Human bladder uroepithelial cells synergize with monocytes to promote IL-10 synthesis and other cytokine responses to Uropathogenic Escherichia coli

Urinary tract infections are a major source of morbidity for women and the elderly, with Uropathogenic Escherichia coli (UPEC) being the most prevalent causative pathogen. Studies in recent years have defined a key anti-inflammatory role for Interleukin-10 (IL-10) in urinary tract infection mediated by UPEC and other uropathogens. We investigated the nature of the IL-10-producing interactions between UPEC and host cells by utilising a novel co-culture model that incorporated lymphocytes, mononuclear and uroepithelial cells in histotypic proportions. This co-culture model demonstrated synergistic IL-10 production effects between monocytes and uroepithelial cells following infection with UPEC. Membrane inserts were used to separate the monocyte and uroepithelial cell types during infection and revealed two synergistic IL-10 production effects based on contact-dependent and soluble interactions. Analysis of a comprehensive set of immunologically relevant biomarkers in monocyte-uroepithelial cell co-cultures highlighted that multiple cytokine, chemokine and signalling factors were also produced in a synergistic or antagonistic fashion. These results demonstrate that IL-10 responses to UPEC occur via multiple interactions between several cells types, implying a complex role for infection-related IL-10 during UTI. Development and application of the co-culture model described in this study is thus useful to define the degree of contact dependency of biomarker production to UPEC, and highlights the relevance of histotypic co-cultures in studying complex host-pathogen interactions.

Of tolerance in mice and men : studies in APECED and Aire

Autoimmune diseases affect 5 % of the population and come in many forms, such as diabetes, rheumatoid arthritis and MS. However, how and why autoimmune diseases arise are not yet fully resolved. In this thesis, the onset of autoimmunity was investigated using both patient samples and a mouse model of autoimmunity. Autoimmune diseases are usually complex, due to a number of different causative genes and environmental factors. However, a few monogenic autoimmune diseases have been described, which are caused by mutations in only one gene per disease. One of such disease is called APECED (autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy) and is enriched in the Finnish population. The causative gene behind APECED is named AIRE from AutoImmune REgulator. How malfunction of just one gene product can cause the multitude of disease components found in APECED is not yet resolved. This thesis sought out to find out more about the functions of AIRE, in order to reveal why APECED and other autoimmune diseases arise and what goes wrong? Usually, immune cells are taught to distinguish between self and non-self during their development. That way, immune cells can fight off bacteria and microbes while leaving the tissues and organs of the host organism itself unharmed. In APECED, the development of immune cells called αβ T cells is incomplete. The cells are not able to fully distinguish between self and non-self. This leads to autodestruction of self tissues and autoimmune disease. One of the achievements of this thesis was the finding that the development of another set of T cells called γδ T cells is not affected by AIRE in mice or in men. Instead, we found that another type of immune cell important in tolerance, called the dendritic cell is defective in APECED patients and is not able to respond to microbial stimulus in a normal fashion. Finally, we studied Aire-deficient mice and found that autoantibodies expressed in the mice were not targeted against the same molecules as those found in APECED patients. This indicates differences in the autoimmune pathology in mice and men. More work is still required before we understand the mechanisms of tolerance and autoimmunity well enough to be able to cure APECED, let alone the more complex autoimmune diseases. Yet altogether, the findings of this thesis work bring us one step closer to finding out why and how APECED and common autoimmune diseases arise.

Studies on the pro-oxidative properties and neurotoxic potential of Angeli's salt-derived nitroxyl (HNO/NO-)

The biological function of nitric oxide and its oxidized forms has received a great deal of attention over the past two decades. However much less attention has been focused on the reduced nitric oxide, nitroxyl (HNO). Unlike NO, HNO is highly reactive species and thus it needs to be generated by using donor compounds under experimental conditions. Currently there is only one donor available, Angeli s salt, which releases HNO in a controlled fashion under pysiological conditions. Prior studies have shown the pro-oxidative and cytotoxic potential of Angeli s salt compared to NO donors. The high reactivity of HNO with cysteine thiols is considered to form the biochemical basis for its unique properties compared to other nitrogen oxides. Such thiol modification cold result in disturbances of vital cellular functions and subsequently to death of disturbance sensitive cells, such as neurons. Therefore modification of proteins and lipids was studied in vitro and the potential neurotoxicity was studied in vivo by local infusion of Angeli s salt into the rat central nervous system. The results show that under aerobic in vitro conditions, HNO can, subsequent to autoxidation, cause irreversible oxidative modification of proteins and lipids. These effects are not however seen in cell culture or following infusion of Angeli s salt directly into the rat central nervous tissue likely due to presence of lower oxygen and higher thiol concentration. However, due to high reactivity with thiols, HNO can cause irreversible inactivation of cysteine modification sensitive enzymes such as cysteine proteases papain in vitro and cathepsin B in cell culture. Furthermore it was shown that infusion of HNO releasing Angeli s salt into the rat central nervous system causes necrotic cell death and motor dysfunction following infusion into the lumbal intrathecal space. In conclusion, the acute neurotoxic potential of Angeli s salt was shown to be relatively low, but still higher compared to NO donors. HNO was shown to affect numerous cellular processes which could result in neurotoxicity if HNO was produced in vivo.

Gas-liquid interfacial area in stirred vessels: The effect of an immiscible liquid phase

The presence of an inert immiscible organic phase in gas�liquid dispersions in stirred vessels influences the interfacial area in a more complex fashion than hitherto reported. As the organic phase fraction is increased, the interfacial area expressed on the basis of a unit volume of dispersion or aqueous phase, first increases, passes through a maximum and then decreases. This trend is observed irrespective of whether the area is determined by chemical means or by physical method. It is found that for low values of inert phase fraction, the average bubble size decreases whereas the gas holdup increases, resulting in increased interfacial area. The lower average bubble size is found to be due to partial prevention of coalescence as the bubbles size generated in the impeller region actually increases with the organic phase fraction. The actual values of interfacial areas depend on the nature of the organic phase. It is also found that the organic phase provides a parallel path for mass transfer to occur, when the solubility of gas in it is high.

Diversity Multiplexing Tradeoff of Asynchronous Cooperative Relay Networks

The assumption of nodes in a cooperative communication relay network operating in synchronous fashion is often unrealistic. In the present paper we consider two different models of asynchronous operation in cooperative-diversity networks experiencing slow fading and examine the corresponding diversity-multiplexing tradeoffs (DMT). For both models, we propose protocols and distributed space-time codes that asymptotically achieve the transmit diversity bound for all multiplexing gains and for number of relays N >= 2.

The missing link of crime analysis: A systematic approach to testing competing hypotheses

Crime analysts have traditionally received little guidance from academic researchers in key tasks in the analysis process, specifically the testing of multiple hypotheses and evaluating evidence in a scientific fashion. This article attempts to fill this gap by outlining a method (the Analysis of Competing Hypotheses) of systematically analysing multiple explanations for crime problems. The method is systematic, avoids many cognitive errors common in analysis, and is explicit. It is argued that the implementation of this approach makes analytic products audit-able, the reasoning underpinning them transparent, and provides intelligence managers a rational professional development tool for individual analysts.

Molecular basis of the kidney filtration barrier : Role of the nephrin protein complex

The kidney filtration barrier consists of fenestrated endothelial cell layer, glomerular basement membrane and slit diaphragm (SD), the specialized junction between glomerular viscelar epithelial cells (podocytes). Podocyte injury is associated with the development of proteinuria, and if not reversed the injury will lead to permanent deterioration of the glomerular filter. The early events are characterized by disruption of the integrity of the SD, but the molecular pathways involved are not fully understood. Congenital nephrotic syndrome of the Finnish type (CNF) is caused by mutations in NPHS1, the gene encoding the SD protein nephrin. Lack of nephrin results in loss of the SD and massive proteinuria beginning before birth. Furthermore, nephrin expression is decreased in acquired human kidney diseases including diabetic nephropathy. This highlights the importance of nephrin and consequently SD in regulating the kidney filtration function. However, the precise molecular mechanism of how nephrin is involved in the formation of the SD is unknown. This thesis work aimed at clarifying the role of nephrin and its interaction partners in the formation of the SD. The purpose was to identify novel proteins that associate with nephrin in order to define the essential molecular complex required for the establishment of the SD. The aim was also to decipher the role of novel nephrin interacting proteins in podocytes. Nephrin binds to nephrin-like proteins Neph1 and Neph2, and to adherens junction protein P-cadherin. These interactions have been suggested to play a role in the formation of the SD. In this thesis work, we identified densin as a novel interaction partner for nephrin. Densin was localized to the SD and it was shown to bind to adherens junction protein beta-catenin. Furthermore, densin was shown to behave in a similar fashion as adherens junction proteins in cell-cell contacts. These results indicate that densin may play a role in cell adhesion and, therefore, may contribute to the formation of the SD together with nephrin and adherens junction proteins. Nephrin was also shown to bind to Neph3, which has been previously localized to the SD. Neph3 and Neph1 were shown to induce cell adhesion alone, whereas nephrin needed to trans-interact with Neph1 or Neph3 from the opposite cell surface in order to make cell-cell contacts. This was associated with the decreased tyrosine phosphorylation of nephrin. These data extend the current knowledge of the molecular composition of the nephrin protein complex at the SD and also provide novel insights of how the SD may be formed. This thesis work also showed that densin was up-regulated in the podocytes of CNF patients. Neph3 was up-regulated in nephrin deficient mouse kidneys, which share similar podocyte alterations and lack of the SD as observed in CNF patients podocytes. These data suggest that densin and Neph3 may have a role in the formation of morphological alterations in podocytes detected in CNF patients. Furthermore, this thesis work showed that deletion of beta-catenin specifically from adult mouse podocytes protected the mice from the development of adriamycin-induced podocyte injury and proteinuria compared to wild-type mice. These results show that beta-catenin play a role in the adriamycin induced podocyte injury. Podocyte injury is a hallmark in many kidney diseases and the changes observed in the podocytes of CNF patient share characteristics with injured podocytes observed in chronic kidney diseases. Therefore, the results obtained in this thesis work suggest that densin, Neph3 and beta-catenin participate in the molecular pathways which result in morphological alterations commonly detected in injured podocytes in kidney diseases.

Writing fashion���s future: the gods and monsters of the Anthropocene

This paper identifies two narratives of the Anthropocene and explores how they play out in the realm of future-looking fashion production. Each narrative draws on mythic comparisons to gods and monsters to express humanity’s dilemmas, albeit from different perspectives. The first is a Malthusian narrative of collapse and scarcity, brought about by the monstrous, unstoppable nature of human technology set loose on the natural world. In this vein, philosopher Slavoj Zizek (2010) draws on Biblical analogies, likening ecological crisis to one of the four horsemen of the apocalypse. To find a myth to suit the present times, novelist A.S Byatt (2011) proposes Ragnarök, a Norse myth in which the gods destroy themselves. In contrast, the second narrative is one of technological cornucopia. Stewart Brand (2009, 27), self-described ‘eco-pragmatist’ writes, ‘we are as gods and we have to get good at it’. In his view, human technologies offer the only hope to mitigating the problems caused by human technology – Brand suggests harnessing nuclear power, bioengineering of crops and the geoengineering of the planet as the way forward. Similarly, the French philosopher Bruno Latour (2012, 274), exhorts us to “love our monsters”, likening our technologies to Doctor Frankenstein’s monster – set loose upon the world, and then reviled by his creator. For both Brand and Latour, human technology may be monstrous, but it must also be turned toward solutions. Within this schema, hopeful visions of the future of fashion are similarly divided. In the techno-enabled cornucopian future, the fashion industry embraces wearable technology, speed and efficiency. Technologies such as waterless dyeing, 3D printing and self-cleaning garments shift fashion into a new era of cleaner production. Meanwhile, in the narrative of scarcity, a more cautious approach sees fashion return to a new localism and valuing of the hand-made in a time of shrinking resources. Through discussion of future-looking fashion designers, brands, and activists, this paper explores how they may align along a spectrum to one of these two grand narratives of the future. The paper will discuss how these narratives may unconsciously shape the perspective of both producers and users around the fashion of today and the fashion of tomorrow. This paper poses the question: what stories can be written for fashion���s future in the Anthropocene, and are they fated, or can they be re-written?

Complexes of Rare-Earth Metals with Meconic Acid

Two series of complexes of meconic acid (H3 Mec) with rare-earths have been prepared by varying the preparative procedure. The compounds have the general formulae, [Ln(Mec) (H2O)2]·3 H2O (whereLn=La, Ce, Pr, Nd, Sm, Ho and Y) and [Ln(HMec) (H2 Mec) (H2O)2]·4 H2O (whereLn=La, Pr, Nd and Sm). The infrared spectral data indicate that the carboxylate groups are bound to the rare-earth metal in a bidentate fashion. Thermal studies indicate that two water molecules are coordinated in each case. The complexes are probably polymeric.

Preference and performance of Diachasmimorpha kraussii (Fullaway) (Hymenoptera: Braconidae) on five commercial fruit species

Diachasmimorpha kraussii is a polyphagous endoparasitoid of dacine fruit flies. The fruit fly hosts of D. krausii, in turn, attack a wide range of fruits and vegetables. The role that fruits play in host selection behaviour of D. kraussii has not been previously investigated. This study examines fruit preference of D. kraussii through a laboratory choice-test trial and field fruit sampling. In the laboratory trial, oviposition preference and offspring performance measures (sex ratio, developmental time, body length, hind tibial length) of D. kraussii were investigated with respect to five fruit species [Psidium guajava L. (guava), Prunis persica L. (peach), Malus domestica Borkh. (apple), Pyrus communis L. (pear) and Citrus sinensis L. (orange)], and two fruit fly species (Bactrocera jarvisi and B. tryoni). Diachasmimorpha kraussii responded to infested fruit of all fruit types in both choice and no-choice tests, but showed stronger preference for guava and peach in the choice tests irrespective of the species of fly larvae within the fruit. The wasp did not respond to uninfested fruit. The offspring performance measures differed in a non-consistent fashion between the fruit types, but generally wasp offspring performed better in guava, peach and orange. The offspring sex ratio, except for one fruit/fly combination (B. jarvisi in apple), was always female biased. The combined results suggest that of the five fruits tested, guava and peach are the best fruit substrates for D. krausii. Field sampling indicated a non-random use of available, fruit fly infested fruit by D. kraussii. Fruit fly maggots within two fruit species, Plachonia careya and Terminalia catappa, had disproportionately higher levels of D. krausii parasitism than would be expected based on the proportion of different infested fruit species sampled, or levels of fruit fly infestation within those fruit.

Relaxation Labeling with Learning Automata

Relaxation labeling processes are a class of mechanisms that solve the problem of assigning labels to objects in a manner that is consistent with respect to some domain-specific constraints. We reformulate this using the model of a team of learning automata interacting with an environment or a high-level critic that gives noisy responses as to the consistency of a tentative labeling selected by the automata. This results in an iterative linear algorithm that is itself probabilistic. Using an explicit definition of consistency we give a complete analysis of this probabilistic relaxation process using weak convergence results for stochastic algorithms. Our model can accommodate a range of uncertainties in the compatibility functions. We prove a local convergence result and show that the point of convergence depends both on the initial labeling and the constraints. The algorithm is implementable in a highly parallel fashion.

Photodimerization of olefins in solid state

Photochemical transformations of organic solids provide an exciting area of research with new synthetic possibilities. These reactions are generally governed by topochemical factors rather than the normal rules of chemical reactivity. Defects play a crucial role in some of the reactions. Some of the transformations such as the photodimerization of 4, 4'-dimethoxystilbene occur in a single crystal fashion.

Conformal Field Theory Methods for Variants of Schramm-Loewner Evolutions

This thesis consists of an introduction, four research articles and an appendix. The thesis studies relations between two different approaches to continuum limit of models of two dimensional statistical mechanics at criticality. The approach of conformal field theory (CFT) could be thought of as the algebraic classification of some basic objects in these models. It has been succesfully used by physicists since 1980's. The other approach, Schramm-Loewner evolutions (SLEs), is a recently introduced set of mathematical methods to study random curves or interfaces occurring in the continuum limit of the models. The first and second included articles argue on basis of statistical mechanics what would be a plausible relation between SLEs and conformal field theory. The first article studies multiple SLEs, several random curves simultaneously in a domain. The proposed definition is compatible with a natural commutation requirement suggested by Dubédat. The curves of multiple SLE may form different topological configurations, ``pure geometries''. We conjecture a relation between the topological configurations and CFT concepts of conformal blocks and operator product expansions. Example applications of multiple SLEs include crossing probabilities for percolation and Ising model. The second article studies SLE variants that represent models with boundary conditions implemented by primary fields. The most well known of these, SLE(kappa, rho), is shown to be simple in terms of the Coulomb gas formalism of CFT. In the third article the space of local martingales for variants of SLE is shown to carry a representation of Virasoro algebra. Finding this structure is guided by the relation of SLEs and CFTs in general, but the result is established in a straightforward fashion. This article, too, emphasizes multiple SLEs and proposes a possible way of treating pure geometries in terms of Coulomb gas. The fourth article states results of applications of the Virasoro structure to the open questions of SLE reversibility and duality. Proofs of the stated results are provided in the appendix. The objective is an indirect computation of certain polynomial expected values. Provided that these expected values exist, in generic cases they are shown to possess the desired properties, thus giving support for both reversibility and duality.

Boosting the productivity and profitability of northern Australian beef enterprises: Exploring innovation options using simulation modelling and systems analysis

The financial health of beef cattle enterprises in northern Australia has declined markedly over the last decade due to an escalation in production and marketing costs and a real decline in beef prices. Historically, gains in animal productivity have offset the effect of declining terms of trade on farm incomes. This raises the question of whether future productivity improvements can remain a key path for lifting enterprise profitability sufficient to ensure that the industry remains economically viable over the longer term. The key objective of this study was to assess the production and financial implications for north Australian beef enterprises of a range of technology interventions (development scenarios), including genetic gain in cattle, nutrient supplementation, and alteration of the feed base through introduced pastures and forage crops, across a variety of natural environments. To achieve this objective a beef systems model was developed that is capable of simulating livestock production at the enterprise level, including reproduction, growth and mortality, based on energy and protein supply from natural C4 pastures that are subject to high inter-annual climate variability. Comparisons between simulation outputs and enterprise performance data in three case study regions suggested that the simulation model (the Northern Australia Beef Systems Analyser) can adequately represent the performance beef cattle enterprises in northern Australia. Testing of a range of development scenarios suggested that the application of individual technologies can substantially lift productivity and profitability, especially where the entire feedbase was altered through legume augmentation. The simultaneous implementation of multiple technologies that provide benefits to different aspects of animal productivity resulted in the greatest increases in cattle productivity and enterprise profitability, with projected weaning rates increasing by 25%, liveweight gain by 40% and net profit by 150% above current baseline levels, although gains of this magnitude might not necessarily be realised in practice. While there were slight increases in total methane output from these development scenarios, the methane emissions per kg of beef produced were reduced by 20% in scenarios with higher productivity gain. Combinations of technologies or innovative practices applied in a systematic and integrated fashion thus offer scope for providing the productivity and profitability gains necessary to maintain viable beef enterprises in northern Australia into the future.

The UPAL process: a direct method of preparing cast aluminium alloy-graphite particle composites

A direct method of preparing cast aluminium alloy-graphite particle composites using uncoated graphite particles is reported. The method consists of introducing and dispersing uncoated but suitably pretreated graphite particles in aluminium alloy melts, and casting the resulting composite melts in suitable permanent moulds. The optical pretreatment required for the dispersion of the uncoated graphite particles in aluminium alloy melts consists of heating the graphite particles to 400° C in air for 1 h just prior to their dispersion in the melts. The effects of alloying elements such as Si, Cu and Mg on the dispersability of pretreated graphite in molten aluminium have also been reported. It was found that additions of about 0.5% Mg or 5% Si significantly improve the dispersability of graphite particles in aluminium alloy melts as indicated by the high recoveries of graphite in the castings of these composites. It was also possible to disperse upto 3% graphite in LM 13 alloy melts and retain the graphite particles in a well distributed fashion in the castings using the pre-heat-treated graphite particles. The observations in this study have been related to the information presently available on wetting between graphite and molten aluminium in the presence of different elements and our own thermogravimetric analysis studies on graphite particles. Physical and mechanical properties of LM 13-3% graphite composite made using pre-heat-treated graphite powder, were found to be adequate for many applications, including pistons which have been successfully used in internal combustion engines.