13,318 research outputs found

    Examples of works to practice staccato technique in clarinet instrument

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    Klarnetin staccato tekniğini güçlendirme aşamaları eser çalışmalarıyla uygulanmıştır. Staccato geçişlerini hızlandıracak ritim ve nüans çalışmalarına yer verilmiştir. Çalışmanın en önemli amacı sadece staccato çalışması değil parmak-dilin eş zamanlı uyumunun hassasiyeti üzerinde de durulmasıdır. Staccato çalışmalarını daha verimli hale getirmek için eser çalışmasının içinde etüt çalışmasına da yer verilmiştir. Çalışmaların üzerinde titizlikle durulması staccato çalışmasının ilham verici etkisi ile müzikal kimliğe yeni bir boyut kazandırmıştır. Sekiz özgün eser çalışmasının her aşaması anlatılmıştır. Her aşamanın bir sonraki performans ve tekniği güçlendirmesi esas alınmıştır. Bu çalışmada staccato tekniğinin hangi alanlarda kullanıldığı, nasıl sonuçlar elde edildiği bilgisine yer verilmiştir. Notaların parmak ve dil uyumu ile nasıl şekilleneceği ve nasıl bir çalışma disiplini içinde gerçekleşeceği planlanmıştır. Kamış-nota-diyafram-parmak-dil-nüans ve disiplin kavramlarının staccato tekniğinde ayrılmaz bir bütün olduğu saptanmıştır. Araştırmada literatür taraması yapılarak staccato ile ilgili çalışmalar taranmıştır. Tarama sonucunda klarnet tekniğin de kullanılan staccato eser çalışmasının az olduğu tespit edilmiştir. Metot taramasında da etüt çalışmasının daha çok olduğu saptanmıştır. Böylelikle klarnetin staccato tekniğini hızlandırma ve güçlendirme çalışmaları sunulmuştur. Staccato etüt çalışmaları yapılırken, araya eser çalışmasının girmesi beyni rahatlattığı ve istekliliği daha arttırdığı gözlemlenmiştir. Staccato çalışmasını yaparken doğru bir kamış seçimi üzerinde de durulmuştur. Staccato tekniğini doğru çalışmak için doğru bir kamışın dil hızını arttırdığı saptanmıştır. Doğru bir kamış seçimi kamıştan rahat ses çıkmasına bağlıdır. Kamış, dil atma gücünü vermiyorsa daha doğru bir kamış seçiminin yapılması gerekliliği vurgulanmıştır. Staccato çalışmalarında baştan sona bir eseri yorumlamak zor olabilir. Bu açıdan çalışma, verilen müzikal nüanslara uymanın, dil atış performansını rahatlattığını ortaya koymuştur. Gelecek nesillere edinilen bilgi ve birikimlerin aktarılması ve geliştirici olması teşvik edilmiştir. Çıkacak eserlerin nasıl çözüleceği, staccato tekniğinin nasıl üstesinden gelinebileceği anlatılmıştır. Staccato tekniğinin daha kısa sürede çözüme kavuşturulması amaç edinilmiştir. Parmakların yerlerini öğrettiğimiz kadar belleğimize de çalışmaların kaydedilmesi önemlidir. Gösterilen azmin ve sabrın sonucu olarak ortaya çıkan yapıt başarıyı daha da yukarı seviyelere çıkaracaktır

    A direct-laser-written heart-on-a-chip platform for generation and stimulation of engineered heart tissues

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    In this dissertation, we first develop a versatile microfluidic heart-on-a-chip model to generate 3D-engineered human cardiac microtissues in highly-controlled microenvironments. The platform, which is enabled by direct laser writing (DLW), has tailor-made attachment sites for cardiac microtissues and comes with integrated strain actuators and force sensors. Application of external pressure waves to the platform results in controllable time-dependent forces on the microtissues. Conversely, oscillatory forces generated by the microtissues are transduced into measurable electrical outputs. After characterization of the responsivity of the transducers, we demonstrate the capabilities of this platform by studying the response of cardiac microtissues to prescribed mechanical loading and pacing. Next, we tune the geometry and mechanical properties of the platform to enable parametric studies on engineered heart tissues. We explore two geometries: a rectangular seeding well with two attachment sites, and a stadium-like seeding well with six attachment sites. The attachment sites are placed symmetrically in the longitudinal direction. The former geometry promotes uniaxial contraction of the tissues; the latter additionally induces diagonal fiber alignment. We systematically increase the length for both configurations and observe a positive correlation between fiber alignment at the center of the microtissues and tissue length. However, progressive thinning and “necking” is also observed, leading to the failure of longer tissues over time. We use the DLW technique to improve the platform, softening the mechanical environment and optimizing the attachment sites for generation of stable microtissues at each length and geometry. Furthermore, electrical pacing is incorporated into the platform to evaluate the functional dynamics of stable microtissues over the entire range of physiological heart rates. Here, we typically observe a decrease in active force and contraction duration as a function of frequency. Lastly, we use a more traditional ?TUG platform to demonstrate the effects of subthreshold electrical pacing on the rhythm of the spontaneously contracting cardiac microtissues. Here, we observe periodic M:N patterns, in which there are ? cycles of stimulation for every ? tissue contractions. Using electric field amplitude, pacing frequency, and homeostatic beating frequencies of the tissues, we provide an empirical map for predicting the emergence of these rhythms

    Relations between soil organic carbon, soil structure and physical processes in an agricultural topsoil : The role of soil mineral constituents

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    A better understanding of the interactions between soil organic carbon (SOC) and mineral constituents (e.g. clay and reactive oxide phases) and their consequences for soil structure and physical processes is important for assessing the potential for, and benefits of, carbon sequestration in arable soils. This thesis investigated the factors determining topsoil SOC content at the field scale for an arable field with large var-iations in soil properties. Relationships between SOC, soil pore size distributions, macropore network characteristics, water flow and solute transport were also exam-ined using intact soil samples from the field. The spatial variation in SOC content at the Bjertorp field was mainly explained by the oxalate-extractable aluminum (Alox) content followed by carbon input from crops that was estimated from crop yield. In contrast, clay and oxalate-extractable iron (Feox) seemed not to play a major role in SOC stabilization/accumulation, pos-sibly due to the occurrence of stagnant water in soils with larger clay contents. It was concluded that reactive Al phases may be important for physico-chemical stabiliza-tion of SOC for arable topsoils in humid continental climates. Multiple linear regression analysis revealed that an increase of SOC was associ-ated with relatively large increases of porosities in the 0.2–5 µm and 480–720 µm diameter classes, which can contribute to enhancing both water supply to crops and water flow rates. The degree of preferential solute transport under steady state near-saturated conditions was reduced with larger volumes of small macropores (240–480 µm diameter) and mesopores (30–100 µm diameter), whereas it was not corre-lated with measures of macropore connectivity. The statistical analysis indicated that SOC had only limited effects on the degree of preferential transport, being overshad-owed by the large variation in clay content across the field

    Towards A Graphene Chip System For Blood Clotting Disease Diagnostics

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    Point of care diagnostics (POCD) allows the rapid, accurate measurement of analytes near to a patient. This enables faster clinical decision making and can lead to earlier diagnosis and better patient monitoring and treatment. However, despite many prospective POCD devices being developed for a wide range of diseases this promised technology is yet to be translated to a clinical setting due to the lack of a cost-effective biosensing platform.This thesis focuses on the development of a highly sensitive, low cost and scalable biosensor platform that combines graphene with semiconductor fabrication tech-niques to create graphene field-effect transistors biosensor. The key challenges of designing and fabricating a graphene-based biosensor are addressed. This work fo-cuses on a specific platform for blood clotting disease diagnostics, but the platform has the capability of being applied to any disease with a detectable biomarker.Multiple sensor designs were tested during this work that maximised sensor ef-ficiency and costs for different applications. The multiplex design enabled different graphene channels on the same chip to be functionalised with unique chemistry. The Inverted MOSFET design was created, which allows for back gated measurements to be performed whilst keeping the graphene channel open for functionalisation. The Shared Source and Matrix design maximises the total number of sensing channels per chip, resulting in the most cost-effective fabrication approach for a graphene-based sensor (decreasing cost per channel from £9.72 to £4.11).The challenge of integrating graphene into a semiconductor fabrication process is also addressed through the development of a novel vacuum transfer method-ology that allows photoresist free transfer. The two main fabrication processes; graphene supplied on the wafer “Pre-Transfer” and graphene transferred after met-allisation “Post-Transfer” were compared in terms of graphene channel resistance and graphene end quality (defect density and photoresist). The Post-Transfer pro-cess higher quality (less damage, residue and doping, confirmed by Raman spec-troscopy).Following sensor fabrication, the next stages of creating a sensor platform involve the passivation and packaging of the sensor chip. Different approaches using dielec-tric deposition approaches are compared for passivation. Molecular Vapour Deposi-tion (MVD) deposited Al2O3 was shown to produce graphene channels with lower damage than unprocessed graphene, and also improves graphene doping bringing the Dirac point of the graphene close to 0 V. The packaging integration of microfluidics is investigated comparing traditional soft lithography approaches and the new 3D printed microfluidic approach. Specific microfluidic packaging for blood separation towards a blood sampling point of care sensor is examined to identify the laminar approach for lower blood cell count, as a method of pre-processing the blood sample before sensing.To test the sensitivity of the Post-Transfer MVD passivated graphene sensor de-veloped in this work, real-time IV measurements were performed to identify throm-bin protein binding in real-time on the graphene surface. The sensor was function-alised using a thrombin specific aptamer solution and real-time IV measurements were performed on the functionalised graphene sensor with a range of biologically relevant protein concentrations. The resulting sensitivity of the graphene sensor was in the 1-100 pg/ml concentration range, producing a resistance change of 0.2% per pg/ml. Specificity was confirmed using a non-thrombin specific aptamer as the neg-ative control. These results indicate that the graphene sensor platform developed in this thesis has the potential as a highly sensitive POCD. The processes developed here can be used to develop graphene sensors for multiple biomarkers in the future

    Early Neanderthal social and behavioural complexity during the Purfleet Interglacial: handaxes in the latest Lower Palaeolithic.

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    Only a handful of ‘flagship’ sites from the Purfleet Interglacial (Marine Isotope Stage 9, c. 350-290,000 years ago) have been properly examined, but the archaeological succession at the proposed type-site at Purfleet suggests a period of complexity and transition, with three techno-cultural groups represented in Britain. The first was a simple toolkit lacking handaxes (the Clactonian), and the last a more sophisticated technology presaging the coming Middle Palaeolithic (simple prepared core or proto-Levallois technology). Sandwiched between were Acheulean groups, whose handaxes comprise the great majority of the extant archaeological record of the period – these are the focus of this study. It has previously been suggested that some features of the Acheulean in the Purfleet Interglacial were chronologically restricted, particularly the co-occurrence of ficrons and cleavers. These distinctive forms may have exceeded pure functionality and were perhaps imbued with a deeper social and cultural meaning. This study supports both the previously suggested preference for narrow, pointed morphologies, and the chronologically restricted pairing of ficrons and cleavers. By drawing on a wide spatial and temporal range of sites these patterns could be identified beyond the handful of ‘flagship’ sites previously studied. Hypertrophic ‘giants’ have now also been identified as a chronologically restricted form. Greater metrical variability was found than had been anticipated, leading to the creation of two new sub-groups (IA and IB) which are tentatively suggested to represent spatial and perhaps temporal patterning. The picture in the far west of Britain remains unclear, but the possibility of different Acheulean groups operating in the Solent area, and a late survival of the Acheulean, are both suggested. Handaxes with backing and macroscopic asymmetry may represent prehensile or ergonomic considerations not commonly found on handaxes from earlier interglacial periods. It is argued that these forms anticipate similar developments in the Late Middle Palaeolithic in an example of convergent evolution

    Investigating the mechanism of human beta defensin-2-mediated protection of skin barrier in vitro

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    The human skin barrier is a biological imperative. Chronic inflammatory skin diseases, such as Atopic Dermatitis (AD), are characterised by a reduction in skin barrier function and an increased number of secondary infections. Staphyloccocus aureus (S. aureus) has an increased presence on AD lesional skin and contributes significantly to AD pathology. It was previously demonstrated that the damage induced by a virulence factor of S. aureus, V8 protease, which causes further breakdown in skin barrier function, can be reduced by induction of human β- defensin (HBD)2 (by IL-1β) or exogenous HBD2 application. Induction of this defensin is impaired in AD skin. This thesis examines the mechanism of HBD2-mediated barrier protection in vitro; demonstrating that in this system, HBD2 was not providing protection through direct protease inhibition, nor was it altering keratinocyte proliferation or migration, or exhibiting specific localisation within the monolayer. Proteomics data demonstrated that HBD2 did not induce expression of known antiproteases but suggested that HBD2 stimulation may function by modulating expression of extracellular matrix proteins, specifically collagen- IVα2 and Laminin-β-1. Alternative pathways of protection initiated by IL-1β and TNFα stimulation were also investigated, as well as their influence over generalised wound healing. Finally, novel 3D human skin epidermal models were used to better recapitulate the structure of human epidermis and examine alterations to skin barrier function in a more physiological system. These data validate the barrier-protective properties of HBD2 and extended our knowledge of the consequences of exposure to this peptide in this context

    Optimising acoustic cavitation for industrial application

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    The ultrasonic horn is one of the most commonly used acoustic devices in laboratories and industry. For its efficient application to cavitation mediated process, the cavitation generated at its tip as a function of its tip-vibration amplitudes still needed to be studied in detail. High-speed imaging and acoustic detection are used to investigate the cavitation generated at the tip of an ultrasonic horn, operating at a fundamental frequency, f0, of 20 kHz. Tip-vibration amplitudes are sampled at fine increments across the range of input powers available. The primary bubble cluster under the tip is found to undergo subharmonic periodic collapse, with concurrent shock wave emission, at frequencies of f0/m, with m increasing through integer values with increasing tip-vibration amplitude. The contribution of periodic shock waves to the noise spectra of the acoustic emissions is confirmed. Transitional input powers for which the value of m is indistinct, and shock wave emission irregular and inconsistent, are identified through Vrms of the acoustic detector output. For cavitation applications mediated by bubble collapse, sonications at transitional powers may lead to inefficient processing. The ultrasonic horn is also deployed to investigate the role of shock waves in the fragmentation of intermetallic crystals, nominally for ultrasonic treatment of Aluminium melt, and in a novel two-horn configuration for potential cavitation enhancement effects. An experiment investigating nitrogen fixation via cavitation generated by focused ultrasound exposures is also described. Vrms from the acoustic detector is again used to quantify the acoustic emissions for comparison to the sonochemical nitrite yield and for optimisation of sonication protocols at constant input energy. The findings revealed that the acoustic cavitation could be enhanced at constant input energy through optimisation of the pulse duration and pulse interval. Anomalous results may be due to inadequate assessment for the nitrate generated. The studies presented in this thesis have illustrated means of improving the cavitation efficiency of the used acoustic devices, which may be important to some selected industrial processes

    Statistical Learning for Gene Expression Biomarker Detection in Neurodegenerative Diseases

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    In this work, statistical learning approaches are used to detect biomarkers for neurodegenerative diseases (NDs). NDs are becoming increasingly prevalent as populations age, making understanding of disease and identification of biomarkers progressively important for facilitating early diagnosis and the screening of individuals for clinical trials. Advancements in gene expression profiling has enabled the exploration of disease biomarkers at an unprecedented scale. The work presented here demonstrates the value of gene expression data in understanding the underlying processes and detection of biomarkers of NDs. The value of novel approaches to previously collected -omics data is shown and it is demonstrated that new therapeutic targets can be identified. Additionally, the importance of meta-analysis to improve power of multiple small studies is demonstrated. The value of blood transcriptomics data is shown in applications to researching NDs to understand underlying processes using network analysis and a novel hub detection method. Finally, after demonstrating the value of blood gene expression data for investigating NDs, a combination of feature selection and classification algorithms were used to identify novel accurate biomarker signatures for the diagnosis and prognosis of Parkinson’s disease (PD) and Alzheimer’s disease (AD). Additionally, the use of feature pools based on previous knowledge of disease and the viability of neural networks in dimensionality reduction and biomarker detection is demonstrated and discussed. In summary, gene expression data is shown to be valuable for the investigation of ND and novel gene biomarker signatures for the diagnosis and prognosis of PD and AD
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