The majority of cancer research projects mainly focus on the epithelial cancer cell, while the role of the tumour stroma has been largely neglected. Conventional 2D techniques, such as well plates and other kinds of tissue culture plastic, and animal models are mainly used to broaden our understanding of how tumours arise, develop, and induce metastasis. However, there is accumulating evidence suggesting a tremendous impact of the non‐cancerous tumour stroma on carcinogenesis, while other publications illustrate the great importance of advanced 3D in vitro models for cancer research. The overall goal of this work was to investigate how cancer associated fibroblasts (CAFs; the most abundant component in the tumour stroma) and normal prostate fibroblasts (NPFs), isolated from patients diagnosed with aggressive forms of prostate cancer, contribute to angiogenesis, an important hallmark of cancer progression. For this purpose, a 3D in vitro angiogenesis co‐culture model was established. At first, two (semi‐) synthetic hydrogel platforms, gelatine methacrylate (GelMA) and star‐shaped (star)PEG‐heparin hydrogels were characterised and their physicochemical properties were compared with each other. Interestingly, GelMA gels shrank while starPEG‐heparin gels swelled in cell culture medium over the course of 24 hours. The cell concentration, in addition to the stiffness, was critical for the formation of endothelial networks, and the knowledge of swelling behaviour enabled the adjustment of initial cell density to ensure the density between both gel types was comparable. Moreover, preliminary tests with mesenchymal stem cells demonstrated that the hydrogel can be actively remodelled, as evaluated by stiffness parameters at day one and seven of incubation. Growth factors (GFs) affect cellular fate and behaviour, and storage, presentation and administration of such chemokines can be critical for certain cellular applications. Due to the high anionic charge density of heparin, starPEG‐heparin hydrogels are known to reversibly immobilise several GFs and thereby might mimic the GF reservoir of the extra cellular matrix. Thus, transport processes of GFs with low and high heparin affinity inside these hydrogels were analysed by fluorescence correlation spectroscopy and a bulk diffusion approach. Results indicated that diffusion constants were synergistically decreased with increasing size and heparin affinity of the diffusant. Next, the capability of endothelial cells (ECs) to self‐assemble and organise into 3D capillary networks was tested in GelMA, starPEG‐heparin and Matrigel hydrogels. Only starPEG‐heparin hydrogels allowed the formation of interconnected capillaries in macroscopic hydrogel samples. However, as it is widely used to test for pro‐ and anti‐angiogenic agents, the 2D Matrigel angiogenesis assay was included for subsequent co‐culture experiments of ECs and fibroblasts in order to investigate how the stromal cells influence the formation of endothelial networks. For a detailed characterisation of 3D structures, a conventionally applied 2D method (Maximum Intensity Projection for 3D reconstructed images, MIP) was compared to an optimised 3D analysing tool. As a result, it was discovered that MIP analysis did not allow for an accurate determination of 3D endothelial network parameters, and can result in misleading interpretations of the data set. Indirect co‐cultures of hydrogel‐embedded ECs with a 2D layer of fibroblasts showed that fibroblast‐derived soluble factors, including stromal cell‐derived factor 1 and interleukin 8, affected endothelial network properties. However, only co‐encapsulation of ECs and fibroblasts in starPEG‐heparin hydrogel discs revealed remarkable changes in endothelial network parameters between CAF and NPF samples. In detail, the total length and branching of the capillaries was increased. For two donor pairs, the diameter of capillaries was decreased in CAF samples compared to NPF samples, underlining the high physiological relevance of this model. In contrast, significant differences in 2D Matrigel assays were not detected between, CAF, NPF and control (ECs only) samples. In summary, a 3D angiogenesis co‐culture system was successfully developed and used to characterise stromal‐endothelial interactions in detail. The combination of advanced biomaterials (starPEG‐heparin) and 3D analysing techniques goes beyond conventional 2D in vitro cancer research, and opens new avenues for the development of more complex models to further improve the acquisition of more biologically relevant data.

In dieser Arbeit wurden zwei serologische Teste zur Unterscheidung inzidenter und prävalenter Proben etabliert und validiert, welche auf der Reifung des Immunsystems in der frühen HIV-Infektion basieren. Im BED-ELISA werden anhand von anti-HIV-gp41-spezifischen IgG-Antikörperspiegeln die Proben klassifiziert. Die Aviditäts-Methode (AI) unterscheidet die Bindungsfähigkeit der Antikörper an spezifische Antigene. Das Probenpanel wurde in einem weiteren Inzidenztest, dem IDE-V3-ELISA (Kooperation F. Barin), gemessen welcher den Anstieg der Antikörperreaktivität gegen zwei verschiedene immundominante Epitope nutzt. Wirtsspezifische Marker und virale Eigenschaften wurden untersucht, um Merkmale zu identifizieren, welche die Sensitivität und Spezifität der Teste verbessern könnten. Mit dem BED-ELISA wurde eine Pilotstudie unter Berliner HIV-Patienten durchgeführt. Zur Vereinfachung des Probentransports in Studien wurde der Einfluss einer Filtertrocknung der Plasmaproben auf die Infektiosität von HIV, Stabilität der HIV-RNA und die Antikörperreaktivität im BED-ELISA untersucht. In den Testen wurden inzidente Plasmaproben mit folgenden Sensitivitäten und Spezifitäten richtig klassifiziert: 80% und 86% (BED-ELISA); 74% und 82% (AI); 73% und 84% (IDE-V3). Von allen untersuchten wirtsspezifischen Faktoren korrelierte nur der Gehalt an Antikörpern der IgG3-Subklasse mit der Fehlklassifikation der Proben. Für die Pilotstudie wurden zwischen Feb. 2005 und Nov. 2007 von 132 erstmalig HIV-1 positiv diagnostizierten Patienten Proben genommen und im BED-ELISA analysiert (51% Anteil inzidente Infektionen). Die Antikörperreaktivitäten blieben nach der Filtertrocknung erhalten, so das auf der Grundlage der Ergebnisse eine deutschlandweite Inzidenzstudie mit Filter-getrockneten Plasmaproben geplant wurde, die seit Januar 2008 im Auftrag des BMG zur Verbesserung der Datenlage zur HIV-Inzidenz in Deutschland durchgeführt wird. / In this PhD thesis two methods that can differentiate between incident and prevalent infections were established and validated. Both tests are based on the maturation of the immune system during early HIV-infection. The BED-ELISA uses anti-HIV-gp41 specific IgG-antibody levels for differentiation. The avidity method (AI) is based on the binding-capacity of the antibodies to specific antigens in the presence of a chaotropic agent. The sample panel was also evaluated using an additional incidence ELISA, the IDE-V3-ELISA (cooperation with F. Barin). This test is also based on the antibody''s reactivity to two different immune dominant epitopes, allowing incident and prevalent infections to be differentiated. Host specific factors and viral determinants were analysed to provide information that could lead to improvements in the sensitivity and specificity of the incidence tests. With the BED-ELISA a pilot study with HIV-infected patients in Berlin was carried out. The inactivation of HIV-1 after filter-drying of samples, the stability of viral RNA and reactivity of antibodies in the BED-ELISA were analysed to simplify the transport of samples in future studies. Incident plasma samples were identified correctly with following sensitivities and specificity’s: 80% and 86% (BED-ELISA); 74% and 82% (AI); 73% and 84% (IDE-V3). Of all host factors analysed, only the titre of IgG3-antibodies correlated with the incorrect classification of samples. In the pilot study samples from 132 newly diagnosed HIV-positive patients were obtained between February 2005 and November 2007 and analysed in the BED-ELISA (51% proportion of incident infections). It could be shown that filter-drying of plasma samples rendered HIV non-infectious but did not influence antibody reactivity. Based on these results, a German HIV incidence study using filter-dried plasma samples, designed to improve knowledge of HIV-incidence in Germany, was sponsored by the BMG and has been ongoing since January 2008.

The objective of this research is to develop fundamental understanding of cell-substrate (CS) and cell-cell (CC) interactions in the culture space for time evolving cell cultures. Space resolved CC and CS interactions are important indicators of cell-density distribution, localized cellular behavior, and multiple cell-layers which are differentiators of normal and abnormal cell behavior. In this research, CS and CC interactions and the variations therein due to a) Cell growth, 2) cell-drug interaction, and 3) effect of Cytotoxin were studied using multielectrode, multi-frequency Electrochemical Impedance Spectroscopy (EIS). Contemporary impedance based methods sense either CC or CS interaction as a space averaged macroscopic quantity. A major contribution of this research is that, both CC and CS interactions are recorded and analyzed with spatio-temporal resolution. This research led to the development of an automated cell culture monitoring system, namely, CellMap. A planar eight electrode sensor was fabricated on a glass substrate and interfaced with a switching circuit. The switching circuit sequentially selects consecutive electrodes upon input of a 5V trigger pulse which is generated by the frequency response analyzer at the end of each frequency scan, thereby facilitating automated switching and recording of multielectrode dataset. Calibration standards and protocols were developed to null the channel parasitics of individual channels. A set of eight impedance measurements for eight electrodes constitutes a "frame". Frames are recorded at regular time intervals over the desired course of time. Impedance mapping of adhesion, spreading, motility and detachment of OvCa429 ovarian cancer cells was performed over a period of 70 hours. The cell-layer resistance, which indicates cell-cell contact, increased as a function of time until confluence, and decreased thereafter due to cell death and detachment. This was also confirmed by optical microscopy observations. Similarly, the cell layer Constant Phase Element (CPE) parameters, which were found to correlate well with cell density distribution, also increased as a function of time until confluence and decreased thereafter. Additionally, the cell-growth mapping revealed that the CellMap system is able to resolve non-uniform cell distributions in the culture space, which may be useful in differentiating between normal and pathological cells.

The diversity of microorganisms and the influence of their enzymatic activities in soil are critical to the maintenance of good soil health. Changes in these parameters may be the earliest predictors of soil quality changes, potentially indicating anthropogenic influences. The goal of this study was to investigate the soil microbial diversity and function of grasslands along an urbanization gradient. Soil samples were collected in the Potchefstroom municipal area, South Africa, at specific sites. Sampling sites were described as urban, suburban and rural - according to the V-I-S (Vegetation-Impervious surface-Soil) model of Ridd (1995). Soil samples were collected over a warmer, wet season (May) and a colder, dry season (August) over two years (2007 and 2008). Collected soil samples were characterised using certain physical and chemical parameters. Plant species composition and abundance were determined at each site, along with basic site data (soil compaction, percentage ground cover, percentage bare ground, percentage organic material present). The Shannon-Weaver diversity index was used to calculate biodiversity values for all the investigated sites regarding collected plant species composition. The microbial component of the soil was quantified and characterized using culture-dependent and culture-independent techniques. Culture-dependent techniques included the investigation of the aerobic heterotrophic bacteria and fungi. Organisms were plated out on different media, and the bacterial component was broadly grouped using morphology. Dominant organisms were identified by sequencing of PCR amplified 16S ribosomal DNA fragments. Shannon-Weaver index for bacterial diversity was determined for each of the sites. Denaturing gradient gel electrophoresis (DGGE) profiling of selected bacterial communities were also conducted. Microbial community function was determined using enzyme assays of five major groups of enzymes, namely (i) dehydrogenase; (ii) β-glucosidase; (iii) acid phosphatase, (iv) alkaline phosphatase and (v) urease. Plant species results were then brought into context with microbiological diversity and functionality results using multivariate statistics. Physical and chemical parameters of the collected soil samples revealed patterns present along the urbanization gradient. The pH values were mostly higher in the sub-urban and urban sites than in the rural sites. Electrical conductivity values were generally highest in the sub-urban sites. Plant species composition revealed trends along the urbanization gradient. Ordinations clearly grouped the plant species into rural, sub-urban and urban groups regarding plant species composition. Rural sites had the highest number of plant species. Shannon-Weaver values regarding the plant diversity supported the plant species composition data indicating higher plant diversity in the rural areas, followed by the sub-urban and the urban areas. Plant structural data indicated that forbs were most numerous in the rural sites, and less so in the urban sites. Higher average aerobic heterotrophic bacterial levels were present in the urban soil samples. The bacterial levels were lower in the sub-urban and rural soil samples. Subsequent identification of the dominant bacteria in the soil samples revealed organisms of the genus Bacillus dominated the aerobic heterotrophic bacterial communities in the soil samples. Bacillus species dominated the soil samples along the urbanization gradient. Shannon-Weaver indices based on culture-dependent methods indicated that urban sites had the highest biodiversity. These results could have been exaggerated, because of an overestimation of the number of bacterial morphotypes present in samples. Fungal levels were higher in the soil from samples collected at the rural samples sites. The culture-independent method (DGGE) was not optimized and inconclusive results were obtained. Enzyme assays revealed that potential dehydrogenase, β-glucosidase and urease activity followed a trend along the urbanization gradient, with urban samples registering the highest values and rural sites the lowest. Enzymes involved in carbohydrate catabolism (β-glucosidase and dehydrogenase) registered significantly higher potential activity in urban sites than the sub-urban and rural sites. The results could indicate that urban sites have the potential to lose carbon at higher rates than the rural sites. This aspect may need further investigation. Higher potential urease activity could indicate higher N-cycling in the urban soil environment. Ordination results for soil-, plant- and microbial diversity as well as microbial functionality indicated certain trends along the urbanization gradient. Plant species composition and structure data indicated that urbanization has a definite effect on the plant communities in the urban ecosystem. Results regarding aerobic heterotrophic bacteria populations and potential enzyme activity of the dehydrogenase, β-glucosidase (both active in the carbon cycle) and urease (active in the nitrogen cycle) illustrated clear trends along the urbanization gradient. In conclusion, results indicated that urbanization has an effect on plant species composition, and the population and function of aerobic heterotrophic bacteria and the fungal population. Furthermore, this study demonstrated the potential of using microbial diversity and activity as tools to investigate carbon utilization and storage along an urban-rural gradient. / MSc (Environmental Sciences), North-West University, Potchefstroom Campus, 2011

The diversity of microorganisms and the influence of their enzymatic activities in soil are critical to the maintenance of good soil health. Changes in these parameters may be the earliest predictors of soil quality changes, potentially indicating anthropogenic influences. The goal of this study was to investigate the soil microbial diversity and function of grasslands along an urbanization gradient. Soil samples were collected in the Potchefstroom municipal area, South Africa, at specific sites. Sampling sites were described as urban, suburban and rural - according to the V-I-S (Vegetation-Impervious surface-Soil) model of Ridd (1995). Soil samples were collected over a warmer, wet season (May) and a colder, dry season (August) over two years (2007 and 2008). Collected soil samples were characterised using certain physical and chemical parameters. Plant species composition and abundance were determined at each site, along with basic site data (soil compaction, percentage ground cover, percentage bare ground, percentage organic material present). The Shannon-Weaver diversity index was used to calculate biodiversity values for all the investigated sites regarding collected plant species composition. The microbial component of the soil was quantified and characterized using culture-dependent and culture-independent techniques. Culture-dependent techniques included the investigation of the aerobic heterotrophic bacteria and fungi. Organisms were plated out on different media, and the bacterial component was broadly grouped using morphology. Dominant organisms were identified by sequencing of PCR amplified 16S ribosomal DNA fragments. Shannon-Weaver index for bacterial diversity was determined for each of the sites. Denaturing gradient gel electrophoresis (DGGE) profiling of selected bacterial communities were also conducted. Microbial community function was determined using enzyme assays of five major groups of enzymes, namely (i) dehydrogenase; (ii) β-glucosidase; (iii) acid phosphatase, (iv) alkaline phosphatase and (v) urease. Plant species results were then brought into context with microbiological diversity and functionality results using multivariate statistics. Physical and chemical parameters of the collected soil samples revealed patterns present along the urbanization gradient. The pH values were mostly higher in the sub-urban and urban sites than in the rural sites. Electrical conductivity values were generally highest in the sub-urban sites. Plant species composition revealed trends along the urbanization gradient. Ordinations clearly grouped the plant species into rural, sub-urban and urban groups regarding plant species composition. Rural sites had the highest number of plant species. Shannon-Weaver values regarding the plant diversity supported the plant species composition data indicating higher plant diversity in the rural areas, followed by the sub-urban and the urban areas. Plant structural data indicated that forbs were most numerous in the rural sites, and less so in the urban sites. Higher average aerobic heterotrophic bacterial levels were present in the urban soil samples. The bacterial levels were lower in the sub-urban and rural soil samples. Subsequent identification of the dominant bacteria in the soil samples revealed organisms of the genus Bacillus dominated the aerobic heterotrophic bacterial communities in the soil samples. Bacillus species dominated the soil samples along the urbanization gradient. Shannon-Weaver indices based on culture-dependent methods indicated that urban sites had the highest biodiversity. These results could have been exaggerated, because of an overestimation of the number of bacterial morphotypes present in samples. Fungal levels were higher in the soil from samples collected at the rural samples sites. The culture-independent method (DGGE) was not optimized and inconclusive results were obtained. Enzyme assays revealed that potential dehydrogenase, β-glucosidase and urease activity followed a trend along the urbanization gradient, with urban samples registering the highest values and rural sites the lowest. Enzymes involved in carbohydrate catabolism (β-glucosidase and dehydrogenase) registered significantly higher potential activity in urban sites than the sub-urban and rural sites. The results could indicate that urban sites have the potential to lose carbon at higher rates than the rural sites. This aspect may need further investigation. Higher potential urease activity could indicate higher N-cycling in the urban soil environment. Ordination results for soil-, plant- and microbial diversity as well as microbial functionality indicated certain trends along the urbanization gradient. Plant species composition and structure data indicated that urbanization has a definite effect on the plant communities in the urban ecosystem. Results regarding aerobic heterotrophic bacteria populations and potential enzyme activity of the dehydrogenase, β-glucosidase (both active in the carbon cycle) and urease (active in the nitrogen cycle) illustrated clear trends along the urbanization gradient. In conclusion, results indicated that urbanization has an effect on plant species composition, and the population and function of aerobic heterotrophic bacteria and the fungal population. Furthermore, this study demonstrated the potential of using microbial diversity and activity as tools to investigate carbon utilization and storage along an urban-rural gradient. / MSc (Environmental Sciences), North-West University, Potchefstroom Campus, 2011

Over the past ten years, the development of High Throughput (HT) synthetic chemistry techniques has allowed the rapid preparation of libraries of hundreds to thousands of compounds. These tools are now extensively used for drug and material discovery programmes. The subsequent development of analytical capabilities to carry out qualitative and quantitative assessment of the compounds generated by HT synthesis as well as their HT screening has led to a dramatic broadening of the scope of HT techniques, ranging from image based analysis techniques to mass spectrometry (MS). Based on the latter, a range of solid phase and solution phase analytical constructs was developed to enable the qualitative and quantitative assessment of mixtures of small compounds, using positive electrospray MS as the sole analytical tool. A version of the construct allowed HT reactivity profiling to be carried out on a range of ten carboxylic acids, ten aldehydes and ten isonitriles in the Ugi 4-component condensation reaction. The effect of various parameters such as the concentration of the monomers on the reactivity was investigated. The elaboration of a HT Hammett parameter assessment method was made possible by the development of an electrophilic version of the construct. The value of the Hammett value was afforded by means of combinatorial Hammett plots and values were successfully evaluated in a HT mode for around thirty anilines with substituents in the meta and para position of the aromatic ring. Finally, analytical constructs were used in an attempt to evaluate enzyme reaction kinetics via the labelling of peptides and small drug fragment with coded constructs, to afford affinity determinations between the enzyme (protease) and peptidic or fragment based substrates.

Wood is a material with an enormous number of applications. For decades, the development of wastewater treatment technologies tailored for the wood sector has focused on those industries that have water as an integral part of the industrial production, such as paper and pulp. However, there is a large and potentially growing sector that has been neglected, which is formed by industries in which water is not part of their production line, as for example, the wood floor and furniture industries (named wood-based dry industries). These industries still produces relatively low volumes of highly polluted wastewaters, with COD up to 30,000 mg/L, due to cleaning/washing procedure (named cleaning wastewaters). These cleaning wastewaters are often sent to the municipal wastewater treatment plant after dilution with potable water. Once there, recalcitrant pollutants are diluted and discharged into recipient water bodies or trapped in the municipal wastewater sludge. Another type of contaminated water these “dry industries” often generate in high volumes, and which is usually discharged with no previous treatment, is storm-water containing contaminants that have leached from large wood storage areas. The overall aim of this thesis was to increase the level of knowledge and competence and to present on-site wastewater treatment options for wood-based dry industries using the wood floor industry as a case-study, with a focus on combined treatment methods and solutions applicable to both the cleaning wastewater and storm-water. Among the treatment technologies investigated, electrocoagulation was studied both as a standalone treatment and combined with sorption using activated carbon. The combined treatment achieved a COD reduction of approximately 70%. Some advanced oxidation processes (AOP) were also studied: a COD reduction of approximately 70% was achieved by photo-Fenton, but the most successful AOP was ozone combined with UV light, were a COD reduction around 90% was achieved, with additional improvement in the biodegradability of the treated effluent. Ozone also proved to be effective in degrading organic compounds (approximately 70% COD reduction) and enhanced the biodegradability of the storm-water runoff from wood storage areas. The results have shown that the application of ozone can be considered an option for treatment of cleaning wastewaters and possibly for storm-water biodegradation enhancement. / Trä är ett material med ett stort antal möjliga användningsområden. Inom träindustrin har utvecklingen av vattenbehandlingsmetoder varit inriktat på de branscher som har vatten som en del av produktionen, såsom papper- och massaindustrin. Men det finns en stor och potentiellt växande sektor inom träindustrin som har försummats, den utgörs av industrier som inte har vatten som en del av produktionen, t.ex. trägolv och trämöbel industrier. Trots detta så producerar dessa industrier fortfarande relativt kraftigt förorenade avloppsvatten med t.ex. COD-värden upp till 30000 mg/l men i relativt låga volymer. Dessa avloppsvatten uppkommer vid rengöring av maskiner och städning av lokaler, varefter de oftast efter utspädning med dricksvatten skickas till det kommunala reningsverket. Väl där späds det förorenade vattnet vidare ut med annat inkommande vatten men passerar dock till stor del obehandlat och släpps ut i mottagande vattendrag eller så fastnar föroreningarna i avloppsslamet. Dagvatten är en annan typ av förorenat vatten från dessa "torra industrier" som ofta genereras i stora volymer och innehåller föroreningar som lakats från de trämaterial som förvaras i de stora upplag som ofta förekommer vid denna typ av industrier. Det övergripande syftet med avhandlingen var att öka kunskapen och kompetensen för att kunna miljömässigt riktigt och ekonomiskt billigt behandla industriavloppsvatten lokalt på plats inom trävaruindustrin, genom att använda en trä-golvsindustri som fallstudie. Fokus lades på kombinerade behandlingsmetoder och lösningar som skulle kunna vara lämpliga både för industriavloppsvatten och dagvatten. Ett antal behandlingstekniker har undersökts; elektrokoagulering studerades både som en fristående behandling och i kombination med aktivt kol. Den kombinerade behandlingen gav en COD-reduktion på ungefär 70 %. Flera avancerade oxidationsprocesser (AOP) studerades också, och en COD-reduktion på cirka 70% uppnåddes med en kombination av UV-ljus och Fenton behandling. Den mest framgångsrika behandlingen var ozon i kombination med UV-ljus där en COD-reduktion runt 90 % uppnåddes varvid en avsevärd förbättring av den biologisk nedbrytbarhet på det behandlade avloppsvattenet erhölls. Ozon visade sig också vara effektivt för nedbrytning av organiska föreningar (ca 70% COD reduktion) och förbättrade den biologiska nedbrytbarheten av föroreningarna i dagvattnet från den studerade industrin. Resultaten har visat att ozon kan anses vara ett lämpligt alternativ för att behandla industriavloppsvatten inom trävarusektorn och möjligen för att öka den biologiska nedbrytbarheten av dagvattnet från dessa industrier / Integrated Approach for Handling of Industrial Wastewater and Stormwater / Triple Helix Collaboration on Industrial Water Conservation in Småland and the Islands

No description available.

Doctor of Philosophy / Department of Chemistry / Stefan H. Bossmann / Cancer is one of the leading causes of death in the world. Billions of dollars are spent to treat cancer every year. This clearly shows the need for developing improved treatment techniques that are affordable to every person. Early diagnosis and imaging of tumors is equally important for the battle against this disease. This dissertation will discuss new approaches for discovering and developing novel detection and treatment techniques for cancer using organic ligands, and Fe/Fe3O4 core/shell magnetic nanoparticles. A series of o-phenylenediamine derivatives with nitro-, methyl- and chloro- substituents were synthesized and studied their ability to act as anticancer agents by using steady-state, UV/Vis-, and fluorescence spectroscopy. In the absence of zinc(II), intercalation with DNA is the most probable mode of interaction. Upon addition of zinc(II), DNA-surface binding of the supramolecular aggregates was observed. The interaction of the supramolecular (-ligand-Zn2+-)n aggregates with MDA 231 breast cancer cells led to significant cell death in the presence of UVA at λ=313 nm displaying their potential as anticancer agents. Bimagnetic Fe/Fe3O4 core/shell nanoparticles (MNPs) were designed for cancer targeting after intratumoral or intravenous administration. Their inorganic center was protected by dopamine-oligoethylene glycol ligands. TCPP (4-tetracarboxyphenyl porphyrin), a fluorescent dye, was attached to the dopamine-oligoethylene glycol ligands. These modified nanoparticles have the ability to selectively accumulate within the cancerous cells. They are suitable candidates for local hyperthermia treatment. We have observed a temperature increase of 11 ºC in live mice when subcutaneously injecting the MNPs at the cancer site and applying an alternating magnetic field The system is also suitable for Magnetic Resonance Imaging (MRI), which is a diagnostic tool to obtain images of the tumors. Our superparamagnetic iron oxide nanoparticles have the ability to function as T1 weighted imaging agents or positive contrasting agents. We were able to image tumors in mice using MRI. Various proteases are over-expressed by numerous cancer cell lines and, therefore, of diagnostic value. Our diagnostic nanoplatforms, designed for the measurement of protease activities in various body fluids (blood, saliva, and urine), comprise Fe/Fe3O4 core/shell nanoparticles featuring consensus sequences, which are specific for the target protease. Linked to the consensus sequence is a fluorescent organic dye (e.g. TCPP). Cleavage of the sequence by the target protease can be detected as a significant increase in fluorescence occurring from TCPP. We were able to correlate our diagnostic results with cancer prognosis.

<div>The eradication of yaws a neglected tropical disease caused by Treponema pallidum subsp. pertenue, which affects children living in very deprived hard to reach rural communities is constrained by the lack of rapid, accurate diagnosis. I sought to develop a molecular point-of-care test for the diagnosis of yaws. A Loop-mediated isothermal amplification (LAMP) assay with primers targeting the conserved gene, tp0967, with visual detection by lateral flow test strip was developed and optimized. The limit of detection was evaluated while 63 samples from clinical cases of yaws and 5 samples with PCR-confirmed syphilis were used to determine the sensitivity and specificity of the assay compared to the current molecular testing protocol. Reagents were dried in tubes and tested up to 14 days. The developed LAMP assay was found to be optimal when run at 65oC in a water bath for 30 minutes. The limit of detection was 2.7*104 DNA copies/ml. The sensitivity of the LAMP assay using unextracted and DNA extracted samples were 0.67 and 1.00 respectively. None of the syphilis samples tested positive in any of the assays. We show the development of a fast and sensitive LAMP assay for yaws detected by lateral flow test strip. Using extracted DNA, the assay sensitivity is at par with gold standard detection. The assay can be adapted to minimal sample processing required for in-field detection without DNA extraction.</div><div><br></div>