Cardiac contraction at the level of the sarcomere is regulated by the thin filament (TF) composed of actin, alpha tropomyosin (TPM), and the troponin (Tn) complex (cTnT: cTnC: cTnI). The "gate-keeper" protein, α-TPM, is a highly conserved α-helical, coiled-coil dimer that spans actin and regulates myosin-actin interactions. The N-terminus of one α-TPM dimer inter-digitates with the C-terminus of the adjacent dimer in a head-to-tail fashion forming the flexible and cooperative TPM-overlap that is necessary for myofilament activation. Two dilated cardiomyopathy (DCM) causing mutations in TPM (D84N and D230N) and one hypertrophic cardiomyopathy (HCM) causing mutation (E62Q), all identified in large, unrelated, multigenerational families, were utilized to study how primary alterations in protein structure cause functional deficits. We hypothesize that structural changes from a single point mutation propagate along the -helical coiled-coil of TPM, thus affecting its regulatory function. Structural effects of the mutations studied via differential scanning calorimetry (DSC) on TPM alone revealed significant changes in the thermal unfolding temperatures of both the C- and N-termini for all mutants compared to WT, indicating that mutational effects propagate to both ends of TPM, thus affecting the overlap region. Although, of note, the proximal termini to the mutation has shown more significant structural changes compared to WT. DSC analysis on fully reconstituted TF’s (Tn:TPM:Actin) revealed effects on the TPM-Actin cooperativity of activation, affecting interaction strength (thermal stability), and the rigidity of TPM moving along actin (FWHM). To characterize the resultant functional effect of these discrete changes in thermal stability and TPM rigidity, ATPase assays were used to measure actomyosin activation in the presence and absence of Ca2+. Together, these data will provide a molecular level understanding of the structural and functional deficits caused by these mutations to help elucidate the mechanisms leading to disease.

The structural adhesives widely used in structural strengthening applications are thermoset ambient cure adhesive polymers. At ambient temperatures, these polymers are in a relatively hard and inflexible state. At higher temperatures, the material becomes soft and flexible. The region where the molecular mobility changes dramatically is known as the glass transition temperature Tg and often is presented as a single value. Epoxy polymers exhibit a significant reduction in mechanical properties near glass transition temperature Tg when they are exposed to elevated temperatures. Glass transition temperature Tg is used to characterise the change in epoxy adhesive properties with changing temperature. The mechanical properties of epoxies tend to improve with curing temperature. This is because the crosslink density between the adhesive molecular structures increases during the curing process consequently the Tg improves. The aims of this work are first to demonstrate the importance of curing temperature. Second, to investigate the influence of glass transition temperature !! improvement on the performance of EB-FRP strengthened steel structures in flexure at ambient and elevated temperatures. Third, to compare analytical results with experimental results from the flexure tests results. Finally, to compare the current design guideline recommendations with the flexure tests results. The most commonly used methods to evaluate Tg Dynamic Mechanical Analysis (DMA) and Differential Scanning Calorimetry (DSC) were used to study Tg. Two off-shelf structural adhesives were investigated to understand their property variation with temperature. Epoxy coupons were cured at different elevated temperature and humidity environments up to 28 days. A combination of two extreme relative humidity of 0 and 100% and variable curing temperatures between 15 to 80°C were considered. From a test matrix of 300 DMA and over 250 DSC coupons these conclusions were drawn. First, ambient cured thermosets have a linear relationship between Tg and curing temperature, but Tg is reduced if a certain temperature is reached. Second, a fully cured adhesive requires heating treatment. Without a curing regime, designed Tg may never be achieved. Finally, curing time is crucial at the low curing temperatures while it is less significant at the higher curing temperature. The results of Tg investigation were used to select appropriate curing temperature that the adhesives resistance to temperature can be maximised without damaging the mechanical properties. The study helps designs to understand and assess the behaviour of these two adhesives when they are exposed to extreme temperatures. The study increases the awareness that a fully cured adhesive may never be achieved at ambient or low temperatures. It is important to find the mechanical properties and Tg when the coupons are exposed to the same curing temperature. To investigate the influence of glass transition temperature Tg improvement on the performance of EB-FRP strengthened steel structures in flexure at ambient and elevated temperature, nine three metre length beams were designed to behave as a concrete-steel composite bridge deck. The beams were tested in four-point bending. Lap shear, DMA test, and pull-off adhesion samples were prepared and cured at the same conditions and tested at ambient temperature. Six beams were tested under only mechanically loading at ambient temperature, including the control specimen. Five beams were tested at ambient temperature to show the effects of adhesive curing on FRP strengthened sections. A significant increase of load capacity of the adhesive joints was achieved due to the curing of the joints at elevated temperature. The failure occurred was in the same manner. An increase in the load capacity was observed with increasing curing temperature. An increase of approximately 25% was noticed in the ultimate load capacity of the specimens cured at 50°C compared to the specimens cured at 30°C. The load capacity of lap-shear specimens cured at 50°C was 28% higher than the specimens cured at 30°C. Three specimens were tested under mechanical and thermal loading. A bespoke thermal chamber was designed and fabricated to apply a controlled thermal loading. The beams were loaded mechanically up to 350kN, first. The temperature of the specimens was then increased at a rate of 0.8°C/min. The sustained load 350kN remained constant during the heating phase. Digital Image Correlation (DIC) technique was used to detect the slippage of the tip of the FRP plates. The only specimen cured at 30°C showed relatively poor performance compared to the two specimens cured at 50°C. The plate ends started to slip when the adhesive storage modulus from the DMA runs reduced approximately by 15 and 18% for the beams cured at 30 and 50°C respectively. Pull-off adhesion tests confirmed that adequate surface preparation of over 25 MPa was achieved The flexural model for the composite steel section represented to predicate load-deflection behaviour of the specimens using semi-experimental constitutive material law. The model successfully predicts the load-deflection behaviour of specimens, considering the strain hardening contribution. A bond stress analysis is also presented, which counts for the effect of FRP plate moment effect. The experimental and theoretical FRP plate slippage assuming only adhesive degradation with temperature are compared. The analytical bond models cannot predict the experimental failure because the linear elastic material properties were assumed and the failure was adhesion.

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Yes / In this study, a comparison of different methods to predict drug−polymer solubility was carried out on binary systems consisting of five model drugs (paracetamol, chloramphenicol, celecoxib, indomethacin, and felodipine) and polyvinylpyrrolidone/vinyl acetate copolymers (PVP/VA) of different monomer weight ratios. The drug−polymer solubility at 25 °C was predicted using the Flory−Huggins model, from data obtained at elevated temperature using thermal analysis methods based on the recrystallization of a supersaturated amorphous solid dispersion and two variations of the melting point depression method. These predictions were compared with the solubility in the low molecular weight liquid analogues of the PVP/VA copolymer (N-vinylpyrrolidone and vinyl acetate). The predicted solubilities at 25 °C varied considerably depending on the method used. However, the three thermal analysis methods ranked the predicted solubilities in the same order, except for the felodipine−PVP system. Furthermore, the magnitude of the predicted solubilities from the recrystallization method and melting point depression method correlated well with the estimates based on the solubility in the liquid analogues, which suggests that this method can be used as an initial screening tool if a liquid analogue is available. The learnings of this important comparative study provided general guidance for the selection of the most suitable method(s) for the screening of drug−polymer solubility. / The Irish Research Council and Eli Lilly S.A. through an Irish Research Council Enterprise Partnership Scholarship for C.M.B., in part by The Royal Society in the form of Industrial Fellowship awarded to G.A., and in part by a research grant from Science Foundation Ireland (SFI) under Grant Number SFI/12/RC/2275 (for A.M.H., L.T., K.P., and A.K.).

Mit der Entwicklung und Einführung ökologischer Bauweise im Neubau sowie neuen Baustoffsystemen in Sandwichbauweise wird es zunehmend erforderlich, neue effektive Befestigungsvarianten zu entwickeln, die eine dauerhafte Fixierung auch unter sicherheitstechnischen Bestimmungen sowie aus Garantie- bzw. haftungsrechtlichen Gründen ermöglichen. Die aus der Praxis bisher bekannten chemischen Befestigungssysteme (Zweikomponentenverbundmörtel, Verbundankerpatronen) weisen hinsichtlich der Applikation unter bautechnischen Bedingungen noch einige Nachteile auf. Dazu gehören vor allem längere Aushärtungszeiten zur Realisierung der abschließenden Verbundfestigkeit, Inhomogenitäten im Verbund, der Einsatz toxischer Verbindungen und eine Limitierung der Applikationsmöglichkeiten in horizontalen und Überkopf-Einsatzbereichen sowie Hohlkammersystemen. Alle zuvor genannten Punkte haben bis jetzt die Nutzung solcher Verbundwerkstoffe als universale Anwendungsmöglichkeit verhindert. Ein neues chemisches Befestigungssystem, welches aus Novolak gehärteten mit Hexamethylentetramin (Hexa) und anorganischen Füllstoff besteht, wurde für Applikationen in Beton entwickelt. Das Bindemittel härtet bei der Temperaturzuführung aus. Die unkatalysierte Befestigungsmasse zeigt bei einer Temperatur zwischen 150-300 °C eine hohe Reaktivität. Die Vorteile dieses Systems sind die unbegrenzte Lagerfähigkeit der vorgemischten härtbaren Masse sowie die Gewährleistung einer homogenen Netzwerkstruktur im gesamten Verbund und sie ist frei von giftigen und flüchtigen Substanzen. Auf den Einsatz toxischer Substanzen wurde verzichtet. In dieser Arbeit wurde die Gesamtkinetik der Reaktion während des Aushärtungsprozesses dieser Polymerkomposite untersucht. Die DSC- (nicht-isothermen, isothermen) und MDSC-Untersuchungen haben sich als ein sicheres Verfahren zur Qualitätskontrolle des Aushärtezustands der Befestigungssysteme herausgestellt. Parallel zur nicht-isothermischen und isothermischen DSC wurden Leitfähigkeitsmessungen durchgeführt, um den Endpunkt der Aushärtungsreaktion zu bestimmen. / The development and introduction of ecological construction methods and the use of sandwich materials make it necessary to develop new fixing systems and technologies. Dealing with the application in concrete and other substrates commercial chemical fixing systems show some disadvantages up to date. Especially the rather long curing time in order to realize the final bond strength, inhomogenities in the composite, the partial use of toxic substances and application limits of such systems in horizontal direction as well as hollow section materials has so far prevented the use of such composites for all-purpose applications. A new chemical fixing system, which consists of hexamethylene tetramine (hexa) cured novolac and inorganic filler, was developed for application in concrete. It is applied by a thermo-curing procedure. The uncatalyzed curable mixture has a high reactivity at temperature between 150-300 °C. Compared with commercial chemical fixing systems, the premixed curable mass has many benefits. First it has a unique storage stability and second, it is free of toxic and volatile substances. Another important aspect is, it is self-foaming. In this study was investigated the overall kinetics of the reaction during the curing process of these polymer composites. An appropriate method for this experiment proved to be the DSC in isothermal and non-isothermal mode and MDSC. This turned out to be a safe quality control technique for these systems. Parallel to the non-isothermal and isothermal DSC conductivity measurements have been performed to determine the end point of the curing reaction.

Ice structuring proteins (ISPs) naturally exist in many foods consumed as part of the human diet including plants or fish. ISPs from winter wheat grass have gained interest in the pharmaceutical and food industries as a non-toxic, natural and cost-effective product, which is easy to prepare as a crude extract. However, they have not been purified reproducibly and studied in detail to elucidate their structures, mechanism of actions and difference(s). ISPs from the apoplast region of cold acclimated winter wheat leaves were extracted through vacuum infiltration and purified using heat and ethanol precipitations, size exclusion and anionic exchange fast protein liquid chromatography techniques. The ISPs showed both significant inhibition of ice growth and thermal hysteresis activities. The non-acclimated apoplastic extracts from winter wheat leaves contained similar proteins without any abovementioned activities. The ISPs contained disulfide bridges, similar to thaumatin-like proteins (TLPs) and partially similar to ISPs from winter rye leaves and carrot. ISPs remained active after thermal treatment (i.e., pasteurization conditions) and over a wide range of pH (3-12). There are very few quantitative assays to measure the activity of antifreeze proteins (AFPs, or Ice Structuring Proteins, ISPs), which often suffer from various inaccuracies and inconsistencies. Some methods rely only on unassisted visual assessment. When microscopy is used to measure ice crystal size, it is critical that standardized procedures be adopted, especially when image analysis software is used to quantify sizes. Differential Scanning Calorimetry (DSC) has been used to measure the thermal hysteresis activity (TH) of AFPs. In this study, DSC was used isothermally to measure enthalpic changes associated with structural rearrangements as a function of time. Differences in slopes of thermograms between winter wheat ISP or AFP type I containing samples, and those without ISP or AFP type I were demonstrated. ISP or AFP type I containing samples had much higher slopes compared to those without ISP or AFP type I. Samples with higher concentration of ISP or AFP type I showed higher slope values. The proteinaceous activity of ISPs or AFP type I was confirmed by demonstrating changes in samples with and without proteases. A proposed mechanism of this method is discussed.

The diploma thesis deals with the preparation, crosslinking and characterization of collagen films from various animal sources. Collagen from pig, Tilapia, horse, cow and crocodile was used to prepare collagen films. Chemical crosslinking agents EDC/NHS and Lyofix were used to crosslink the prepared films. In the experimental part, differential scanning calorimetry (DSC) method was optimized to determine the denaturation temperature of individual collagen films before and after crosslinking. In addition, the ability of films to swell and degrade has been analyzed. The presence of characteristic groups present in the collagen structure was verified using infrared spectroscopy. The sample morphology was analyzed using Scanning Electron Cryomicroscopy (Cryo-SEM). The results show that EDC/NHS is a better collagen crosslinking agent compared to Lyofix. The best source for the preparation of thermally stable films is piggy collagen, whose denaturation temperature after crosslinking with EDC/NHS was about 69 °C and could represent more than adequate substitution for cow collagen, which is currently most used in the field of tissue engineering and food industry.

The problem of inaccurate measurement techniques for quantifying isothermal solidification kinetics during transient liquid phase (TLP) bonding in binary and ternary systems; and resulting uncertainty in the accuracy of analytical and numerical models has been addressed by the development of a new technique using differential scanning calorimetry (DSC). This has enabled characterization of the process kinetics in binary and ternary solid/liquid diffusion couples resulting in advancement of the fundamental theoretical understanding of the mechanics of isothermal solidification. The progress of isothermal solidification was determined by measuring the fraction of liquid remaining after an isothermal hold period of varying length. A 'TLP half sample', or a solid/liquid diffusion couple was setup in the sample crucible of a DSC enabling measurement of the heat flow relative to a reference crucible containing a mass of base metal. A comparison of the endotherm from melting of an interlayer with the exotherm from solidification of the residual liquid gives the fraction of liquid remaining. The Ag-Cu and Ag-Au-Cu systems were employed in this study. Metallurgical techniques were used to compliment the DSC results. The effects of sample geometry on the DSC trace have been characterized. The initial interlayer composition, the heating rate, the reference crucible contents, and the base metal coating must be considered in development of the experimental parameters. Furthermore, the effects of heat conduction into the base metal, baseline shift across the initial melting endotherm, and the exclusion of primary solidification upon cooling combine to systematically reduce the measured fraction of liquid remaining. These effects have been quantified using a modified temperature program, and corrected using a universal factor. A comparison of the experimental results with the predictions of various analytical solutions for isothermal solidification reveals that the moving interface solution can accurately predict the interface kinetics given accurate diffusion data. The DSC method has been used to quantify the process kinetics of isothermal solidification in a ternary alloy system, with results compared to a finite difference model for interface motion. The DSC results show a linear relationship between the interface position and the square root of the isothermal hold time. While the numerical simulations do not agree well with the experimental interface kinetics due to a lack of accurate thermodynamic data, the model does help develop an understanding of the isothermal solidification mechanics. Compositional shift at the solid/liquid interface has been measured experimentally and compared with predictions. The results show that the direction of tie-line shift can be predicted using numerical techniques. Furthermore, tie-line shift has been observed in the DSC results. This study has shown that DSC is an accurate and valuable tool in the development of parameters for processes employing isothermal solidification, such as TLP bonding.

The problem of inaccurate measurement techniques for quantifying isothermal solidification kinetics during transient liquid phase (TLP) bonding in binary and ternary systems; and resulting uncertainty in the accuracy of analytical and numerical models has been addressed by the development of a new technique using differential scanning calorimetry (DSC). This has enabled characterization of the process kinetics in binary and ternary solid/liquid diffusion couples resulting in advancement of the fundamental theoretical understanding of the mechanics of isothermal solidification. The progress of isothermal solidification was determined by measuring the fraction of liquid remaining after an isothermal hold period of varying length. A 'TLP half sample', or a solid/liquid diffusion couple was setup in the sample crucible of a DSC enabling measurement of the heat flow relative to a reference crucible containing a mass of base metal. A comparison of the endotherm from melting of an interlayer with the exotherm from solidification of the residual liquid gives the fraction of liquid remaining. The Ag-Cu and Ag-Au-Cu systems were employed in this study. Metallurgical techniques were used to compliment the DSC results. The effects of sample geometry on the DSC trace have been characterized. The initial interlayer composition, the heating rate, the reference crucible contents, and the base metal coating must be considered in development of the experimental parameters. Furthermore, the effects of heat conduction into the base metal, baseline shift across the initial melting endotherm, and the exclusion of primary solidification upon cooling combine to systematically reduce the measured fraction of liquid remaining. These effects have been quantified using a modified temperature program, and corrected using a universal factor. A comparison of the experimental results with the predictions of various analytical solutions for isothermal solidification reveals that the moving interface solution can accurately predict the interface kinetics given accurate diffusion data. The DSC method has been used to quantify the process kinetics of isothermal solidification in a ternary alloy system, with results compared to a finite difference model for interface motion. The DSC results show a linear relationship between the interface position and the square root of the isothermal hold time. While the numerical simulations do not agree well with the experimental interface kinetics due to a lack of accurate thermodynamic data, the model does help develop an understanding of the isothermal solidification mechanics. Compositional shift at the solid/liquid interface has been measured experimentally and compared with predictions. The results show that the direction of tie-line shift can be predicted using numerical techniques. Furthermore, tie-line shift has been observed in the DSC results. This study has shown that DSC is an accurate and valuable tool in the development of parameters for processes employing isothermal solidification, such as TLP bonding.

Incorporation of monoacetylferrocene to the sulfonated polystyrene ionomers imparted some changes in the properties of sulfonated polystyrene. Sulfonation was carried out by acetic anhydride and concentrated sulphuric acid. The sulfonation reaction and the degree of sulfonation were determined by analytical titration and adiabatic bomb calorimeter . For this purpose, sulfonated polystyrene (SPS) samples with varying percentages of sulfonation were prepared between 0.85% and 6.51%. Monoacetyl ferrocene was used in equivalent amount of sulfonation through addition procedure. FTIR Spectroscopy was one of the major techniques used to support the successful addition of AcFe to the SPS samples. Altering the sulfonation degree did not change the characteristic peak positions, but increased the peak intensities with increasing the degrees of sulfonation. Mechanical properties of resultant polymers were investigated. As a result, elastic modulus of polymers decreased by the amount of monoacetylferrocene. Thermal characteristic were found by Differential Scanning Calorimeter (DSC). Thermal analysis revealed that sulfonated polystyrene samples after addition of monoacetylferrocene displayed lower values of Tg. Microscopic analysis were made by Scanning Electron Microscopy (SEM) and single phase for each sample was observed. Besides, energy dispersed micro analysis showed an increase in the intensity of the iron (II) peaks that is related to the amount of monoacetylferrocene added to the SPS samples. Flame retardancy for each polymer was also examined and found that addition of monoacetylferrocene to sulfonated polystyrene does not change the Limiting Oxygen Index value (LOI)(17). However, LOI value for polystyrene is 18.