Lack of intraspecific biological variation between two geographical populations of Oomyzus sokolowskii (Hymenoptera: Eulophidae), a gregarious larval–pupal parasitioid of Plutella xylostella (Lepidoptera: Plutellidae)

The chalcid, Oomyzus sokolowskii Kurdjumov has been recorded in many parts of the world as a major larval-pupal, gregarious endoparasitoid of the diamondback moth, Plutella xylostella (Linnaeus), a serious pest of brassica vegetable crops worldwide. This study investigated intraspecific variation between two populations of O. sokiolowskii, one from Cape Verde Islands, West Africa and the other from Hangzhou, China. In all crosses and backcrosses between the two geographical populations, the numbers of progeny and sex ratio of progeny were similar to those obtained within each of the populations, demonstrating complete reproductive compatibility between the two populations. The two populations showed similar responses to temperature with respect to development time and survival of immature stages. Observations on the interactions between the two O. sokolowskii populations and Cotesia plutellae (Kurdjumov), another major parasitoid of P. xylostella, showed that neither population could achieve successful parasitism of P. xylostella larvae already parasitized by C. plutellac. However, both O. sokolowskii populations could achieve hyperparasitism by ovipositing into a mid-late stage larva of C. plutellae developing inside the primary host. Contrary to earlier reports, no evidence of intraspecific variations in ability to hyperparasitize between these two populations of O. sokolowskii was found.

A proposed new classification system for whiplash associated disorders - implications for assessment and management

The development of chronic symptoms following whiplash injury is common and contributes substantially to costs associated with this condition. The currently used Quebec Task Force classification system of whiplash associated disorders is primarily based on the severity of signs and symptoms following injury and its usefulness has been questioned. Recent evidence is emerging that demonstrates differences in physical and psychological impairments between individuals who recover from the injury and those who develop persistent pain and disability. Motor dysfunction, local cervical mechanical hyperalgesia and psychological distress are present soon after injury in all whiplash injured persons irrespective of recovery. In contrast those individuals who develop persistent moderate/severe pain and disability show a more complex picture, characterized by additional impairments of widespread sensory hypersensitivity indicative of underlying disturbances in central pain processing as well as acute posttraumatic stress reaction, with these changes present from soon after injury. Based on this heterogeneity a new classification system is proposed that takes into account measurable disturbances in motor, sensory and psychological dysfunction. The implications for the management of this condition are discussed. (C) 2004 Elsevier Ltd. All rights reserved.

Nervous and muscle system development in Phascolion strombus (Sipuncula)

Recent interpretations of developmental gene expression patterns propose that the last common metazoan ancestor was segmented, although most animal phyla show no obvious signs of segmentation. Developmental studies of non-model system trochozoan taxa may shed light on this hypothesis by assessing possible cryptic segmentation patterns. In this paper, we present the first immunocytochemical data on the ontogeny of the nervous system and the musculature in the sipunculan Phascolion strombus. Myogenesis of the first anlagen of the body wall ring muscles occurs synchronously and not subsequently from anterior to posterior as in segmented spiralian taxa (i.e. annelids). The number of ring muscles remains constant during the initial stages of body axis elongation. In the anterior-posteriorly elongated larva, newly formed ring muscles originate along the entire body axis between existing myocytes, indicating that repeated muscle bands do not form from a posterior growth zone. During neurogenesis, the Phascolion larva expresses a non-metameric, paired, ventral nerve cord that fuses in the mid-body region in the late-stage elongated larva. Contrary to other trochozoans, Phascolion lacks any larval serotonergic structures. However, two to three FMRFamide-positive cells are found in the apical organ. In addition, late larvae show commissure-like neurones interconnecting the two ventral nerve cords, while early juveniles exhibit a third, medially placed FMRFamidergic ventral nerve. Although we did not find any indications for cryptic segmentation, certain neuro-developmental traits in Phascolion resemble the conditions found in polychaetes (including echiurans) and myzostomids and support a close relationship of Sipuncula and Annelida.

Zebrafish as a model for caveolin-associated muscle disease; caveolin-3 is required for myofibril organization and muscle cell patterning

Caveolae are an abundant feature of many animal cells. However, the exact function of caveolae remains unclear. We have used the zebrafish, Danio rerio, as a system to understand caveolae function focusing on the muscle-specific caveolar protein, caveolin-3 (Cav3). We have identified caveolin-1 (alpha and beta), caveolin-2 and Cav3 in the zebrafish. Zebrafish Cav3 has 72% identity to human CAV3, and the amino acids altered in human muscle diseases are conserved in the zebrafish protein. During embryonic development, cav3 expression is apparent by early segmentation stages in the first differentiating muscle precursors, the adaxial cells and slightly later in the notochord. cav3 expression appears in the somites during mid-segmentation stages and then later in the pectoral fins and facial muscles. Cav3 and caveolae are located along the entire sarcolemma of late stage embryonic muscle fibers, whereas beta-dystroglycan is restricted to the muscle fiber ends. Down-regulation of Cav3 expression causes gross muscle abnormalities and uncoordinated movement. Ultrastructural analysis of isolated muscle fibers reveals defects in myoblast fusion and disorganized myofibril and membrane systems. Expression of the zebrafish equivalent to a human muscular dystrophy mutant, CAV3P104L, causes severe disruption of muscle differentiation. In addition, knockdown of Cav3 resulted in a dramatic up-regulation of eng1a expression resulting in an increase in the number of muscle pioneer-like cells adjacent to the notochord. These studies provide new insights into the role of Cav3 in muscle development and demonstrate its requirement for correct intracellular organization and myoblast fusion.

Expression profiling correlates with treatment response in women with advanced serous epithelial ovarian cancer

The majority of epithelial ovarian carcinomas are of serous subtype, with most women presenting at an advanced stage. Approximately 70% respond to initial chemotherapy but eventually relapse. We aimed to find markers of treatment response that might be suitable for routine use, using the gene expression profile of tumor tissue. Thirty one women with histologically-confirmed late-stage serous ovarian cancer were classified into 3 groups based on response to treatment (nonresponders, responders with relapse less than 12 months and responders with no relapse within 12 months). Gene expression profiles of these specimens were analyzed with respect to treatment response and survival (minimum 36 months follow-up). Patients' clinical features did not correlate with prognosis, or with specific gene expression patterns of their tumors. However women who did not respond to treatment could be distinguished from those who responded with no relapse within 12 months based on 34 gene transcripts (p < 0.02). Poor prognosis was associated with high expression of inhibitor of differentiation-2 (ID2) (p = 0.001). High expression of decorin (DCN) and ID2 together was strongly associated with reduced survival (p = 0.003), with an estimated 7-fold increased risk of dying (95% CI 1.9-29.6; 14 months survival) compared with low expression (44 months). Immunohistochemical analysis revealed both nuclear and cytoplasmic distribution of ID2 in ovarian tumors. High percentage of nuclear staining vas associated with poor survival, although not statistically significantly. In conclusion, elevated expression of ID2 and DCN was significantly associated with poor prognosis in a homogeneous group of ovarian cancer patients for whom survival could not be predicted from clinical factors. (c) 2006 Wiley-Liss, Inc.

Dating paleochannel iron ore by (U-Th)/He analysis of supergene goethite, Hamersley province, Australia

(U-Th)/He dating of late-stage authigenic goethite, combined with corrections for diffusive loss of He-4 by the He-4/He-3 methodology, reveals strong correlation between a sample's age and its depth in ferruginized channel sediments from the Yandicoogina deposit, Western Australia. Corrected ages, ranging from ca. 18 Ma near the surface to ca. 5 Ma at the bottom of the profile, indicate that ferruginization of the aggraded channels becomes progressively younger with depth. This trend is consistent with goethite precipitation at the groundwater-atmosphere interface during water table drawdown driven by the aridification of Western Australia during the Neogene. The results demonstrate that the (U-Th)/He system is ideal for dating goethite if diffusive loss corrections are applied. The approach is suitable for dating weathering reactions on Earth and should also be suitable for dating Fe oxyhydroxides in the Martian regolith.

An operational approach to object-oriented software development

The traditional waterfall software life cycle model has several weaknesses. One problem is that a working version of a system is unavailable until a late stage in the development; any omissions and mistakes in the specification undetected until that stage can be costly to maintain. The operational approach which emphasises the construction of executable specifications can help to remedy this problem. An operational specification may be exercised to generate the behaviours of the specified system, thereby serving as a prototype to facilitate early validation of the system's functional requirements. Recent ideas have centred on using an existing operational method such as JSD in the specification phase of object-oriented development. An explicit transformation phase following specification is necessary in this approach because differences in abstractions between the two domains need to be bridged. This research explores an alternative approach of developing an operational specification method specifically for object-oriented development. By incorporating object-oriented concepts in operational specifications, the specifications have the advantage of directly facilitating implementation in an object-oriented language without requiring further significant transformations. In addition, object-oriented concepts can help the developer manage the complexity of the problem domain specification, whilst providing the user with a specification that closely reflects the real world and so the specification and its execution can be readily understood and validated. A graphical notation has been developed for the specification method which can capture the dynamic properties of an object-oriented system. A tool has also been implemented comprising an editor to facilitate the input of specifications, and an interpreter which can execute the specifications and graphically animate the behaviours of the specified systems.

Recent and Miocene carbonate sediments from Indonesia. Available in 2 volumes.

Mapping and sediment sampling in reefs of the Pulau Seribu group (southwest Java Sea) shows the existence of ten physiographic zones and subzones represented by seven lithofacies. Reefs in the northern part of the archipelago are smaller, more closely spaced and morphologically sim pler than those in the south. This pattern is attributed to differences in subsidence rate. A th reedimensional model is proposed for the evo lution of these reefs but borehole data are requi red to test this model. Miocene limestones are described in detail from hydrocarbon reservoirs in the Batu Raja Formation of the same area. Brief comparisons a re made with surface outcrops of approximately coeval carbonate developments. The lithofacies developed within these limestones reflect variations in hydrodynam ic regime and basement topography . Ele\le.n diagenetic processes affected the Batu Raja limestones and the dist ribution of these is primarily related to sealevel fluctuations. Early diagenesis was marine and characterised by micritisation and preCipitation of fibrous and bladed cements. Dolomitisat ion occurred in the mixed- water zone and its variable intensity is attributed to the configuration of the carbonate body relative to this zone. Subsequently the limestones were subjected to freshwater phreatic zone diagenesis resulting in dissolution and cementation, and a t a late stage underwent burial compaction. Secondary porosity, which \ar9e1.y determines the suitability of these limestones as hydrocarbon reserVOirs, is a function of the variable intensity of dissolution and cementation, burial compaction, dolomitisation and possibly micrite neomorphism. The sedimentary processes that generated the Batu Raja buildups are inferred f rom comparisons with the Pulau Seribu and other Recent analogues. The contrasting pinnacle form of the Pulau Seribu patch reefs compared with the low relief of the Batu Raja buUdups results from differences in the initial substrate topography and subsequent subsidence rate

Quantification of visual field loss in age-related macular degeneration

Presentation Purpose:To determine methods of quantifying the sensitivity loss in the central 10o visual field in a cross section of patients at various stages of age-related macular degeneration (AMD). Methods:Standard and short-wavelength automated perimetry (SAP and SWAP) visual fields were collected using program 10-2 of the Humphrey Field Analyzer, in 44 eyes of 27 patients with AMD and 41 eyes of 22 normal subjects. Stereoscopic fundus photographs were graded by two independent observers and the stage of disease determined. Global indices were compared for their ability to delineate the normal visual field from early stages of AMD and to differentiate between stages. Results:Mean Deviation (MD) and Pattern Standard Deviation (PSD) varied significantly with stage of disease in SAP (both p<0.001) and SWAP (both p<0.001), but post-hoc analysis revealed overlap of functional values between stages. Global indices of focal loss, PSD and local spatial variability (LSV) were the most sensitive to detecting differences between normal subjects and early stage AMD patients, in SAP and SWAP, respectively. Overall, defects were confined to the central 5°. SWAP defects were consistently greater in depth and area than those in SAP. The most vulnerable region of the 10° field to sensitivity loss with increasing stage of AMD was the central 1°, in which the sensitivity decline was -4.8dB per stage in SAP and -4.9dB per stage in SWAP. Based on the pattern deviation defect maps, a severity index of AMD visual field loss was derived. Threshold variability was considerably increased in late stage AMD eyes. Conclusions:Global indices of focal loss were more sensitive to the detection of early stage AMD from normal. The sensitivity decline with advancing stage of AMD was greater in SWAP compared to SAP, however the trend was not strong across all stages of disease. The less commonly used index LSV represents relatively statistically unmanipulated summary measure of focal loss. A new severity index is described which is sensitive to visual field change in AMD, measures visual field defects on a continuous scale and may serve as a useful measure of functional change in AMD in longitudinal studies. Keywords: visual fields • age-related macular degeneration • perimetry

Visual field and structural correlates of progression in age-related macular degeneration

Presentation Purpose:To examine the correlation of central visual field loss and progression of structural changes in the macular area in age-related macular degeneration (AMD). Methods:Central 10° standard and short-wavelength automated perimetry (SWAP) visual fields were acquired in 39 eyes of 24 patients with AMD using a Humphrey Field Analyzer. Stereoscopic fundus photographs were graded1 by two independent observers and the stage of disease determined2. Custom software mapped perimetric data onto fundus images in order to relate structural changes to functional loss. Results:Mean deviation (MD) in standard perimetry changed from 0.04 dB at stage 1 to -12.39 dB at stage 4 (r2=0.48, p<0.001). The group mean SWAP MD was -5.26 dB at stage 1 and increased to -17.08 dB at stage 4 (r2=0.53, p<0.001). Pattern standard deviation (PSD) also increased with advancing stage in standard perimetry; 1.32 dB to 8.67 dB at stage 1 and 4, respectively (r2=0.54, p<0.001). In SWAP, PSD increased from 2.86 dB to 5.63 dB at stage 1 and stage 4 (r2=0.43, p<0.001). Defect frequency was greater in SWAP than standard perimetry. Early stage defects occurred with the greatest frequency at eccentricities of 3.2° and 5.1° in standard perimetry and at 4.2° in SWAP. Late stage defects were most frequent at 1° eccentricity in standard perimetry and at 1° and 9° in SWAP. MD declined with increasing affected retinal area over the central 3000µm; by 0.20 dB (r2=0.67, p<0.001) and 0.18 dB (r2=0.49, p<0.001) per % increase in defect area for standard perimetry and SWAP respectively. 41% of defects were associated with structural changes on the retina in standard perimetry and 43% in SWAP. Conclusions:Sensitivity decreased with advancing stage of AMD, with a greater effect demonstrated in SWAP compared to standard perimetry. The central field became less uniform as stage increased. SWAP defects occurred at similar locations but were deeper and wider than corresponding defects in standard perimetry. Central loss in SWAP is a sensitive marker of functional progression in AMD.1. Bird et al. (1995) Surv Ophthalmol 39:367-3742. van Leeuwen et al. (2003) Arch Ophthalmol 121:519-526

Influência da paridade, do tipo de parto e do nível de atividade física sobre a musculatura do assoalho pélvico em mulheres na pós-menopausa

The post-menopause stage is characterized by hormonal and organic alterations of ovarian failure. One of the most important of these is muscles alterations of the pelvic floor (MPF). According to current literature, in young women gynecological and obstetric factors, as well as lifestyles and habits influence that loss of function. However, there is still uncertainty about the influence of those variables in the MPF functions in post-menopause women. Thus, this study aimed at seeing if there is an influence from number of births, the type of birth and the level of physical activity on the MPF of post-menopause women. Another objective of this study was to compare MPF force in women who had had vaginal births with those who had been subjected to cesarean sections, those with different levels of physical activity and those with artificial and natural menopause in the initial and latter stages. Furthermore, the test of muscular force was compared to perineometry. Using observational, analytical and transversal observations, 100 women in the post-menopausal stage of life, between the ages of 45 and 65, were examined. They were divided according to the menopausal stage into three groups: women who had undergone hysterectomies, those in the initial stages of postmenopause and those in the late stage of postmenpause. The patients were questioned about social, demographic, gynecological and obstetric factors. All the volunteers were submitted to a physical examination where their height and weight were measured to arrive at the corporal mass index and their waist measurements were taken. The evaluation of the pelvic floor was conducted with muscular force tests and perineometry. These results were analyzed with statistical description and ANOVA statistical tests, multiple regression and Kolmogorov-Smirnov evaluations. The results showed homogeneity with regard to social demographic and anthropometric characteristics among the women in the final test sample (n=85). It was also seen that most of the women in all three groups were married (p=0.51) and catholic (p=0.13). The average per capital income varied between $R585.47 (+/-466.67) and $R1,271.83 (+/-1,748.95), with no significant difference between the groups (p=0.05). The G>6 group presented an average age between 58.95 (+/-3.96) which was significantly greater that the G<6 group´s average age (53.21+/- 3.88) (p=0.000). There was no difference between the groups´ anthropometric characteristics of weight (p=0.32), height (p=0.72) and corporal mass index (p=0.34), nor in the waist measurements (p=0.33). Furthermore, no significant difference was noted in the MPF function of women who had had normal births, cesarean sections or a combination of the two (TFM p=0.897; perineum measurement p=0.502). Likewise, no differences were seen in the MPF function of women who had one, two to three or four or more births (TFM p=0.28, perineum measurement p=0.13). Finally, no difference was perceived among those with different levels of physical activity (TFM p=0.663; perineum measurement p=0.741). Therefore, we found that the type of delivery, number of births and physical activity had no influence on the muscular function of the pelvic floor among the women studied. It is believed that decline in muscular function in post-menopause women is fundamentally related to the process of aging.

Synthesis and Properties of a Series of 1,1,n,n-Tetramethyl[n](2,11)teropyrenophanes

The work described in this thesis revolves around the 1,1,n,ntetramethyl[n](2,11)teropyrenophanes, which are a series of [n]cyclophanes with a severely bent, board-shaped polynuclear aromatic hydrocarbons (PAH). The thesis is divided into seven Chapters. The first Chapter conatins an overview of the seminal work on [n]cyclophanes of the first two members of the “capped rylene” series of PAHs: benzene and pyrene. Three different general strategies for the synthesis of [n]cyclophanes are discussed and this leads in to a discussion of some slected syntheses of [n]paracyclopahnes and [n](2,7)pyrenophanes. The chemical, structural, spectroscopic and photophysical properties of these benzene and pyrene-derived cyclophanes are discussed with emphasis on the changes that occur with changes in the structure of the aromatic system. Chapter 1 concludes with a brief introduction to [n]cyclophanes of the fourth member of the capped rylene series of PAHs: teropyrene. The focus of the work described in Chapter 2 is the synthesis of of 1,1,n,ntetramethyl[n](2,11)teropyrenophane (n = 6 and 7) using a double-McMurry strategy. While the synthesis 1,1,7,7-tetramethyl[7](2,11)teropyrenophane was successful, the synthesis of the lower homologue 1,1,6,6-tetramethyl[6](2,11)teropyrenophane was not. The conformational behaviour of [n.2]pyrenophanes was also studied by 1H NMR spectroscopy and this provided a conformation-based rationale for the failure of the synthesis of 1,1,6,6-tetramethyl[6](2,11)teropyrenophane. Chapter 3 contains details of the synthesis of 1,1,n,n-tetramethyl[n](2,11)teropyrenophanes (n = 7-9) using a Wurtz / McMurry strategy, which proved to be more general than the double McMurry strategy. The three teropyrenophanes were obtained in ca. 10 milligram quantities. Trends in the spectroscopic properties that accompany changes in the structure of the teropyrene system are discussed. A violation of Kasha’s rule was observed when the teropyrenophanes were irradiated at 260 nm. The work described in the fourth Chapter concentrates on the development of gram-scale syntheses of 1,1,n,n-tetramethyl[n](2,11)teropyrenophanes (n = 7–10) using the Wurtz / McMurry strategy. Several major modifications to the orginal synthetic pathway had to be made to enable the first several steps to be performed comfortably on tens of grams of material. Solubility problems severely limited the amount of material that could be produced at a late stage of the synthetic pathways leading to the evennumbered members of the series (n = 8, 10). Ultimately, only 1,1,9,9- tetramethyl[9](2,11)teropyrenophane was synthesized on a multi-gram scale. In the final step in the synthesis, a valence isomerization / dehydrogenation (VID) reaction, the teropyrenophane was observed to become unstable under the conditions of its formation at n = 8. The synthesis of 1,1,10,10-tetramethyl[10](2,11)teropyrenophane was achieved for the first time, but only on a few hundred milligram scale. In Chapter 5, the results of an investigation of the electrophilic aromatic bromination of the 1,1,n,n-tetramethyl[n](2,11)teropyrenophanes (n = 7–10) are presented. Being the most abundant cyclophane, most of the work was performed on 1,1,9,9-tetramethyl[9](2,11)teropyrenophane. Reaction of this compound with varying amounts of of bromine revealed that bromination occurs most rapidly at the symmetryrelated 4, 9, 13 and 18 positions (teropyrene numbering) and that the 4,9,13,18- tetrabromide could be formed exclusively. Subsequent bromination occurs selectively on the symmetry-related 6, 7, 15 and 16 positions (teropyrene numbering), but considerably more slowly. Only mixtures of penta-, hexa-, hepta and octabromides could be formed. Bromination reactions of the higher and lower homologues (n = 7, 8 and 10) revealed that the reactivity of the teropyrene system increased with the degree of bend. Crystal structures of some tetra-, hexa-, hepta- and octa-brominated products were obtained. The goal of the work described in Chapter 6 is to use 1,1,9,9- tetramethyl[9](2,11)teropyrenophane as a starting material for the synthesis of warped nanographenophanes. A bromination, Suzuki-Miyaura, cyclodehydrogenation sequence was unsuccessful, as was a C–H arylation / cyclodehydrogenation approach. Itami’s recently-developed K-region-selective annulative -extension (APEX) reaction proved to be successful, affording a giant [n]cyclophane with a C84 PAH. Attempted bay-region Diels-Alder reactions and some cursory host-guest chemistry of teropyrenophanes are also discussed. In Chapter 7 a synthetic approach toward a planar model compound, 2,11-di-tbutylteropyrene, is described. The synthesis could not be completed owing to solubility problems at the end of the synthetic pathway.

Stable carbon and oxygen isotope ratios of planktonic foraminifera from the equatorial Atlantic

Carbon isotopic records of nutrient-depleted surface water place constraints on the past fertility of the oceans and on past atmospheric pCO2 levels. The best records of nutrient-depleted delta13C are obtained from planktonic foraminifera living in the thick mixed layers of the western equatorial and tropical Atlantic Ocean. We have produced a composite, stacked Globigerinoides sacculifer delta13C record from the equatorial Atlantic, which exhibits significant spectral power at the 100,000- and 41,000-year Milankovitch periods, but no power at the 23,000-year period. Similar to the record presented by Shackleton and Pisias [1985], surface-deep ocean Delta delta13C produced with the G. sacculifer record leads the delta18O ice volume record. However, the glacial-interglacial amplitudes of Delta delta13C differ between our record and Shackleton and Pisias [1985] record. Although large changes in Delta delta13C occur in the equatorial Atlantic during early stages of the last three glacial cycles, surface-deep Delta delta13C at glacial maxima (18O stage 2, late stage 6, and late stage 8) was only about 0.2? greater than during the subsequent interglacial. Our results imply that nutrient-driven pCO2 changes account for about one third of the pCO2 decrease observed in ice cores, and consequently, Delta delta13C should not be used as a proxy pCO2 index. Enough variance in the ice core pCO2 records remains to be explained that conclusions about pCO2 and ice volume phase relationships should also be reexamined. As much as 40 ppm pCO2 change still has not been accounted for by models of past physics and chemistry of the ocean.

A long non-coding RNA targets microRNA miR-34a to regulate colon cancer stem cell asymmetric division.

The roles of long non-coding RNAs (lncRNAs) in regulating cancer and stem cells are being increasingly appreciated. Its diverse mechanisms provide the regulatory network with a bigger repertoire to increase complexity. Here we report a novel LncRNA, Lnc34a, that is enriched in colon cancer stem cells (CCSCs) and initiates asymmetric division by directly targeting the microRNA miR-34a to cause its spatial imbalance. Lnc34a recruits Dnmt3a via PHB2 and HDAC1 to methylate and deacetylate the miR-34a promoter simultaneously, hence epigenetically silencing miR-34a expression independent of its upstream regulator, p53. Lnc34a levels affect CCSC self-renewal and colorectal cancer (CRC) growth in xenograft models. Lnc34a is upregulated in late-stage CRCs, contributing to epigenetic miR-34a silencing and CRC proliferation. The fact that lncRNA targets microRNA highlights the regulatory complexity of non-coding RNAs (ncRNAs), which occupy the bulk of the genome.

Studies in asymmetric and heterocyclic synthesis: I. chiral ketones II. Quinolones III. Trifluoromethylated pyrones

This thesis is split into three sections based on three different areas of research. In the first section, investigations into the α-alkylation of ketones using a novel chiral auxiliary is reported. This chiral auxiliary was synthesised containing a pyrrolidine ring in the chiral arm and was applied in the preparation of α-alkylated ketones which were obtained in up to 92% ee and up to 63% yield over two steps. Both 3-pentanone and propiophenone based ketones were used in the investigation with a variety of both alkyl and benzyl based electrophiles. The novel chiral auxiliary was also successful when applied to Michael and aldol reactions. A diamine precursor en route to the chiral auxiliary was also applied as an organocatalyst in a Michael reaction, with the product obtained in excellent enantioselectivity. In the second section, investigations into potential anti-quorum sensing molecules are reported. The bacteria Pseudomonas aeruginosa is an antibiotic-resistant pathogen that demonstrates cooperative behaviours and communicates using small chemical molecules in a process termed quorum sensing. A variety of C-3 analogues of the quorum sensing molecules used by P. aeruginosa were synthesised. Expanding upon previous research within the group, investigations were carried out into alternative protecting group strategies of 2-heptyl-4-(1H)- quinolone with the aim of improving the yields of products of cross-coupling reactions. In the third section, investigations into fluorination and trifluoromethylation of 2-pyrones, pyridones and quinolones is reported. The incorporation of a fluorine atom or a trifluoromethyl group into a molecule is important in pharmaceutical drug discovery programmes as it can lead to increased lipophilicity and bioavailability, however late-stage incorporation is rarely reported. Both direct fluorination and trifluoromethylation were attempted. Eight trifluoromethylated 2-pyrones, five trifluoromethylated 2-pyridones and a trifluoromethylated 2-quinolone were obtained in a late-stage synthesis from their respective iodinated precursors using methyl fluorosulfonyldifluoroacetate as a trifluoromethylating reagent.