Malaria vaccine: roadblocks and possible solutions

Malaria remains the most prevalent and devastating parasitic disease worldwide. Vaccination is considered to be an approach that will complement other strategies for prevention and control of the disease in the future. In the last 10 years, intense studies aimed at the development of a malaria vaccine have provided important knowledge of the nature of the host immunological mechanisms of protection and their respective target antigens. It became well established that protective immune responses can be generated against the distinct stages of Plasmodium. However, in general, protective immune responses are directed at stage-specific antigens. The elucidation of the primary structure of these antigens made possible the generation of synthetic and recombinant proteins that are being extensively used in experimental immunizations against the infection. Today, several epitopes of limited polymorphism have been described and protective immunity can be generated by immunization with them. These epitopes are being tested as primary candidates for a subunit vaccine against malaria. Here we critically review the major roadblocks for the development of a malaria vaccine and provide some insight on how these problems are being solved

Liquid cooling solutions for rotating permanent magnet synchronous machines

In the design of electrical machines, efficiency improvements have become very important. However, there are at least two significant cases in which the compactness of electrical machines is critical and the tolerance of extremely high losses is valued: vehicle traction, where very high torque density is desired at least temporarily; and direct-drive wind turbine generators, whose mass should be acceptably low. As ever higher torque density and ever more compact electrical machines are developed for these purposes, thermal issues, i.e. avoidance of over-temperatures and damage in conditions of high heat losses, are becoming of utmost importance. The excessive temperatures of critical machine components, such as insulation and permanent magnets, easily cause failures of the whole electrical equipment. In electrical machines with excitation systems based on permanent magnets, special attention must be paid to the rotor temperature because of the temperature-sensitive properties of permanent magnets. The allowable temperature of NdFeB magnets is usually significantly less than 150 ËšC. The practical problem is that the part of the machine where the permanent magnets are located should stay cooler than the copper windings, which can easily tolerate temperatures of 155 ËšC or 180 ËšC. Therefore, new cooling solutions should be developed in order to cool permanent magnet electrical machines with high torque density and because of it with high concentrated losses in stators. In this doctoral dissertation, direct and indirect liquid cooling techniques for permanent magnet synchronous electrical machines (PMSM) with high torque density are presented and discussed. The aim of this research is to analyse thermal behaviours of the machines using the most applicable and accurate thermal analysis methods and to propose new, practical machine designs based on these analyses. The Computational Fluid Dynamics (CFD) thermal simulations of the heat transfer inside the machines and lumped parameter thermal network (LPTN) simulations both presented herein are used for the analyses. Detailed descriptions of the simulated thermal models are also presented. Most of the theoretical considerations and simulations have been verified via experimental measurements on a copper tooth-coil (motorette) and on various prototypes of electrical machines. The indirect liquid cooling systems of a 100 kW axial flux (AF) PMSM and a 110 kW radial flux (RF) PMSM are analysed here by means of simplified 3D CFD conjugate thermal models of the parts of both machines. In terms of results, a significant temperature drop of 40 ÌŠC in the stator winding and 28 ÌŠC in the rotor of the AF PMSM was achieved with the addition of highly thermally conductive materials into the machine: copper bars inserted in the teeth, and potting material around the end windings. In the RF PMSM, the potting material resulted in a temperature decrease of 6 ÌŠC in the stator winding, and in a decrease of 10 ÌŠC in the rotor embedded-permanentmagnets. Two types of unique direct liquid cooling systems for low power machines are analysed herein to demonstrate the effectiveness of the cooling systems in conditions of highly concentrated heat losses. LPTN analysis and CFD thermal analysis (the latter being particularly useful for unique design) were applied to simulate the temperature distribution within the machine models. Oil-immersion cooling provided good cooling capability for a 26.6 kW PMSM of a hybrid vehicle. A direct liquid cooling system for the copper winding with inner stainless steel tubes was designed for an 8 MW directdrive PM synchronous generator. The design principles of this cooling solution are described in detail in this thesis. The thermal analyses demonstrate that the stator winding and the rotor magnet temperatures are kept significantly below their critical temperatures with demineralized water flow. A comparison study of the coolant agents indicates that propylene glycol is more effective than ethylene glycol in arctic conditions.

Catalytic upgrading of biomass extractives to fine chemicals over supported ionic liquid catalysts (SILCAs)

Behovet av förnyelsebar energi ökar ständigt eftersom det finns en strävan att minska beroendet av fossila bränslen. Dessutom är tillgÃ¥ngar av fossila bränslen begränsade. Miljövänliga processer för bioraffinaderier erbjuder en stor möjlighet för produktion av energi, bränslen och kemikalier. Den finska och svenska skogsindustrin har en lÃ¥ng tradition i utnyttjandet av skogsbiomassor. Bioraffinaderier som integreras med pappers- och cellulosaindustrin kan frambringa bÃ¥de ekonomiska och ekologiska fördelar i framställning av traditionella och biobaserade produkter. I doktorsarbetet studerades omvandling av extraktivämnen till finkemikalier som kan användas t.ex. av läkemedelsindustrin. Extraktivämnen fÃ¥s ur biomassa. I forskningsarbetet framställdes biobaserade finkemikalier med hjälp av katalysatorer som baserar sig pÃ¥ joniska vätskor. Biomassan bestÃ¥r av cellulosa, hemicellulosa, lignin och extraktivämnen, vilka huvudsakligen är terpener, vaxer och fettsyror. Extraktivämen är vedens komponenter, som kan separeras ur vedmaterialet med hjälp av neutrala lösningsmedel. Joniska vätskekatalysatorer som var immobiliserade pÃ¥ fasta bärare utnyttjades för isomerisering av α,β-pinenoxider samt hydrogenering citral. Inverkan av joniska vätskor pÃ¥ katalysatorns aktivitet och reaktionernas produktfördelning undersöktes under varierande reaktionsbetingelser. Kinetiska modeller för pinenoxidens isomeriseringsreaktioner beskrev väl experimentellt upptäckta skillnader mellan olika katalysatorer. --------------------------------------------------- Uusiutuvan energian tarve on kasvussa, koska riippuvuutta fossiilisista polttoaineista pyritään vähentämään. Tämän lisäksi fossiilisten polttoaineiden varannot ovat rajalliset. Ympäristöystävälliset biojalostusprosessit ovat näin ollen suuri mahdollisuus energian, polttoaineiden ja kemikaalien tuotannossa. Suomen ja Ruotsin metsäteollisuudella on pitkät perinteet metsäbiomassojen hyödyntämisessä. Paperi- ja selluteollisuuden yhteyteen integroiduilla biojalostamoilla voidaan luoda taloudellisia ja ympäristöllisiä etuja sekä perinteisten että biopohjaisten tuotteiden valmistuksessa. Väitöstyössä on tutkittu biomassan uuteaineiden kemiallista muuntamista hienokemikaaleiksi, joita voidaan käyttää esimerkiksi lääkeaineteollisuudessa. Biopohjaisia hienokemikaaleja on valmistettu biomassan uuteaineista ionisiin nesteisiin perustuvilla katalyyteillä. Biomassa koostuu selluloosasta, hemiselluloosasta, ligniinistä sekä uuteaineista, jotka ovat pääosin terpeenejä, vahoja tai rasvahappoja. Uuteaineet ovat puun komponentteja, jotka voidaan erottaa puusta neutraalien liuottimien avulla. Kiinteän kantajan päälle immobilisoituja ionisia nestekatalyyttejä (Supported Ionic Liquid Catalyst) hyödynnettiin α,β-pineenioksidien isomerisointireaktioissa sekä sitraalin vedytysreaktioissa. Ionisten nesteiden vaikutusta katalyyttien aktiivisuuteen sekä reaktioiden tuotejakaumaan tutkittiin erilaisissa reaktio-olosuhteissa. Pineenioksidien isomerisointireaktioiden kineettiset mallit kuvasivat hyvin kokeellisesti todettuja katalyyttien eroavaisuuksia.

Surface studies of limestones and dolostones : characterisation using various techniques and batch dissolution experiments with hydrochloric acid solutions

In this thesis, stepwise titration with hydrochloric acid was used to obtain chemical reactivities and dissolution rates of ground limestones and dolostones of varying geological backgrounds (sedimentary, metamorphic or magmatic). Two different ways of conducting the calculations were used: 1) a first order mathematical model was used to calculate extrapolated initial reactivities (and dissolution rates) at pH 4, and 2) a second order mathematical model was used to acquire integrated mean specific chemical reaction constants (and dissolution rates) at pH 5. The calculations of the reactivities and dissolution rates were based on rate of change of pH and particle size distributions of the sample powders obtained by laser diffraction. The initial dissolution rates at pH 4 were repeatedly higher than previously reported literature values, whereas the dissolution rates at pH 5 were consistent with former observations. Reactivities and dissolution rates varied substantially for dolostones, whereas for limestones and calcareous rocks, the variation can be primarily explained by relatively large sample standard deviations. A list of the dolostone samples in a decreasing order of initial reactivity at pH 4 is: 1) metamorphic dolostones with calcite/dolomite ratio higher than about 6% 2) sedimentary dolostones without calcite 3) metamorphic dolostones with calcite/dolomite ratio lower than about 6% The reactivities and dissolution rates were accompanied by a wide range of experimental techniques to characterise the samples, to reveal how different rocks changed during the dissolution process, and to find out which factors had an influence on their chemical reactivities. An emphasis was put on chemical and morphological changes taking place at the surfaces of the particles via X-ray Photoelectron Spectroscopy (XPS) and Scanning Electron Microscopy (SEM). Supporting chemical information was obtained with X-Ray Fluorescence (XRF) measurements of the samples, and Inductively Coupled Plasma-Mass Spectrometry (ICP-MS) and Inductively Coupled Plasma-Optical Emission Spectrometry (ICP-OES) measurements of the solutions used in the reactivity experiments. Information on mineral (modal) compositions and their occurrence was provided by X-Ray Diffraction (XRD), Energy Dispersive X-ray analysis (EDX) and studying thin sections with a petrographic microscope. BET (Brunauer, Emmet, Teller) surface areas were determined from nitrogen physisorption data. Factors increasing chemical reactivity of dolostones and calcareous rocks were found to be sedimentary origin, higher calcite concentration and smaller quartz concentration. Also, it is assumed that finer grain size and larger BET surface areas increase the reactivity although no certain correlation was found in this thesis. Atomic concentrations did not correlate with the reactivities. Sedimentary dolostones, unlike metamorphic ones, were found to have porous surface structures after dissolution. In addition, conventional (XPS) and synchrotron based (HRXPS) X-ray Photoelectron Spectroscopy were used to study bonding environments on calcite and dolomite surfaces. Both samples are insulators, which is why neutralisation measures such as electron flood gun and a conductive mask were used. Surface core level shifts of 0.7 ± 0.1 eV for Ca 2p spectrum of calcite and 0.75 ± 0.05 eV for Mg 2p and Ca 3s spectra of dolomite were obtained. Some satellite features of Ca 2p, C 1s and O 1s spectra have been suggested to be bulk plasmons. The origin of carbide bonds was suggested to be beam assisted interaction with hydrocarbons found on the surface. The results presented in this thesis are of particular importance for choosing raw materials for wet Flue Gas Desulphurisation (FGD) and construction industry. Wet FGD benefits from high reactivity, whereas construction industry can take advantage of slow reactivity of carbonate rocks often used in the facades of fine buildings. Information on chemical bonding environments may help to create more accurate models for water-rock interactions of carbonates.

Skin secretion of Siphonops paulensis (Gymnophiona, Amphibia) forms voltage-dependent ionic channels in lipid membranes

The effect of the skin secretion of the amphibian Siphonops paulensis was investigated by monitoring the changes in conductance of an artificial planar lipid bilayer. Skin secretion was obtained by exposure of the animals to ether-saturated air, and then rinsing the animals with distilled water. Artificial lipid bilayers were obtained by spreading a solution of azolectin over an aperture of a Delrin cup inserted into a cut-away polyvinyl chloride block. In 9 of 12 experiments, the addition of the skin secretion to lipid bilayers displayed voltage-dependent channels with average unitary conductance of 258 ± 41.67 pS, rather than nonspecific changes in bilayer conductance. These channels were not sensitive to 4-acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic acid or tetraethylammonium ion, but the experimental protocol used does not permit us to specify their characteristics.

Mathematical modeling of electro-rotation spectra of small particles in liquid solutions: Application to human erythrocyte aggregates

Electro-rotation can be used to determine the dielectric properties of cells, as well as to observe dynamic changes in both dielectric and morphological properties. Suspended biological cells and particles respond to alternating-field polarization by moving, deforming or rotating. While in linearly polarized alternating fields the particles are oriented along their axis of highest polarizability, in circularly polarized fields the axis of lowest polarizability aligns perpendicular to the plane of field rotation. Ellipsoidal models for cells are frequently applied, which include, beside sphere-shaped cells, also the limiting cases of rods and disks. Human erythrocyte cells, due to their particular shape, hardly resemble an ellipsoid. The additional effect of rouleaux formation with different numbers of aggregations suggests a model of circular cylinders of variable length. In the present study, the induced dipole moment of short cylinders was calculated and applied to rouleaux of human erythrocytes, which move freely in a suspending conductive medium under the effect of a rotating external field. Electro-rotation torque spectra are calculated for such aggregations of different length. Both the maximum rotation speeds and the peak frequencies of the torque are found to depend clearly on the size of the rouleaux. While the rotation speed grows with rouleaux length, the field frequency nup is lowest for the largest cell aggregations where the torque shows a maximum.

Ionic radiocontrast inhibits endothelium-dependent vasodilation of the canine renal artery in vitro: possible mechanism of renal failure following contrast medium infusion

To determine if radiocontrast impairs vascular relaxation of the renal artery, segments (4-5 mm in length) of canine renal artery were suspended in vitro in organ chambers to measure isometric force (95% O2/5% CO2, at 37ºC). Arterial segments with and without endothelium were placed at the optimal point of their length-tension relation and incubated with 10 µM indomethacin to prevent synthesis of endogenous prostanoids. The presence of nonionic radiocontrast (iohexol, Omnipaque 350, 1 ml in 25 ml control solution, 4% (v/v)) did not alter endothelium-dependent relaxation to acetylcholine in rings precontracted with both norepinephrine and prostaglandin F2alpha (N = 6). When the rings were precontracted with prostaglandin F2alpha, the presence of ionic contrast did not inhibit the relaxation of the arteries. However, in canine renal arteries contracted with norepinephrine, the presence of ionic radiocontrast (diatrizoate meglumine and diatrizoate sodium, MD-76, 1 ml in 25 ml control solution, 4% (v/v)) inhibited relaxation in response to acetylcholine, sodium nitroprusside (N = 6 in each group), and isoproterenol (N = 5; P < 0.05). Rings were relaxed less than 50% of norepinephrine contraction. Following removal of the contrast, vascular relaxation in response to the agonists returned to normal. These results indicate that ionic radiocontrast nonspecifically inhibits vasodilation (both cAMP-mediated and cGMP-mediated) of canine renal arteries contracted with norepinephrine. This reversible impairment of vasodilation could inhibit normal renal perfusion and act as a mechanism of renal failure following radiocontrast infusion. In the adopted experimental protocol the isoproterenol-induced relaxation of renal arteries precontracted with norepinephrine was more affected, suggesting a pivotal role of the cAMP system.

Solid-state reference and ion-selective electrodes : towards portable potentiometric sensing

Potentiometric sensors are very attractive tools for chemical analysis because of their simplicity, low power consumption and low cost. They are extensively used in clinical diagnostics and in environmental monitoring. Modern applications of both fields require improvements in the conventional construction and in the performance of the potentiometric sensors, as the trends are towards portable, on-site diagnostics and autonomous sensing in remote locations. The aim of this PhD work was to improve some of the sensor properties that currently hamper the implementation of the potentiometric sensors in modern applications. The first part of the work was concentrated on the development of a solid-state reference electrode (RE) compatible with already existing solid-contact ion-selective electrodes (ISE), both of which are needed for all-solid-state potentiometric sensing systems. A poly(vinyl chloride) membrane doped with a moderately lipophilic salt, tetrabutylammonium-tetrabutylborate (TBA-TBB), was found to show a satisfactory stability of potential in sample solutions with different concentrations. Its response time was nevertheless slow, as it required several minutes to reach the equilibrium. The TBA-TBB membrane RE worked well together with solid-state ISEs in several different situations and on different substrates enabling a miniature design. Solid contacts (SC) that mediate the ion-to-electron transduction are crucial components of well-functioning potentiometric sensors. This transduction process converting the ionic conduction of an ion-selective membrane to the electronic conduction in the circuit was studied with the help of electrochemical impedance spectroscopy (EIS). The solid contacts studied were (i) the conducting polymer (CP) poly(3,4-ethylienedioxythiophene) (PEDOT) and (ii) a carbon cloth having a high surface area. The PEDOT films were doped with a large immobile anion poly(styrene sulfonate) (PSS-) or with a small mobile anion Cl-. As could be expected, the studied PEDOT solid-contact mediated the ion-toelectron transduction more efficiently than the bare glassy carbon substrate, onto which they were electropolymerized, while the impedance of the PEDOT films depended on the mobility of the doping ion and on the ions in the electrolyte. The carbon cloth was found to be an even more effective ion-to-electron transducer than the PEDOT films and it also proved to work as a combined electrical conductor and solid contact when covered with an ion-selective membrane or with a TBA-TBB-based reference membrane. The last part of the work was focused on improving the reproducibility and the potential stability of the SC-ISEs, a problem that culminates to the stability of the standard potential E°. It was proven that the E° of a SC-ISE with a conducting polymer as a solid contact could be adjusted by reducing or oxidizing the CP solid contact by applying current pulses or a potential to it, as the redox state of the CP solid-contact influences the overall potential of the ISE. The slope and thus the analytical performance of the SC-ISEs were retained despite the adjustment of the E°. The shortcircuiting of the SC-ISE with a conventional large-capacitance RE was found to be a feasible instrument-free method to control the E°. With this method, the driving force for the oxidation/reduction of the CP was the potential difference between the RE and the SC-ISE, and the position of the adjusted potential could be controlled by choosing a suitable concentration for the short-circuiting electrolyte. The piece-to-piece reproducibility of the adjusted potential was promising, and the day-today reproducibility for a specific sensor was excellent. The instrumentfree approach to control the E° is very attractive considering practical applications.

Managing open access workflows at the University of St Andrews: challenges and Pathfinder solutions

Presentation of Janet Aucock, at the FinELib Consortium Seminar (Aineistopäivä), April 16, 2015 in Helsinki.

Influence of multi-phase phenomena on semibatch crystallization processes of aqueous solutions

Crystal properties, product quality and particle size are determined by the operating conditions in the crystallization process. Thus, in order to obtain desired end-products, the crystallization process should be effectively controlled based on reliable kinetic information, which can be provided by powerful analytical tools such as Raman spectrometry and thermal analysis. The present research work studied various crystallization processes such as reactive crystallization, precipitation with anti-solvent and evaporation crystallization. The goal of the work was to understand more comprehensively the fundamentals, phenomena and utilizations of crystallization, and establish proper methods to control particle size distribution, especially for three phase gas-liquid-solid crystallization systems. As a part of the solid-liquid equilibrium studies in this work, prediction of KCl solubility in a MgCl2-KCl-H2O system was studied theoretically. Additionally, a solubility prediction model by Pitzer thermodynamic model was investigated based on solubility measurements of potassium dihydrogen phosphate with the presence of non-electronic organic substances in aqueous solutions. The prediction model helps to extend literature data and offers an easy and economical way to choose solvent for anti-solvent precipitation. Using experimental and modern analytical methods, precipitation kinetics and mass transfer in reactive crystallization of magnesium carbonate hydrates with magnesium hydroxide slurry and CO2 gas were systematically investigated. The obtained results gave deeper insight into gas-liquid-solid interactions and the mechanisms of this heterogeneous crystallization process. The research approach developed can provide theoretical guidance and act as a useful reference to promote development of gas-liquid reactive crystallization. Gas-liquid mass transfer of absorption in the presence of solid particles in a stirred tank was investigated in order to gain understanding of how different-sized particles interact with gas bubbles. Based on obtained volumetric mass transfer coefficient values, it was found that the influence of the presence of small particles on gas-liquid mass transfer cannot be ignored since there are interactions between bubbles and particles. Raman spectrometry was successfully applied for liquid and solids analysis in semi-batch anti-solvent precipitation and evaporation crystallization. Real-time information such as supersaturation, formation of precipitates and identification of crystal polymorphs could be obtained by Raman spectrometry. The solubility prediction models, monitoring methods for precipitation and empirical model for absorption developed in this study together with the methodologies used gives valuable information for aspects of industrial crystallization. Furthermore, Raman analysis was seen to be a potential controlling method for various crystallization processes.

Purchasing Process of Industrial Solutions – Added Value, Difficulties and Good Practices

Purpose of this study is to clarify the industrial solutions purchasing process from purchaser companies’ point of view. Also customer’s view on value generating aspects and difficulties in purchases will be discussed as well as different purchas-ing entities where customers have ended up in their solution purchases. Current solution literature is mainly concentrated in supplier views and customer perspec-tive has been left without adequate attention. However, knowledge of the customer and the identification of customer need are at the core of a successful solution business. The focus of this thesis is on Finnish companies’ solution purchases that have been realized during last five years. Industrial solutions in this case are facto-ries or other large industrial plants. Industrial solutions’ purchasing process will be opened all the way from discovering the need until the start-up of the plant. Of in-terest is the customer experience of the success of the acquisition and the pur-chaser’s view on good practices allowing a successful procurement project.

Osmotic dehydration of sweet potato (Ipomoea batatas) in ternary solutions

The aim of this work was to evaluate the osmotic dehydration of sweet potato (Ipomoea batatas) using hypertonic sucrose solutions, with or without NaCl, at three different concentrations, at 40 °C. Highest water losses were obtained when the mixture of sucrose and NaCl was used. The addition of NaCl to osmotic solutions increases the driving force of the process and it is verified that the osmotic dehydration process is mainly influenced by changes in NaCl concentration, but the positive effect of the salt-sucrose interaction on soluble solids also determined the decrease of solid gain when solutes were at maximum concentrations. Mass transfer kinetics were modeled according to Peleg, Fick and Page's equations, which presented good fittings of the experimental data. Peleg's equation and Page's model presented the best fitting and showed excellent predictive capacity for water loss and salt gain data. The effective diffusivity determined using Fick's Second Law applied to slice geometry was found to be in the range from 3.82 x 10-11 to 7.46 x 10-11 m²/s for water loss and from 1.18 x 10-10 to 3.38 x 10-11 m²/s for solid gain.