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    Optimisation of automated gas metal arc fillet welding

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    Gas Metal Arc Welding (GMAW) has been one of the most widely used industrial welding processes since around the middle of the 20th Century. However, the large number of input parameters and variables makes it extremely challenging to understand exactly what impact the variation of each of the inputs (and their interactions with each other) has on the resultant fillet weld. Although the GMAW welding process is a mature and generally well understood process, there is little to no evidence of research specifically focused on understanding what impact the torch orientation (travel angle and gun angle) and parameter interactions have on the resultant fillet weld geometry and structure. The purpose of this study is to provide an improved understanding of the main GMAW process parameters (current, voltage, travel speed, shielding gas flow rate, electrode, travel angle and gun angle), which can then be applied to a robotic welding set up in order to optimise the process by minimising heat input, distortion and cost whilst achieving satisfactory penetration and leg length. Artificial Neural Networks (ANNs) and Regression analysis were used to identify the key parameters and interactions that impact a fillet weld geometry.;These results highlighted that the torch travel angle was significant in determining both the shape and also the level of asymmetry between the horizontal and vertical leg lengths of the fillet weld. Finite Element Analysis was then used to determine how the fillet weld geometry impacts the temperature distribution and distortion of the fillet welded assembly.;The FEA model demonstrated that varying the fillet weld geometry impacts the temperature distribution and distortion of the fillet welded structure. Specifically the results suggest that welding the fillet with a larger horizontal leg length appears to generate less overall deflection on the baseplate. This reinforces that that in order to control the level of distortion of a welded structure it is important to tightly control the size and shape of the fillet weld. A Schlieren study was conducted to visualise the behaviour of the shielding gas around the filet weld. This study highlighted that the shielding gas flow rate can be significantly reduced, for a fillet weld, without compromising the quality of the weld.;This improved understanding, from the ANN, FEA and visualisation studies has the potential to generate significant benefits if applied to a robotic welding set up. Creating a more robust process that can be optimised to achieve a target geometry, minimise the heat input and distortion and minimise the overall cost of the weld.Gas Metal Arc Welding (GMAW) has been one of the most widely used industrial welding processes since around the middle of the 20th Century. However, the large number of input parameters and variables makes it extremely challenging to understand exactly what impact the variation of each of the inputs (and their interactions with each other) has on the resultant fillet weld. Although the GMAW welding process is a mature and generally well understood process, there is little to no evidence of research specifically focused on understanding what impact the torch orientation (travel angle and gun angle) and parameter interactions have on the resultant fillet weld geometry and structure. The purpose of this study is to provide an improved understanding of the main GMAW process parameters (current, voltage, travel speed, shielding gas flow rate, electrode, travel angle and gun angle), which can then be applied to a robotic welding set up in order to optimise the process by minimising heat input, distortion and cost whilst achieving satisfactory penetration and leg length. Artificial Neural Networks (ANNs) and Regression analysis were used to identify the key parameters and interactions that impact a fillet weld geometry.;These results highlighted that the torch travel angle was significant in determining both the shape and also the level of asymmetry between the horizontal and vertical leg lengths of the fillet weld. Finite Element Analysis was then used to determine how the fillet weld geometry impacts the temperature distribution and distortion of the fillet welded assembly.;The FEA model demonstrated that varying the fillet weld geometry impacts the temperature distribution and distortion of the fillet welded structure. Specifically the results suggest that welding the fillet with a larger horizontal leg length appears to generate less overall deflection on the baseplate. This reinforces that that in order to control the level of distortion of a welded structure it is important to tightly control the size and shape of the fillet weld. A Schlieren study was conducted to visualise the behaviour of the shielding gas around the filet weld. This study highlighted that the shielding gas flow rate can be significantly reduced, for a fillet weld, without compromising the quality of the weld.;This improved understanding, from the ANN, FEA and visualisation studies has the potential to generate significant benefits if applied to a robotic welding set up. Creating a more robust process that can be optimised to achieve a target geometry, minimise the heat input and distortion and minimise the overall cost of the weld

    Laser metal deposition of the Ti-5553 alloy on forged substrate for aerospace applications

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    This work aims to characterise the metallurgical properties of the Ti-5553 alloy deposited with Laser Metal Deposition (LMD) to investigate the feasibility of fabricating features on large Ti-5553 components such as the Bogie Beam. In this work, two LMD systems have been used to deposit Ti-5553 on forged and heat-treated Ti-5553 substrate under a range of various process parameters. The microstructural features have been investigated using optical and scanning electron microscopy, as well as with electron back-scatter diffraction and energy dispersive spectroscopy. Residual stresses have been evaluated using the multiple-axis contour method. Microhardness and tensile properties have been evaluated and interrelated with the underlying microstructure. Thermal modelling techniques have been used to predict the solidification conditions and thermal history of deposited components. The microstructure was shown to exhibit large columnar β-grains oriented with the build direction and columnar dendrites. The laser power was shown to influence both the β-grain size and crystallographic texture, which varied between a cube and a h001i // BD fibre. The powder feed rate was shown to influence the β-grain size and promote the existence of regions of fine equiaxed β-grains interspersed throughout the microstructure. During deposition, the development of residual heat in previouslydeposited layers can facilitate the β → α transformation. The microhardness in the as-deposited condition is generally low, but regions of precipitated α are significantly harder. Moderate strength and ductility was observed in the as-deposited condition. A region of tensile stresses exist adjacent to the free surfaces of the deposited blocks, while compressive stresses characterise their cores. Following sub-β-transus heat-treatment, the microhardness and tensile strength are much improved, but displays severely anisotropic ductility due to the anisotropic nature of the underlying columnar β grains. Failure in this condition is a mixed-mode of intergranular and transgranular fracture. Residual stresses are adequately relieved during the heat-treatment.This work aims to characterise the metallurgical properties of the Ti-5553 alloy deposited with Laser Metal Deposition (LMD) to investigate the feasibility of fabricating features on large Ti-5553 components such as the Bogie Beam. In this work, two LMD systems have been used to deposit Ti-5553 on forged and heat-treated Ti-5553 substrate under a range of various process parameters. The microstructural features have been investigated using optical and scanning electron microscopy, as well as with electron back-scatter diffraction and energy dispersive spectroscopy. Residual stresses have been evaluated using the multiple-axis contour method. Microhardness and tensile properties have been evaluated and interrelated with the underlying microstructure. Thermal modelling techniques have been used to predict the solidification conditions and thermal history of deposited components. The microstructure was shown to exhibit large columnar β-grains oriented with the build direction and columnar dendrites. The laser power was shown to influence both the β-grain size and crystallographic texture, which varied between a cube and a h001i // BD fibre. The powder feed rate was shown to influence the β-grain size and promote the existence of regions of fine equiaxed β-grains interspersed throughout the microstructure. During deposition, the development of residual heat in previouslydeposited layers can facilitate the β → α transformation. The microhardness in the as-deposited condition is generally low, but regions of precipitated α are significantly harder. Moderate strength and ductility was observed in the as-deposited condition. A region of tensile stresses exist adjacent to the free surfaces of the deposited blocks, while compressive stresses characterise their cores. Following sub-β-transus heat-treatment, the microhardness and tensile strength are much improved, but displays severely anisotropic ductility due to the anisotropic nature of the underlying columnar β grains. Failure in this condition is a mixed-mode of intergranular and transgranular fracture. Residual stresses are adequately relieved during the heat-treatment

    Investigating a role for CaMKIIδ in mediating the cardiotoxic effects of anti-cancer tyrosine kinase inhibitors

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    Introduction: Tyrosine kinase inhibitors (TKIs) have dramatically improved cancer treatment but are known to cause cardiotoxicity. The pathophysiological consequences of TKI therapy are likely to manifest across different cell types of the heart, yet there is little understanding of the differential adverse cellular effects. Cardiac fibroblasts (CFs) play a pivotal role in the repair and remodelling of the heart following insult or injury, yet their involvement in anticancer drug induced cardiotoxicity has been largely overlooked. Here, we examine and compare the direct effects of two TKIs, sunitinib malate and imatinib mesylate, on CFs and progenitor cardiac myocytes (PCMs).Methodology: CFs and PCMs were treated with sunitinib and imatinib (0.1-10μM) for 18 hours and then subject to in vitro analyses to determine the role of Ca2+/calmodulin dependent protein kinase II (CaMKII) in the cardiotoxic mechanism of TKIs. Variations in cell phenotype were monitored via brightfield imaging. Changes in cell viability were determined via MTT assays and flow cytometry. Western blot and immunofluorescent imaging were utilised to investigate potential changes in protein expression. Changes in calcium mobility were investigated using a Fluo4-AM intracellular calcium release assay and mitochondrial function was explored using MitoSOX Red live cell imaging and an Oroborous oxygraph O2k respirometer.Results/Discussion: In investigating the cardiotoxic mechanism of anti-cancer TKIs, this project has shown that (i) TKI treatment leads to contractile and non-contractile cellular dysfunction and death, (ii) TKI treatment, particularly sunitinib treatment, increases intracellular [Ca2+] release and cellular oxidative stress in CFs by increasing reactive oxygen species (ROS) production via effects at the level of the mitochondria, correlating with increased oxidation and autonomous activation of CaMKII and (iii) CaMKII inhibition via KN-93 reduces the detrimental effects of sunitinib and imatinib treatment at the level of the mitochondria, but this does not improve CF viability. Interestingly, the study found that TKI treatment had no effect on intracellular [Ca2+] release in PCMs and actually reduced CaMKII phosphorylation, despite previous reports of pathophysiological changes in CMs that are similar to those obtained in CFs here. This study also established that the PCMs used here do not express key CM Ca2+ handling proteins and this makes them unsuitable to investigate the cardiotoxic mechanism of TKIs.Conclusion: These findings highlight a new role for CaMKII in TKI-induced cardiotoxicity, particularly at the level of the mitochondria, and confirm differential off-target toxicity in both contractile and non-contractile cardiac cells, consistent with the differential selectivity of sunitinib and imatinib.Introduction: Tyrosine kinase inhibitors (TKIs) have dramatically improved cancer treatment but are known to cause cardiotoxicity. The pathophysiological consequences of TKI therapy are likely to manifest across different cell types of the heart, yet there is little understanding of the differential adverse cellular effects. Cardiac fibroblasts (CFs) play a pivotal role in the repair and remodelling of the heart following insult or injury, yet their involvement in anticancer drug induced cardiotoxicity has been largely overlooked. Here, we examine and compare the direct effects of two TKIs, sunitinib malate and imatinib mesylate, on CFs and progenitor cardiac myocytes (PCMs).Methodology: CFs and PCMs were treated with sunitinib and imatinib (0.1-10μM) for 18 hours and then subject to in vitro analyses to determine the role of Ca2+/calmodulin dependent protein kinase II (CaMKII) in the cardiotoxic mechanism of TKIs. Variations in cell phenotype were monitored via brightfield imaging. Changes in cell viability were determined via MTT assays and flow cytometry. Western blot and immunofluorescent imaging were utilised to investigate potential changes in protein expression. Changes in calcium mobility were investigated using a Fluo4-AM intracellular calcium release assay and mitochondrial function was explored using MitoSOX Red live cell imaging and an Oroborous oxygraph O2k respirometer.Results/Discussion: In investigating the cardiotoxic mechanism of anti-cancer TKIs, this project has shown that (i) TKI treatment leads to contractile and non-contractile cellular dysfunction and death, (ii) TKI treatment, particularly sunitinib treatment, increases intracellular [Ca2+] release and cellular oxidative stress in CFs by increasing reactive oxygen species (ROS) production via effects at the level of the mitochondria, correlating with increased oxidation and autonomous activation of CaMKII and (iii) CaMKII inhibition via KN-93 reduces the detrimental effects of sunitinib and imatinib treatment at the level of the mitochondria, but this does not improve CF viability. Interestingly, the study found that TKI treatment had no effect on intracellular [Ca2+] release in PCMs and actually reduced CaMKII phosphorylation, despite previous reports of pathophysiological changes in CMs that are similar to those obtained in CFs here. This study also established that the PCMs used here do not express key CM Ca2+ handling proteins and this makes them unsuitable to investigate the cardiotoxic mechanism of TKIs.Conclusion: These findings highlight a new role for CaMKII in TKI-induced cardiotoxicity, particularly at the level of the mitochondria, and confirm differential off-target toxicity in both contractile and non-contractile cardiac cells, consistent with the differential selectivity of sunitinib and imatinib

    Genetic factors that determine host resistance to bacterial infection

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    Antibiotic resistance is one of the major challenges that we face today. Not only in a medical sense, but also for a country’s national security, as the use of a bioweapon is an ever increasing concern. To help combat these threats, understanding how bacteria interact with their host could be a key research area. By understanding which human genes confer resistance or susceptibility to bacteria during infection could possibly lead the way in developing new drug targets to stop infection. This thesis focuses on Salmonella enterica serovar typhimurium infection of U937 cells and examines the role the gene SLC7A11 plays in the infection process a previous work identified that SLC7A11 gene mutations decreased susceptibility to infection. SLC7A11 CRISPR #1 U937 cells were infected with Salmonella enterica serovar typhimurium to help understand if this gene did provide resistance when knocked out. This infection was carried out alongside WT U937 cells and WT U937 cells which were both exposed to Salmonella enterica serovar typhimurium with the drug sulfasalazine. This drug is a known inhibitor of SLC7A11.From the results it can be seen that inhibition of SLC7A11 may cause a trend towards beneficial effects in stopping the infection of macrophages by Salmonella enterica serovar typhimurium. However, with p-values of 0.60 for 5 ng/ml of sulfasalazine, 0.11 for 10 ng/ml of sulfasalazine and 0.06 for SLC7A11 knockout, our current findings are not statistically significant.In conclusion, the inhibition of SLC7A11 by sulfasalazine may inhibit the infection of macrophages by the infecting bacteria Salmonella enterica serovar typhimurium. This could lead to the development of host directed therapies to combat bacterial infection, with the use of pharmaceutical inhibitors of not only SLC7A11 but also other identified genes.Antibiotic resistance is one of the major challenges that we face today. Not only in a medical sense, but also for a country’s national security, as the use of a bioweapon is an ever increasing concern. To help combat these threats, understanding how bacteria interact with their host could be a key research area. By understanding which human genes confer resistance or susceptibility to bacteria during infection could possibly lead the way in developing new drug targets to stop infection. This thesis focuses on Salmonella enterica serovar typhimurium infection of U937 cells and examines the role the gene SLC7A11 plays in the infection process a previous work identified that SLC7A11 gene mutations decreased susceptibility to infection. SLC7A11 CRISPR #1 U937 cells were infected with Salmonella enterica serovar typhimurium to help understand if this gene did provide resistance when knocked out. This infection was carried out alongside WT U937 cells and WT U937 cells which were both exposed to Salmonella enterica serovar typhimurium with the drug sulfasalazine. This drug is a known inhibitor of SLC7A11.From the results it can be seen that inhibition of SLC7A11 may cause a trend towards beneficial effects in stopping the infection of macrophages by Salmonella enterica serovar typhimurium. However, with p-values of 0.60 for 5 ng/ml of sulfasalazine, 0.11 for 10 ng/ml of sulfasalazine and 0.06 for SLC7A11 knockout, our current findings are not statistically significant.In conclusion, the inhibition of SLC7A11 by sulfasalazine may inhibit the infection of macrophages by the infecting bacteria Salmonella enterica serovar typhimurium. This could lead to the development of host directed therapies to combat bacterial infection, with the use of pharmaceutical inhibitors of not only SLC7A11 but also other identified genes

    Investigating the anti-inflammatory effects of non-ionic surfactant vesicles

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    Inflammation can be an unwanted consequence or cause of debilitating diseases of infectious and non-infectious aetiologies. Sepsis can be a result of an uncontrolled immune response to bacterial infections (including MRSA, E. coli and P. Aeruginosa) or viral infections (including SARS-CoV-2 and Influenza). Immune dysfunction can also cause autoimmune diseases including rheumatoid arthritis, ulcerative colitis and Crohn’s disease. Current anti-inflammatory medications have a number of deficiencies including lack of specificity and undesirable side effects. Herein the potential of Non-ionic surfactant vesicles (NISV) as an anti-inflammatory drug and their mode of action is investigated. NISV were found to have a wide array of anti-inflammatory effects on macrophages in vitro including down-regulation of IL-6, IL-12 and multiple chemokines regardless of whether cells were stimulated with LPS, Poly(I:C) or Pam3csk4. The individual components of NISV, monopalmityol glycerol (MPG), dicetyl phosphate (DCP) and cholesterol) did not replicate the immunomodulatory effects found in macrophages, proving the formulation of NISV is essential for the anti-inflammatory effects. Liposomes were shown to augment LPS and Poly(I:C) stimulation of macrophages, inducing upregulation of pro-inflammatory cytokines including IL-6 and TNF-α, demonstrating that the anti-inflammatory effects of NISV are not a common feature of all vesicular formulations. Transcriptomic analyses showed consistent anti-inflammatory effects, and indicated down-regulation of NF-κB as an important aspect of the anti-inflammatory effects mediated by NISV. Metabolomic analysis show NISV disrupt the Warburg effect by reducing production of itaconate and succinate, indicating anti-inflammatory downstream effects. The mechanism through which NISV down-regulate NF-κB is unknown. However, the NISV’s primary component, MPG, demonstrates structural similarity to the sphingolipid, sphingosine-1-phosphate (S1P). As S1P is an immune mediator that acts through NF-κB, future work should explore the hypothesis that MPG disrupts S1P signalling.Inflammation can be an unwanted consequence or cause of debilitating diseases of infectious and non-infectious aetiologies. Sepsis can be a result of an uncontrolled immune response to bacterial infections (including MRSA, E. coli and P. Aeruginosa) or viral infections (including SARS-CoV-2 and Influenza). Immune dysfunction can also cause autoimmune diseases including rheumatoid arthritis, ulcerative colitis and Crohn’s disease. Current anti-inflammatory medications have a number of deficiencies including lack of specificity and undesirable side effects. Herein the potential of Non-ionic surfactant vesicles (NISV) as an anti-inflammatory drug and their mode of action is investigated. NISV were found to have a wide array of anti-inflammatory effects on macrophages in vitro including down-regulation of IL-6, IL-12 and multiple chemokines regardless of whether cells were stimulated with LPS, Poly(I:C) or Pam3csk4. The individual components of NISV, monopalmityol glycerol (MPG), dicetyl phosphate (DCP) and cholesterol) did not replicate the immunomodulatory effects found in macrophages, proving the formulation of NISV is essential for the anti-inflammatory effects. Liposomes were shown to augment LPS and Poly(I:C) stimulation of macrophages, inducing upregulation of pro-inflammatory cytokines including IL-6 and TNF-α, demonstrating that the anti-inflammatory effects of NISV are not a common feature of all vesicular formulations. Transcriptomic analyses showed consistent anti-inflammatory effects, and indicated down-regulation of NF-κB as an important aspect of the anti-inflammatory effects mediated by NISV. Metabolomic analysis show NISV disrupt the Warburg effect by reducing production of itaconate and succinate, indicating anti-inflammatory downstream effects. The mechanism through which NISV down-regulate NF-κB is unknown. However, the NISV’s primary component, MPG, demonstrates structural similarity to the sphingolipid, sphingosine-1-phosphate (S1P). As S1P is an immune mediator that acts through NF-κB, future work should explore the hypothesis that MPG disrupts S1P signalling

    Hardware tools for optogenetic neuroscience experimentation

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    Optogenetics confers the ability to precisely control the activity of neural populations with cell type specificity in response to illumination, providing a distinct advantage over the indiscriminate action of electrical stimulation. This added specificity offers considerable potential for advancement of experimental neuroscience, with applications ranging from improved understandings of neural circuits to the development of novel neuroprosthesis. The work presented here focuses on the development of hardware tools for optogeneticexperimentation; divided between the development of micro-LED neural probes, and electronic hardware for stimulation/recording control. The development of neural probes with both optical stimulation and electrical recording sites (commonly known as optrodes), capable of providing illumination up to 100 mW/mm2 is illustrated. A hybrid fabrication technique integrating micro-LEDs withmonolithic probes was demonstrated; offering an attractive technique for the development of neural probes with multi-spectral stimulation capabilities. To utilise such optoelectronic neural probes, a lightweight (sub 3g), low form factor (≈18x15x10mm) wireless stimulation system was realised; offering individual control of up to 16 µLED channels. Microprocessor control enables flexible control of intensity, pulse width and repetition rate with a temporal resolution of 0.1ms; facilitating creation of diverse optical stimulation patterns. IR communication allows user selection of pre-uploaded stimulation protocols or direct uploading of stimulation protocols to the system’s memory. A bi-directional neural stimulation/recording system was created to harness the ability of optrode probes, allowing electrical/optical stimulation combined with recording of up to 16 channels at a sampling rate of 20kHz. These features were translated to a prototype wireless SD card based logger (permitting recording at 1kHz). Exemplar closed loop algorithms based on threshold crossing events were implemented on these systems.Optogenetics confers the ability to precisely control the activity of neural populations with cell type specificity in response to illumination, providing a distinct advantage over the indiscriminate action of electrical stimulation. This added specificity offers considerable potential for advancement of experimental neuroscience, with applications ranging from improved understandings of neural circuits to the development of novel neuroprosthesis. The work presented here focuses on the development of hardware tools for optogeneticexperimentation; divided between the development of micro-LED neural probes, and electronic hardware for stimulation/recording control. The development of neural probes with both optical stimulation and electrical recording sites (commonly known as optrodes), capable of providing illumination up to 100 mW/mm2 is illustrated. A hybrid fabrication technique integrating micro-LEDs withmonolithic probes was demonstrated; offering an attractive technique for the development of neural probes with multi-spectral stimulation capabilities. To utilise such optoelectronic neural probes, a lightweight (sub 3g), low form factor (≈18x15x10mm) wireless stimulation system was realised; offering individual control of up to 16 µLED channels. Microprocessor control enables flexible control of intensity, pulse width and repetition rate with a temporal resolution of 0.1ms; facilitating creation of diverse optical stimulation patterns. IR communication allows user selection of pre-uploaded stimulation protocols or direct uploading of stimulation protocols to the system’s memory. A bi-directional neural stimulation/recording system was created to harness the ability of optrode probes, allowing electrical/optical stimulation combined with recording of up to 16 channels at a sampling rate of 20kHz. These features were translated to a prototype wireless SD card based logger (permitting recording at 1kHz). Exemplar closed loop algorithms based on threshold crossing events were implemented on these systems

    Computational investigation of immersion quenching : understanding of boiling conjugate heat transfer

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    Quenching is a metallurgical procedure used to alter material properties of metals and alloys. Although used extensively throughout human history, its design relies heavily on experience and often the trial and error method. Therefore, the availability of computational tools capable of describing the physics during quenching would help design facilities efficiently, lower costs, and even make the process more environmentally friendly.This work aims to develop and validate a numerical procedure for immersion quenching using computational fluid dynamics. The methodology employs the partitioned approach. An energy equation and Eulerian two-fluid model describe the solid and fluid region, respectively. The heat transfer information is exchanged at the regions' interface.In this thesis, various aspects of the methodology are discussed. Yet, the primary attention is given to the wall boiling and the conjugate heat transfer, which are crucial. Furthermore, during an attempt to formulate stability criteria, the numerical Biot number has been developed as a potential candidate accounting for all three phases, solid, liquid and vapour.The code validation is split into three chapters. The first investigates conjugate heat transfer without boiling in a backward-facing step geometry. The next is concentrated on a hot thin horizontal plate submerged in water, and the last describes the quenching system behaviour during immersion quenching of a cylinder in a vertical orientation.The numerical results proved excellent accuracy for conjugate heat transfer problem without boiling. A good agreement with validation data is also achieved when boiling occurs, yet complications are observed at locations where vapour movement is obstructed. Vapour volume fraction tends to be mesh sensitive, affecting the solid temperature _eld in its proximity. Such behaviour can be often prevented using phase change within the inner fluid mesh. However, doing so, the user limits the solver capabilities as vapour obstruction is often desirable.Quenching is a metallurgical procedure used to alter material properties of metals and alloys. Although used extensively throughout human history, its design relies heavily on experience and often the trial and error method. Therefore, the availability of computational tools capable of describing the physics during quenching would help design facilities efficiently, lower costs, and even make the process more environmentally friendly.This work aims to develop and validate a numerical procedure for immersion quenching using computational fluid dynamics. The methodology employs the partitioned approach. An energy equation and Eulerian two-fluid model describe the solid and fluid region, respectively. The heat transfer information is exchanged at the regions' interface.In this thesis, various aspects of the methodology are discussed. Yet, the primary attention is given to the wall boiling and the conjugate heat transfer, which are crucial. Furthermore, during an attempt to formulate stability criteria, the numerical Biot number has been developed as a potential candidate accounting for all three phases, solid, liquid and vapour.The code validation is split into three chapters. The first investigates conjugate heat transfer without boiling in a backward-facing step geometry. The next is concentrated on a hot thin horizontal plate submerged in water, and the last describes the quenching system behaviour during immersion quenching of a cylinder in a vertical orientation.The numerical results proved excellent accuracy for conjugate heat transfer problem without boiling. A good agreement with validation data is also achieved when boiling occurs, yet complications are observed at locations where vapour movement is obstructed. Vapour volume fraction tends to be mesh sensitive, affecting the solid temperature _eld in its proximity. Such behaviour can be often prevented using phase change within the inner fluid mesh. However, doing so, the user limits the solver capabilities as vapour obstruction is often desirable

    Investigations on the mechanisms of non-photochemical laser-induced nucleation and sonocrystallisation

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    In recent years, a number of authors have steered Non-Photochemical Laser-induced Nucleation (NPLIN) and sonocrystallisation from mystery towards viable and valuableapplication for improved control over the industrial crystallisation of drug substances. However, the underlying mechanisms of nucleation induction from the phenomena generated by laser irradiation and ultrasonic wave propagation are both still underinvestigation. So far, a complex picture of bubbles and localised pressure fluctuations at the interplay of clusters and crystals has been provided. This thesis presents detection of bubble fields in order to provide mechanistic insight into NPLIN and sonocrystallisation. On the underlying mechanisms of the NPLIN effect, doubts have been cast on the initially proposed effects of the optical electric field acting directly upon solute clusters. Recently,it has been proposed that at laser pulse energies below the threshold for optical breakdown of the liquid, impurity particle heating generates transient vapour cavities, the associatedphenomena of which provide opportune conditions for nucleation induction. However, there have been a lack of experimental attempts to detect vapour cavities in order to support this mechanism. Chapter 4 provides significant evidence of nucleation induction within an unfocused beamline via cavitation generated by particle heating. For the first time, single-pulse (1064 nm, 6ns) laser-induced nucleation of ammonium chloride was captured with high-speed imaging. Observations at 100000 fps allowed for the detection of multiple micron-sized bubbles before the appearance and growth of multiple primary crystal nuclei within the irradiated volume of the solution. Further compelling evidence for the impurity particle-heating mechanism is provided by needle hydrophonemeasurements, in which the effect of solute concentration alongside solution filtration and iron oxide nanoparticle doping prior to irradiation were investigated. Signal processing allowed for quantification of the broadband noise produced by bubbles that were generated on laser irradiation. Overall, the results demonstrate a direct relationship between absorbing particles, cavitation generation and crystal nucleation, which haspowerful implications for discussions behind the mechanism for laser-induced nucleation. The effects of propagating ultrasound waves through a liquid occur via the generation of acoustic cavitation: the growth and collapse of vapour cavities under an applied ultrasound field. This mode of cavitation generation is well established for inducing crystal nucleation and fragmentation. However, few previous sonocrystallisation studies have involved measurement of cavitation activity in the generated sound field. Moreover, the physical properties of a liquid have been reported to significantly affect the cavitation activity, under the same applied ultrasound parameters. Chapter 5 presents a comparison of cavitation activity in typical crystallisation solvents, under a high-power ultrasound field. A setup was established in order to perform needle hydrophone measurements, from which the acoustic pressure and broadband integrated voltage were obtained at increasing drive powers. The broadband noise measurements are discussed in relation to the solvent physical properties.Previous paracetamol (PCM) sonocrystallisation studies involving the application of highpower ultrasound fields have reported (i) the selective crystallisation of the elusive metastable form II and (ii) higher impurity rejection in the presence of acetanilide andmetacetamol, both on comparison with silent conditions. However, the mechanisms behind these observations remain unclear. Chapter 6 provides an investigation of PCM cooling sonocrystallisation, with a focus on the mechanisms for polymorphism and purity effects. It was established that, under the same applied frequency, the selective crystallisation of form II relied upon the application of cavitation energy above a threshold,together with both high supersaturation and rapid growth conditions. Meanwhile, greater impurity purging with cavitation generation was attributed to nucleation induction at significantly lower supersaturation levels, as opposed to cavitation phenomena promoting impurity rejection. Moreover, a morphology change from equant to columnar crystals of PCM form I was observed in the presence of impurities only under an applied cavitationfield, which was attributed to the acceleration of surface integration caused by stable cavitation phenomena. This effect has not before been reported and it is expected to influence the development of industrial sonocrystallisation processes for drug substancepurification.In recent years, a number of authors have steered Non-Photochemical Laser-induced Nucleation (NPLIN) and sonocrystallisation from mystery towards viable and valuableapplication for improved control over the industrial crystallisation of drug substances. However, the underlying mechanisms of nucleation induction from the phenomena generated by laser irradiation and ultrasonic wave propagation are both still underinvestigation. So far, a complex picture of bubbles and localised pressure fluctuations at the interplay of clusters and crystals has been provided. This thesis presents detection of bubble fields in order to provide mechanistic insight into NPLIN and sonocrystallisation. On the underlying mechanisms of the NPLIN effect, doubts have been cast on the initially proposed effects of the optical electric field acting directly upon solute clusters. Recently,it has been proposed that at laser pulse energies below the threshold for optical breakdown of the liquid, impurity particle heating generates transient vapour cavities, the associatedphenomena of which provide opportune conditions for nucleation induction. However, there have been a lack of experimental attempts to detect vapour cavities in order to support this mechanism. Chapter 4 provides significant evidence of nucleation induction within an unfocused beamline via cavitation generated by particle heating. For the first time, single-pulse (1064 nm, 6ns) laser-induced nucleation of ammonium chloride was captured with high-speed imaging. Observations at 100000 fps allowed for the detection of multiple micron-sized bubbles before the appearance and growth of multiple primary crystal nuclei within the irradiated volume of the solution. Further compelling evidence for the impurity particle-heating mechanism is provided by needle hydrophonemeasurements, in which the effect of solute concentration alongside solution filtration and iron oxide nanoparticle doping prior to irradiation were investigated. Signal processing allowed for quantification of the broadband noise produced by bubbles that were generated on laser irradiation. Overall, the results demonstrate a direct relationship between absorbing particles, cavitation generation and crystal nucleation, which haspowerful implications for discussions behind the mechanism for laser-induced nucleation. The effects of propagating ultrasound waves through a liquid occur via the generation of acoustic cavitation: the growth and collapse of vapour cavities under an applied ultrasound field. This mode of cavitation generation is well established for inducing crystal nucleation and fragmentation. However, few previous sonocrystallisation studies have involved measurement of cavitation activity in the generated sound field. Moreover, the physical properties of a liquid have been reported to significantly affect the cavitation activity, under the same applied ultrasound parameters. Chapter 5 presents a comparison of cavitation activity in typical crystallisation solvents, under a high-power ultrasound field. A setup was established in order to perform needle hydrophone measurements, from which the acoustic pressure and broadband integrated voltage were obtained at increasing drive powers. The broadband noise measurements are discussed in relation to the solvent physical properties.Previous paracetamol (PCM) sonocrystallisation studies involving the application of highpower ultrasound fields have reported (i) the selective crystallisation of the elusive metastable form II and (ii) higher impurity rejection in the presence of acetanilide andmetacetamol, both on comparison with silent conditions. However, the mechanisms behind these observations remain unclear. Chapter 6 provides an investigation of PCM cooling sonocrystallisation, with a focus on the mechanisms for polymorphism and purity effects. It was established that, under the same applied frequency, the selective crystallisation of form II relied upon the application of cavitation energy above a threshold,together with both high supersaturation and rapid growth conditions. Meanwhile, greater impurity purging with cavitation generation was attributed to nucleation induction at significantly lower supersaturation levels, as opposed to cavitation phenomena promoting impurity rejection. Moreover, a morphology change from equant to columnar crystals of PCM form I was observed in the presence of impurities only under an applied cavitationfield, which was attributed to the acceleration of surface integration caused by stable cavitation phenomena. This effect has not before been reported and it is expected to influence the development of industrial sonocrystallisation processes for drug substancepurification

    Mathematical modelling of droplet evaporation

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    This thesis concerns the theoretical modelling and analysis of sessile droplets of liquids as they evaporate in different modes of evaporation. The thesis focuses on diffusion limited evaporation in which the diffusion of vapour in the surrounding atmosphere governs the evaporation rate of the droplet.;First, we investigate the combined influences of the initial contact angle and the substrate conductivity on droplet evaporation. In particular, we highlight that for droplets with large contact angles the lifetime of the droplet does not vary strongly with either the mode of evaporation or the conductivity of the substrate.;Next, we investigate the evaporation of thin sessile droplets on thin substrates in two situations in which the influence of the thermal properties of the system is strong. Specifically, we obtain closed form asymptotic solutions for the evolution of the droplet when the substrate has a high thermal resistance relative to the droplet, and when the saturation concentration of the vapour depends strongly on temperature.;Finally, we develop a model for the evaporation of thin two-dimensional sessile droplets evaporating either singly or as a pair. We find that in large domains the lifetime of the droplet depends logarithmically on the size of the domain, and more weakly on the mode of evaporation and the separation between the droplets. In particular, we quantify the shielding effect that the droplets have on each other, and how it extends the lifetime of the droplets.This thesis concerns the theoretical modelling and analysis of sessile droplets of liquids as they evaporate in different modes of evaporation. The thesis focuses on diffusion limited evaporation in which the diffusion of vapour in the surrounding atmosphere governs the evaporation rate of the droplet.;First, we investigate the combined influences of the initial contact angle and the substrate conductivity on droplet evaporation. In particular, we highlight that for droplets with large contact angles the lifetime of the droplet does not vary strongly with either the mode of evaporation or the conductivity of the substrate.;Next, we investigate the evaporation of thin sessile droplets on thin substrates in two situations in which the influence of the thermal properties of the system is strong. Specifically, we obtain closed form asymptotic solutions for the evolution of the droplet when the substrate has a high thermal resistance relative to the droplet, and when the saturation concentration of the vapour depends strongly on temperature.;Finally, we develop a model for the evaporation of thin two-dimensional sessile droplets evaporating either singly or as a pair. We find that in large domains the lifetime of the droplet depends logarithmically on the size of the domain, and more weakly on the mode of evaporation and the separation between the droplets. In particular, we quantify the shielding effect that the droplets have on each other, and how it extends the lifetime of the droplets

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