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This dissertation studies the context-aware application with its proposed algorithms at client side. The required context-aware infrastructure is discussed in depth to illustrate that such an infrastructure collects the mobile user’s context information, registers service providers, derives mobile user’s current context, distributes user context among context-aware applications, and provides tailored services. The approach proposed tries to strike a balance between the context server and mobile devices. The context acquisition is centralized at the server to ensure the reusability of context information among mobile devices, while context reasoning remains at the application level. Hence, a centralized context acquisition and distributed context reasoning are viewed as a better solution overall. The context-aware search application is designed and implemented at the server side. A new algorithm is proposed to take into consideration the user context profiles. By promoting feedback on the dynamics of the system, any prior user selection is now saved for further analysis such that it may contribute to help the results of a subsequent search. On the basis of these developments at the server side, various solutions are consequently provided at the client side. A proxy software-based component is set up for the purpose of data collection. This research endorses the belief that the proxy at the client side should contain the context reasoning component. Implementation of such a component provides credence to this belief in that the context applications are able to derive the user context profiles. Furthermore, a context cache scheme is implemented to manage the cache on the client device in order to minimize processing requirements and other resources (bandwidth, CPU cycle, power). Java and MySQL platforms are used to implement the proposed architecture and to test scenarios derived from user’s daily activities. To meet the practical demands required of a testing environment without the impositions of a heavy cost for establishing such a comprehensive infrastructure, a software simulation using a free Yahoo search API is provided as a means to evaluate the effectiveness of the design approach in a most realistic way. The integration of Yahoo search engine into the context-aware architecture design proves how context aware application can meet user demands for tailored services and products in and around the user’s environment. The test results show that the overall design is highly effective, providing new features and enriching the mobile user’s experience through a broad scope of potential applications.

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Topoisomerase inhibitors are effective for antibacterial and anticancer therapy because they can lead to the accumulation of the intermediate DNA cleavage complex formed by the topoisomerase enzymes, which trigger cell death. Here we report the application of a novel enzyme-based high-throughput screening assay to identify natural product extracts that can lead to increased accumulation of the DNA cleavage complex formed by recombinant Yersinia pestistopoisomerase I as part of a larger effort to identify new antibacterial compounds. Further characterization and fractionation of the screening positives from the primary assay led to the discovery of a depside, anziaic acid, from the lichen Hypotrachyna sp. as an inhibitor for both Y. pestis and Escherichia colitopoisomerase I. In in vitro assays, anziaic acid exhibits antibacterial activity against Bacillus subtilis and a membrane permeable strain of E. coli. Anziaic acid was also found to act as an inhibitor of human topoisomerase II but had little effect on human topoisomerase I. This is the first report of a depside with activity as a topoisomerase poison inhibitor and demonstrates the potential of this class of natural products as a source for new antibacterial and anticancer compounds.

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The DTRF2014 is a realization of the the fundamental Earth-fixed coordinate system, the International Terrestrial Reference System (ITRS). It has been computed by the Deutsches Geodätisches Forschungsinstitut der Technischen Universität München (DGFI-TUM). The DTRF2014 consists of station positions and velocities of 1712 globally distributed geodetic observing stations of the observation techniques VLBI, SLR, GNSS and DORIS. Additionally, for the first time, non-tidal atmospheric and hydrological loading is considered in the solution. The DTRF2014 was released in August 2016 and incorporates observation data of the four techniques up 2014. The observation data were processed and submitted by the corresponding technique services: IGS (International GNSS Service, http://igscb.jpl.nasa.gov) IVS (International VLBI Service, http://ivscc.gsfc.nasa.gov) ILRS (International Laser Ranging Service, http://ilrs.gsfc.nasa.gov) IDS (International DORIS Service, http://ids-doris.org). The DTRF2014 is an independent ITRS realization. It is computed on the basis of the same input data as the realizations JTRF2014 (JPL, Pasadena) and ITRF2014 (IGN, Paris). The three realizations of the ITRS differ conceptually. While DTRF2014 and ITRF2014 are based on station positions at a reference epoch and velocities, the JTRF2014 is based on time series of station positions. DTRF2014 and ITRF2014 result from different combination strategies: The ITRF2014 is based on the combination of solutions, the DTRF2014 is computed by the combination of normal equations. The DTRF2014 comprises 3D coordinates and coordinate changes of 1347 GNSS-, 113 VLBI-, 99 SLR- and 153 DORIS-stations. The reference epoch is 1.1.2005, 0h UTC. The Earth Orientation Parameters (EOP) - that means the coordinates of the terrestrial and the celestial pole, UT1-UTC and the Length of Day (LOD) - were simultaneously estimated with the station coordinates. The EOP time series cover the period from 1979.7 to 2015.0. The station names are the official IERS identifiers: CDP numbers or 4-character IDs and DOMES numbers (http://itrf.ensg.ign.fr/doc_ITRF/iers_sta_list.txt). The DTRF2014 solution is available in one comprehensive SINEX file and four technique-specific SINEX files, see below. A detailed description of the solution is given on the website of DGFI-TUM (http://www.dgfi.tum.de/en/science-data-products/dtrf2014/). More information can be made available by request.

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Nanostructured copper containing materials of CuO, Cu3(PO4)3 and Cu2P2O7 have been prepared by solid-state pyrolysis of molecular CuCl2·NC5H4OH (I), CuCl2·CNCH2C6H4OH (II), oligomeric [Cu(PPh3)Cl]4 (III), N3P3[OC6H4CH2CN·CuCl]6[PF6] (IV), N3P3[OC6H5]5[OC5H4N·Cu][PF6] (V), polymeric chitosan·(CuCl2)n (VI) and polystyrene-co-4-vinylpyridine PS-b-4-PVP·(CuCl2) (VII) precursors. The products strongly depend on the precursor used. The pyrolytic products from phosphorus-containing precursors (III), (IV) and (V) are Cu phosphates or pyrophosphates, while non-phosphorous-containing precursors (VI) and (VII), result in mainly CuO. The use of chitosan as a solid-state template/stabilizer induces the formation of CuO and Cu2O nanoparticles. Copper pyrophosphate (Cu2P2O7) deposited on Si using (IV) as the precursor exhibits single-crystal dots of average diameter 100 nm and heights equivalent to twice the unit cell b-axis (1.5–1.7 nm) and an areal density of 5.1–7.7 Gigadots/in.2. Cu2P2O7 deposited from precursor (VI) exhibits unique labyrinthine high surface area deposits. The morphology of CuO deposited on Si from pyrolysis of (VI) depends on the polymer/Cu meta ratio. Magnetic measurements performed using SQUID on CuO nanoparticle networks suggest superparamagnetic behavior. The results give insights into compositional, shape and morphological control of the as-formed nanostructures through the structure of the precursors.

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A large number of optically active drugs and natural products contain α-functionalised ketones or simple derivatives thereof. Furthermore, chiral α-alkylated ketones are useful synthons and have found widespread use in total synthesis. The asymmetric alkylation of ketones represents one of the most powerful and longstanding procedures in organic chemistry. Surprisingly, however, only one effective methodology is available, and this involves the use of chiral auxiliaries. This is discussed in Chapter 1, which also provides a background of other key topics discussed throughout the thesis. Expanding on the existing methodology of chiral auxiliaries, Chapter 2 details the synthesis of a novel chiral auxiliary containing a pyrrolidine ring and its use in the asymmetric preparation of α-alkylated ketones with good enantioselectivity. The synthesis of racemic α-alkylated ketones as reference standards for GC chromatography is also reported in this chapter. Chapter 3 details a new approach to chiral α-alkylated ketones using an intermolecular chirality transfer methodology. This approach employs the use of simple non-chiral dimethylhydrazones and their asymmetric alkylation using the chiral diamine ligands, (+)- and (-)-sparteine. The methodology described represents the first example of an asymmetric alkylation of non-chiral azaenolates. Enantiomeric ratios up to 83 : 17 are observed. Chapter 4 introduces the first aldol-Tishchenko reaction of an imine derivative for the preparation of 1,3-aminoalcohol precursors. 1,3-Aminoalcohols can be synthesised via indirect routes involving various permutations of stepwise construction with asymmetric induction. Our approach offers an alternative highly diastereomeric route to the synthesis of this important moiety utilising N-tert-butanesulfinyl imines in an aldol-Tishchenko-type reaction. Chapter 5 details the experimental procedures for all of the above work. Chapter 6 discusses the results of a separate research project undertaken during this PhD. 2-alkyl-quinolin-4-ones and their N-substituted derivatives have several important biological functions such as the role of Pseudomonas quinolone signal (PQS) in quorum sensing. Herein, we report the synthesis of its biological precursor, 2-heptyl-4-hydroxy-quinoline (HHQ) and possible isosteres of PQS; the C-3 Cl, Br and I analogues. N-Methylation of the iodide was also feasible and the usefulness of this compound showcased in Pd-catalysed cross-coupling reactions, thus allowing access to a diverse set of biologically important molecules.

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Major factors influencing food development and food marketing strategies in global market places at present can be attributable to the changing age structure of the population. The significant shifts in global age structure will inevitably lead to the number of people aged 60 reaching an all-time high of one billion by the year 2020. The rapidly growing population of ageing people globally represents a large, neglected and very much under-developed category within the Food Industry. The primary focus of this study was the integration of knowledge creation techniques at early NPD stages, for the development of market-oriented new health promoting foods for the ageing population. The methodology of this study was centered on an exploratory sequential mixed methods strategy. Stage one of the study involved in-depth semi-structured interviews with 16 Stakeholders to facilitate the need identification stage of the NPD process. The main outputs identified were the need for: the fortification of foods for a preventative nutrition approach, the development of foods that targeted age-related conditions such as cognitive, heart, gut and bone health, the integration of ageing compensatory packaging adaptations and the creation of marketing messages with an active lifestyle message. Stage two consisted of a market-oriented computer assisted NPD technique, a user centered design interaction (UCD) to integrate consumers as co-creators throughout the idea generation stage of the NPD process. The most important product attributes identified in this stage included: products targeted at brain and cognitive health, liquid based beverages, easy to use packaging with environmentally friendly elements, simplistic marketing with a clear focus on health not age and realistic health claims constructed with consumer friendly terminology. Finally, Stage three used an abbreviated means-end chain (MEC) analysis to complete the concept development stage of the NPD process. This stage identified commercial information that could be used by food firms for the development of positioning and communication strategies. Equally, the information generated could be of high strategic importance to governments, policy makers, health professionals and medical professionals. The values and goals listed in this stage included: better overall health, active lifestyle, optimum nutrition and wellbeing feelings. Overall, this research illustrated that knowledge creation techniques can assist firms in the development of market-oriented health promoting foods for the ageing population.

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This dissertation studies the context-aware application with its proposed algorithms at client side. The required context-aware infrastructure is discussed in depth to illustrate that such an infrastructure collects the mobile user’s context information, registers service providers, derives mobile user’s current context, distributes user context among context-aware applications, and provides tailored services. The approach proposed tries to strike a balance between the context server and mobile devices. The context acquisition is centralized at the server to ensure the usability of context information among mobile devices, while context reasoning remains at the application level. Hence, a centralized context acquisition and distributed context reasoning are viewed as a better solution overall. The context-aware search application is designed and implemented at the server side. A new algorithm is proposed to take into consideration the user context profiles. By promoting feedback on the dynamics of the system, any prior user selection is now saved for further analysis such that it may contribute to help the results of a subsequent search. On the basis of these developments at the server side, various solutions are consequently provided at the client side. A proxy software-based component is set up for the purpose of data collection. This research endorses the belief that the proxy at the client side should contain the context reasoning component. Implementation of such a component provides credence to this belief in that the context applications are able to derive the user context profiles. Furthermore, a context cache scheme is implemented to manage the cache on the client device in order to minimize processing requirements and other resources (bandwidth, CPU cycle, power). Java and MySQL platforms are used to implement the proposed architecture and to test scenarios derived from user’s daily activities. To meet the practical demands required of a testing environment without the impositions of a heavy cost for establishing such a comprehensive infrastructure, a software simulation using a free Yahoo search API is provided as a means to evaluate the effectiveness of the design approach in a most realistic way. The integration of Yahoo search engine into the context-aware architecture design proves how context aware application can meet user demands for tailored services and products in and around the user’s environment. The test results show that the overall design is highly effective,providing new features and enriching the mobile user’s experience through a broad scope of potential applications.

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Abstract Purpose The purpose of the study is to review recent studies published from 2007-2015 on tourism and hotel demand modeling and forecasting with a view to identifying the emerging topics and methods studied and to pointing future research directions in the field. Design/Methodology/approach Articles on tourism and hotel demand modeling and forecasting published in both science citation index (SCI) and social science citation index (SSCI) journals were identified and analyzed. Findings This review found that the studies focused on hotel demand are relatively less than those on tourism demand. It is also observed that more and more studies have moved away from the aggregate tourism demand analysis, while disaggregate markets and niche products have attracted increasing attention. Some studies have gone beyond neoclassical economic theory to seek additional explanations of the dynamics of tourism and hotel demand, such as environmental factors, tourist online behavior and consumer confidence indicators, among others. More sophisticated techniques such as nonlinear smooth transition regression, mixed-frequency modeling technique and nonparametric singular spectrum analysis have also been introduced to this research area. Research limitations/implications The main limitation of this review is that the articles included in this study only cover the English literature. Future review of this kind should also include articles published in other languages. The review provides a useful guide for researchers who are interested in future research on tourism and hotel demand modeling and forecasting. Practical implications This review provides important suggestions and recommendations for improving the efficiency of tourism and hospitality management practices. Originality/value The value of this review is that it identifies the current trends in tourism and hotel demand modeling and forecasting research and points out future research directions.

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The study of the Upper Jurassic-Lower Cretaceous deposits (Higueruelas, Villar del Arzobispo and Aldea de Cortés Formations) of the South Iberian Basin (NW Valencia, Spain) reveals new stratigraphic and sedimentological data, which have significant implications on the stratigraphic framework, depositional environments and age of these units. The Higueruelas Fm was deposited in a mid-inner carbonate platform where oncolitic bars migrated by the action of storms and where oncoid production progressively decreased towards the uppermost part of the unit. The overlying Villar del Arzobispo Fm has been traditionally interpreted as an inner platform-lagoon evolving into a tidal-flat. Here it is interpreted as an inner-carbonate platform affected by storms, where oolitic shoals protected a lagoon, which had siliciclastic inputs from the continent. The Aldea de Cortés Fm has been previously interpreted as a lagoon surrounded by tidal-flats and fluvial-deltaic plains. Here it is reinterpreted as a coastal wetland where siliciclastic muddy deposits interacted with shallow fresh to marine water bodies, aeolian dunes and continental siliciclastic inputs. The contact between the Higueruelas and Villar del Arzobispo Fms, classically defined as gradual, is also interpreted here as rapid. More importantly, the contact between the Villar del Arzobispo and Aldea de Cortés Fms, previously considered as unconformable, is here interpreted as gradual. The presence of Alveosepta in the Villar del Arzobispo Fm suggests that at least part of this unit is Kimmeridgian, unlike the previously assigned Late Tithonian-Middle Berriasian age. Consequently, the underlying Higueruelas Fm, previously considered Tithonian, should not be younger than Kimmeridgian. Accordingly, sedimentation of the Aldea de Cortés Fm, previously considered Valangian-Hauterivian, probably started during the Tithonian and it may be considered part of the regressive trend of the Late Jurassic-Early Cretaceous cycle. This is consistent with the dinosaur faunas, typically Jurassic, described in the Villar del Arzobispo and Aldea de Cortés Fms.

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In the near future, geopolymers or alkali-activated cementitious materials will be used as new high-performance construction materials of low environmental impact with a reasonable cost. This material is a good candidate to partially replace ordinary portland cement (OPC) in concrete as a major construction material that plays an outstanding role in the construction industry of different structures. Geopolymer materials are inorganic polymers based on alumina and silica units; they are synthesized from a wide range of dehydroxylated alumina-silicate powders condensed with alkaline silicate in a highly alkaline environment. Geopolymeric materials can be produced from a wide range of alumina-silica, including natural products--such as natural pozzolan and metakaolin--or coproducts--such as fly ash (coal and lignite), oil fuel ash, blast furnace or steel slag, and silica fume--and provide a route toward sustainable development. Using lesser amounts of calcium-based raw materials, lower manufacturing temperature, and lower amounts of fuel result in reduced carbon emissions for geopolymer cement manufacture up to 22 to 72% in comparison with portland cement. A study has been done by the authors to investigate the intrinsic nature of different types of Iranian natural pozzolans to determine the activators and methods that could be used to produce a geopolymer concrete based on alkali-activated natural pozzolan (AANP) and optimize mixture design. The mechanical behavior and durability of these types of geopolymer concrete were investigated and compared with normal OPC concrete mixtures cast by the authors and also reported in the literature. This paper summarizes the main conclusions of the research regarding pozzolanic activity, activator properties, engineering and durability properties, applications and evaluation of carbon footprint, and cost for AANP concrete.

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Due to diminishing petroleum reserves, unsteady market situation and the environmental concerns associated with utilization of fossil resources, the utilization of renewables for production of energy and chemicals (biorefining) has gained considerable attention. Biomass is the only sustainable source of organic compounds that has been proposed as petroleum equivalent for the production of fuels, chemicals and materials. In fact, it would not be wrong to say that the only viable answer to sustainably convene our future energy and material requirements remain with a bio-based economy with biomass based industries and products. This has prompted biomass valorization (biorefining) to become an important area of industrial research. While many disciplines of science are involved in the realization of this effort, catalysis and knowledge of chemical technology are considered to be particularly important to eventually render this dream to come true. Traditionally, the catalyst research for biomass conversion has been focused primarily on commercially available catalysts like zeolites, silica and various metals (Pt, Pd, Au, Ni) supported on zeolites, silica etc. Nevertheless, the main drawbacks of these catalysts are coupled with high material cost, low activity, limited reusability etc. – all facts that render them less attractive in industrial scale applications (poor activity for the price). Thus, there is a particular need to develop active, robust and cost efficient catalytic systems capable of converting complex biomass molecules. Saccharification, esterification, transesterification and acetylation are important chemical processes in the valorization chain of biomasses (and several biomass components) for production of platform chemicals, transportation fuels, food additives and materials. In the current work, various novel acidic carbons were synthesized from wastes generated from biodiesel and allied industries, and employed as catalysts in the aforementioned reactions. The structure and surface properties of the novel materials were investigated by XRD, XPS, elemental analysis, SEM, TEM, TPD and N2-physisorption techniques. The agro-industrial waste derived sulfonic acid functionalized novel carbons exhibit excellent catalytic activity in the aforementioned reactions and easily outperformed liquid H2SO4 and conventional solid acids (zeolites, ion-exchange resins etc). The experimental results indicated strong influence of catalyst pore-structure (pore size, pore-volume), concentration of –SO3H groups and surface properties in terms of the activity and selectivity of these catalysts. Here, a large pore catalyst with high –SO3H density exhibited the highest esterification and transesterification activity, and was successfully employed in biodiesel production from fatty acids and low grade acidic oils. Also, a catalyst decay model was proposed upon biodiesel production and could explain that the catalyst loses its activity mainly due to active site blocking by adsorption of impurities and by-products. The large pore sulfonated catalyst also exhibited good catalytic performance in the selective synthesis of triacetin via acetylation of glycerol with acetic anhydride and out-performed the best zeolite H-Y with respect to reusability. It also demonstrated equally good activity in acetylation of cellulose to soluble cellulose acetates, with the possibility to control cellulose acetate yield and quality (degree of substitution, DS) by a simple adjustment of reaction time and acetic anhydride concentration. In contrast, the small pore and highly functionalized catalysts obtained by hydrothermal method and from protein rich waste (Jatropha de-oiled waste cake, DOWC), were active and selective in the esterification of glycerol with fatty acids to monoglycerides and saccharification of cellulosic materials, respectively. The operational stability and reusability of the catalyst was found to depend on the stability of –SO3H function (leaching) as well as active site blocking due to adsorption of impurities during the reaction. Thus, our results corroborate the potential of DOWC derived sulfated mesoporous active carbons as efficient integrated solid acid catalysts for valorization of biomass to platform chemicals, biofuel, bio-additive, surfactants and celluloseesters.

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This article presents the methodology and main results obtained in Spain within the FORMAR project, a European-funded project under the Leonardo Da Vinci scheme (Lifelong Learning Programme), whose main goal is to jointly develop training resources and modules to improve the skills on sustainability issues of buildings maintenance and refurbishment workers, in three different European countries: Spain, Portugal (Project Coordinator) and France. The Units of Short-term Training (UST) developed within this project are focused on the VET of carpenters, painters, bricklayers, building technicians and installers of solar panels, and a transversal unit containing basic concepts on sustainable construction and nearly Zero Energy Buildings (n-ZEB) is also developed. In parallel, clients’ guides for the aforementioned professionals are also implemented to improve the information provided to clients and owners in order to support the procurement decisions regarding building products and materials. Therefore, the project provides an opportunity to exchange experiences between organizations of these three European countries, as the UST will be developed simultaneously in each of them, exploring opportunities for training, guidance and exchange of experience. Even though the UST will have a common structure and contents, they will be slightly different in each country to adapt them to the different specific training needs and regulations of Spain, Portugal and France. This paper details, as a case study, the development process of the UST for carpenters and building technicians in Spain, including the analysis of needs and existing training materials, the main contents developed and the evaluation and testing process of the UST, which involves the active participation of several stakeholders of this sector as well as a classroom testing to obtain the students’ feedback.

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We present a generalization of the complete intersection in products of projective space (CICY) construction of Calabi–Yau manifolds. CICY three-folds and four-folds have been studied extensively in the physics literature. Their utility stems from the fact that they can be simply described in terms of a ‘configuration matrix’, a matrix of integers from which many of the details of the geometries can be easily extracted. The generalization we present is to allow negative integers in the configuration matrices which were previously taken to have positive semi-definite entries. This broadening of the complete intersection construction leads to a larger class of Calabi–Yau manifolds than that considered in previous work, which nevertheless enjoys much of the same degree of calculational control. These new Calabi–Yau manifolds are complete intersections in (not necessarily Fano) ambient spaces with an effective anticanonical class. We find examples with topology distinct from any that has appeared in the literature to date. The new manifolds thus obtained have many interesting features. For example, they can have smaller Hodge numbers than ordinary CICYs and lead to many examples with elliptic and K3-fibration structures relevant to F-theory and string dualities.

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New psychoactive substances (NPSs) have appeared on the recreational drug market at an unprecedented rate in recent years. Many are not new drugs but failed products of the pharmaceutical industry. The speed and variety of drugs entering the market poses a new complex challenge for the forensic toxicology community. The detection of these substances in biological matrices can be difficult as the exact compounds of interest may not be known. Many NPS are sold under the same brand name and therefore users themselves may not know what substances they have ingested. The majority of analytical methods for the detection of NPSs tend to focus on a specific class of compounds rather than a wide variety. In response to this, a robust and sensitive method was developed for the analysis of various NPS by solid phase extraction (SPE) with gas chromatography mass spectrometry (GCMS). Sample preparation and derivatisation were optimised testing a range of SPE cartridges and derivatising agents, as well as derivatisation incubation time and temperature. The final gas chromatography mass spectrometry method was validated in accordance with SWGTOX 2013 guidelines over a wide concentration range for both blood and urine for 23 and 25 analytes respectively. This included the validation of 8 NBOMe compounds in blood and 10 NBOMe compounds in urine. This GC-MS method was then applied to 8 authentic samples with concentrations compared to those originally identified by NMS laboratories. The rapid influx of NPSs has resulted in the re-analysis of samples and thus, the stability of these substances is crucial information. The stability of mephedrone was investigated, examining the effect that storage temperatures and preservatives had on analyte stability daily for 1 week and then weekly for 10 weeks. Several laboratories identified NPSs use through the cross-reactivity of these substances with existing screening protocols such as ELISA. The application of Immunalysis ketamine, methamphetamine and amphetamine ELISA kits for the detection of NPS was evaluated. The aim of this work was to determine if any cross-reactivity from NPS substances was observed, and to determine whether these existing kits would identify NPS use within biological samples. The cross- reactivity of methoxetamine, 3-MeO-PCE and 3-MeO-PCP for different commercially point of care test (POCT) was also assessed for urine. One of the newest groups of compounds to appear on the NPS market is the NBOMe series. These drugs pose a serious threat to public health due to their high potency, with fatalities already reported in the literature. These compounds are falsely marketed as LSD which increases the chance of adverse effects due to the potency differences between these 2 substances. A liquid chromatography tandem mass spectrometry (LC-MS/MS) method was validated in accordance with SWGTOX 2013 guidelines for the detection for 25B, 25C and 25I-NBOMe in urine and hair. Long-Evans rats were administered 25B-, 25C- and 25I-NBOMe at doses ranging from 30-300 µg/kg over a period of 10 days. Tail flick tests were then carried out on the rats in order to determine whether any analgesic effects were observed as a result of dosing. Rats were also shaved prior to their first dose and reshaved after the 10-day period. Hair was separated by colour (black and white) and analysed using the validated LC-MS/MS method, assessing the impact hair colour has on the incorporation of these drugs. Urine was collected from the rats, analysed using the validated LC-MS/MS method and screened for potential metabolites using both LC-MS/MS and quadrupole time of flight (QToF) instrumentation.