Viral RNA dependent RNA polymerases (RdRps) are enzymes which enable RNA viruses to replicate their genome and to prepare mRNA for translation of viral proteins. Due to its relative evolutionary conservation RdRps are good targets for drug design. In this work we present a structure of the RdRp (3Dpol ) of Aichi virus, which has not been solved yet. Aichi virus is a human pathogen that causes gastroenteritis. Aichi virus is also used as a model organism for studying cognate viruses which virulence is more dangerous, for example: Rhinovirus, Hepatitis A virus, SARS virus, hepatitis C virus, yellow fever, and West-Nile virus. In addition to structural studies of Aichi virus 3Dpol we also tested a previously published hypothesis that, 3Dpol is recruited to the membrane through phosphatidylinositol 4 phosphate (PI4P) - an important regulatory lipid. Membranes highly enriched in PI4P are formed in cells infected by single stranded positive sense RNA (plus ssRNA) viruses. Finally we tested the influence of ribonucleotides on the 3Dpol protein stability. (In Czech)

Syngas production and hydrogen separation technologies are very mature, and also extremely important for energy and chemical industries. Furthermore, these processes are the most expensive elements for many applications such as hydrogen production from renewable sources. Enhancing or intensifying these very mature technologies is very challenging, but would have tremendous impact on the performance and economics of many processes. Traditional Integrated Gasification Combined Cycle (IGCC) for syngas production need to include a carbon capture process in order to regulate their carbon dioxide emission as more and more countries and regions have implemented carbon tax policy. Integration of this process with Pd membrane has long been considered a key component to make it more feasible. With these two technologies combined together, we can produce high purity hydrogen while capturing carbon dioxide and toxic gases from the syngas product. Besides, although manufacturing the membrane reactor is expensive, after considering the carbon tax factor, it actually is more economically preferable compare with the traditional Pressure Swing Adsorption (PSA) process. Most research on Pd membrane technology has been conducted at lab scale; nonetheless, the contribution of a palladium membrane technology to economic and societal development requires its commercialization, diffusion and utilization. To generate enough incentives for commercialization, it is necessary to demonstrate the scalability and robustness of the membranes in industrial settings. Consequently, a multitube membrane module suitable for IGCC system was designed and manufactured and sent to National Carbon Capture Center (NCCC) for testing. This work developed a Computational Fluid Dynamics (CFD) model for the module and validated the model utilizing the pilot-scale experimental data generated under industrial conditions. The model was then up-scaled and used to determine the intrinsic phenomena of palladium membrane scale up. This study reveals the technical/engineering requirements for the effective design of large-scale multitube membrane modules. Mass transfer limitations and concentration polarization effects were studied quantitatively with the developed model. Methods for diminishing the concentration polarization effect were proposed and tested through the simulations such as i) increasing convective forces and ii) designing baffles to create gas recirculation. For scaled-up membrane modules, mass transfer limitation is an important parameter to consider as large modules showed severe concentration polarization effects. IGCC systems produce H2 from coal combustion; other ways of H2 production include steam-reforming processes, using natural gas or bio-ethanol as the reactant. The product contains a mixture of H2, CH4, CO, CO2 and steam. Thus, steam-reforming processes are often followed by a Pressure Swing Adsorption (PSA) unit in order to obtain pure hydrogen. Palladium membrane, on the other hand, can be integrated with steam-reforming processes and achieve the simultaneous production and purification of H2 in a single unit by reaching process intensification. Higher H2 production rate can be reached by process intensification as one of the products H2 is constantly being removed. Temperature control is a very important topic in steam reforming processes, as the reaction is overall highly endothermic; although implementing an in-unit membrane improves H2 production rate, it also makes the temperature control more difficult as the reaction equilibrium is altered by the removal of one of the products H2. Hereby, an experimental study of catalytic membrane reactor (CMR) was carried out along with both isothermal and non-isothermal CFD simulations that are validated by the experimental data in order to visualize the temperature distribution inside the reactor and understand the influence of the operating conditions including temperature, pressure and the sweep gas flow patter on the permeate side.

A novel approach for the design and synthesis of membrane separation systems has been developed. The theory is shown to be applicable to both batch and continuous membrane operations, and has been formulated in such a way that it is valid for any type of membrane. In this thesis, however, only vapour permeation and pervaporation membranes are incorporated for illustration purposes. The method, which employs a graphical technique, allows one to calculate and visualise the change in composition of the retentate. An integral part of the approach was the derivation of the Membrane Residue Curve Map (M-RCM), and the related differential material balance which describes it. By definition, this plot shows the change, in time, of the retentate composition in a batch still. However, it has been shown that the M-RCM is applicable to conventional continuously-operated membrane units, as well as infinite reflux membrane columns. Finite reflux columns and cascades have been examined by using column sections (CS): any column, or arrangement, no matter how complex, can be broken down into smaller units, namely CS. The development of the Difference Point Equation (DPE) for non-constant flow allowed one to generate, and interpret, profiles for individual CS’s, which can ultimately be connected to form a membrane column arrangement. The profiles, which are more complex than those obtained in the M-RCM, exhibit a unique behavior. Since there is varying flow, the reflux is continually changing, orientating the profile so as to seek a stable node that is “mobile”. Thus, the movement of CS profile is dictated by the location and direction of the pinch point locus. Finally, having membrane permeators examined in an analogous manner to other separation methods, allows for easy synthesis and design of combinations of different processes. Hybrid distillation-membrane systems are analyzed by incorporating CS’s and the appropriate DPE’s which describe each. Investigating the arrangement as a thermally-coupled column introduces a novel way of synthesizing hybrids. Regions of feasibility, which are dictated by the relevant pinch point loci of each separation method, are ultimately sought.

Thesis advisor: Jianmin Gao / My graduate research has used engineered peptides to perturb the non-covalent interactions in protein folding, protein-protein association and protein-membrane association. We have focused on understanding the fundamental principles of molecular recognition behind protein-protein and protein-membrane interactions, and further using these principles in protein engineering. This thesis includes three projects. I) Towards Small Molecule Receptors for Membrane Lipids: A Case Study on Phosphatidylserine The lipid composition and distribution of cell membranes play important roles in regulating the physiology of the cell. The lipid composition of plasma membranes is one characteristic feature that can be used to identify cell types and functions. Molecules that specifically recognize a particular lipid are useful as imaging probes for targeting cells or tissues of interest. Protein based lipid binding probes have intrinsic limitations due to their large size and poor pharmacokinetic properties such as slow clearance rate and poor in vivo stability. A plausible strategy to achieve a probe with small size and high binding affinity and selectivity is to use a peptide to mimic the protein lipid-binding domains. As a case study, a cyclic peptide that specifically targets phosphatidylserine containing membranes has been developed. This cyclic peptide is potentially capable of imaging apoptosis in vivo, and the strategy of developing this cyclic peptide can be generalized to the design of peptide-based probes for other lipid species. My research has pointed out a challenging but feasible way to design a peptide that achieves specificity and affinity similar to lipid-binding proteins. (II) Study of Apoptotic Cell Membrane (ACM) Permeant Molecules Noninvasive imaging of apoptosis is highly desirable for the diagnosis of a variety of diseases, as well as for the early prognosis of anticancer treatments. One characteristic feature of apoptotic cells that has been targeted for developing specific biomarkers is enhanced membrane permeability compared to that of healthy cells. Several unrelated molecules that are capable of selectively penetrating the apoptotic cell membrane (ACM) have recently been reported. However, the origin of the altered ACM permeability is poorly understood, as is the scope of molecular structures that can permeate through the ACM. Herein, we report a systematic investigation on the altered ACM permeability. Our results show that simple modifications of commonly used dyes (e.g. fluorescein) afford specific entry into cells at the early stages of apoptosis. The ACM appears to be permeable to molecules of various functional groups and charge, but does discriminate against molecules of large size. The new findings reported here greatly expand the pool of small molecules for imaging cell death, thus facilitating the development of noninvasive imaging agents for apoptosis. (III) Study of Aromatic-Fluorinated Aromatic Interactions in Peptide Systems Therapeutic proteins have been through a remarkable expansion in the last two decades. A general problem that they are facing is poor stability. Protein engineering focuses on solving this problem by incorporating unnatural amino acids into protein sequences to purposefully modify protein structures. Fluorinated aliphatic amino acids have been demonstrated to be effective in stabilizing protein structures and functioning as recognition motifs. In contrast, fluorinated aromatic amino acids are less studied. We investigated the effect of perturbation of fluorination on aromatic residues on the stability of protein model systems, as well as the influence on protein-protein association behavior. The results of this study provided a fundamental understanding of aromatic interactions in protein systems, and guidelines for protein engineering with fluorinated aromatics for stabilizing protein structures or directing specific protein-protein interactions. / Thesis (PhD) — Boston College, 2012. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

Co-polymer facade materials have recently become a popular option in the building industry as an alternative to glazing. Ethylene Tetra-Fluoro-Ethylene (ETFE) foil has been successfully used in many projects as an innovative solution to energy-conscious design challenges. In addition, the use of ETFE membrane has resulted in significant savings in cost and structural support requirements, compared with conventional glazing, due to its low weight. There is a lack of detailed published data reporting its thermal behaviour. This study focuses on the examination of heat transfer through the ETFE membrane, and more specifically heat loss and solar gains. The document examines the impact of the material on the energy use of a building, as well as thermal comfort and interior conditions. Through field-testing and computer simulations the research evaluates the material’s thermal properties to obtain results that will assist in estimating the suitability of ETFE foil use in comparison to glass. Field-testing is used to perform a comparison of the thermal and energy behaviour of a fritted double ETFE cushion to a double glazed cover. The two experimental devices under examination present nearly identical energy consumption due to heating requirements. The experimental findings are implemented in Integrated Environmental Solutions (IES) and used to identify the necessary steps to accurately reproduce the thermal and energy behaviour associated with both covering materials. Further simulations were undertaken to provide a comparison of several types of ETFE cushions to various types of double glass. More specifically, the types examined are a clear double ETFE roof cover and a fritted double ETFE roof cover in comparison to a standard double glazed roof and a low-E double glazed roof. The roofs covers are examined in relation to energy requirements for both the heating and cooling of a space. Such an assessment of performance will provide information for further investigation to improve the material’s features and optimise energy performance.

The aim of this study was to further understand the fouling and cleaning mechanisms of synthetic membranes used to filter an industrially relevant feed. The main focus of this study was to understand the fouling layer properties during pressure driven filtration. A relatively new technique known as Fluid Dynamic Gauging (FDG) was applied to examine the fouling layer thickness. This work comprised of four main themes with overlapping objectives: (i) the optimisation of Spent Sulphite Liquor fouling and cleaning conditions, (ii) the optimisation of molasses fouling and cleaning conditions, (iii) the investigation of the effect of a simple pre-treatment upon the membrane separation performance, and (iv) the application of the FDG in the study of polymeric membranes. An understanding of the mechanisms involved in fouling and cleaning of microfiltration and ultrafiltration membranes used to filter molasses and SSL has been attained. The variables affecting permeate flux and quality were optimised and mechanistic information concerning the synergistic effects between fouling and cleaning was gathered. The application of a simple NaOH pre-treatment was found to affect both the type of foulant species attaching to the membrane surface, and resulted in an altered separation and cleaning performance. Zeta potential measurements, FTIR and AFM demonstrated that both in-pore and surface fouling was present. The data collected indicated that for both membranes evaluated, different fouling species were found to have attached, depending upon the pre-treatment protocol used. These findings are significant, as they offer support to the recommendations made by some polymeric membrane manufacturers that conditioning protocols should include a NaOH step. However, in the SSL system examined, the effect of NaOH pre-treatment resulted in an improvement in the subsequent performance only over the first two or three complete filtration cycles. It is therefore necessary to study membrane systems over multiple fouling and cleaning cycles before a recommendation can be made. An improved understanding of the interaction between the surface chemistry and surface physics during membrane filtration of complex food based material will benefit both membrane manufactures and food industry based users. The technique of Fluid Dynamic Gauging was incorporated into an existing system and validated to monitor the development of cake layers over time. The FDG was also used to optimise conditions and track the thickness of the cake layer during multiple fouling cycles and its removal rate during cleaning, as an aid to understanding removal mechanisms. It has been shown that operating conditions have to be carefully chosen to minimise the effect of membrane fouling. The results show that FDG is a versatile and powerful technique for characterising the dynamics and mechanical behaviour of fouling layers on membrane surfaces. A particular advantage of the FDG technique is its ability to determine the thickness of fouling layers where other techniques would find difficulty. For example, the layers formed in this study were opaque, and consequently the determination of the development of deposit thickness with time would have been very challenging using conventional optical microscopy techniques.

In this research it was shown that the electroless plated palladium deposited as large number of randomly oriented grains, which were separated by grain boundaries (GB). The nano-scale dimensions of these grain boundaries allowed the diffusion of helium through the palladium membrane. This implied that in a dense palladium membrane, the grain boundary network was so convoluted that helium flux could be neglected. The transmission electron microscope (TEM) images of the palladium at room temperature showed grains of about 50 nm in size and nuclei of about 5 nm in size. The TEM images of a pre-annealed Pd sample at 500ºC in hydrogen atmosphere for 48 hours, showed big grains of 100 to 200 nm in size and most of the grain boundary intersections had dihedral angles very close to 120°. However, the pre-annealed Pd sample at 500ºC in helium atmosphere for 48 hours, showed grains of the size of 70 to 100 nm and many of the grain boundary intersections did not show dihedral angles of 120°. This proved that high temperature annealing not only caused significant grain growth and grain boundary (straightening) migration, but also the grain boundary migration was faster in hydrogen than in helium atmosphere. Also, the hydrogen and helium characterization of the palladium membranes showed that the leak formed faster in hydrogen than in helium. Thus, combining the TEM observations with the membrane characterization results, it is possible to conclude that grain boundary migration is one of the most probable reasons for leak formation in palladium composite membranes. The TEM images of the pre-annealed Pd sample also showed that the grain boundaries can achieve an equilibrium configuration within 48 hours of annealing at 500°C in hydrogen. This research helped in better understanding of the role of grain boundary migration on the leak formation in the composite palladium membranes and this information can be useful for the production of leak resistant stable membranes in the future.

This project was focused on the synthesis of novel Polymers of Intrinsic Microporosity (PIMs) that are soluble in common low boiling point solvents so that self-standing films can be prepared for gas permeability measurements. The common building unit of these novel PIMs was triptycene and its derivatives. Modification of these triptycene compounds enabled the alteration of the polymeric backbone, so that we could tune the gas permeability properties. Modifications included the substitution of different functional groups (e.g. addition of methyl groups) and also the extension via benzoannulation of the triptycene structure. The synthesis of the PIMs was based around three different polymerisation techniques. The first one involved the formation of triptycene-based polyimides (PIs) using a triptycene based dianhydride, prepared in a multistep synthesis. Shorter and cheaper synthetic routes were attempted, but all to no avail. The resulting triptycene monomer was reacted with a variety of commercial and non-commercial bisanilines for the formation of several PIM-PIs, all exhibiting different performances. Robust self-standing films were obtained for two of these PIM polyimides. In addition to the formation of polyimides, the synthesis of Tröger’s Base (TB) polymers, also based on triptycene components, were achieved. This type of polymerisation involves the reaction between a “bisaniline” monomer and a source of “formaldehyde”, such as dimethoxymethane (DMM), in a strong acid media, typically trifluoroacetic acid (TFA). Modification of these triptycene-based bisanilines has led to the formation of TB-PIMs, all with distinctive gas permeation properties. TB-PIM copolymers (reaction between two different bisaniline monomers with DMM and TFA) were synthesised in an attempt to further tune the performance of the polymers. Finally, the preparation of polybenzodioxan polymers based around extended triptycene monomers (i.e. benzotriptycenes) was studied. By using a variety of substituted benzotriptycene biscatechol monomers and performing the polymerisation using tetrafluoroterephthalonitrile, in the presence of K2CO3, the synthesis of a series of substituted benzotriptycene polybenzodioxane polymers was successfully achieved and the polymers showed enhanced gas permeation properties.

Photocatalytic membranes have been designed using two types of fine-scale alumina fibres, namely Nano Alumina Fibre (NAF) from Metallurg Engineering, Estonia and commercially available Saffil® Alumina Fibre (SAF) produced by Saffil Limited, UK. NAF fibres have an average diameter of about 15 nm and SAF about 4 μm. Membranes were produced in various ways. The fibre network architecture within the membranes, along with their porosity, specific surface area and mechanical properties, have been examined. These NAF-SAF membranes were impregnated with titania-based sol-gel coatings, to produce photocatalytic membranes. Their mechanical properties, specific surface area and flow properties were assessed and photocatalytic potential was measured by studying rates of degradation of aqueous dye solution. Membranes with photo-active top layers were designed by sedimentation of a fibrous layer of NAF-SAF, containing titania nanoparticles on a pre-sedimented support layer. Two types of photocatalyst were used, one a commercially available anatase nanopowder and the other silver-coated anatase. The latter was produced via modification of the first. Optimisation of the nanoparticle loadings was performed via assessing their photocatalytic efficiency. Specific permeability values were obtained experimentally and by prediction from the pore architecture. A novel form of photo-active membrane was designed by direct casting of milled SAF and titania-based sol-gel into circular moulds. Effects of fibre milling time and fibre to sol-gel ratio on their performance were studied, besides mechanical properties, porosity and specific surface area. Their flow properties and photocatalytic efficiency were also examined. Due to the availability of these fibres, especially the high production rates (kg/h range) and low cost of NAF, these membranes offer potential for large scale application.

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