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Introduction: Transforming growth factor-β1 (TGF-β1) is a key cytokine that promotes fibrosis after injury in many adult tissues. Here, we hypothesise that delivery of human recombinant decorin (hr-decorin), a natural antagonist of TGF-β1, loaded into gellan-based biomembrane sheet dressings and fluid gel eye drops, prevents cutaneous and corneal scarring after injury. Methods: Gellan-based wound dressings loaded with hr-decorin were characterised for swelling, release profile of hr-decorin, systemic absorption of hr-decorin and human skin reactions. Topical gellan-based fluid gels loaded with hr-decorin were also tested for penetration of hr-decorin into the cornea and aqueous humour (AqH). The effect of hr-decorin on cell migration, differentiation and expression of scar-associated molecules of TGF-β1-stimulated human dermal fibroblasts (HDF) was also evaluated. Results: Gellan-based wound dressings had a high fluid uptake capacity, no adverse reactions on human skin, and sustained local release but no systemic absorption of hr-decorin after application to pig mid-dermal burns. Gellan-based fluid gel eye drops also released hr-decorin over time, which penetrated the cornea and was detected in AqH. The mRNA expression of scar-associated molecules in cultured TGF-β1-stimulated HDF was significantly decreased by hr-decorin, but no changes at the protein level were detected. Conclusion: The results suggest that delivery of Decorin through gellan-based wound dressing and fluid gel eye drop formulations have the potential for translation into therapies for cutaneous and corneal scarring.

Introduction: Multiple sclerosis is a disabling disease with impact on the social, financial and occupational life of an individual. Diagnosis of Multiple sclerosis even with the McDonald criteria, sometimes can take many years, by which time the patient has already accumulated significant disability. Hence the need for early diagnosis and prompt treatment for a better prognosis highlighted in different MS studies. Visual dysfunction in patients with Multiple sclerosis is a common finding. Asymptomatic visual loss has been highlighted in various studies. In the United Kingdom, studies have focused on genetics, environmental factors, assessment of neurological state (EDSS, MSFC) along with MRI of the brain and spinal cord. There is no single study in the UK that has looked at the visual pathway in Multiple sclerosis and correlated with the neurological outcomes. Aim: Correlation of structure and function of visual pathway in Multiple Sclerosis Methodology: We recruited 55 (110 eyes) patients with relapsing remitting MS and 25 controls (50 eyes) into this project with specific inclusion and exclusion criteria. Power calculations were done based on the parameters used for the study. Coefficient of reliability and variability was tested prior to the study in a subset of control patients. Logistic regression model with odds ratio was used to assess the ability of each test to differentiate disease from control. Subgroup analysis was done for the optic neuritis group and the group receiving disease-modifying therapy. Function of the visual pathway was assessed using Sloan contrast charts along with HRR colour chart and HVF indices. Structure of the visual pathway was mainly assessed using different protocols from Optical Coherence Tomography. Ethical approval was obtained through the North Midlands IRAS and Keele University. Results: The structure of the visual pathway correlates significantly with function of vision. This in turn correlates with neurological function. Visual tests are more sensitive than neurological testing by EDSS and hence can be used in diagnosis and to determine prognosis in RRMS. GCIP index, EDI OCT and posterior pole protocols on OCT have revealed useful and valuable information that can be translated into clinical use to manage patients with MS. Conclusion: Sloan contrast charts and HRR colour testing are sensitive measures of disease progression. Visual field test indices on the Humphrey’s field test closely relate to RNFL thickness on posterior pole OCT. GCIP and EDI-OCT show different clinico-pathological staging in MS. Visual parameters have synergistic power in evaluating the disease process in MS. Visual testing for structure and function is a valuable addition to the routine assessment of MS patients. Visual assessment helps in detection of the spectrum of disease in MS with specifics to the range of manifestations and severities of illness. Multiple sclerosis like many other diseases exhibit the iceberg phenomenon. The iceberg phenomenon describes a situation in which a large percentage of a problem is subclinical or otherwise hidden from view. Thus, only the "tip of the iceberg" is apparent to the clinician. Visual assessments help in uncovering disease below the sea level by early detection and subsequent better disease control. Visual studies in MS using the parameters in this study must be considered for routine use in our day to day practice in diagnosis and managing patients more effectively.

As we navigate the environment, images flow over our retinae and produce complex moving patterns including contraction and expansion. These in turn serve to inform us about our movement in the world, as well as about the positions and relative motions of the objects around us. The processes underlying the perception of radial motion were explored using psychophysics, eye tracking and functional magnetic resonance imaging (fMRI). The initial experiments studied how adaptation to radial motion affects discrimination using partially-coherent dot stimuli. Adaptation increased absolute detection thresholds in the adapted direction, but had no effect on the discrimination of higher pedestals. The change in sensitivity is consistent with a divisive inhibition mechanism, as well as with one based on proportion estimates. An orientation discrimination experiment adds support for the latter. Directed attention to one component of a motion-balanced transparently-moving stimulus impairs sensitivity to a level comparable to that following adaptation, although there were large inter-subject differences. A novel approach using relative velocity adjustments of transparently-moving dot fields was used to investigate the reference frame of motion adaptation, which is shown to be mainly retinotopic and diminished by gaze modulations. Finally, fMRI was used to probe the neural substrates of radial motion perception, including retinotopic mapping, localisation of MT/MST, and selectivity for contraction and expansion within the MT+ complex.

Glaucoma describes a group of optic neuropathies characterised by progressive irreversible loss of visual function. Within this thesis, a health economic model was constructed to map service provision from diagnosis considering two competing strategies: the current practice of annual visual field (VF) monitoring against the proposed guidelines of performing 6 VFs in the first two years. The constructed model found the proposed practice to be cost effective at a willingness to pay ceiling ratio of £30,000 per quality adjusted life year (QALY), identifying an incremental cost effectiveness ratio (ICER) of £21,679. The findings of the model however were potentially sensitive to the modelled infrastructure improvement costs required to undertake the proposed guidelines and a costing study to more accurately ascertain these costs was recommended. Following this study, statistical analysis of 473,252 VFs was undertaken to investigate trends in initial identification and progression rates whilst also narrowing their parameters within the health economic model. Consequently, the average level of glaucomatous vision loss at diagnosis was found to be improving by 0.11 dB per year on average whilst proportions of patients with ‘advanced’ loss at diagnosis fell significantly from 30% to 21%. Average progression rates were found to have fallen from -0.11 dB per year to -0.06 dB per year whilst average rates of loss in older eyes ( > 70 years) were found to progress faster than in younger eyes ( < 60 years). Furthermore, testing frequency was found not to vary by visual impairment risk factors. The constructed health economic model was subsequently updated to incorporate the more narrowly defined parameter distributions whilst also being re-specified to incorporate societal costs of visual impairment to count the true costs of the disease. This resulted in an improved ICER of £11,382. In conclusion, it is likely that implementing the proposed guidelines of 6 VFs in the first two years is more cost-effective than annual monitoring. This argument is further reinforced once societal costs are accounted for however a scoping study to examine the required costs of improving the glaucoma monitoring infrastructure is required.

<p>Detta projekt har syftat till att presentera en uppdatering av en befintlig produkt</p><p>genom modifiering av yttre design samt effektivisering av slutmonteringsarbetet.</p><p>Produkten, H.KOM-panelen (en elektronik minnestavla), är en del av H.KOM™-</p><p>systemet som vänder sig till människor med minnesrelaterade sjukdomar. Projektet</p><p>har utförts mot Sensagon AB, stationerat i Vällingby.</p><p>Utgångspunkten för projektet är Sensagons befintliga H.KOM-panel. Produkten är</p><p>en enhet som via ljussignal ger en påminnelse till användaren om att övervakade</p><p>objekt är i avvikande position från sitt normalläge. Exempel på objekt som</p><p>övervakas av systemet är elektriska apparater, dörrar och fönster. Dessa objekt</p><p>förses med givare som i sin tur via radiosignal skickar informationen till H.KOMpanelen.</p><p>Det uppdrag som gavs var att omdesigna H.KOM-panelen för en mer rationell</p><p>slutmonteringsprocess samt att förnya den yttre designen.</p><p>Projektet har omfattat en funktionsanalys för att strukturera upp funktionerna i</p><p>produkten. Ett antal idéskisser skapades och tillsammans med handledare från</p><p>högskolan och företaget gjordes ett urval.</p><p>Koncept genererades och ett nytt urval gjordes tillsammans med handledarna.</p><p>Genom att analysera koncepten via Pugh-matris, QFD och DFA valdes slutligen ett</p><p>koncept ut som bearbetades vidare till en prototyp.</p><p>Modellen motsvarar de krav som ställts med avseende på företagets övergripande</p><p>specifikation. Grundformen harmonierar även med andra delar ingående i</p><p>H.KOM™ systemet.</p><p>Konceptet har en enkel design med få delar samt en färgsättning och utformning</p><p>som gör att den smälter in i de flesta miljöer.</p><p>Slutliga dimensioner på den nya H.KOM panelen måste i första hand anpassas efter</p><p>det ingående kretskortets dimension som troligen blir styrande.</p><p>Arbetet har resulterat i en förstudie av Sensagons H.KOM-panel. Vägen från</p><p>problemformulering till slutresultat finns presenterat i text i denna rapport och</p><p>visualiseras med hjälp av frihandsskisser och CAD-ritningar.</p>

The cavity within the transmembrane staphylococcal α-hemolysin (αHL) pore is roughly a sphere of diameter ~45 Å (volume ~32,600 Å3). The alpha-hemolysin gene was modified to introduce exogenous polypeptide sequences between positions 105 and 106 of αHL. These modified αHLs were assembled either by themselves or with wild-type (W) subunits to form stable homoheptamers and heteroheptamers, respectively. First, the ability to accommodate Gly/Ser-rich polypeptide sequences in the central cavity was tested. Concatemerized Gly/Ser-containing sequences ("loops", L; L(10n + 5), n = 0 to 21) were inserted by genetic approaches. Detailed analysis of bilayer recordings and electrophoretic migration patterns of assembled pores indicate that the upper capacity of the cavity is ~175 amino acids. Then two different polypeptides were placed in the cavity to introduce novel functional properties to the αHL pore. By introducing tandem repeats of elastin-like polypeptide sequences (VPGGG), αHL pores (E101W6) that featured a temperature-responsive gating mechanism were obtained. The temperature-dependent properties of E101W6 pores were monitored by single-channel current recording in planar lipid bilayers. The amplitude and the frequency of the transient blockades increased as the temperature increased, while their duration decreased. The hydrophobic collapse of the inserted ELP loop is proposed for the source of the observed sigmoidal two-state transition for normalized closed states of E101W6 pores. Lastly, an αHL pore was designed to detect proteins from the cis side of the membrane. The heat-stable protein kinase inhibitor (PKI) sequence was inserted into the mid-position of the Gly/Ser loop, which was generated by previous project (L105 construct). The heteromeric pore with the PKI-containing loop (P1151W6) was able to detect cAMP-dependent protein kinase catalytic subunit (PKA) at single molecular level. These engineered αHL pores provide numerous possibilities as tools for drug delivery, cryopreservation, or molecular sensing.

Detta projekt har syftat till att presentera en uppdatering av en befintlig produkt genom modifiering av yttre design samt effektivisering av slutmonteringsarbetet. Produkten, H.KOM-panelen (en elektronik minnestavla), är en del av H.KOM™- systemet som vänder sig till människor med minnesrelaterade sjukdomar. Projektet har utförts mot Sensagon AB, stationerat i Vällingby. Utgångspunkten för projektet är Sensagons befintliga H.KOM-panel. Produkten är en enhet som via ljussignal ger en påminnelse till användaren om att övervakade objekt är i avvikande position från sitt normalläge. Exempel på objekt som övervakas av systemet är elektriska apparater, dörrar och fönster. Dessa objekt förses med givare som i sin tur via radiosignal skickar informationen till H.KOMpanelen. Det uppdrag som gavs var att omdesigna H.KOM-panelen för en mer rationell slutmonteringsprocess samt att förnya den yttre designen. Projektet har omfattat en funktionsanalys för att strukturera upp funktionerna i produkten. Ett antal idéskisser skapades och tillsammans med handledare från högskolan och företaget gjordes ett urval. Koncept genererades och ett nytt urval gjordes tillsammans med handledarna. Genom att analysera koncepten via Pugh-matris, QFD och DFA valdes slutligen ett koncept ut som bearbetades vidare till en prototyp. Modellen motsvarar de krav som ställts med avseende på företagets övergripande specifikation. Grundformen harmonierar även med andra delar ingående i H.KOM™ systemet. Konceptet har en enkel design med få delar samt en färgsättning och utformning som gör att den smälter in i de flesta miljöer. Slutliga dimensioner på den nya H.KOM panelen måste i första hand anpassas efter det ingående kretskortets dimension som troligen blir styrande. Arbetet har resulterat i en förstudie av Sensagons H.KOM-panel. Vägen från problemformulering till slutresultat finns presenterat i text i denna rapport och visualiseras med hjälp av frihandsskisser och CAD-ritningar.

This numerical study explored the mechanisms responsible for the re-initiation of a detonation, which quenched while diffracting over a half-cylinder obstacle. Its purpose was to accurately predict when detonation re-initiations occur, determine roles of re-initiation mechanisms, and compare effects of chemical models. The model used reactive Euler equations with the one-step Arrhenius or two-step chain-branching chemical models, calibrated to post-shock conditions to reproduce the ignition delay. Simulations were validated using the stoichiometric methane-oxygen experiments of Bhattacharjee et al.. The model accurately predicted detonation re-initiation conditions found in experiments with good qualitative and quantitative agreement. While the one-step model was sufficient in predicting re-initiation, the two-step model reproduced finer details. Kelvin-Helmholtz and Richtmyer-Meshkov instabilities did not appear to influence detonation re-initiation of the Mach stem. Detonation re-initiation occurred due to adiabatic compression of the Mach stem, or transport of a flame along the wall jet. Transverse detonations were poorly reproduced.

Abstract   The purpose of this essay is to find difficulties and risks in the re-engineering process when restructuring to Model-View-Controller (MVC). A thoroughly theory study has been conducted to be able to understand the important steps in the re-engineering process. The methods and concepts of this essay are re-engineering, UML, system development life cycle, design patterns and MVC. The science approach used is design science where the artifact being developed are a set of models. In the analysis phase of the process the system is analyzed. The result of the analysis is notes of difficulties found and models showing the structure of the system. The results from the analysis is used to answer the questions. The steps taken in the re-engineering process are identified and described. All risks and difficulties found when following these steps are described. The guiding knowledge of this essay is to show when it's worth the effort of re-engineering the system instead of starting over from the beginning. When the problems are overwhelming and to time consuming re-engineering is not the best option.