. I also have divided the pieces into three recital programs to show the idiosyncratic characteristics of the composers. I have endeavored to select pieces based on the technical and artistic challenges that they offer, thereby allowing me to grow as a pianist and an artist. My goal is to gain a thorough understanding of not only the pieces but also the musical styles of both composers.

SELECTED REPERTOIRE OF THE GILLET COMPETITION FROM 1996 TO 2006

There are many bassoon competitions around the world- and one of the most famous is the Gillet competition, sponsored by the International Double Reed Society. In 1981, it was established as an annual event, the "Femand Gillet Bassoon Competition"- a title expanded in 2000 to the "Femand Gillet-Hugo Fox Bassoon Competition." My goal was to explore the history of the competition, the availability of the repertoire selected for each competition, and the difficulties performing each piece. Through this journey, I was able to discover the variety of material chosen and how it was used, the quality, value, and the importance of the repertoire in each competition. For example, Ferdinand David's Concertino op.12, the style of the piece provides romantic, operatic type lyricism, a flashy presto section and finale, makes it as a standard romantic piece in the bassoon repertoire; Otmar Nussio's Variations on an Air by Pergolesi, contains a slow theme and few diverse variations, which provides a contemporary style music with the traditional music form and descriptive quality. The result of learning this repertoire proves that different styles of music in the competition demonstrate the artistry of the bassoon repertoire and music history in relationship of the development of the instrument. My first dissertation recital featured: Concerto for Bassoon, K. 191 by Wolfgang Amadeus Mozart; Concertino by Marcel Bitsch; Metamorphoses by Leslie Bassett; and Sonatine by Alexandre Tansman. My second recital featured: Concerto in E minor, RV 484 by Antonio Vivaldi; On the Summer Map of Stars by Gordon Kerry; Concertino Opus12 by Ferdinand David; Elegie by Jacques Hetu; and Interferences by Roger Boutry. My third recital featured: Cello Suite No.2 in D minor, BWV1008 by Johann Sebastian Bach; Combinaciones: Sonatina para Fagot y Piano by Salvador Ranieri; Andante e Rondo Ungarese Opus 35 by Carl Maria von Weber; and Variations on an Air by Pergolesi for Bassoon and Piano by Otmar Nussio.

SELECTED CHARACTER PIECES OF FRÉDÉRIC CHOPIN (1810-1849), FRANZ LISZT (1811-1886) AND JOHANNES BRAHMS (1833-1897)

During the 19th century, Frédéric Chopin (1810-1849), Franz Liszt (1811- 1886), and Johannes Brahms (1833-1897) were among the most recognized composers of character pieces. Their compositions have been considered a significant milestone in piano literature. Frédéric Chopin (1810-1849) did not give descriptive titles to his character pieces. He grouped them into several genres such as Mazurkas, Polonaises. His Mazurkas and Polonaises are influenced by Polish dance music and inspired by the polish national idiom. Franz Liszt (1811-1886) was influenced in many ways by Chopin, and adopted Chopin’s lyricism, melodic style, and tempo rubato. However, Liszt frequently drew on non-musical subjects (e.g., art, literature) for inspiration. “Harmonies poétiques et religieuses” and “Années de pèlerinage” are especially representative of character pieces in which poetic and pictorial imagination are reflected. Johannes Brahms (1833-1897) was a conservative traditionalist, synthesizing Romantic expression and Classical tradition remarkably well. Like Chopin, Brahms avoided using programmatic titles for his works. The titles of Brahms’ short character pieces are often taken from traditional lyrical or dramatic genres such as ballade, rhapsody and scherzo. Because of his conservatism, Brahms was considered the main rival of Liszt in the Romantic Period. Brahms character pieces in his third period (e.g., Scherzo Op.4, Ballades of Op.10, and Rhapsodies of Op.79) are concise and focused. The form of Brahms’ character pieces is mostly simple ternary (ABA), and his style is introspective and lyrical. Through this recording project, I was able to get a better understanding of the styles of Chopin, Brahms and Liszt through their character pieces. This recording dissertation consists of two CDs recorded in the Dekelboum Concert Hall at the University of Maryland, College Park. These recordings are documented on compact disc recordings that are housed within the University of Maryland Library System.

Resolution beyond the diffraction limit for regularized object restoration

We propose a new formulation of Miller's regularization theory, which is particularly suitable for object restoration problems. By means of simple geometrical arguments, we obtain upper and lower bounds for the errors on regularized solutions. This leads to distinguish between ' Holder continuity ' which is quite good for practical computations and ` logarithmic continuity ' which is very poor. However, in the latter case, one can reconstruct local weighted averages of the solution. This procedure allows for precise valuations of the resolution attainable in a given problem. Numerical computations, made for object restoration beyond the diffraction limit in Fourier optics, show that, when logarithmic continuity holds, the resolution is practically independent of the data noise level. © 1980 Taylor & Francis Group, LLC.

Southern Ocean biogeography and taxonomic resolution: what's in the name?

We examined the taxonomic resolution of zooplankton data required to identify ocean basin scale biogeographic zonation in the Southern Ocean. A 2,154 km transect was completed south of Australia. Sea surface temperature (SST) measured at 1 min intervals showed that seven physical zones were sampled. Zooplankton were collected at a spatial resolution of similar to 9.2 km with a continuous plankton recorder, identified to the highest possible taxonomic resolution and enumerated. Zooplankton assemblage similarity between samples was calculated using the Bray-Curtis index for the taxonomic levels of species, genus, family, order and class after first log(10)(x + 1) (LA) and then presence/absence (PA) transformation of abundance data. Although within and between zone sample similarity increased with decreasing taxonomic resolution, for both data transformations, cluster analysis demonstrated that the biogeographic separation of zones remained at all taxonomic levels when using LA data. ANOSIM confirmed this, detecting significant differences in zooplankton assemblage structure between all seven a priori determined physical zones for all taxonomic levels when using the LA data. In the case of the PA data for the complete data set, and both LA and PA data for a crustacean only data set, no significant differences were detected between zooplankton assemblages in the Polar frontal zone (PFZ) and inter-PFZ at any taxonomic level. Loss of information at resolutions below the species level, particularly in the PA data, prevented the separation of some zones. However, the majority of physical zones were biogeographically distinct from species level to class using both LA and PA transformations. Significant relationships between SST and zooplankton community structure, summarised as NMDS scores, at all taxonomic levels, for both LA and PA transformations, and complete and crustacean only data sets, highlighted the biogeographic relevance of low resolution taxonomic data. The retention of biogeographic information in low taxonomic resolution data shows that data sets collected with different taxonomic resolutions may be meaningfully merged for the post hoc generation of Southern Ocean time series.