Hydrogen-bonding in the structures of the hydrated proton-transfer compounds of isonipecotamide with the isomeric indole-2 and indole-3-carboxylic acids

The structures of two hydrated proton-transfer compounds of 4-piperidinecarboxamide (isonipecotamide) with the isomeric heteroaromatic carboxylic acids indole-2-carboxylic acid and indole-3-carboxylic acid, namely 4-carbamoylpiperidinium indole-2-carboxylate dihydrate (1) and 4-carbamoylpiperidinium indole-3-carboxylate hemihydrate (2) have been determined at 200 K. Crystals of both 1 and 2 are monoclinic, space groups P21/c and P2/c respectively with Z = 4 in cells having dimensions a = 10.6811(4), b = 12.2017(4), c = 12.5456(5) Å, β = 96.000(4)o (1) and a = 15.5140(4), b = 10.2908(3), c = 9.7047(3) Å, β = 97.060(3)o (2). Hydrogen-bonding in 1 involves a primary cyclic interaction involving complementary cation amide N-H…O(carboxyl) anion and anion hetero N-H…O(amide) cation hydrogen bonds [graph set R22(9)]. Secondary associations involving also the water molecules of solvation give a two-dimensional network structure which includes weak water O-H…π interactions. In the three-dimensional hydrogen-bonded structure of 2, there are classic centrosymmetric cyclic head-to-head hydrogen-bonded amide-amide interactions [graph set R22(8)] as well as lateral cyclic amide-O linked amide-amide extensions [graph set R24(8)]. The anions and the water molecule, which lies on a twofold rotation axis, are involved in secondary extensions.

Jams, jelly beans and the fruits of passion - art book (26 Pages)

Statement: Jams, Jelly Beans and the Fruits of Passion Let us search, instead, for an epistemology of practice implicit in the artistic, intuitive processes which some practitioners do bring to situations of uncertainty, instability, uniqueness, and value conflict. (Schön 1983, p40) Game On was born out of the idea of creative community; finding, networking, supporting and inspiring the people behind the face of an industry, those in the mist of the machine and those intending to join. We understood this moment to be a pivotal opportunity to nurture a new emerging form of game making, in an era of change, where the old industry models were proving to be unsustainable. As soon as we started putting people into a room under pressure, to make something in 48hrs, a whole pile of evolutionary creative responses emerged. People refashioned their craft in a moment of intense creativity that demanded different ways of working, an adaptive approach to the craft of making games – small – fast – indie. An event like the 48hrs forces participants’ attention onto the process as much as the outcome. As one game industry professional taking part in a challenge for the first time observed: there are three paths in the genesis from idea to finished work: the path that focuses on mechanics; the path that focuses on team structure and roles, and the path that focuses on the idea, the spirit – and the more successful teams put the spirit of the work first and foremost. The spirit drives the adaptation, it becomes improvisation. As Schön says: “Improvisation consists on varying, combining and recombining a set of figures within the schema which bounds and gives coherence to the performance.” (1983, p55). This improvisational approach is all about those making the games: the people and the principles of their creative process. This documentation evidences the intensity of their passion, determination and the shit that they are prepared to put themselves through to achieve their goal – to win a cup full of jellybeans and make a working game in 48hrs. 48hr is a project where, on all levels, analogue meets digital. This concept was further explored through the documentation process. All of these pictures were taken with a 1945 Leica III camera. The use of this classic, film-based camera, gives the images a granularity and depth, this older slower technology exposes the very human moments of digital creativity. ____________________________ Schön, D. A. 1983, The Reflective Practitioner: How Professionals Think in Action, Basic Books, New York

Trading spaces : on the lore and limitations of latent semantic analysis

Two decades after its inception, Latent Semantic Analysis(LSA) has become part and parcel of every modern introduction to Information Retrieval. For any tool that matures so quickly, it is important to check its lore and limitations, or else stagnation will set in. We focus here on the three main aspects of LSA that are well accepted, and the gist of which can be summarized as follows: (1) that LSA recovers latent semantic factors underlying the document space, (2) that such can be accomplished through lossy compression of the document space by eliminating lexical noise, and (3) that the latter can best be achieved by Singular Value Decomposition. For each aspect we performed experiments analogous to those reported in the LSA literature and compared the evidence brought to bear in each case. On the negative side, we show that the above claims about LSA are much more limited than commonly believed. Even a simple example may show that LSA does not recover the optimal semantic factors as intended in the pedagogical example used in many LSA publications. Additionally, and remarkably deviating from LSA lore, LSA does not scale up well: the larger the document space, the more unlikely that LSA recovers an optimal set of semantic factors. On the positive side, we describe new algorithms to replace LSA (and more recent alternatives as pLSA, LDA, and kernel methods) by trading its l2 space for an l1 space, thereby guaranteeing an optimal set of semantic factors. These algorithms seem to salvage the spirit of LSA as we think it was initially conceived.

Rational design of serine protease inhibitors

Proteases regulate a spectrum of diverse physiological processes, and dysregulation of proteolytic activity drives a plethora of pathological conditions. Understanding protease function is essential to appreciating many aspects of normal physiology and progression of disease. Consequently, development of potent and specific inhibitors of proteolytic enzymes is vital to provide tools for the dissection of protease function in biological systems and for the treatment of diseases linked to aberrant proteolytic activity. The studies in this thesis describe the rational design of potent inhibitors of three proteases that are implicated in disease development. Additionally, key features of the interaction of proteases and their cognate inhibitors or substrates are analysed and a series of rational inhibitor design principles are expounded and tested. Rational design of protease inhibitors relies on a comprehensive understanding of protease structure and biochemistry. Analysis of known protease cleavage sites in proteins and peptides is a commonly used source of such information. However, model peptide substrate and protein sequences have widely differing levels of backbone constraint and hence can adopt highly divergent structures when binding to a protease’s active site. This may result in identical sequences in peptides and proteins having different conformations and diverse spatial distribution of amino acid functionalities. Regardless of this, protein and peptide cleavage sites are often regarded as being equivalent. One of the key findings in the following studies is a definitive demonstration of the lack of equivalence between these two classes of substrate and invalidation of the common practice of using the sequences of model peptide substrates to predict cleavage of proteins in vivo. Another important feature for protease substrate recognition is subsite cooperativity. This type of cooperativity is commonly referred to as protease or substrate binding subsite cooperativity and is distinct from allosteric cooperativity, where binding of a molecule distant from the protease active site affects the binding affinity of a substrate. Subsite cooperativity may be intramolecular where neighbouring residues in substrates are interacting, affecting the scissile bond’s susceptibility to protease cleavage. Subsite cooperativity can also be intermolecular where a particular residue’s contribution to binding affinity changes depending on the identity of neighbouring amino acids. Although numerous studies have identified subsite cooperativity effects, these findings are frequently ignored in investigations probing subsite selectivity by screening against diverse combinatorial libraries of peptides (positional scanning synthetic combinatorial library; PS-SCL). This strategy for determining cleavage specificity relies on the averaged rates of hydrolysis for an uncharacterised ensemble of peptide sequences, as opposed to the defined rate of hydrolysis of a known specific substrate. Further, since PS-SCL screens probe the preference of the various protease subsites independently, this method is inherently unable to detect subsite cooperativity. However, mean hydrolysis rates from PS-SCL screens are often interpreted as being comparable to those produced by single peptide cleavages. Before this study no large systematic evaluation had been made to determine the level of correlation between protease selectivity as predicted by screening against a library of combinatorial peptides and cleavage of individual peptides. This subject is specifically explored in the studies described here. In order to establish whether PS-SCL screens could accurately determine the substrate preferences of proteases, a systematic comparison of data from PS-SCLs with libraries containing individually synthesised peptides (sparse matrix library; SML) was carried out. These SML libraries were designed to include all possible sequence combinations of the residues that were suggested to be preferred by a protease using the PS-SCL method. SML screening against the three serine proteases kallikrein 4 (KLK4), kallikrein 14 (KLK14) and plasmin revealed highly preferred peptide substrates that could not have been deduced by PS-SCL screening alone. Comparing protease subsite preference profiles from screens of the two types of peptide libraries showed that the most preferred substrates were not detected by PS SCL screening as a consequence of intermolecular cooperativity being negated by the very nature of PS SCL screening. Sequences that are highly favoured as result of intermolecular cooperativity achieve optimal protease subsite occupancy, and thereby interact with very specific determinants of the protease. Identifying these substrate sequences is important since they may be used to produce potent and selective inhibitors of protolytic enzymes. This study found that highly favoured substrate sequences that relied on intermolecular cooperativity allowed for the production of potent inhibitors of KLK4, KLK14 and plasmin. Peptide aldehydes based on preferred plasmin sequences produced high affinity transition state analogue inhibitors for this protease. The most potent of these maintained specificity over plasma kallikrein (known to have a very similar substrate preference to plasmin). Furthermore, the efficiency of this inhibitor in blocking fibrinolysis in vitro was comparable to aprotinin, which previously saw clinical use to reduce perioperative bleeding. One substrate sequence particularly favoured by KLK4 was substituted into the 14 amino acid, circular sunflower trypsin inhibitor (SFTI). This resulted in a highly potent and selective inhibitor (SFTI-FCQR) which attenuated protease activated receptor signalling by KLK4 in vitro. Moreover, SFTI-FCQR and paclitaxel synergistically reduced growth of ovarian cancer cells in vitro, making this inhibitor a lead compound for further therapeutic development. Similar incorporation of a preferred KLK14 amino acid sequence into the SFTI scaffold produced a potent inhibitor for this protease. However, the conformationally constrained SFTI backbone enforced a different intramolecular cooperativity, which masked a KLK14 specific determinant. As a consequence, the level of selectivity achievable was lower than that found for the KLK4 inhibitor. Standard mechanism inhibitors such as SFTI rely on a stable acyl-enzyme intermediate for high affinity binding. This is achieved by a conformationally constrained canonical binding loop that allows for reformation of the scissile peptide bond after cleavage. Amino acid substitutions within the inhibitor to target a particular protease may compromise structural determinants that support the rigidity of the binding loop and thereby prevent the engineered inhibitor reaching its full potential. An in silico analysis was carried out to examine the potential for further improvements to the potency and selectivity of the SFTI-based KLK4 and KLK14 inhibitors. Molecular dynamics simulations suggested that the substitutions within SFTI required to target KLK4 and KLK14 had compromised the intramolecular hydrogen bond network of the inhibitor and caused a concomitant loss of binding loop stability. Furthermore in silico amino acid substitution revealed a consistent correlation between a higher frequency of formation and the number of internal hydrogen bonds of SFTI-variants and lower inhibition constants. These predictions allowed for the production of second generation inhibitors with enhanced binding affinity toward both targets and highlight the importance of considering intramolecular cooperativity effects when engineering proteins or circular peptides to target proteases. The findings from this study show that although PS-SCLs are a useful tool for high throughput screening of approximate protease preference, later refinement by SML screening is needed to reveal optimal subsite occupancy due to cooperativity in substrate recognition. This investigation has also demonstrated the importance of maintaining structural determinants of backbone constraint and conformation when engineering standard mechanism inhibitors for new targets. Combined these results show that backbone conformation and amino acid cooperativity have more prominent roles than previously appreciated in determining substrate/inhibitor specificity and binding affinity. The three key inhibitors designed during this investigation are now being developed as lead compounds for cancer chemotherapy, control of fibrinolysis and cosmeceutical applications. These compounds form the basis of a portfolio of intellectual property which will be further developed in the coming years.

Athletes series

The researcher was invited to photograph athletes in the lead-up to the 2006 Commonwealth Games held in Melbourne. She photographed four indigenous athletes, to produce a series of four large-scale cotton rag prints, 1 meter x 1 meter, printed onto photorag paper from digital files. “My photographic practice can be described as both political and spiritual, in the sense that as an Aboriginal Indigenous artist I take stock of the rationalising effect of the technologies I use, and create work that evokes nature and spirit. My methods often involve re-photographing or digitally re-working landscape photographs and adding historical or cultural icons of significance. Working with Indigenous athletes has been an honour and a pleasure. I admire the athletes’ passion and dedication to their chosen sport, and above all their humility, which seems a trait somewhat in contrast to what it takes to attain the highest levels of achievement. Indigenous athletes are wonderful role models for all Australians, and in making creative work that places their luminary presence with the land, I am aligning sportspeople with a deep sense of nature and spirit.” – Leah King-Smith. These works were commissioned by the National Portrait Gallery for the exhibition FLASH: Australian Athletes in Focus. The exhibition was a significant element in Melbourne2006 Festival, the cultural festival of the Commonwealth Games. The exhibition was prominently reviewed in Portrait: Magazine of Australian and International Portraiture and was subsequently remounted at Old Parliament House, Canberra (15 July to 12 November, 2006). One image was used for the front cover of Art Monthly, (March 2006).

Immunohistochemical detection of survivin in canine lymphoma

Survivin is a member of the family of proteins known as 'inhibitors of apoptosis proteins'. Survivin has a role in cellular decisions concerning division and survival and is frequently expressed in neoplastic cells. The aim of the present study was to investigate immunohistochemically the expression of survivin in normal canine tissues and in canine lymphoma. A representative range of fetal and adult normal tissues as well as biopsy samples from dogs with lymphoma were assembled in tissue arrays. The lymphomas were classified according to the revised Kiel and to the Revised European American Lymphoma - World Health Organization (REAL-WHO) schemes. Polyclonal and monoclonal antisera cross-reactive with canine survivin identified cytoplasmic expression of the molecule in a broad range of normal canine cells. The same reagents demonstrated cytoplasmic labelling of more than 5% of cells in all 83 lymphoma samples tested with polyclonal antiserum and in 67 of 82 (82%) of samples tested with monoclonal antiserum. Survivin was expressed by a wide range of canine lymphoma subtypes, but the expression of this molecule in normal canine tissues must be considered if novel therapies targeting survivin are applied to the management of canine lymphoma. © 2010 Elsevier Ltd.

4-(4-Aminophenylsulfonyl)aniline-3,5-dinitrobenzoic acid (1/1)

In the title co-crystalline adduct of the drug Dapsone with 3,5-dinitrobenzoic acid, C~12~H~12~N~2~O~2~S . C~7~H~4~N~4~O~6~, the dihedral angle between the two aromatic rings of the Dapsone molecule is 75.4(2)deg. and those between these rings and that of the 3,5-dinitrobenzoic acid are 64.5(2) and 68.4(2)deg. A strong inter-species carboxylic acid O-H---N(amine) hydrogen-bond is found, which together with intermolecular amine N-H...O hydrogen-bonding associations with carboxyl, nitro and sulfone O-atom acceptors as well as weak pi-pi interactions between one of the Dapsone phenyl rings and the 3,5-dinitrobenzoic acid ring [minimum ring centroid separation 3.774(2)Ang.], give a two-dimensional network structure.

Improved facial expression recognition via uni-hyperplane classification

Large margin learning approaches, such as support vector machines (SVM), have been successfully applied to numerous classification tasks, especially for automatic facial expression recognition. The risk of such approaches however, is their sensitivity to large margin losses due to the influence from noisy training examples and outliers which is a common problem in the area of affective computing (i.e., manual coding at the frame level is tedious so coarse labels are normally assigned). In this paper, we leverage the relaxation of the parallel-hyperplanes constraint and propose the use of modified correlation filters (MCF). The MCF is similar in spirit to SVMs and correlation filters, but with the key difference of optimizing only a single hyperplane. We demonstrate the superiority of MCF over current techniques on a battery of experiments.

4-Amino-N-(4,6-dimethylpyrimidin-2-yl)benzenesulfonamide-4-nitrobenzoic acid

In the asymmetric unit of the title co-crystal, C12H14N4O2S . C7H5NO4 there are two independent but conformationally similar heterodimers, which are formed through intermolecular N-H...O(carboxy) and carboxyl O-H...N hydrogen-bond pairs, giving a cyclic motif [graph set R2/2(8)]. The dihedral angles between the rings in the sulfonamide molecules are 78.77(8) and 82.33(9)deg. while the dihedral angles between the ring and the CO2H group in the acids are 2.19(9) and 7.02(10)deg. A two-dimensional structure parallel to the ab plane is generated from the heterodimer units through hydrogen-bonding associations between NH2 and sulfone groups. Between neighbouring two-dimensional arrays there are two types of aromatic pi-pi stacking interactions involving either one of the pyrimidine rings and a 4-nitrobenzoic acid molecule [minimum ring centroid separation = 3.5886(9)A] or two acid molecules [minimum ring centroid separation = 3.7236(10)A].

Sourdough & other stories : a story told in parts (a mosaic novel and exegesis)

The mosaic novel - with its independent 'story-tiles' linking together to form a complete narrative - has the potential to act as a reflection on the periodic resurfacing of unconscious memories in the conscious lives of fictional characters. This project is an exploration of the mosaic text as a fictional analogue of involuntary memory. These concepts are investigated as they appear in traditional fairy tales and engaged with in this thesis's creative component, Sourdough and Other Stories (approximately 80,000 words), a mosaic novel comprising sixteen interconnected 'story-tiles'. Traditional fairy tales are non-reflective and conducive to forgetting (i.e. anti-memory); fairy tale characters are frequently portrayed as psychologically two-dimensional, in that there is no examination of the mental and emotional distress caused when children are stolen/ abandoned/ lost and when adults are exiled. Sourdough and Other Stories is a creative examination of, and attempted to remedy, this lack of psychological depth. This creative work is at once something more than a short story collection, and something that is not a traditional novel, but instead a culmination of two modes of writing. It employs the fairy tale form to explore James' 'thorns in the spirit' (1898, p.199) in fiction; the anxiety caused by separation from familial and community groups. The exegesis, A Story Told in Parts - Sourdough and Other Stories is a critical essay (approximately 20,000 words in length), a companion piece to the mosaic novel, which analyses how my research question proceeded from my creative work, and considers the theoretical underpinnings of the creative work and how it enacts the research question: 'Can a writer use the structural possibilities of the mosaic text to create a fictional work that is an analogue of an involuntary memory?' The cumulative effect of the creative and exegetical works should be that of a dialogue between the two components - each text informing the other and providing alternate but complementary lenses with which to view the research question.

UK pre-pack reforms : pause for thought in Australia?

On 31 March 2011 the UK Government announced new measures to regulate the use of pre-packaged sales in administration. The legislation is not expected until later in 2011, but the announcement heralds a shift in regulatory attitudes towards pre-packs in the UK which should give all local pre-pack advocates pause for thought when considering the merits of embracing the procedure in Australia. In the Jan-March 2011 edition of the Australian Insolvency Journal, an interesting article by Nicholas Crouch and Shabnam Amirbeaggi extolled the virtues of pre-packs and called for “legislative reform to embrace pre-packs” in Australia. By way of reply (and in a spirit of constructive debate) this article respectfully contends that while pre-packs certainly have their place in preserving business value in certain circumstances, Australia should be careful not to sleepwalk into adopting a procedure which legitimises phoenixing at the expense of creditor confidence and participation in our insolvency regime.

Photoclickable surfaces for profluorescent covalent polymer coatings

The nitrile imine-mediated tetrazole-ene cycloaddition reaction (NITEC) is introduced as a powerful and versatile conjugation tool to covalently ligate macromolecules onto variable (bio)surfaces. The NITEC approach is initiated by UV irradiation and proceeds rapidly at ambient temperature yielding a highly fluorescent linkage. Initially, the formation of block copolymers by the NITEC methodology is studied to evidence its efficacy as a macromolecular conjugation tool. The grafting of polymers onto inorganic (silicon) and bioorganic (cellulose) surfaces is subsequently carried out employing the optimized reaction conditions obtained from the macromolecular ligation experiments and evidenced by surface characterization techniques, including X-ray photoelectron spectroscopy and FT-IR microscopy. In addition, the patterned immobilization of variable polymer chains onto profluorescent cellulose is achieved through a simple masking process during the irradiation. Photoinduced nitrile imine-alkene 1,3-dipolar cycloaddition (NITEC) is employed to covalently bind well-defined polymers onto silicon oxide or cellulose. A diaryl tetrazole-functionalized molecule is grafted via silanization or amidification, respectively. Under UV light, a reactive nitrile imine rapidly forms and reacts with maleimide-functionalized polymers yielding a fluorescent linkage. Via a masking method, polymeric fluorescent patterns are achieved.

Experimental and theoretical investigation of ligand effects on the synthesis of ZnO nanoparticles

ZnO nanoparticles with highly controllable particle sizes(less than 10 nm) were synthesized using organic capping ligands in Zn(Ac)2 ethanolic solution. The molecular structure of the ligands was found to have significant influence on the particle size. The multi-functional molecule tris(hydroxymethyl)-aminomethane (THMA) favoured smaller particle distributions compared with ligands possessing long hydrocarbon chains that are more frequently employed. The adsorption of capping ligands on ZnnOn crystal nuclei (where n = 4 or 18 molecular clusters of(0001) ZnO surfaces) was modelled by ab initio methods at the density functional theory (DFT) level. For the molecules examined, chemisorption proceeded via the formation of Zn...O, Zn...N, or Zn...S chemical bonds between the ligands and active Zn2+ sites on ZnO surfaces. The DFT results indicated that THMA binds more strongly to the ZnO surface than other ligands, suggesting that this molecule is very effective at stabilizing ZnO nanoparticle surfaces. This study, therefore, provides new insight into the correlation between the molecular structure of capping ligands and the morphology of metal oxide nanostructures formed in their presence.

Democratization and Violence: European and International Perspectives

It is a startling fact that when in the mid-80s a ‘third wave’ of democracy took hold in Latin America and Eastern Europe, both democracy and violence were simultaneously on the rise worldwide. Almost by definition democracies represent an institutionalized framework and a way of life that ensures non-violent means to share power between communities of people with widely differing values and beliefs. As Keane (2004) points out, ‘violence is anathema to [democracy’s] spirit and substance’ (p. 1). Accordingly, the process of democratization was accompanied by expectations that violence would generally decrease, and that these countries would embark on a process of reducing levels of violence as Western European countries had done earlier in the 19th and 20th century.

Linear and nonlinear propagation of localised plasmon in metallic nanostructures

A major challenge in modern photonics and nano-optics is the diffraction limit of light which does not allow field localisation into regions with dimensions smaller than half the wavelength. Localisation of light into nanoscale regions (beyond its diffraction limit) has applications ranging from the design of optical sensors and measurement techniques with resolutions as high as a few nanometres, to the effective delivery of optical energy into targeted nanoscale regions such as quantum dots, nano-electronic and nano-optical devices. This field has become a major research direction over the last decade. The use of strongly localised surface plasmons in metallic nanostructures is one of the most promising approaches to overcome this problem. Therefore, the aim of this thesis is to investigate the linear and non-linear propagation of surface plasmons in metallic nanostructures. This thesis will focus on two main areas of plasmonic research –– plasmon nanofocusing and plasmon nanoguiding. Plasmon nanofocusing – The main aim of plasmon nanofocusing research is to focus plasmon energy into nanoscale regions using metallic nanostructures and at the same time achieve strong local field enhancement. Various structures for nanofocusing purposes have been proposed and analysed such as sharp metal wedges, tapered metal films on dielectric substrates, tapered metal rods, and dielectric V-grooves in metals. However, a number of important practical issues related to nanofocusing in these structures still remain unclear. Therefore, one of the main aims of this thesis is to address two of the most important of issues which are the coupling efficiency and heating effects of surface plasmons in metallic nanostructures. The method of analysis developed throughout this thesis is a general treatment that can be applied to a diversity of nanofocusing structures, with results shown here for the specific case of sharp metal wedges. Based on the geometrical optics approximation, it is demonstrated that the coupling efficiency from plasmons generated with a metal grating into the nanofocused symmetric or quasi-symmetric modes may vary between ~50% to ~100% depending on the structural parameters. Optimal conditions for nanofocusing with the view to minimise coupling and dissipative losses are also determined and discussed. It is shown that the temperature near the tip of a metal wedge heated by nanosecond plasmonic pulses can increase by several hundred degrees Celsius. This temperature increase is expected to lead to nonlinear effects, self-influence of the focused plasmon, and ultimately self-destruction of the metal tip. This thesis also investigates a different type of nanofocusing structure which consists of a tapered high-index dielectric layer resting on a metal surface. It is shown that the nanofocusing mechanism that occurs in this structure is somewhat different from other structures that have been considered thus far. For example, the surface plasmon experiences significant backreflection and mode transformation at a cut-off thickness. In addition, the reflected plasmon shows negative refraction properties that have not been observed in other nanofocusing structures considered to date. Plasmon nanoguiding – Guiding surface plasmons using metallic nanostructures is important for the development of highly integrated optical components and circuits which are expected to have a superior performance compared to their electronicbased counterparts. A number of different plasmonic waveguides have been considered over the last decade including the recently considered gap and trench plasmon waveguides. The gap and trench plasmon waveguides have proven to be difficult to fabricate. Therefore, this thesis will propose and analyse four different modified gap and trench plasmon waveguides that are expected to be easier to fabricate, and at the same time acquire improved propagation characteristics of the guided mode. In particular, it is demonstrated that the guided modes are significantly screened by the extended metal at the bottom of the structure. This is important for the design of highly integrated optics as it provides the opportunity to place two waveguides close together without significant cross-talk. This thesis also investigates the use of plasmonic nanowires to construct a Fabry-Pérot resonator/interferometer. It is shown that the resonance effect can be achieved with the appropriate resonator length and gap width. Typical quality factors of the Fabry- Pérot cavity are determined and explained in terms of radiative and dissipative losses. The possibility of using a nanowire resonator for the design of plasmonic filters with close to ~100% transmission is also demonstrated. It is expected that the results obtained in this thesis will play a vital role in the development of high resolution near field microscopy and spectroscopy, new measurement techniques and devices for single molecule detection, highly integrated optical devices, and nanobiotechnology devices for diagnostics of living cells.