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De nos jours, le bloc est le produit le plus vendu en préfabrication, avec un chiffre d’affaires de 418 millions d’euros en 2015 (chiffres issus de la Fédération de l’Industrie du Béton). Toutefois, ce résultat atteste d’une baisse de production constatée depuis 2012.Dans ce contexte économique difficile, les industriels cherchent à optimiser la formulation de leurs produits. Les particularités de ceux-ci (consistance sèche et teneur en air moyenne comprise entre 7 et 15 %) rendent impossible l’utilisation des outils existants.L’objectif de la thèse est alors de mettre au point une méthode de formulation adaptée aux blocs, permettant d’optimiser le rapport coûts/performances. Cela implique de diminuer le dosage en ciment, matériau le plus couteux du béton et également le plus négatif en termes d’émissions de CO2. Pour cela un squelette granulaire optimal doit être utilisé.La méthodologie de formulation mise au point se déroule ainsi en deux étapes. La première consiste à sélectionner le mélange granulaire présentant l’arrangement maximal. La deuxième détermine les volumes des autres constituants (ciment, eau efficace, air et addition) en fonction des exigences de consistance et de performances mécaniques. Les travaux ont permis d’obtenir un modèle d’empilement compressible adapté à la mise en place des mélanges granulaires secs à l’aide d’une presse vibrante et d’un moule de bloc. Celui-ci calcule la compacité des mélanges granulaires dans de telles conditions et permet de sélectionner le mélange optimal. Les travaux ont également permis de relier les propriétés aux états frais et durcis à la formulation des bétons secs. La résolution du système d’équations obtenu permet de déterminer la formulation qui optimise le rapport coûts/performances.Un outil numérique regroupant ces résultats est développé. Il nécessite de renseigner un ensemble de données (squelettes granulaires, masses volumiques réelles, coûts, etc.), ainsi que les exigences de consistance et de performances mécaniques. Il propose alors la formulation optimisant le rapport coûts/performances. Celle-ci peut ensuite être testée à échelle réduite sur des cubes car les résultats ont permis de relier les performances mécaniques des cubes et des blocs. / Construction’s sector is knowing an important mutation and is confronted with unpresented stakes with major importance for next decades: population growth and needs in accommodation and infrastructures, climate change, uses of durable and natural resources, societal expectations from consumers as well as territorial’s stakeholders. Concrete precast industry is strongly enlisted to answer at these news needs, for the constructive systems proposed as well as for the production processes of concrete’s products. The stake is especially important for concrete masonry units with a production in France in 2017 of 6.7 million tons. These products are realized using press which compact concrete with vibration and pression. Blocs are made of dry cast concrete with average air content between 7 and 15%. Today, formulation methodologies are adapted to delayed demoulding products and so not made for bloc concrete.This thesis aims to develop a formulation methodology adapted to blocs and to their process, in order to optimize their performances in economic conditions. This implies disposing of robust tools able to determine optimal proportions for each constituent, considering process specifications. Especially, it is necessary to use an optimized aggregates mix.The formulation methodology developed runs through two steps. The first one consists in choosing the aggregates mix with maximal packing density. The second one determines other constituents volumes (cement, efficient water, air and addition) according to consistency and mechanical performances requirements. The compressive packing model (F.de Larrard) is adapted to dry aggregates mix casting with vibrating press in a bloc mold. Results also make it possible to connect fresh and hardened properties to the formulation of dry cast concretes. Solving the system of equations gives the formulation optimizing the ratio costs/performances.

Monoclonal antibodies (mAbs) represent one of the fastest growing classes of therapeutic proteins. This success is due to a number of attractive properties such as high binding affinity, specificity, low immunogenicity and high aqueous solubility. Despite this, mAbs can suffer from undesirable physical instabilities, especially reversible self-association (RSA), which can lead to aggregation and phase separation. One aspect of formulation is therefore to find solution conditions which minimise mAb aggregation propensity during storage at high concentrations. Hence, the buffer, excipient and pH must be carefully considered to obtain the optimal formulation. Currently, if a platform formulation process is non-ideal for a particular candidate mAb, then an alternative strategy is to utilise high-throughput screening to measure various physical parameters indicative of physical stability. Arginine (in the form of hydrochloride salt Arg·HCl) is often used in formulations exhibiting high RSA and a propensity for aggregation. The interaction of Arg with the protein surface is complex and dependent on both the salt form and concentration. Here the focus was on the glutamate salt of arginine (Arg·Glu), to quantify its effect on mAb conformational and colloidal stability under different pH conditions. Arg·Glu was able to decrease the propensity of the mAbs to aggregate, particularly at pH values closer to their pI.The work also included the use of in vitro cell culture models to examine cell viability in the presence of the various arginine salts over a range of osmolalities. Whilst Arg·Glu is composed of two naturally occurring amino acids and both of which are considered non-toxic individually, the effect of the increased concentrations of their combination, on cells has not been explored previously. In vitro cell lines were chosen to represent the subcutaneous tissue, the effect of Arg·Glu on cell viability was compared against NaCl, Arg·HCl and sodium glutamate (NaGlu). The work concluded there was no additional toxicity associated with the presence of Arg·Glu in the cell culture models studied, therefore Arg·Glu has the potential as an excipient as it reduces aggregation and is nontoxic. Another aspect of the work was to assess the use of solution NMR spectroscopy as an orthogonal technique in mAb formulation characterisation. 1H NMR spectroscopy was used to measure a number of experimental parameters for high concentration mAb solution. The work proposed that 1H NMR spectroscopy can serve as a valuable orthogonal method for mAb characterization and formulation.

Protein aggregation is a frequently cited problem during the development of liquid protein formulations, which is especially problematic since each protein exhibits different aggregation behaviour. Aggregation can be controlled by judicious choice of solution conditions, such as salt and buffer type and concentration, pH, and small molecule additives. However, finding conditions is still a trial and error process. In order to improve formulation development, a fundamental understanding of how excipients impact upon protein aggregation would significantly contribute to the development of stable protein therapeutics. The underlying mechanisms that control effects of excipients on protein behaviour are poorly understood. This dissertation is directed at understanding how excipients alter the conformational and colloidal stability of proteins and the link to aggregation. This knowledge can be used for finding novel ways of either predicting or preventing/inhibiting protein aggregation. Experiments using static and dynamic light scattering, intrinsic fluorescence, turbidity and electrophoretic light scattering were conducted to study the effect of solution conditions such as pH, salt type and concentration on protein aggregation behaviour for three model systems: lysozyme, insulin and a monoclonal antibody. Emphasis is placed on understanding the effects of solution additives on protein-protein interactions and the link to aggregation. This understanding has allowed the rational development of stable formulations with novel additives, such as arginine containing dipeptides and polycations.

A major challenge in drug development is ensuring that each new candidate drug is delivered to the appropriate location, in a timely manner and at an optimal concentration. Low drug solubility, drug instability, drug degradation, drug toxicity, or rapid clearance from the body can reduce the effectiveness of an otherwise promising drug candidate. Formulations such as nano/microparticles and melt extruded pellets made with synthetic and natural polymers are effective solutions for the advancement of drug delivery technology. These polymeric formulations can provide controlled release of therapeutic agents by delivering constant doses over long periods, cyclic dosages, and tunable release of both hydrophilic and hydrophobic drugs in order to improve the bioavailability and bioactivity of a drug. PLGA-based nanoparticles formed by emulsion or nanoprecipitation techniques can be designed to have a range of degradation times. Particle degradation and drug release kinetics can be controlled by the physiochemical properties of the polymer, such as molecular weight, hydrophobicity, and polydispersity. This study is focused on developing polymeric-based delivery systems for small and large molecules as treatment strategies for arthrofibrosis and bone tissue engineering. In developing arthrofibrotic treatments, several mechanosignaling and biochemical pathways were targeted using small molecule therapeutics such as blebbistatin (a myosin II ATPase inhibitor), paclitaxel (a microtubule stabilizer), sulfasalazine (a kappa B suppressor), beta-aminopropionitrile (a lysyl oxidase inhibitor) and cis-hydroxyproline (inhibits the formation of stable triple helix structure of collagen). The aforementioned drugs were delivered either via PLGA micro/nanoparticles or via pellets formed by melt extrusion. From the studies performed, it was found that blebbistatin delivered by PLGA nanoparticles could reversibly inhibit fibroblast contractile activity and could significantly inhibit collagen synthesis. These findings lay the foundations for further optimization of drug dosing and potentially enabling a new drug delivery technology for treating arthrofibrosis. Sulfasalazine delivered by melt extruded PLGA pellets significantly inhibited myofibroblast numbers as deduced from α-SMA expression and col1A1 gene expression results and thus can be considered a potential treatment for arthrofibrosis. For bone tissue engineering, plasmids encoding differentiation promoting factors or growth factors such as BMP-2 (pBMP-2), FGF-2 (pFGF-2), PDGF (pPDGF) and VEGF (pVEGF) were delivered via polyethylenimine (PEI), a cationic carrier that interacts electrostatically with negatively charged DNA. The formed nanoplexes were either tested directly or by coating them onto biocompatible titanium metal implants and cultured with human bone marrow derived mesenchymal stem cells (hBMSCs). We found that the combinatorial delivery of pBMP-2 and pFGF-2 significantly enhanced bone regeneration as deduced from Runx-2, alkaline phosphatase and osteocalcin gene expression results as well as from data yielded from alizarin red staining assays and atomic absorption spectroscopy where calcium ion levels were measured. It was also found that pBMP-2 nanoplex-coated titanium discs could significantly enhance bone regenerative gene expression for osteocalcin, Runx-2, and alkaline phosphatase as well as enhance calcium ion expression in human adipose derived mesenchymal stem cells (hADMSCs). Thus, it can be concluded that pFGF-2 and pBMP-2 nanoplexes have osteogenic potential and our studies demonstrate a new methodology with the potential to modify titanium disc implant surfaces for the purposes of enhancing osseointegration.

Aliskiren (ALS) is a direct renin inhibitor with low bioavailability and high drug cost. The goal of this study was to increase the bioavailability of ALS through nanoformulation. The optimized formulation was then evaluated in spontaneously hypertensive rats (SHRs). We developed an ALS poly(lactic-co-glycolic) acid nanoparticle (ALS-NP) through the emulsion–diffusion–evaporation method with various solvents, stabilizer concentrations, and centrifugation speeds. SHRs were orally dosed with 30 mg/kg ALS or dose equivalent ALS-NP. Several parameters were assayed in plasma and/or urine at baseline and 24 h post-dose, while pharmacokinetic analysis included serial sampling. The optimum formulation was found with ethyl acetate, a 1.00% w/v didodecyldimethylammonium bromide concentration, and a 10,000 r/min (15,554 g) centrifugation speed. A 168% relative bioavailability was observed as a result of ALS-NP administration along with significant, as determined by Student’s t-test, increases in the maximum ALS plasma concentration (p = 0.0189) and the area under the plasma concentration–time curve from 0 to infinity (p = 0.0095). Conversely, a reduction was found in oral volume of distribution (p = 0.0009) and oral clearance (p = 0.0298). Blood urea nitrogen increased significantly after dosing in both groups (p < 0.0001 and p < 0.0001); however, no statistical difference was found between endpoint levels (p > 0.05) following one-way analysis of variance (ANOVA). Kidney injury molecule-1 increased following ALS dosing (p = 0.0486), while ALS-NP showed a decrease (p = 0.027) which was also significantly decreased compared to ALS-Final (p = 0.0008) when examined using two-way ANOVA. Urinary potassium excretion decreased significantly, as shown by two-way ANOVA, only in the ALS group (p = 0.0274) which was also significantly reduced compared to ALS-NP-Final (p = 0.016). Using the current formulation and at the dosage tested, ALS-NP showed a more favorable pharmacokinetic profile and positive kidney changes compared to ALS in regard to select outcomes. Thus, NP formulation may further improve ALS renoprotection in addition to increasing bioavailabilty.

This thesis presents the first-known exact solutions for vibration of stepped circular Mindlin plates. The considered circular plate is of several step-wise variation in thickness in the radial direction. The Mindlin first order shear deformable plate theory is employed to derive the governing differential equations for the annular and circular segments. The exact solutions to these differential equations may be expressed in terms of the Bessel functions of the first and second kinds and the modified Bessel functions of the first and second kinds. The governing homogenous system of equations is assembled by implementing the essential and natural boundary conditions and the segment interface conditions. Vibration solutions are presented for circular Mindlin plates of different edge support conditions and various combinations of step-wise thickness variations. These exact vibration results may serve as important benchmark values for researchers to validate their numerical methods for such circular plate problems / Master of Engineering (Civil)

In 1986, Vietnam opened up the country’s economy by launching the Doi Moi (renovation) policy, which made the process of economic liberalisation possible. Accordingly, Ho Chi Minh City, the country’s biggest city, has undergone rapid growth of population, urbanisation and industrialisation. While achieving remarkable economic growth, the city faces considerable urban environmental challenges. The rapid growth of urbanisation and industry has placed increasing pressure on available freshwater resources, through excessive water use and increasing volumes of untreated wastewater. Firstly, the urban water sector has had to meet growing demand for water use for domestic purposes during the dry season. Secondly, groundwater levels have experienced a substantial drawdown in outlying urban districts as a result of over-abstraction. Thirdly, rapidly expanding industrial activities are causing severe demand on water resources. The city’s major supply sources have developed an alarming level of pollutants discharged by industry. The aim of this thesis is to formulate an integrated approach to the sustainable management of water resources in Ho Chi Minh City. In order to achieve this, the research was designed to examine institutional frameworks and arrangements and to explore the perception of water value by water users and stakeholders. The underlying reasons for ineffective management are anchored in fragmented management practices which result from inadequate institutional frameworks and arrangements, inadequate regulations and inappropriate water governance. Weak enforcement of law and insufficient cooperation between government agencies and departments in Ho Chi Minh City and their counterparts in neighbouring provinces also limit management efficacy. The research results show that stakeholders have different perceptions of water resources. Overall, water value has been considered as a social and economic good by both the urban respondents and government officials. However, most urban residents view water as a social good rather than an economic one. Public involvement in the water sector is limited. Most urban dwellers have little understanding and knowledge about the city’s water issues or the available channels to access information on water resources. Many government officials are inadequately trained, poorly qualified, inexperienced and have irrelevant or outdated background knowledge about their field of management. Government respondents did not provide consistent data and information on the water profile because there is no shared common information on water issues in place. Findings from the fieldwork show that decentralisation, privatisation and using rainwater as a potential alternative water source are preferred. Finally, the study proposes a schematic revision of existing management structures and mechanisms between local government agencies. This thesis proposes a model for a water conservation strategy for which the management and use of water resources is aligned with adequate institutional arrangements and effective regulations. Water governance and management of water resources need to work with economic and urbanisation growth. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1331639 / Thesis (Ph.D.) - University of Adelaide, School of Social Sciences, 2008

In 1986, Vietnam opened up the country’s economy by launching the Doi Moi (renovation) policy, which made the process of economic liberalisation possible. Accordingly, Ho Chi Minh City, the country’s biggest city, has undergone rapid growth of population, urbanisation and industrialisation. While achieving remarkable economic growth, the city faces considerable urban environmental challenges. The rapid growth of urbanisation and industry has placed increasing pressure on available freshwater resources, through excessive water use and increasing volumes of untreated wastewater. Firstly, the urban water sector has had to meet growing demand for water use for domestic purposes during the dry season. Secondly, groundwater levels have experienced a substantial drawdown in outlying urban districts as a result of over-abstraction. Thirdly, rapidly expanding industrial activities are causing severe demand on water resources. The city’s major supply sources have developed an alarming level of pollutants discharged by industry. The aim of this thesis is to formulate an integrated approach to the sustainable management of water resources in Ho Chi Minh City. In order to achieve this, the research was designed to examine institutional frameworks and arrangements and to explore the perception of water value by water users and stakeholders. The underlying reasons for ineffective management are anchored in fragmented management practices which result from inadequate institutional frameworks and arrangements, inadequate regulations and inappropriate water governance. Weak enforcement of law and insufficient cooperation between government agencies and departments in Ho Chi Minh City and their counterparts in neighbouring provinces also limit management efficacy. The research results show that stakeholders have different perceptions of water resources. Overall, water value has been considered as a social and economic good by both the urban respondents and government officials. However, most urban residents view water as a social good rather than an economic one. Public involvement in the water sector is limited. Most urban dwellers have little understanding and knowledge about the city’s water issues or the available channels to access information on water resources. Many government officials are inadequately trained, poorly qualified, inexperienced and have irrelevant or outdated background knowledge about their field of management. Government respondents did not provide consistent data and information on the water profile because there is no shared common information on water issues in place. Findings from the fieldwork show that decentralisation, privatisation and using rainwater as a potential alternative water source are preferred. Finally, the study proposes a schematic revision of existing management structures and mechanisms between local government agencies. This thesis proposes a model for a water conservation strategy for which the management and use of water resources is aligned with adequate institutional arrangements and effective regulations. Water governance and management of water resources need to work with economic and urbanisation growth. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1331639 / Thesis (Ph.D.) - University of Adelaide, School of Social Sciences, 2008

In 1986, Vietnam opened up the country’s economy by launching the Doi Moi (renovation) policy, which made the process of economic liberalisation possible. Accordingly, Ho Chi Minh City, the country’s biggest city, has undergone rapid growth of population, urbanisation and industrialisation. While achieving remarkable economic growth, the city faces considerable urban environmental challenges. The rapid growth of urbanisation and industry has placed increasing pressure on available freshwater resources, through excessive water use and increasing volumes of untreated wastewater. Firstly, the urban water sector has had to meet growing demand for water use for domestic purposes during the dry season. Secondly, groundwater levels have experienced a substantial drawdown in outlying urban districts as a result of over-abstraction. Thirdly, rapidly expanding industrial activities are causing severe demand on water resources. The city’s major supply sources have developed an alarming level of pollutants discharged by industry. The aim of this thesis is to formulate an integrated approach to the sustainable management of water resources in Ho Chi Minh City. In order to achieve this, the research was designed to examine institutional frameworks and arrangements and to explore the perception of water value by water users and stakeholders. The underlying reasons for ineffective management are anchored in fragmented management practices which result from inadequate institutional frameworks and arrangements, inadequate regulations and inappropriate water governance. Weak enforcement of law and insufficient cooperation between government agencies and departments in Ho Chi Minh City and their counterparts in neighbouring provinces also limit management efficacy. The research results show that stakeholders have different perceptions of water resources. Overall, water value has been considered as a social and economic good by both the urban respondents and government officials. However, most urban residents view water as a social good rather than an economic one. Public involvement in the water sector is limited. Most urban dwellers have little understanding and knowledge about the city’s water issues or the available channels to access information on water resources. Many government officials are inadequately trained, poorly qualified, inexperienced and have irrelevant or outdated background knowledge about their field of management. Government respondents did not provide consistent data and information on the water profile because there is no shared common information on water issues in place. Findings from the fieldwork show that decentralisation, privatisation and using rainwater as a potential alternative water source are preferred. Finally, the study proposes a schematic revision of existing management structures and mechanisms between local government agencies. This thesis proposes a model for a water conservation strategy for which the management and use of water resources is aligned with adequate institutional arrangements and effective regulations. Water governance and management of water resources need to work with economic and urbanisation growth. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1331639 / Thesis (Ph.D.) - University of Adelaide, School of Social Sciences, 2008