Characterising novel anti-biofilm targets for the treatment of chronic Pseudomonas aeruginosa infection in the cystic fibrosis lung

The global rise in antibiotic resistance is a significant problem facing healthcare professionals. In particular within the cystic fibrosis (CF) lung, bacteria can establish chronic infection and resistance to a wide array of antibiotic therapies. One of the principle pathogens associated with chronic infection in the CF lung is Pseudomonas aeruginosa. P. aeruginosa can establish chronic infection in the CF lung partly through the use of the biofilm mode of growth. This biofilm mode of growth offers a considerable degree of protection from a wide variety of challenges such as the host immune system or antibiotic therapy. The threat posed by the emergence of chronic pathogens is prompting the development of next generation antimicrobials. The biofilm mode of growth is often central to the establishment of chronic infection and the development of antibiotic resistance. Thus, targeting biofilm formation has emerged as one of the principle strategies for the development of next generation antimicrobials. In this thesis two separate approaches were used to identify potential anti - biofilm targets. The first strategy focused on the identification of novel genes with a role in a biofilm formation. High throughput screening identified almost 300 genes which had a role in biofilm formation. A number of these genes were characterised at a phenotypic and a molecular level. The second strategy focused on the identification of compounds capable of inhibiting biofilm formation. A collection of marine sponge isolated bacteria were screened for the ability to inhibit the central pathway regulating biofilm formation, quorum sensing. A number of distinct isolates were identified that had quorum sensing inhibition activity from which, a Pseudomonas isolate was selected for further characterisation. A specific compound capable of inhibiting quorum sensing was identified using chemical analytical technologies in the supernatant of this marine isolate.

Optical micro- and nanofibres: Higher mode generation and particle manipulation studies

This thesis is centred on two experimental fields of optical micro- and nanofibre research; higher mode generation/excitation and evanescent field optical manipulation. Standard, commercial, single-mode silica fibre is used throughout most of the experiments; this generally produces high-quality, single-mode, micro- or nanofibres when tapered in a flame-heated, pulling rig in the laboratory. Single mode fibre can also support higher transverse modes, when transmitting wavelengths below that of their defined single-mode regime cut-off. To investigate this, a first-order Laguerre-Gaussian beam, LG01 of 1064 nm wavelength and doughnut-shaped intensity profile is generated free space via spatial light modulation. This technique facilitates coupling to the LP11 fibre mode in two-mode fibre, and convenient, fast switching to the fundamental mode via computer-generated hologram modulation. Following LP11 mode loss when exponentially tapering 125μm diameter fibre, two mode fibre with a cladding diameter of 80μm is selected fir testing since it is more suitable for satisfying the adiabatic criteria for fibre tapering. Proving a fruitful endeavour, experiments show a transmission of 55% of the original LP11 mode set (comprising TE01, TM01, HE21e,o true modes) in submicron fibres. Furthermore, by observing pulling dynamics and progressive mode-lass behaviour, it is possible to produce a nanofibre which supports only the TE01 and TM01 modes, while suppressing the HE21e,o elements of the LP11 group. This result provides a basis for experimental studies of atom trapping via mode-interference, and offers a new set of evanescent field geometries for sensing and particle manipulation applications. The thesis highlights the experimental results of the research unit’s Cold Atom subgroup, who successfully integrated one such higher-mode nanofibre into a cloud of cold Rubidium atoms. This led to the detection of stronger signals of resonance fluorescence coupling into the nanofibre and for light absorption by the atoms due to the presence of higher guided modes within the fibre. Theoretical work on the impact of the curved nanofibre surface on the atomic-surface van der Waals interaction is also presented, showing a clear deviation of the potential from the commonly-used flat-surface approximation. Optical micro- and nanofibres are also useful tools for evanescent-field mediated optical manipulation – this includes propulsion, defect-induced trapping, mass migration and size-sorting of micron-scale particles in dispersion. Similar early trapping experiments are described in this thesis, and resulting motivations for developing a targeted, site-specific particle induction method are given. The integration of optical nanofibres into an optical tweezers is presented, facilitating individual and group isolation of selected particles, and their controlled positioning and conveyance in the evanescent field. The effects of particle size and nanofibre diameter on pronounced scattering is experimentally investigated in this systems, as are optical binding effects between adjacent particles in the evanescent field. Such inter-particle interactions lead to regulated self-positioning and particle-chain speed enhancements.

A microscopic study of structural and electronic properties of functionalized silicon surfaces based on first-principles

Surface modification of silicon with organic monolayers tethered to the surface by different linkers is an important process in realizing future (opto-)electronic devices. Understanding the role played by the nature of the linking group and the chain length on the adsorption structures and electronic properties of these assemblies is vital to advance this technology. This Thesis is a study of such properties and contributes in particular to a microscopic understanding of induced changes in the work function of experimentally studied functionalized silicon surfaces. Using first-principles density functional theory (DFT), at the first step, we provide predictions for chemical trends in the work function of hydrogenated silicon (111) surfaces modified with various terminations. For nonpolar terminating atomic species such as F, Cl, Br, and I, the change in the work function is directly proportional to the amount of charge transferred from the surface, thus relating to the difference in electronegativity of the adsorbate and silicon atoms. The change is a monotonic function of coverage in this case, and the work function increases with increasing electronegativity. Polar species such as −TeH, −SeH, −SH, −OH, −NH2, −CH3, and −BH2 do not follow this trend due to the interaction of their dipole with the induced electric field at the surface. In this case, the magnitude and sign of the surface dipole moment need to be considered in addition to the bond dipole to generally describe the change in work function. Compared to hydrogenated surfaces, there is slight increase in the work function of H:Si(111)-XH, where X = Te, Se, and S, whereas reduction is observed for surfaces covered with −OH, −CH3, and −NH2. Next, we study the hydrogen passivated Si(111) surface modified with alkyl chains of the general formula H:Si–(CH2)n–CH2 and H:Si–X–(CH2)n–CH3, where X = NH, O, S and n = (0, 1, 3, 5, 7, 9, 11), at half coverage. For (X)–Hexyl and (X)–Dodecyl functionalization, we also examined various coverages up to full monolayer grafting in order to validate the result of half covered surface and the linker effect on the coverage. We find that it is necessary to take into account the van der Waals interaction between the alkyl chains. The strongest binding is for the oxygen linker, followed by S, N, and C, irrespective of chain length. The result revealed that the sequence of the stability is independent of coverage; however, linkers other than carbon can shift the optimum coverage considerably and allow further packing density. For all linkers apart from sulfur, structural properties, in particular, surface-linker-chain angles, saturate to a single value once n > 3. For sulfur, we identify three regimes, namely, n = 0–3, n = 5–7, and n = 9–11, each with its own characteristic adsorption structures. Where possible, our computational results are shown to be consistent with the available experimental data and show how the fundamental structural properties of modified Si surfaces can be controlled by the choice of linking group and chain length. Later we continue by examining the work function tuning of H:Si(111) over a range of 1.73 eV through adsorption of alkyl monolayers with general formula -[Xhead-group]-(CnH2n)-[Xtail-group], X = O(H), S(H), NH(2). The work function is practically converged at 4 carbons (8 for oxygen), for head-group functionalization. For tail-group functionalization and with both head- and tail-groups, there is an odd-even effect in the behavior of the work function, with peak-to-peak amplitudes of up to 1.7 eV in the oscillations. This behavior is explained through the orientation of the terminal-group's dipole. The shift in the work function is largest for NH2-linked and smallest for SH-linked chains and is rationalized in terms of interface dipoles. Our study reveals that the choice of the head- and/or tail-groups effectively changes the impact of the alkyl chain length on the work function tuning using self-assembled monolayers and this is an important advance in utilizing hybrid functionalized Si surfaces. Bringing together the understanding gained from studying single type functionalization of H:Si(111) with different alkyl chains and bearing in mind how to utilize head-group, tail-group or both as well as monolayer coverage, in the final part of this Thesis we study functionalized H:Si(111) with binary SAMs. Aiming at enhancing work function adjustment together with SAM stability and coverage we choose a range of terminations and linker-chains denoted as –X–(Alkyl) with X = CH3, O(H), S(H), NH(2) and investigate the stability and work function of various binary components grafted onto H:Si(111) surface. Using binary functionalization with -[NH(2)/O(H)/S(H)]-[Hexyl/Dodecyl] we show that work function can be tuned within the interval of 3.65-4.94 eV and furthermore, enhance the SAM’s stability. Although direct Si-C grafted SAMs are less favourable compared to their counterparts with O, N or S linkage, regardless of the ratio, binary functionalized alkyl monolayers with X-alkyl (X = NH, O) is always more stable than single type alkyl functionalization with the same coverage. Our results indicate that it is possible to go beyond the optimum coverage of pure alkyl functionalized SAMs (50%) by adding a linker with the correct choice of the linker. This is very important since dense packed monolayers have fewer defects and deliver higher efficiency. Our results indicate that binary anchoring can modify the charge injection and therefore bond stability while preserving the interface electronic structure.

Satisfaction and acceptance with learning management systems

More and more often, universities make the decision to implement integrated learning management systems. Nevertheless, these technological developments are not realized without any trouble, and are achieved with more or less success and user satisfaction (Valenduc, 2000). It is why the presented study aims at identifying the factors influencing learning management system satisfaction and acceptance among students. The Technology Acceptance model created by Wixom and Todd (2005) studies information system acceptance through user satisfaction, and has the benefit of incorporating several ergonomic factors. More precisely, the survey, based on this model, investigates behavioral attitudes towards the system, perceived ease of use, perceived usefulness, as well as system satisfaction, information satisfaction and also incorporates two groups of factors affecting separately the two types of satisfaction. The study was conducted on a representative sample of 593 students from a Brussels university which had recently implemented an integrated learning management system. The results show on one hand, the impact of system reliability, accessibility, flexibility, lay-out and functionalities offered on system satisfaction. And on the other hand, the impact of information accuracy, intelligibility, relevance, exhaustiveness and actualization on information satisfaction. In conclusion, the results indicate the applicability of the theoretical model with learning management systems, and also highlight the importance of each aforementioned factor for a successful implantation of such a system in universities.

Multi-touch accceptance: perceived disorientation and consequences on task engagement

The research project takes place within the technology acceptability framework which tries to understand the use made of new technologies, and concentrates more specifically on the factors that influence multi-touch devices’ (MTD) acceptance and intention to use. Why be interested in MTD? Nowadays, this technology is used in all kinds of human activities, e.g. leisure, study or work activities (Rogowski and Saeed, 2012). However, the handling or the data entry by means of gestures on multi-touch-sensitive screen imposes a number of constraints and consequences which remain mostly unknown (Park and Han, 2013). Currently, few researches in ergonomic psychology wonder about the implications of these new human-computer interactions on task fulfillment.This research project aims to investigate the cognitive, sensori-motor and motivational processes taking place during the use of those devices. The project will analyze the influences of the use of gestures and the type of gesture used: simple or complex gestures (Lao, Heng, Zhang, Ling, and Wang, 2009), as well as the personal self-efficacy feeling in the use of MTD on task engagement, attention mechanisms and perceived disorientation (Chen, Linen, Yen, and Linn, 2011) when confronted to the use of MTD. For that purpose, the various above-mentioned concepts will be measured within a usability laboratory (U-Lab) with self-reported methods (questionnaires) and objective indicators (physiological indicators, eye tracking). Globally, the whole research aims to understand the processes at stakes, as well as advantages and inconveniences of this new technology, to favor a better compatibility and adequacy between gestures, executed tasks and MTD. The conclusions will allow some recommendations for the use of the DMT in specific contexts (e.g. learning context).

Distribution of HPV genotypes in cervical intraepithelial lesions and cervical cancer in Tanzanian women.

BACKGROUND: Infection with human papillomavirus (HPV) is associated with uterine cervical intraepithelial neoplasia (CIN) and invasive cancers (ICC). Approximately 80% of ICC cases are diagnosed in under-developed countries. Vaccine development relies on knowledge of HPV genotypes characteristic of LSIL, HSIL and cancer; however, these genotypes remain poorly characterized in many African countries. To contribute to the characterization of HPV genotypes in Northeastern Tanzania, we recruited 215 women from the Reproductive Health Clinic at Kilimanjaro Christian Medical Centre. Cervical scrapes and biopsies were obtained for cytology and HPV DNA detection. RESULTS: 79 out of 215 (36.7%) enrolled participants tested positive for HPV DNA, with a large proportion being multiple infections (74%). The prevalence of HPV infection increased with lesion grade (14% in controls, 67% in CIN1 cases and 88% in CIN2-3). Among ICC cases, 89% had detectable HPV. Overall, 31 HPV genotypes were detected; the three most common HPV genotypes among ICC were HPV16, 35 and 45. In addition to these genotypes, co-infection with HPV18, 31, 33, 52, 58, 68 and 82 was found in 91% of ICC. Among women with CIN2-3, HPV53, 58 and 84/83 were the most common. HPV35, 45, 53/58/59 were the most common among CIN1 cases. CONCLUSIONS: In women with no evidence of cytological abnormalities, the most prevalent genotypes were HPV58 with HPV16, 35, 52, 66 and 73 occurring equally. Although numerical constraints limit inference, findings that 91% of ICC harbor only a small number of HPV genotypes suggests that prevention efforts including vaccine development or adjuvant screening should focus on these genotypes.

Human CD19 and CD40L deficiencies impair antibody selection and differentially affect somatic hypermutation.

Individuals with genetic defects in CD40 ligand (CD40L) or B-cell antigen receptor coreceptor molecules CD19 and CD81 suffer from an antibody deficiency. Still, these patients carry low levels of memory B cells and serum antibodies.

Multi-touch and keyboard/mouse devices comparison in an information search task: influence on cognitive load and task engagement

Nowadays multi-touch devices (MTD) can be found in all kind of contexts. In the learning context, MTD availability leads many teachers to use them in their class room, to support the use of the devices by students, or to assume that it will enhance the learning processes. Despite the raising interest for MTD, few researches studying the impact in term of performance or the suitability of the technology for the learning context exist. However, even if the use of touch-sensitive screens rather than a mouse and keyboard seems to be the easiest and fastest way to realize common learning tasks (as for instance web surfing behaviour), we notice that the use of MTD may lead to a less favourable outcome. The complexity to generate an accurate fingers gesture and the split attention it requires (multi-tasking effect) make the use of gestures to interact with a touch-sensitive screen more difficult compared to the traditional laptop use. More precisely, it is hypothesized that efficacy and efficiency decreases, as well as the available cognitive resources making the users’ task engagement more difficult. Furthermore, the presented study takes into account the moderator effect of previous experiences with MTD. Two key factors of technology adoption theories were included in the study: familiarity and self-efficacy with the technology.Sixty university students, invited to a usability lab, are asked to perform information search tasks on an online encyclopaedia. The different tasks were created in order to execute the most commonly used mouse actions (e.g. right click, left click, scrolling, zooming, key words encoding…). Two different conditions were created: (1) MTD use and (2) laptop use (with keyboard and mouse). The cognitive load, self-efficacy, familiarity and task engagement scales were adapted to the MTD context. Furthermore, the eye-tracking measurement would offer additional information about user behaviours and their cognitive load.Our study aims to clarify some important aspects towards the usage of MTD and the added value compared to a laptop in a student learning context. More precisely, the outcomes will enhance the suitability of MTD with the processes at stakes, the role of previous knowledge in the adoption process, as well as some interesting insights into the user experience with such devices.

Jezelf kunnen zijn komt je levenskwaliteit ten goede: ULB peilt naar situatie van holebien transgenderwerknemers

info:eu-repo/semantics/published

Exploring the benefits of using multi-touch devices in performing information search tasks: An analysis in terms of performance, cognitive load and task engagement

Over the last decade, multi-touch devices (MTD) have spread in a range of contexts. In the learning context, MTD accessibility leads more and more teachers to use them in their classroom, assuming that it will improve the learning activities. Despite a growing interest, only few studies have focused on the impacts of MTD use in terms of performance and suitability in a learning context.However, even if the use of touch-sensitive screens rather than a mouse and keyboard seems to be the easiest and fastest way to realize common learning tasks (as for instance web surfing), we notice that the use of MTD may lead to a less favorable outcome. More precisely, tasks that require users to generate complex and/or less common gestures may increase extrinsic cognitive load and impair performance, especially for intrinsically complex tasks. It is hypothesized that task and gesture complexity will affect users’ cognitive resources and decrease task efficacy and efficiency. Because MTD are supposed to be more appealing, it is assumed that it will also impact cognitive absorption. The present study also takes into account user’s prior knowledge concerning MTD use and gestures by using experience with MTD as a moderator. Sixty university students were asked to perform information search tasks on an online encyclopedia. Tasks were set up so that users had to generate the most commonly used mouse actions (e.g. left/right click, scrolling, zooming, text encoding…). Two conditions were created: MTD use and laptop use (with mouse and keyboard) in order to make a comparison between the two devices. An eye tracking device was used to measure user’s attention and cognitive load. Our study sheds light on some important aspects towards the use of MTD and the added value compared to a laptop in a student learning context.

Antibody deficiency due to a missense mutation in CD19 demonstrates the importance of the conserved tryptophan 41 in immunoglobulin superfamily domain formation.

Immunoglobulin superfamily (IgSF) domains are conserved structures present in many proteins in eukaryotes and prokaryotes. These domains are well-capable of facilitating sequence variation, which is most clearly illustrated by the variable regions in immunoglobulins (Igs) and T cell receptors (TRs). We studied an antibody-deficient patient suffering from recurrent respiratory infections and with impaired antibody responses to vaccinations. Patient's B cells showed impaired Ca(2+) influx upon stimulation with anti-IgM and lacked detectable CD19 membrane expression. CD19 sequence analysis revealed a homozygous missense mutation resulting in a tryptophan to cystein (W52C) amino acid change. The affected tryptophan is CONSERVED-TRP 41 located on the C-strand of the first extracellular IgSF domain of CD19 and was found to be highly conserved, not only in mammalian CD19 proteins, but in nearly all characterized IgSF domains. Furthermore, the tryptophan is present in all variable domains in Ig and TR and was not mutated in 117 Ig class-switched transcripts of B cells from controls, despite an overall 10% amino acid change frequency. In vitro complementation studies and CD19 western blotting of patient's B cells demonstrated that the mutated protein remained immaturely glycosylated. This first missense mutation resulting in a CD19 deficiency demonstrates the crucial role of a highly conserved tryptophan in proper folding or stability of IgSF domains.

Pl2 resistance gene differentiates the pathogenicity in four "Plasmopara halstedii" (sunflower downy mildew) races 304, 704, 314 and 714

In order to clarify the role of Pl2 resistance gene in differentiation the pathogenicity in Plasmopara halstedii (sunflower downy mildew), analyses were carried out in four pathotypes: isolates of races 304 and 314 that do not overcome Pl2 gene, and isolates of races 704 and 714 that can overcome Pl2 gene. Based on the reaction for the P. halstedii isolates to sunflower hybrids varying only in Pl resistance genes, isolates of races 704 and 714 were more virulent than isolates of races 304 and 314. Index of aggressiveness was calculated for pathogen isolates and revealed the presence of significant differences between isolates of races 304 and 314 (more aggressive) and isolates of races 704 and 714 (less aggressive). There were morphological and genetic variations for the four P. halstedii isolates without a correlation with pathogenic diversity. The importance of the Pl2 resistance gene to differentiate the pathogenicity in sunflower downy mildew was discussed.

Contribution to the knowlegde of Galician xenoflora (NW Iberian Peninsula, Spain).

Information on 12 exotic plants of diverse interest for the Galician flora are presented. All of them were collected in Ribeira council (SW of the A Coruña province). The total includes 8 novelties at a regional level (Aeonium haworthii, Aloe mitriformis, Brugmansia × candida, Nephrolepis cordifolia, Osteospermum ecklonis, Pelargonium capitatum, Sedum mexicanum, Sparaxis tricolor), and 2 provincial novelties. In addition, information on two taxa hardly mentioned in the literature on Galician vascular flora is also included. All the cited specimens are deposited at the SANT Herbarium.

Satellite discrimination of Karenia mikimotoi and Phaeocystis harmful algal blooms in European coastal waters: Merged classification of ocean colour data

The detection of dense harmful algal blooms (HABs) by satellite remote sensing is usually based on analysis of chlorophyll-a as a proxy. However, this approach does not provide information about the potential harm of bloom, nor can it identify the dominant species. The developed HAB risk classification method employs a fully automatic data-driven approach to identify key characteristics of water leaving radiances and derived quantities, and to classify pixels into “harmful”, “non-harmful” and “no bloom” categories using Linear Discriminant Analysis (LDA). Discrimination accuracy is increased through the use of spectral ratios of water leaving radiances, absorption and backscattering. To reduce the false alarm rate the data that cannot be reliably classified are automatically labelled as “unknown”. This method can be trained on different HAB species or extended to new sensors and then applied to generate independent HAB risk maps; these can be fused with other sensors to fill gaps or improve spatial or temporal resolution. The HAB discrimination technique has obtained accurate results on MODIS and MERIS data, correctly identifying 89% of Phaeocystis globosa HABs in the southern North Sea and 88% of Karenia mikimotoi blooms in the Western English Channel. A linear transformation of the ocean colour discriminants is used to estimate harmful cell counts, demonstrating greater accuracy than if based on chlorophyll-a; this will facilitate its integration into a HAB early warning system operating in the southern North Sea.

Making modelling count - increasing the contribution of shelf-seas community and ecosystem models to policy development and management

Marine legislation is becoming more complex and marine ecosystem-based management is specified in national and regional legislative frameworks. Shelf-seas community and ecosystem models (hereafter termed ecosystem models) are central to the delivery of ecosystem-based management, but there is limited uptake and use of model products by decision makers in Europe and the UK in comparison with other countries. In this study, the challenges to the uptake and use of ecosystem models in support of marine environmental management are assessed using the UK capability as an example. The UK has a broad capability in marine ecosystem modelling, with at least 14 different models that support management, but few examples exist of ecosystem modelling that underpin policy or management decisions. To improve understanding of policy and management issues that can be addressed using ecosystem models, a workshop was convened that brought together advisors, assessors, biologists, social scientists, economists, modellers, statisticians, policy makers, and funders. Some policy requirements were identified that can be addressed without further model development including: attribution of environmental change to underlying drivers, integration of models and observations to develop more efficient monitoring programmes, assessment of indicator performance for different management goals, and the costs and benefit of legislation. Multi-model ensembles are being developed in cases where many models exist, but model structures are very diverse making a standardised approach of combining outputs a significant challenge, and there is a need for new methodologies for describing, analysing, and visualising uncertainties. A stronger link to social and economic systems is needed to increase the range of policy-related questions that can be addressed. It is also important to improve communication between policy and modelling communities so that there is a shared understanding of the strengths and limitations of ecosystem models.