A furosemida é um fármaco de ação diurética e amplamente utilizado em tratamentos de doenças renais, cardíacas e pulmonares. Sua absorção é problemática e de alta variabilidade inter e intraindividual. Este fármaco tem sido classificado como pertencente às classes II (baixa solubilidade e alta permeabilidade) ou IV (baixa permeabilidade e baixa solubilidade) do Sistema de Classificação de Biofarmacêutica (SCB). Em estudos anteriores da equipe de pesquisa, SPRICIGO e colaboradores (2008) e SILVA (2014) desenvolveram complexos de furosemida com hidroxipropil-&#946;-ciclodextrina que permitiram a otimização da solubilidade deste fármaco. Entretanto, dados sobre a sua permeabilidade intestinal, quando complexado, não foram determinados. Somando-se a isto, a literatura apresenta informações distintas em relação a este parâmetro, o que corrobora a importância de se avaliar a permeabilidade deste fármaco. Diversas técnicas têm sido empregadas para a avaliação da permeabilidade intestinal dos fármacos. No presente trabalho empregou-se o modelo de perfusão in situ de passagem tripla, cuja técnica possibilita avaliar a permeabilidade em três segmentos diferentes em um mesmo animal e ainda, apresenta características interessantes, pois trata-se de um método que proporciona, durante todo o experimento, condições mais próximas daquelas encontradas durante o processo in vivo de absorção de fármacos no intestino tais como: suprimento sanguíneo, inervação intacta, preservação das proteínas transportadoras de membranas e presença da camada de muco. O presente trabalho foi dividido nas seguintes etapas: (i) obtenção da furosemida complexada com hidroxipropil-&#946;-ciclodextrina, (ii) caracterização dos fármacos utilizando técnicas de análises térmicas, (iii) estudo de perfusão in situ de passagem tripla nos três segmentos intestinais (duodeno, jejuno e íleo) de ratos machos Wistar na ausência e na presença de inibidores da glicoproteína P e de enzimas metabolizadoras CYP3A4 com posterior análise estatística do impacto da ciclodextrina e inibidores na permeabilidade da furosemida e; (iv) análise histológica das microvilosidades intestinais após o ensaio de perfusão in situ nos três segmentos intestinais. Os valores encontrados em cada segmento para furosemida complexada foram: 8,58 ± 0,002 x 10-5 cm.s-1; 9,15 ± 0,003 x10-5 cm.s-1 e; 8,06 ± 0,002 x 10-5 cm.s-1, respectivamente para duodeno, jejuno e íleo enquanto que para furosemida pura encontraram-se os seguintes: 3,42 ± 0,08 x 10-5 cm.s-1 para duodeno; 3,87 ± 0,11 x 10-5 cm.s-1 para jejuno e 3,08 ± 0,001 x 10-5 cm.s-1 para íleo. Assim sendo, os valores obtidos para a permeabilidade da furosemida complexada foram significativamente superiores (p < 0,05) aos da furosemida pura, sugerindo que, a ciclodextrina pode ter influência no mecanismo de transporte da furosemida, que é via passiva paracelular. Quanto aos mecanismos envolvidos na permeabilidade da furosemida através dos enterócitos, pode-se sugerir que observou-se pouca influência dos inibidores da glicoproteína P (P-gp) e da enzima CYP3A4, sugerindo que não há uma participação importante destes mecanismos em sua absorção intestinal. / Furosemide, which is a diuretic drug, is widely used in heart, kidney and pulmonary disease treatments. The absorption is problematic with high variability inter and intra individuals. This drug has been classified as belonging to class II (low solubility and high permeability) or IV (low permeability and low solubility) of the Biopharmaceutical Classification System (BCS). In previous studies of the research team, Spricigo and colleagues (2008) and Silva (2014) developed complex of furosemide with hydroxypropyl-&#946;-cyclodextrin which allowed the optimization of the solubility of this drug. However, datas concerning it\'s intestinal permeability, when complexed, have not been determined. Addicted to this, the literature shows many information regarding to this parameter, which confirms the importance of the evaluation of the permeability of this drug. Some techniques have been employed in order to evaluate the intestinal permeability of drugs. In the present work, a triple single-pass intestinal perfusion technique was used for three different segments. This technique enables the evaluation of the permeability of different segments in the same animal and also has interesting features such as: it provides during all the experiment conditions closer to those found in in vivo process of a drug absorption in the gut; blood supply; intact innervations; preservation of membrane transporter proteins and presence of mucus layer. This study was divided into the following steps: (i) obtaining furosemide complexed with hydroxypropyl-&#946;-cyclodextrin, (ii) characterization of drugs using techniques of thermal analysis, (iii) perfusion study in situ triple passage in three segments (duodenum, jejunum and ileum) from male Wistar rats in the absence and presence of inhibitors of P-glycoprotein and metabolizing enzymes CYP3A4 and subsequential statistical analysis of the impact of the cyclodextrin and the inhibitors in the permeability of furosemide and (iv) histological analysis of intestinal microvilli after in situ perfusion assay in three segments. The values found in each segment for complexed furosemide were: 8,58 ± 0,002 x 10-5 cm.s-1; 9,15 ± 0,003 x 10-5 cm.s-1; 8,06 ± 0,002 x 10-5 cm.s-1, respectively for duodenum, jejunum and ileum while for pure furosemide, the values were: 3,42 ± 0,08 x 10-5 cm.s-1 to duodenum; 3,87 ± 0,11 x 10-5 cm.s-1 to jejunum and 3,08 ± 0,001 x 10-5 cm.s-1 to ileum. Thus, the values obtained for the permeability of the complexed furosemide were significantly higher (p < 0,05) than those found for pure furosemide, suggesting that the cyclodextrin might have an influence on the transport mechanism of furosemide, which is passive paracellular route. About the mechanisms involved in the permeability of furosemide through the enterocytes, it can be suggested that there was little effect of P-glycoprotein (P-gp) inhibitors and CYP3A4 enzyme, suggesting that there is an important role of these mechanisms in the furosemide intestinal absorption.

High strength nickel-base superalloys have been used in turbine blades for many years because of their superior performance at high temperatures. In such environments superalloys have limited oxidation and corrosion resistance and to solve this problem, protective coatings are deposited on the surface. The positive effect of coatings is based on protecting the surface zone in contact with hot gas atmosphere with a thermodynamically stable oxide layer that acts as a diffusion barrier. During service life, mechanical properties of metallic coatings can be changed due to the significant interdiffusion between substrate and coating. There are also other degradation mechanisms that affect nickel-base superalloys such as low cycle fatigue, thermo-mechanical fatigue and creep. The focus of this work is on a study of low cycle fatigue and out-of-phase thermo-mechanical fatigue behaviour of three uncoated and coated nickel-base superalloys. Polycrystalline IN792 and two single crystals CMSX-4 and SCB were coated with four different coatings; an overlay coating AMDRY997 (NiCoCrAlYTa), a platinum aluminide modified diffusion coating RT22 and two innovative coatings with a NiW interdiffusion barrier in the interface called IC1 and IC3. A low cycle fatigue and thermo-mechanical fatigue device was designed and set-up to simulate service loading of turbine blades and vanes. The low cycle fatigue tests were run at 500oC and 900oC while the thermo-mechanical fatigue tests were run between 250oC and 900oC.To simulate long service life, some coated specimens were exposed at 1050oC for 2000 h before the tests. The main conclusions are that the presence of the coatings is, in most cases, detrimental to LCF lives of the superalloys at 500oC while the coatings do improve the LCF lives of the superalloys at 900oC. Under TMF loading conditions, the coatings have negative effect on the lifetime of IN792. On single crystals, they are found to improve TMF life of the superalloys, especially at lower strains. The tests also indicate that long-term aging influences the fatigue and fracture behaviour of coated superalloys by oxidation and diffusion mechanisms when compared to non-aged specimens. The aged specimens exhibit longer life in some cases and shorter life during other test conditions. Fatigue cracks were in most cases initiated at the surface of the coatings, growing transgranularly perpendicular to the load axis.

Sammanfattning: Syftet med uppsatsen är att undersöka ungdomsarbetslösheten i Örebro kommun utifrån gymnasieelevernas egna åsikter och upplevelser. Min frågeställning ser alltså ut enligt nedan:Vad utmärker ungdomsarbetslösheten i Örebro kommun?                       Hur stor andel av ungdomarna är arbetslösa?                        Vilka drabbas av arbetslösheten? Hur ser gymnasieelever i Örebro kommun på sin framtid inom arbetsmarknaden? Uppsatsen bygger främst på enkäter som två gymnasieklasser svarat på och detta stärks upp av tidigare forskning som jag har ansett som användbar för att kunna svara på min frågeställning. Nedan följer resultatet av min undersökning: I Örebro kommun är det cirka 2 200 ungdomar i åldrarna 18-29 år som är arbetslösa och siffran ser ungefär likadan ut varje år. De ungdomar som drabbas är de som kommer från en familj där en eller båda föräldrarna är eller har varit arbetslösa, om en eller båda föräldrarna är från ett annat land eller om familjen någon gång fått hjälp i form av socialbidrag. Föräldrarnas egen situation spelar mycket stor roll för barnens framtid. Gymnasieeleverna i Örebro kommun ser olika på sin framtid, en stor del av dem är oroliga, dels på grund av den höga ungdomsarbetslösheten, men även för svårigheten att hitta ett jobb, svårigheten att skaffa sig erfarenheterna som krävs för att få ett jobb. Många ungdomar upplever även att gymnasieskolan inte har hjälpt till att förbereda dem inför arbetslivet.

A furosemida é um fármaco de ação diurética e amplamente utilizado em tratamentos de doenças renais, cardíacas e pulmonares. Sua absorção é problemática e de alta variabilidade inter e intraindividual. Este fármaco tem sido classificado como pertencente às classes II (baixa solubilidade e alta permeabilidade) ou IV (baixa permeabilidade e baixa solubilidade) do Sistema de Classificação de Biofarmacêutica (SCB). Em estudos anteriores da equipe de pesquisa, SPRICIGO e colaboradores (2008) e SILVA (2014) desenvolveram complexos de furosemida com hidroxipropil-&#946;-ciclodextrina que permitiram a otimização da solubilidade deste fármaco. Entretanto, dados sobre a sua permeabilidade intestinal, quando complexado, não foram determinados. Somando-se a isto, a literatura apresenta informações distintas em relação a este parâmetro, o que corrobora a importância de se avaliar a permeabilidade deste fármaco. Diversas técnicas têm sido empregadas para a avaliação da permeabilidade intestinal dos fármacos. No presente trabalho empregou-se o modelo de perfusão in situ de passagem tripla, cuja técnica possibilita avaliar a permeabilidade em três segmentos diferentes em um mesmo animal e ainda, apresenta características interessantes, pois trata-se de um método que proporciona, durante todo o experimento, condições mais próximas daquelas encontradas durante o processo in vivo de absorção de fármacos no intestino tais como: suprimento sanguíneo, inervação intacta, preservação das proteínas transportadoras de membranas e presença da camada de muco. O presente trabalho foi dividido nas seguintes etapas: (i) obtenção da furosemida complexada com hidroxipropil-&#946;-ciclodextrina, (ii) caracterização dos fármacos utilizando técnicas de análises térmicas, (iii) estudo de perfusão in situ de passagem tripla nos três segmentos intestinais (duodeno, jejuno e íleo) de ratos machos Wistar na ausência e na presença de inibidores da glicoproteína P e de enzimas metabolizadoras CYP3A4 com posterior análise estatística do impacto da ciclodextrina e inibidores na permeabilidade da furosemida e; (iv) análise histológica das microvilosidades intestinais após o ensaio de perfusão in situ nos três segmentos intestinais. Os valores encontrados em cada segmento para furosemida complexada foram: 8,58 ± 0,002 x 10-5 cm.s-1; 9,15 ± 0,003 x10-5 cm.s-1 e; 8,06 ± 0,002 x 10-5 cm.s-1, respectivamente para duodeno, jejuno e íleo enquanto que para furosemida pura encontraram-se os seguintes: 3,42 ± 0,08 x 10-5 cm.s-1 para duodeno; 3,87 ± 0,11 x 10-5 cm.s-1 para jejuno e 3,08 ± 0,001 x 10-5 cm.s-1 para íleo. Assim sendo, os valores obtidos para a permeabilidade da furosemida complexada foram significativamente superiores (p < 0,05) aos da furosemida pura, sugerindo que, a ciclodextrina pode ter influência no mecanismo de transporte da furosemida, que é via passiva paracelular. Quanto aos mecanismos envolvidos na permeabilidade da furosemida através dos enterócitos, pode-se sugerir que observou-se pouca influência dos inibidores da glicoproteína P (P-gp) e da enzima CYP3A4, sugerindo que não há uma participação importante destes mecanismos em sua absorção intestinal. / Furosemide, which is a diuretic drug, is widely used in heart, kidney and pulmonary disease treatments. The absorption is problematic with high variability inter and intra individuals. This drug has been classified as belonging to class II (low solubility and high permeability) or IV (low permeability and low solubility) of the Biopharmaceutical Classification System (BCS). In previous studies of the research team, Spricigo and colleagues (2008) and Silva (2014) developed complex of furosemide with hydroxypropyl-&#946;-cyclodextrin which allowed the optimization of the solubility of this drug. However, datas concerning it\'s intestinal permeability, when complexed, have not been determined. Addicted to this, the literature shows many information regarding to this parameter, which confirms the importance of the evaluation of the permeability of this drug. Some techniques have been employed in order to evaluate the intestinal permeability of drugs. In the present work, a triple single-pass intestinal perfusion technique was used for three different segments. This technique enables the evaluation of the permeability of different segments in the same animal and also has interesting features such as: it provides during all the experiment conditions closer to those found in in vivo process of a drug absorption in the gut; blood supply; intact innervations; preservation of membrane transporter proteins and presence of mucus layer. This study was divided into the following steps: (i) obtaining furosemide complexed with hydroxypropyl-&#946;-cyclodextrin, (ii) characterization of drugs using techniques of thermal analysis, (iii) perfusion study in situ triple passage in three segments (duodenum, jejunum and ileum) from male Wistar rats in the absence and presence of inhibitors of P-glycoprotein and metabolizing enzymes CYP3A4 and subsequential statistical analysis of the impact of the cyclodextrin and the inhibitors in the permeability of furosemide and (iv) histological analysis of intestinal microvilli after in situ perfusion assay in three segments. The values found in each segment for complexed furosemide were: 8,58 ± 0,002 x 10-5 cm.s-1; 9,15 ± 0,003 x 10-5 cm.s-1; 8,06 ± 0,002 x 10-5 cm.s-1, respectively for duodenum, jejunum and ileum while for pure furosemide, the values were: 3,42 ± 0,08 x 10-5 cm.s-1 to duodenum; 3,87 ± 0,11 x 10-5 cm.s-1 to jejunum and 3,08 ± 0,001 x 10-5 cm.s-1 to ileum. Thus, the values obtained for the permeability of the complexed furosemide were significantly higher (p < 0,05) than those found for pure furosemide, suggesting that the cyclodextrin might have an influence on the transport mechanism of furosemide, which is passive paracellular route. About the mechanisms involved in the permeability of furosemide through the enterocytes, it can be suggested that there was little effect of P-glycoprotein (P-gp) inhibitors and CYP3A4 enzyme, suggesting that there is an important role of these mechanisms in the furosemide intestinal absorption.

I det här masterarbetet har jag musik för tre olika musikaliska sammanhang; elektronisk pop i samarbete med kurskollega, kortfilmsmusik i samarbete med filmregissör och musik till statistik i samarbete med SCB. De tre delprojekten rör sig inom olika musikaliska uttryck och har olika instrumentering. En frågeställning som genomsyrar tankegångarna i textens reflektioner är vilka likheter i fråga om uttryck och processer de tre olika verken har även om de har olika estetiska ramar och förutsättningar. Arbetet har genomförts i syfte att undersöka hur de olika inriktningarna påverkar och influerar mig som musikskapare. Går det att se hur flödet av influenser ser ut? Vidare tar jag upp olika föreställningar om att som enskild musikskapare arbeta inom olika inriktningar och medieuttryck. Metoden har utgjorts av kompositionsarbete, improvisation, musikproduktion och studioinspelningar. Resultatet av arbetet är tre olika musikverk varav två; kortfilmsmusik och musik till statistik, är en sorts beställningsverk med målet att spelas i den offentliga kulturen. / In this master dissertation, I have created music for three different musical contexts; electronic pop in collaboration with a program colleague from KMH, short film music in collaboration with film director and finally music to statistics in collaboration with Statistics Sweden (SCB. The three sub-projects move within different musical expressions and have different instrumentation. An issue that is central in the reflections of the text is what similarities in terms of expression and processes the three different works have, although they have different aesthetic frameworks. The work aims to find out how the different directions affect and influence me as a music creator. Can you see what the flow of influences looks like? Furthermore, I discuss different conceptions of working as an individual music creator in different directions and media expressions. The method has consisted of composition work, improvisation, music production and studio recordings. The result of the work is three different pieces of music, two of which; short-film music and music for statistics, is a kind of commissioned work with the goal of being played in the public culture.

This Thesis work is part of course work for the Masters Program in Data Science at LTU.  The focus of this work is mainly to review the literature published to identify state-of-art methodologies applied to predict short-term electricity consumption. This includes the exploration of features and models as well-as the discussion of the results attained. Identify opportunities to improve the forecast results for southern Elområde(bidding area)4, Sweden. The application of different modern methods to forecast electricity consumption has been studied and experimented with. This work adapted the CRISP-DM, a Data Science methodology.

No description available.

High step-down dc/dc converters are widely adopted in a variety of areas such as industrial, automotive, and telecommunication. The 48 V power delivery system becomes increasingly popular for powering high-current and low-voltage chips. The Series-Capacitor Buck (SCB) converter doubles the duty ratio and equalizes the current between the two phases. Hard switching has hindered efforts to reduce volume via increased switching frequency, although a monolithically integrated SCB converter has boosted current density. A Series-Resonator Buck (SRB) converter is realized by adding a resonant tank in series with the series capacitor Cs. All switches turn on at zero-voltage (ZVOn), and the low-side switches turn off at zero-current (ZCOff). The design of the SRB converter includes characterizing the design variables' impacts on the converter performances and designing low-loss resonant components as the series resonator. The Series-Resonator Buck converter belongs to the class of quasi-resonant converters. Its resonant frequency is higher than the switching frequency, and its waveforms are quasi-sinusoidal. This work develops a steady-state model of the SRB converter to calculate voltage gain, component peak voltages, and resonant inductor peak current. Each switching cycle is modeled based on the concept of generalized state-space averaging. The soft-switching condition of the high-side switches is derived. The ZVS condition depends on the normalized control variable and the load condition. The gain equation models the load-dependent characteristic and the peak gain boundary. The theoretical peak voltage gain of the SRB converter is smaller than the maximum gain of the SCB converter. A smaller normalized load condition results in a larger peak voltage gain of the SRB converter. The large-signal model of the SRB converter characterizes the low-frequency behavior of the low-pass filters with the series capacitor and the high-frequency behavior of the resonant elements. A design recommendation of t_off f_r<0.5 is suggested to avoid the oscillation between the series capacitor Cs and the output inductors Lo. In other words, the off-duration of the low-side switches is less than half of 1/fr, and therefore the negative damping effect from the parallel resonant tank to the vCs response is reduced. The transfer functions of the SRB converter are presented and compared with those of the SCB converter. The series resonator brings in an extra damping effect to the response of output capacitor voltage. The understanding of the analytical relationships among the resonant tank energy, voltage gain, and component stresses was utilized to guide the converter design of the converter's parameters. A normalized load condition at √2 minimizes the stresses of the series resonator by balancing the peak energy in the resonant elements Lr and Cr. The f_s variation with voltage gain M is less than 10%. The non-resonant components C_s, L_oa, and L_ob are designed according to the specified switching ripples. The ac winding loss complicates the winding design of a resonant inductor. This work replaces the rectangular window with a rhombic window to reduce the eddy current loss caused by the fringing effect. The window ratio k_y is added as a design variable. The impacts of the design variables on the inductance, core loss, and winding loss are discussed. The air-gap length l_g is designed to control the inductance. A larger k_y design results in a short inductor length l_c and a smaller winding loss. The disadvantages include a smaller energy density design and a larger core loss due to the smaller cross-sectional area. In the design example presented in the thesis, the presence of the rhombic shape increases the gap-to-winding distance by two times, and also reduces the y-component of the magnetic field by a factor of two. The total inductor loss is reduced by 56% compared to a conventional design with a rectangular winding window while keeping the same inductance and the same inductor volume. This dissertation implements a resonator, replacing the series capacitor, in an SCB converter. The resultant SRB converter shows a 30% reduction in loss and a 50% increase in power density. The root cause of the divergence issue is identified by modeling the negative damping effect caused by resonant elements. The presented transient design guideline clears the barriers to closed-loop regulation and commercialization of the SRB converter. This work also reshapes winding windows from rectangle to rhombus which is a low-cost change that reduces magnetic loss by half. The theoretical analysis and design procedures are demonstrated in a 200 W prototype with 7% peak efficiency increase compared to the commonly used 30 W commercial SCB product. / Doctor of Philosophy / High step-down dc/dc converters are widely adopted in a variety of areas such as industrial, automotive, and telecommunication areas. The 48 V power delivery system becomes increasingly popular for powering high-current and low-voltage chips. The Series-Capacitor Buck (SCB) converter doubles the duty ratio and equalizes the current between the two phases. Hard switching has hindered efforts to reduce volume via increased switching frequency although a monolithically integrated SCB converter has boosted current density. A Series-Resonator Buck (SRB) converter is realized by adding a resonant tank in series with the series capacitor Cs. All switches turn on at zero-voltage (ZVOn), and the low-side switches turn off at zero-current (ZCOff). The challenges to designing the SRB converter include characterizing the design variables' impacts on the converter performances and designing low-loss resonant components as the series resonator. The resultant SRB converter shows a 30% reduction in loss and a 50% increase in power density. The root cause of the divergence issue is identified by modeling the negative damping effect caused by the resonant elements. The presented transient design guideline clears the barriers of closed-loop regulation and commercialization of the SRB converter. This work also reshapes winding windows from rectangle to rhombus, which is a low-cost change that reduces magnetic loss by half. The theoretical analysis and design procedures are demonstrated in a 200 W prototype with 7% peak efficiency increase compared to the commonly used 30 W commercial SCB product.