An investigation into various elements influencing cycle times, payloads and utilization; the three key factors determining overall Heavy Mining Equipment efficiency.

Hot melt extrusion has attracted recent interest from the pharmaceutical industry and academia as an innovative drug delivery technology. This novel technique has been shown to be a viable and robust method for preparing different drug delivery systems including pellets, implants, tablets, capsules and granules. The aim of this research was to understand hot melt extrusion processing and explore its pharmaceutical applications. Two applications of hot melt extrusion (HME) have been investigated to improve the properties of poorly soluble thermolabile drugs; polymeric solid dispersions and solid state polymorphic transformation. HME is a solvent free, continuous and readily scalable technique which is increasingly being considered as a viable alternative to conventionally used batch techniques. However, the high temperature and shear forces imparted by the extrusion process can limit its applications with heat sensitive active pharmaceutical ingredients (APIs). Artemisinin was selected as a model drug which being thermolabile in nature and possesses processing challenges to processing HME. A low Tg amphiphillic copolymer, Soluplus® was selected as a matrix material. Drug-polymer compatibility was studied using rotational rheometry and thermal characterisation. The drug was found to be completely dissolved within the polymer, although some discolouration of the mixture was observed, indicating degradation of the API. The addition of a small percentage of citric acid to the formulation was found to prevent this degradation by increasing the pH. The dissolution profile of the formulation was approximately five times higher compared to that of the pure drug. The pharmacokinetic study was carried out using Albino rats to calculate bioavailability. The area under plasma concentration time curve (AUC0-24hr) and peak plasma concentration (Cmax) were four times higher for the prepared solid dispersion compared to that of pure artemisinin. Extruded solid dispersions were found to be amorphous in nature and maintained stability for 2 years. A second route to improving the solubility of poorly soluble APIs was also investigated. It was found that under carefully controlled conditions, high temperature extrusion (HTE) could be used to achieve polymorphic transformation with a number of APIs. This solvent-free continuous process was demonstrated with artemisinin, piracetam, carbamazepine and chlorpropamide. Artemisinin was used as a detailed case study of stability, solvent mediated transformation and mechanism of polymrophic transformation during extrusion, using computational modelling and model shear flows. At high temperature, phase transformation from orthorhombic to triclinic crystals was found to occur via the vapour phase. Under mechanical stress the crystalline structure was disrupted, leading to new surfaces being continuously formed and exposed to high temperatures; thus accelerating the transformation process. Polymorphic transformation during HTE was found to comprise three stages; i) preheating and conveying; ii) vapour phase transformation and size reduction and iii) continuous transformation and agglomeration. The triclinic form showed four times greater dissolution rate as compared to the orthorhombic form. The triclinic form showed two fold increase in bioavailability in Albino rats.

Hot melt extrusion has attracted recent interest from the pharmaceutical industry and academia as an innovative drug delivery technology. This novel technique has been shown to be a viable and robust method for preparing different drug delivery systems including pellets, implants, tablets, capsules and granules. The aim of this research was to understand hot melt extrusion processing and explore its pharmaceutical applications. Two applications of hot melt extrusion (HME) have been investigated to improve the properties of poorly soluble thermolabile drugs; polymeric solid dispersions and solid state polymorphic transformation. HME is a solvent free, continuous and readily scalable technique which is increasingly being considered as a viable alternative to conventionally used batch techniques. However, the high temperature and shear forces imparted by the extrusion process can limit its applications with heat sensitive active pharmaceutical ingredients (APIs). Artemisinin was selected as a model drug which being thermolabile in nature and possesses processing challenges to processing HME. A low Tg amphiphillic copolymer, Soluplus® was selected as a matrix material. Drug-polymer compatibility was studied using rotational rheometry and thermal characterisation. The drug was found to be completely dissolved within the polymer, although some discolouration of the mixture was observed, indicating degradation of the API. The addition of a small percentage of citric acid to the formulation was found to prevent this degradation by increasing the pH. The dissolution profile of the formulation was approximately five times higher compared to that of the pure drug. The pharmacokinetic study was carried out using Albino rats to calculate bioavailability. The area under plasma concentration time curve (AUC0-24hr) and peak plasma concentration (Cmax) were four times higher for the prepared solid dispersion compared to that of pure artemisinin. Extruded solid dispersions were found to be amorphous in nature and maintained stability for 2 years. A second route to improving the solubility of poorly soluble APIs was also investigated. It was found that under carefully controlled conditions, high temperature extrusion (HTE) could be used to achieve polymorphic transformation with a number of APIs. This solvent-free continuous process was demonstrated with artemisinin, piracetam, carbamazepine and chlorpropamide. Artemisinin was used as a detailed case study of stability, solvent mediated transformation and mechanism of polymrophic transformation during extrusion, using computational modelling and model shear flows. At high temperature, phase transformation from orthorhombic to triclinic crystals was found to occur via the vapour phase. Under mechanical stress the crystalline structure was disrupted, leading to new surfaces being continuously formed and exposed to high temperatures; thus accelerating the transformation process. Polymorphic transformation during HTE was found to comprise three stages; i) preheating and conveying; ii) vapour phase transformation and size reduction and iii) continuous transformation and agglomeration. The triclinic form showed four times greater dissolution rate as compared to the orthorhombic form. The triclinic form showed two fold increase in bioavailability in Albino rats.

Late-season Bunch Stem Necrosis (BSN) is observed as a necrosis of the cluster stem (rachis) that leads to shriveling of berries on the affected portion of the cluster. Field experiments were conducted over three years at two vineyards in northern Virginia to examine relationships between specific nutrients and the incidence of BSN of Cabernet Sauvignon grapevines. Nutrients, used alone or in combination, included nitrogen, magnesium, and calcium. During the 1997 and 1998 seasons at Leesburg vineyard, applications of nitrogen, magnesium, and calcium produced little change in bloom-time petiole mineral concentration. Fertilizer treatments appeared to have no effect on BSN incidence, but the incidence of BSN was less than or equal 1% in the control plots each year. During the 1996 season at Winchester vineyard, bloom-time leaf petiole and véraison rachis nitrogen concentration of unfertilized (control) vines were 0.80% and 1.16%, respectively. The corresponding control BSN incidence was 41% at harvest time. Application of nitrogen fertilizer at 112 kg/ha actual nitrogen increased bloom-time leaf petiole and véraison cluster stem nitrogen concentration to 1.85% and 2.18%, respectively. The corresponding BSN incidence was reduced to 14% at harvest time. BSN symptoms were not as pronounced during the 1997 season; however, all treatments, including the control plots, had elevated nitrogen levels in 1997. During the 1998 season, bloom-time leaf petiole and véraison rachis nitrogen concentration of unfertilized vines were 0.88% and 0.98%, respectively. The corresponding BSN incidence was 23% at harvest time. Application of nitrogen fertilizer again increased bloom-time leaf petiole and véraison rachis nitrogen concentration to 1.18% and 1.34%, respectively. Corresponding BSN was reduced to 3% at harvest time. Magnesium and calcium had no impact on BSN incidence; however, BSN symptoms were reduced when either was combined with nitrogen fertilizer. The relationship between mineral nutrition and BSN incidence at Leesburg was inconclusive. The BSN of Cabernet Sauvignon at Winchester was, however, positively associated with depressed bloom-time petiole total nitrogen concentrations. Véraison rachis analysis consistently revealed an increase in nitrogen concentration due to application of nitrogen fertilizer. Véraison tissue analysis may be a good diagnostic tool of vine nitrogen status. Magnesium and calcium appeared not to be involved in the disorder. The results illustrate that BSN-prone vineyards should be individually examined for nutrient imbalance or other stresses that may be contributing to BSN. / Master of Science

Esse estudo visa testar a eficiência informacional dos mercados acionários brasileiro e mexicano, através do desenvolvimento de um estudo de eventos. Para viabilização do estudo, o mercado brasileiro será representado pela BOVESPA - Bolsa de Valores de São Paulo e o mercado mexicano pela BMV - Bolsa Mexicana de Valores. Especificamente, esses mercados serão representados pelas ações de empresas que participaram da composição das carteiras teóricas dos Índices IBOVESPA e IpyC (Índice de Precios y Cotizaciones) durante todo o período compreendido entre Janeiro de 2001 e Janeiro de 2006. Foram analisadas as reações dos retornos das ações nesses mercados nos dias próximos às datas das divulgações de resultados trimestrais pelas empresas em busca de evidências de ineficiências. Os resultados encontrados mostraram indícios de eficiência informacional quando as empresas foram consideradas individualmente e indícios de ineficiência informacional quando considerada carteira toda. / This study aims to test the informational efficiency of the Brazilian and Mexican stock markets, through the development of an event study. For this purpose, BOVESPA, the Sao Paulo Stock Exchange will represent the Brazilian stock market while the Mexican Stock Exchange (BMV) will represent the Mexican stock market. Specifically, these markets will be represented by the company stocks that participated of the composition of their stock market indexes, IBOVESPA (BOVESPA Index) and IPyC (Mexican Stock Exchange Index), during the period of January 2001 through January 2006. Stock prices were analyzed for the days around the quarterly results release dates, searching for inefficiency evidence in these markets. The results show signs of information-efficiency when considering each company and information inefficiency when considering the market portfolio.

Esse estudo visa testar a eficiência informacional dos mercados acionários brasileiro e mexicano, através do desenvolvimento de um estudo de eventos. Para viabilização do estudo, o mercado brasileiro será representado pela BOVESPA - Bolsa de Valores de São Paulo e o mercado mexicano pela BMV - Bolsa Mexicana de Valores. Especificamente, esses mercados serão representados pelas ações de empresas que participaram da composição das carteiras teóricas dos Índices IBOVESPA e IpyC (Índice de Precios y Cotizaciones) durante todo o período compreendido entre Janeiro de 2001 e Janeiro de 2006. Foram analisadas as reações dos retornos das ações nesses mercados nos dias próximos às datas das divulgações de resultados trimestrais pelas empresas em busca de evidências de ineficiências. Os resultados encontrados mostraram indícios de eficiência informacional quando as empresas foram consideradas individualmente e indícios de ineficiência informacional quando considerada carteira toda. / This study aims to test the informational efficiency of the Brazilian and Mexican stock markets, through the development of an event study. For this purpose, BOVESPA, the Sao Paulo Stock Exchange will represent the Brazilian stock market while the Mexican Stock Exchange (BMV) will represent the Mexican stock market. Specifically, these markets will be represented by the company stocks that participated of the composition of their stock market indexes, IBOVESPA (BOVESPA Index) and IPyC (Mexican Stock Exchange Index), during the period of January 2001 through January 2006. Stock prices were analyzed for the days around the quarterly results release dates, searching for inefficiency evidence in these markets. The results show signs of information-efficiency when considering each company and information inefficiency when considering the market portfolio.

Bakgrund Medicinska gaser är kalla och torra, därav behövs de befuktas och värmas för att inte åsamka skador på lungorna hos patienter som behandlas i respirator. De vanligaste metoderna är aktiv och passiv befuktning, så kallad heated humidification (HH) och heat and moisture exchanger (HME filter). Syfte Att sammanfatta befintlig forskning om för- och nackdelar samt skillnader som framkommit med aktiv respektive passiv befuktning i respirationsvård på intensivvårdsavdelning. Metod En systematiskt genomförd litteraturstudie med narrativ summering. Sökningar gjordes i databaserna CINAHL, PubMed samt Cochrane. Nio vetenskapliga artiklar med kvantitativ ansats mellan tidsintervallet 2012–2022 inkluderades utifrån PICO. Kvalitetsgranskning utfördes med validerade granskningsmallar från Joanna Briggs Institute. Huvudresultat HH tillförde mindre mekaniskt dead space för intuberade som gav bättre PaCO2 värden, vilket är specifikt fördelaktigt för patienter med acidos. Den metoden är dock mer kostsam och fungerar ej lika effektivt vid stigande rumstemperatur och direkt solljus på apparaturen. Den kräver därav mer kontroller samt tillsyn vid dessa förhållanden. Vid non-invasiv behandling och tracheostomi i respirator ger HME filter inte sämre PaCO2 värden eftersom det större mekaniska dead space den tillför inte har samma negativa effekt vid dessa behandlingar och tillstånd. Den inkrementella kostnaden är bättre för HME filter, men huruvida den ger upphov till fler incidenser av tubocklusion är ej klarlagt. Slutsats Båda befuktningsmetoderna har klara fördelar och nackdelar, därav är det fördelaktigt att ha tillgång till båda metoderna på intensivvårdsavdelningar tillsammans med en tydlig rutin om när metoderna skall användas till patienten. / Background Medical gases are cold and dry, therefore the need for adding humid and heat is highly important, otherwise they can cause damage at the lungs in patients undergoing mechanical ventilation. The most common methods are active and passive humidification so called heated humidification (HH) and heat and moisture exchanger (HME). Aim Summarize existing research on advantages, drawbacks and differences that have emerged with active and passive humidification in respiratory care in the intensive care unit. Method A systematic conducted literature review with a narrative summary to compile the results. Searches were made on the databases CINAHL, PubMed and Cochrane. Nine scientific articles with a quantitative approach between 2012-2022 were included based on PICO. Quality review was performed with validated review templates from Joanna Briggs Institute. Results HH provided less mechanical dead space for intubated patients which provided better PaCO2 values, specifically beneficial for patients with acidosis. However, this method is more expensive and does not work as effectively with increasing room temperature and direct sunlight on the equipment. It therefore requires more controls and supervision in presence of these conditions. In patients undergoing non-invasive mechanical ventilation and in patients with tracheostomy who are mechanically ventilated, HME filters do not give higher PaCO2 values. ​​The increased mechanical dead space it adds does not have the same negative effect in these treatments and conditions. The incremental cost is better for HME filters, but whether it gives rise to more incidences of tube occlusion is not clear. Conclusion Both humidification methods have clear advantages and drawbacks, hence it is advantageous to have access to both methods at intensive care units together with a clear routine about when the methods should be used.

Vid idrott utomhus i minusgrader utsätts andningssystemet för stora påfrestningar, luften är kall och torr vilket skadar och irriterar luftvägarna. För att undvika det kan man använda fukt- och värmeväxlare (HME). Dagens produkter har dålig passform vilket leder till läckage av luft. Syftet med projektet är att fler vinteratleter ska vilja använda HME och därmed förebygga förekomsten av andningssjukdomar. De tre delmålen för projektet är att tillverka minst en prototyp, den tillverkade prototypen ska ha bättre passform än dagens produkter och minst en lösning för slemhantering ska presenteras. Med hjälp av litteraturstudier lades en kunskapsgrund inom området. Verktyg som branschanalys, intressentanalys och målspecifikation gjorde konceptgenereringen rikare. Största delen av projektet lades i prototyptillverkning. Två prototyper kunde till slut presenteras, Winterflow och Winterflow Pro. Det är två additivt tillverkade masker med tillhörande filter som konstruerats i ett datormodelleringsprogram. Prototyperna validerades med hjälp av användartester. Prototyperna upplevs för en del testpersoner ha bättre passform än dagens produkter, men ingen statistisk signifikant skillnad gick att bevisa. Målen och syftet uppfylldes delvis och en bredare grund för vidare forskning fastställdes. / When performing sports outdoors during sub-zero conditions the respiratory system is exposed to great stress, the air is cold and dry, which damages and irritates the airways. To avoid this, the athletes can use heat and moisture exchanging devices (HME). Today’s products have a poor fit, which leads to leakage of the air. The aim of the project is to increase the usage of HME for winter athletes and thereby prevent the occurrence of respiratory diseases. The three objectives for the project are to manufacture at least one prototype, the prototype shall have a better fit than today’s products and at least one solution for handling saliva matter shall be presented. By carrying out literature studies, a foundation of knowledge was laid in the area. With the help of different analysis and tools, the concept generation were richer, resulting in more solutions. The main part of the project was put into prototyping. Two prototypes could be presented at the end, Winterflow and Winterflow Pro. Two additive manufactured masks with associated filters constructed in a computer modelling program. The prototypes were validated by user tests. The prototypes were perceived by some testers to have a better fit than today’s products, but no statistically significance could be proven. The aim and objectives were partly met, and a broader foundation of knowledge for further research was established. / <p>Betygsdatum 2023-06-07</p>

Cupriavidus metallidurans CH34 est une béta-protéobactérie, résistante aux métaux lourds, isolée des sédiments d'une usine de métallurgie non-ferreuse en Belgique. Le génome de cette bactérie contient un chromosome (3.6 Mb), un mégaplasmide (2.6 Mb) et deux plasmides pMOL28 (171 kb) et pMOL30 (234 kb) déjà connus pour porter des gènes de résistance aux métaux lourds. Nous avons d'abord fait le catalogue des gènes impliqués dans la résistance aux métaux lourds et, ensuite, cherché à mesurer leur expression par deux approches transcriptomiques : RT-PCR et puces à ADN. L'analyse du génome montre au moins 170 gènes relatifs à la résistance aux ions métalliques localisés sur les 4 réplicons, principalement sur les deux plasmides. Ces gènes codent essentiellement pour des systèmes d'efflux tel que les HME-RND (transport chimioosmotique avec flux de protons à contresens), les ATPases de type P ou encore pour le système de résistance aux ions Cu(II). Dans le génome de C. metallidurans, nous avons identifié 13 opérons qui codent pour des systèmes HME-RND, seuls trois, localisés sur les plasmides, sont surexprimés en présence de métaux lourds. Huit gènes codent pour des ATPases de type P, dont deux appartiennent à une classe dont les substrats ne sont pas métalliques. Deux ATPases appartiennent à une famille spécialisée pour l'efflux du Cu(II) et les quatre autres à une autre grande famille impliquée dans l'efflux des ions Cd(II), Pb(II) et Zn(II). Les analyses transcriptomiques montrent la surexpression des deux premières classes d'ATPases P en présence des métaux lourds. La mutagenèse du gène zntA (mégaplasmide), codant pour l'une des ATPases, provoque une diminution de la viabilité en présence de Zn(II), Cd(II) et dans une moindre mesure de Pb(II), Tl(I) et Bi(III). Sur pMOL30, la résistance au cuivre implique un groupe de 19 gènes cop codant pour la résistance au cuivre au niveau du périplasme et du cytoplasme, et vraisemblablement pour une forme de stockage du cuivre essentiel. Ces 19 gènes sont surexprimés en présence de cuivre, mais une quinzaine de gènes proches semblent aussi requis pour une expression optimale de la résistance au cuivre. L'annotation des plasmides a mis en évidence la parenté du plasmide pMOL28 avec le plasmide pHG1 (hydrogénotrophie, fixation du CO2) de C. eutrophus H16 et le plasmide pSym (fixation de l'azote) de C. taiwanensis, et chez pMOL30, la présence de deux îlots génomiques concentrant la plupart des résistances aux métaux lourds. Les puces montrent la surexpression de 83 sur 164 gènes dans pMOL28, et de 143 sur 250 gènes dans pMOL30. Elles montrent aussi que les gènes présents sur les deux plasmides sont davantage surexprimés que ceux localisés sur les deux mégaréplicons. Parmi les gènes surexprimés les plus intéressants du plasmide pMOL30, il faut mentionner des transposases tronquées et des gènes impliqués dans la synthèse des membranes (glycosyltransférases). L'analyse de l'expression des gènes plasmidiens de résistance aux métaux lourds montre la surexpression en présence de plusieurs ions métalliques ajoutés indépendamment et pas seulement par les substrats métalliques de ces opérons, ce qui suggère l'intervention de deux types de régulation dont les gènes correspondants sont aussi localisés sur le chromosome et le mégaplasmide. Ce travail met en évidence la spécialisation de la bactérie dans la réponse à un grand spectre de concentrations de métaux lourds, jusqu'à la limite majeure de la toxicité observée pour les bactéries mésophiles hétérotrophes. Cette spécialisation correspond bien aux biotopes industriels de divers continents dans lesquels on l'a trouvée.

Bacteria have evolved sophisticated cellular transport mechanisms to maintain metal homeostasis to not only utilize metals as important cofactors but also to evade the toxicity of these ions. The delicate balance is maintained by several homeostatic mechanisms that range from active cytoplasmic export, modification, sequestration, and periplasmic detoxification of toxic metals to the extracellular milieu. One mechanism involves active periplasmic extrusion of toxic substrates via a transmembrane spanning tripartite protein complex. The mechanism of substrate binding and subsequent efflux has yet to be elucidated. However, genetic, comparative genomic, biochemical, and functional analyses of the components of the heavy-metal efflux family have allowed the development of proposed models for a substrate transport pathway. The goals of this research were to identify the roles these systems play and to further characterize these systems on a molecular level to ultimately understand the mechanism of substrate transport. Elucidating a transport pathway in metal transporters allows for the development of a revised working model, which ultimately can have implications for antimicrobial drug development.