456 research outputs found

    Determination of the absorption length of CO2, Nd:YAG and high power diode laser radiation for a selected grouting material

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    The laser beam absorption lengths of CO2, Nd:YAG and a high power diode laser (HPDL) radiation for a newly developed SiO2/Al2O3-based tile grout have been determined through the application of Beer-Lambert’s law. The findings revealed marked differences in the absorption lengths despite the material having similar beam absorption coefficients for the lasers. The absorption lengths for the SiO2/Al2O3-based tile grout for CO2, Nd:YAG and HPDL radiation were calculated as being 23211 m, 1934 m and 1838 m respectively. Moreover, this method of laser beam absorption length determination, which has hitherto been used predominantly with lasers operated in the pulsed mode, is shown to be valid for use with lasers operated in the continuous wave (CW) mode, depending upon the material being treated

    Developing a low-cost, simple-to-use electrochemical sensor for the detection of circulating tumour DNA in human fluids

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    It is well-known that two major issues, preventing improved outcomes from cancer are late diagnosis and the evolution of drug resistance during chemotherapy, therefore technologies that address these issues can have a transformative effect on healthcare workflows. In this work we present a simple, low-cost DNA biosensor that was developed specifically to detect mutations in a key oncogene (KRAS). The sensor employed was a screen-printed array of carbon electrodes, used to perform parallel measurements of DNA hybridisation. A DNA amplification reaction was developed with primers for mutant and wild type KRAS sequences which amplified target sequences from representative clinical samples to detectable levels in as few as twenty cycles. High levels of sensitivity were demonstrated alongside a clear exemplar of assay specificity by showing the mutant KRAS sequence was detectable against a significant background of wild type DNA following amplification and hybridisation on the sensor surface. The time to result was found to be 3.5 h with considerable potential for optimisation through assay integration. This quick and versatile biosensor has the potential to be deployed in a low-cost, point-of-care test where patients can be screened either for early diagnosis purposes or monitoring of response to therapy

    Grid-Following Voltage Source Converters: Basic Schemes and Current Control Techniques to Operate with Unbalanced Voltage Conditions

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    The growing relevance of voltage source converters (VSCs), and the deep impact they have on the development and maintenance of the electrical grid, increase the necessity of further research on how to deal with nonideal grid conditions from the VSCs control. This paper is aimed to summarize the basic techniques and schemes that might be required for a grid-connected VSC to work under these conditions: grid synchronization schemes, sequence decomposition, current reference generation, and current controllers. At the same time, some alternative schemes that improves the basic ones are cited. Modelling and the two typical current controllers design and tuning under stationary and synchronous reference frames are also exhibited. Given the importance of the current control stage in the VSC behaviour, five control schemes, designed to track negative sequence currents, are shown and tested in simulation and experiments. According to the experiments, it is shown that the standard proportional-resonant controller achieves the best performance in negative sequence tracking due to the robustness of its non-ideal version, the improved implementation thanks to the delta operator, and the non-dependence on grid-synchronization schemes. Alternatively, one approach based on dual synchronous reference frame is also highlighted for easiness of implementation and good performance

    Novel Endochin-Like Quinolones Exhibit Potent In Vitro Activity against Plasmodium knowlesi but Do Not Synergize with Proguanil.

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    Quinolones, such as the antimalarial atovaquone, are inhibitors of the malarial mitochondrial cytochrome bc1 complex, a target critical to the survival of both liver- and blood-stage parasites, making these drugs useful as both prophylaxis and treatment. Recently, several derivatives of endochin have been optimized to produce novel quinolones that are active in vitro and in animal models. While these quinolones exhibit potent ex vivo activity against Plasmodium falciparum and Plasmodium vivax, their activity against the zoonotic agent Plasmodium knowlesi is unknown. We screened several of these novel endochin-like quinolones (ELQs) for their activity against P. knowlesiin vitro and compared this with their activity against P. falciparum tested under identical conditions. We demonstrated that ELQs are potent against P. knowlesi (50% effective concentration, <117?nM) and equally effective against P. falciparum We then screened selected quinolones and partner drugs using a longer exposure (2.5 life cycles) and found that proguanil is 10-fold less potent against P. knowlesi than P. falciparum, while the quinolones demonstrate similar potency. Finally, we used isobologram analysis to compare combinations of the ELQs with either proguanil or atovaquone. We show that all quinolone combinations with proguanil are synergistic against P. falciparum However, against P. knowlesi, no evidence of synergy between proguanil and the quinolones was found. Importantly, the combination of the novel quinolone ELQ-300 with atovaquone was synergistic against both species. Our data identify potentially important species differences in proguanil susceptibility and in the interaction of proguanil with quinolones and support the ongoing development of novel quinolones as potent antimalarials that target multiple species

    Optimisation of an electrochemical DNA sensor for measuring KRAS G12D and G13D point mutations in different tumour types

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    Circulating tumour DNA (ctDNA) is widely used in liquid biopsies due to having a presence in the blood that is typically in proportion to the stage of the cancer and because it may present a quick and practical method of capturing tumour heterogeneity. This paper outlines a simple electrochemical technique adapted towards point-of-care cancer detection and treatment monitoring from biofluids using a label-free detection strategy. The mutations used for analysis were the KRAS G12D and G13D mutations, which are both important in the initiation, progression and drug resistance of many human cancers, leading to a high mortality rate. A low-cost DNA sensor was developed to specifically investigate these common circulating tumour markers. Initially, we report on some developments made in carbon surface pre-treatment and the electrochemical detection scheme which ensure the most sensitive measurement technique is employed. Following pre-treatment of the sensor to ensure homogeneity, DNA probes developed specifically for detection of the KRAS G12D and G13D mutations were immobilized onto low-cost screen printed carbon electrodes using diazonium chemistry and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride/N-hydroxysuccinimide coupling. Prior to electrochemical detection, the sensor was functionalised with target DNA amplified by standard and specialist PCR methodologies (6.3% increase). Assay development steps and DNA detection experiments were performed using standard voltammetry techniques. Sensitivity (as low as 0.58 ng/μL) and specificity (&gt;300%) was achieved by detecting mutant KRAS G13D PCR amplicons against a background of wild-type KRAS DNA from the representative cancer sample and our findings give rise to the basis of a simple and very low-cost system for measuring ctDNA biomarkers in patient samples. The current time to receive results from the system was 3.5 h with appreciable scope for optimisation, thus far comparing favourably to the UK National Health Service biopsy service where patients can wait for weeks for biopsy results

    Patterns of Abdominal Fat Distribution: The Framingham Heart Study

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    OBJECTIVE—The prevalence of abdominal obesity exceeds that of general obesity. We sought to determine the prevalence of abdominal subcutaneous and visceral obesity and to characterize the different patterns of fat distribution in a community-based sample

    Analysis of the oscillations induced by a supersonic jet applied to produce nanofibers

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    Financiado para publicación en acceso aberto: Universidade de Vigo/CISUGHigh-performance fibers are key components for enhancing the mechanical properties of composite materials. The development of high strength nanofibers augurs the production of new nano-composites with outstanding features. However, the robust production of continuous glass nanofibers that can be feasible processed for efficiently manufacturing nanocomposites is still challenging. Recently, Cofiblas (Continuous Fiberizing by Laser melting and Supersonic dragging) was demonstrated as a technique capable of producing continuous glass nanofibers with unlimited length. Cofiblas process has some similarities with the widely known melt blowing technique for the production of polymeric fibers. In both techniques, the design of the gas nozzle is key to ensure the feasibility of the process since the turbulences of the gas jet may induce strong whipping of the filament. This paper gives novel experimental evidences on the correlation of the supersonic gas jet instabilities with the oscillation of the filament in the melt-blowing and Cofiblas processes, relating these oscillations with the presence of shock waves and unsteadiness in the flow, and gives valuable insight into the use of supersonic jets in the melt blowing process as an effective approach for the formation of nanofibers. A thin 3D-axisymmetric model in OpenFOAM® was put to test by comparing the performance of different solvers which were validated by flow visualization of the exit jet using digital holography (DH). In order to perform a realistic and thorough validation, we simulated the optical measurements of the flow from the CFD simulations of the mass density by Abel transform and numerical differentiation. The application of digital holography as the flow visualization technique makes possible both a precise validation of the density maps obtained from the Abel transformation of the 2D-alike results, and the analysis of the shockwave pattern in the air jet. Conversely, the numerical reconstruction of time-averaged holograms is employed to detect unsteadiness in the flow and to analyze the fiber oscillation, which is essential to assess the stability of the process. Lastly, the analysis and comparison of the vibration of the filament using the basic design and the optimized nozzle demonstrates a clear influence of the shock waves and flow unsteadiness in the stability of the filament.Agencia Estatal de Investigación | Ref. PGC2018-094900-B-I00Xunta de Galicia | Ref. ED431C 2019/23Ministerio de Universidades | Ref. FPU20/0311

    Cobalt containing glass fibres and their synergistic effect on the HIF-1 pathway for wound healing applications

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    Introduction and Methods: Chronic wounds are a major healthcare problem, but their healing may be improved by developing biomaterials which can stimulate angiogenesis, e.g. by activating the Hypoxia Inducible Factor (HIF) pathway. Here, novel glass fibres were produced by laser spinning. The hypothesis was that silicate glass fibres that deliver cobalt ions will activate the HIF pathway and promote the expression of angiogenic genes. The glass composition was designed to biodegrade and release ions, but not form a hydroxyapatite layer in body fluid. Results and Discussion: Dissolution studies demonstrated that hydroxyapatite did not form. When keratinocyte cells were exposed to conditioned media from the cobalt-containing glass fibres, significantly higher amounts of HIF-1α and Vascular Endothelial Growth Factor (VEGF) were measured compared to when the cells were exposed to media with equivalent amounts of cobalt chloride. This was attributed to a synergistic effect of the combination of cobalt and other therapeutic ions released from the glass. The effect was also much greater than the sum of HIF-1α and VEGF expression when the cells were cultured with cobalt ions and with dissolution products from the Co-free glass, and was proven to not be due to a rise in pH. The ability of the glass fibres to activate the HIF-1 pathway and promote VEGF expression shows the potential for their use in chronic wound dressings.National Institute for Health Research (Reino Unido) | Ref. II-ES-1010-10094Agencia Estatal de Investigación | Ref. PID2020-117900RB-I0

    Distinct muscle imaging patterns in myofibrillar myopathies

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    Objective: To compare muscle imaging findings in different subtypes of myofibrillar myopathies (MFM) in order to identify characteristic patterns of muscle alterations that may be helpful to separate these genetic heterogeneous muscular disorders. Methods: Muscle imaging and clinical findings of 46 patients with MFM were evaluated (19 desminopathy, 12 myotilinopathy, 11 filaminopathy, 1 alpha B-crystallinopathy, and 3 ZASPopathy). The data were collected retrospectively in 43 patients and prospectively in 3 patients. Results: In patients with desminopathy, the semitendinosus was at least equally affected as the biceps femoris, and the peroneal muscles were never less involved than the tibialis anterior (sensitivity of these imaging criteria to detect desminopathy in our cohort 100%, specificity 95%). In most of the patients with myotilinopathy, the adductor magnus showed more alterations than the gracilis muscle, and the sartorius was at least equally affected as the semitendinosus (sensitivity 90%, specificity 93%). In filaminopathy, the biceps femoris and semitendinosus were at least equally affected as the sartorius muscle, and the medial gastrocnemius was more affected than the lateral gastrocnemius. The semimembranosus mostly showed more alterations than the adductor magnus (sensitivity 88%, specificity 96%). Early adult onset and cardiac involvement was most often associated with desminopathy. In patients with filaminopathy, muscle weakness typically beginning in the 5th decade of life was mostly pronounced proximally, while late adult onset (> 50 years) with distal weakness was more often present in myotilinopathy. Conclusions: Muscle imaging in combination with clinical data may be helpful for separation of distinct myofibrillar myopathy subtypes and in scheduling of genetic analysis
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