En la actualidad, la gestión de riesgos de calidad es un tema de gran importancia en todas las organizaciones. Sus principios, que son eficazmente utilizados en diversos campos, también están siendo aplicados, de manera limitada, en la industria farmacéutica; a pesar de que la fabricación y la utilización de medicamentos implican algún tipo de riesgo. En la industria farmacéutica nacional es conocido que la tecnología utilizada para la fabricación de medicamentos está un poco desactualizado; por ende, los riesgos presentes, en sus distintas etapas de fabricación, pueden influir en directamente en los atributos críticos de calidad (CQA´s) y en la salud del paciente. Es por esta razón que nos propusimos gestionar los riesgos presentes en las etapas de secado de excipientes y envasado de polvos para suspensión oral a través de dos metodologías: Gestión de riesgos y Lean Six sigma (Lean manufacturing, metodología DMAIC) con el objetivo de identificar, mejorar, y controlar los factores que representen desperdicios o riesgos en los procesos de secado y envasado. Los resultados obtenidos en la siguiente investigación demuestran que la utilización de herramientas Lean Six-Sigma pueden ser utilizados para la reducción o eliminación de riesgos presentes en ambientes de producción farmacéutica, mejoran la eficiencia de los procesos incrementando la disponibilidad y rendimiento de los equipos; así como, aumentan la capacidad de proceso. Estas mejoras permiten reducir los riesgos asociados a estas operaciones obteniendo un proceso más seguro y eficiente. Palabras clave: Gestión de riesgo, Lean Manufacturing, Six-sigma, CQA´s, eficiencia, disponibilidad, capacidad / --- At present, the quality risk management is a major issue in all organizations. Its principles, which are effectively used in various fields are also being applied in a limited way, in the pharmaceutical industry; although the manufacturing and use of drugs involve some risk. In the domestic pharmaceutical industry it is known that the technology used for manufacturing drugs is a bit outdated; therefore, the risks involved, at various stages of production can influence directly critical quality attributes (CQA's) and patient health. It is for this reason that we set out to manage the risks in the drying stages of excipients and packaging of powder for oral suspension through two methodologies: Risk Management and Lean Six Sigma (Lean manufacturing, DMAIC methodology) with the aim of identifying, improve, and control the factors that represent waste or risks in drying and packaging. The results obtained in the following research showing that the use of Lean Six Sigma tools can be used to reduce or eliminate risks involved in pharmaceutical production environments, improve process efficiency by increasing the availability and performance of equipment; and increase the processing capacity. These improvements can reduce the risks associated with these operations to obtain a safer and more efficient process Keywords: risk management, Lean Manufacturing, Six Sigma, CQA´s, efficiency, availability, capacity / Tesis

The transition metal complexes cyclopentadienylrhenium tricarbonyl [CpRe(CO)3, Cp = cyclopentadienyl] and (isopropylcyclopentadienyl)rhenium tricarbonyl [(i-PrCp)Re(CO)3, i-Pr = isopropyl] were photolysed in alkanes at low temperature and the resulting alkane complexes, of the general formula Cp'Re(CO)2(alkane) (Cp' = Cp or (i-PrCp)), were studied using NMR spectroscopy. Characteristic proton chemical shifts (δ) and couplings (3JHH) were observed for alkane complexes of several linear, branched and cyclic alkanes of up to eight carbons. Alkanes with chemically distinct methyl (CH3) and/or methylene (CH2) units were observed alternatively binding through each unit to rhenium. No bound methine unit was observed. Large C-H coupling constants (1JCH) were observed for protons of several bound CH3 and CH2 units, indicating the bound C-H is intact. These species are, thus, alkane sigma (σ) complexes, wherein the alkane has an agostic (M-H-C, 3 centre 2 electron) interaction with the rhenium centre. The CH3 binding mode of (i-PrCp)Re(CO)2(1-pentane) was elucidated; sequential deuteration in the bound CH3 revealed an equilibrium isotope effect (EIE) in the remaining proton/s, confirming that only one C-H has an agostic interaction with rhenium at any instant . NMR parameters δ(1H) (-8.22), δ(13C) ( 42.4) and 1JCH (85 Hz) for the complexed C-H reveal it is unequivocally intact and yet strongly interacting with the rhenium centre, hallmarks for the agostic interaction. Intramolecular exchange was identified between pentane complex isomers Cp'Re(CO)2(1-pentane), Cp'Re(CO)2(2-pentane) and Cp'Re(CO)2(3-pentane). Equilibrium constants were determined, revealing a preference for CH2 binding over CH3. The inequivalent hydrogens found in methylene groups of cyclohexane at low temperature permitted simultaneous observation of axial and equatorial C-H protons of a bound CH2 in CpRe(CO)2(cyclohexane); an EIE, upon deuteration, indicated rapid exchange between complexed C-H bonds in the bound CH2 unit. The rhenium centre was found to prefer complexation of the axial C-H bond, over the equatorial, with K ~2.9. Intermolecular exchange of alkane ligands with free solvent was directly observed, in the competitive complexation of the [CpRe(CO)2] fragment to different alkanes in binary mixtures. The preference cyclohexane > cyclopentane > pentane > isobutane was established and equilibrium constants determined. The kinetics were followed by NMR and modelled, revealing rate constants; decay rates were also determined.

<p>Lars Höglund AB is one of Scandinavia’s most qualified manufacturers of sheet metal products and provides custom designed products of very detailed precision. One of the main methods of manufacturing is laser cutting. When Lars Höglund AB signed up a new customer, with high demands in tolerances for the products, Lars Höglund AB thought it would be necessary to know the capability of the laser cutting machine. Also the process of how to retrieve this capability was interesting.</p><p> </p><p>The capability will be researched for the following elements:</p><p> </p><ul type="disc"><li>Cutting right angles in squares with a corner radius of 1 mm</li><li>Cutting corners which are not right angle</li><li>Cutting of circles with constant radius</li></ul><p> </p><p>Measurements were made on 150 pieces of sheet metal details, which had been cut out by the machine.  The data from the measurements where later used to study the capability. The capability study includes such things as calculations of capability indexes C_p and C_pk, the calculations are based on histograms and lean-mean-curves, constructed from the measurement data. The capability of the laser cutting machine was high except for some elements. Those elements with minor capability were the cutting of corner two and three for the rectangles which had a smaller radius than expected, side X for the triangles which were too long and also the diameter of the circles were too big. Advices on how to correct the faults have been given if Lars Höglund AB wants to further more improve the capability of the machine.</p>

We discuss the target space pseudoduality in supersymmetric sigma models on symmetric spaces. We first consider the case where sigma models based on real compact connected Lie groups of the same dimensionality and give examples using three dimensional models on target spaces. We show explicit construction of nonlocal conserved currents on the pseudodual manifold. We then switch the Lie group valued pseudoduality equations to Lie algebra valued ones, which leads to an infinite number of pseudoduality equations. We obtain an infinite number of conserved currents on the tangent bundle of the pseudodual manifold. Since pseudoduality imposes the condition that sigma models pseudodual to each other are based on symmetric spaces with opposite curvatures (i.e. dual symmetric spaces), we investigate pseudoduality transformation on the symmetric space sigma models in the third chapter. We see that there can be mixing of decomposed spaces with each other, which leads to mixings of the following expressions. We obtain the pseudodual conserved currents which are viewed as the orthonormal frame on the pullback bundle of the tangent space of G tilde which is the Lie group on which the pseudodual model based. Hence we obtain the mixing forms of curvature relations and one loop renormalization group beta function by means of these currents. In chapter four, we generalize the classical construction of pseudoduality transformation to supersymmetric case. We perform this both by component expansion method on manifold M and by orthonormal coframe method on manifold SO(M). The component method produces the result that pseudoduality tranformation is not invertible at all points and occurs from all points on one manifold to only one point where riemann normal coordinates valid on the second manifold. Torsion of the sigma model on M must vanish while it is nonvanishing on M tilde, and curvatures of the manifolds must be constant and the same because of anticommuting grassmann numbers. We obtain the similar results with the classical case in orthonormal coframe method. In case of super WZW sigma models pseudoduality equations result in three different pseudoduality conditions; flat space, chiral and antichiral pseudoduality. Finally we study the pseudoduality tansformations on symmetric spaces using two different methods again. These two methods yield similar results to the classical cases with the exception that commuting bracket relations in classical case turns out to be anticommuting ones because of the appearance of grassmann numbers. It is understood that constraint relations in case of non-mixing pseudoduality are the remnants of mixing pseudoduality. Once mixing terms are included in the pseudoduality the constraint relations disappear.

In this thesis, a 14-bit low-power Analog-to-Digital Converter (ADC) is designed for sensor applications. Following on previous work, the ADC is designed to be frequency scalable by 1000 times from 1.67S/s to 1.67kS/s. To reduce power, class AB opamps are used. The design was fabricated in 0.18um CMOS and occupies an area of 0.35mm2. Operating at full-rate as a Delta-Sigma modulator, the ADC achieves 91.8dB peak SNDR while consuming 83uW. In incremental mode, the ADC powers off periodically to achieve frequency scalability, maintaining 84.7dB to 89dB peak SNDR while operating from 1.67S/s to 1.67kS/s.

In this thesis, a 14-bit low-power Analog-to-Digital Converter (ADC) is designed for sensor applications. Following on previous work, the ADC is designed to be frequency scalable by 1000 times from 1.67S/s to 1.67kS/s. To reduce power, class AB opamps are used. The design was fabricated in 0.18um CMOS and occupies an area of 0.35mm2. Operating at full-rate as a Delta-Sigma modulator, the ADC achieves 91.8dB peak SNDR while consuming 83uW. In incremental mode, the ADC powers off periodically to achieve frequency scalability, maintaining 84.7dB to 89dB peak SNDR while operating from 1.67S/s to 1.67kS/s.

Lars Höglund AB is one of Scandinavia’s most qualified manufacturers of sheet metal products and provides custom designed products of very detailed precision. One of the main methods of manufacturing is laser cutting. When Lars Höglund AB signed up a new customer, with high demands in tolerances for the products, Lars Höglund AB thought it would be necessary to know the capability of the laser cutting machine. Also the process of how to retrieve this capability was interesting.   The capability will be researched for the following elements:   <ul type="disc">Cutting right angles in squares with a corner radius of 1 mm Cutting corners which are not right angle Cutting of circles with constant radius   Measurements were made on 150 pieces of sheet metal details, which had been cut out by the machine.  The data from the measurements where later used to study the capability. The capability study includes such things as calculations of capability indexes Cp and Cpk, the calculations are based on histograms and lean-mean-curves, constructed from the measurement data. The capability of the laser cutting machine was high except for some elements. Those elements with minor capability were the cutting of corner two and three for the rectangles which had a smaller radius than expected, side X for the triangles which were too long and also the diameter of the circles were too big. Advices on how to correct the faults have been given if Lars Höglund AB wants to further more improve the capability of the machine.

This thesis work has been performed at Volvo Aero Corporation in Trollhättan, at the department of “hot structures” involving aircraft engine GP7000. The purpose with the study was to investigate the possibility to reduce size of the forging of flanges on the rear turbine frame when purchasing. Thereto examine the parameters that affect the flanges motion during the manufacturing process. The goal was to provide Volvo Aero with foundation to later bring in slimmed forgings. In order to supply the company with a concrete result the report was limited into studying the P-flange. During the manufacturing process the flanges moves. By measuring the deviation from calculated points on nominal geometry relative to scanned geometry after affecting operations, the motion could be mapped. From these studies two proposals for optimization was presented. The first proposal is based on evening out the tilt caused from the TIG-welding operation. Purchasing tilted forgings would compensate the angle and make room for further savings. If the introduction became a success it could eventually mean that a whole operation (roughing) might be removed. Due to insufficient knowledge about whether the tilt would change as expected after introduction, it requires another analyze after implemented before material can be reduced. The second proposal is based on reducing material solely on the point´s motion. Calculating with four sigma safety (99,379%) on the movements gave information about how much excess material that could be reduced on the forgings. Considerations about whether decreased material would modify the movement pattern have been taken into account. The result shows that 10 % from the bought in forgings can be removed directly. The authors suggest that Volvo Aero begin with the tilt-proposal as a first step in bringing in slimmed forgings. For future work the company could implement the approach taken on this report to the other flanges. / Examensarbetet har utförts vid Volvo Aero Corporation i Trollhättan på avdelningen ”heta strukturer” där bakre motorfästet till flygplansmotorn GP7000 utvecklas. Rapporten avhandlar en studie av P-flänsen på bakre motorfästet. Syftet med arbetet var att undersöka vilka parametrar som påverkar flänsens rörelse under tillverkningsprocessen.  Målet var att utreda möjligheten att införa ett slimmat flänssmide. För att hinna skapa ett konkret resultat avgränsades arbetet till att endast granska P-flänsen. Flänsarna rör sig under tillverkningsprocessen. Genom att mäta avvikelser från punkter utsatta på nominell geometri i förhållande till skannad geometri efter påverkan av tillverkningsprocessen kunde rörelsen kartläggas. Utifrån kartläggningen skapades två förslag. Det första förslaget baserades på en vinkling av flänsen. Förslaget skall kompensera lutningen som orsakas av TIG-svetsningen. Ett lyckat införande skulle eventuellt kunna innebära att en hel operation (grovsvarvning) skulle kunna avlägsnas. På grund av otillräcklig kunskap om huruvida lutningen skulle förändras efter införandet krävs analys av utfallet innan material kan reduceras. Det andra förslaget baserades enbart på punktavvikelser. Avvikelserna var normalfördelade vilket möjliggjorde statistiska beräkningar där fyra sigma (99,379%) i säkerhet användes för att skapa ett säkerhetsintervall för punkternas avvikelse. Resultatet från beräkningarna utgjorde underlaget för mängden överflödigt flänssmide som med säkerhet kunde reduceras vid inköp. Resultatet påvisar att cirka 10 % av inköpt flänssmide kan tas bort. Författarna föreslår att Volvo Aero använder sig av förslag ett eftersom ett mer slimmat smide enklare kan införas på sikt. För framtida arbeten rekommenderas företaget att applicera tillvägagångssättet från rapporten till undersökning av de resterande flänssmidena på GP 7000 TEC. Analysen utförd i rapporten kan även beaktas då nya smidesgeometrier till andra projekt skall utvecklas.

This thesis focuses on the design and analysis of an optimal filter that is capable of making one-step-ahead prediction of a bandlimited signal while attenuating unwanted noise. First, the filter optimization based on the least mean-square-error criterion is presented. Then, an exact expression for the achievable minimum mean square error (MMSE) is derived with the aid of the Toeplitz form method and Szego theory. Based on this MMSE expression, the formulae for estimating the optimal filter¡¦s in-band prediction error and out-of-band noise attenuation are derived. Finally, the optimal filter is applied to sigma-delta modulation. It shows that the modulation performance and stability are intimately related to the filter performance and can be accurately estimated by the derived formulae.

With its successful deployment by the legendary CEO Jack Welch of General Electrics, the Six Sigma methodology of management has achieved wide recognition and popularity among corporations around the globe. This Six Sigma concept for quality management has been sprouting in Taiwan and waiting to be blossomed. The purpose of this case study is to redefine the Six Sigma concept based on the framework of DMAIC (Define-Measure-Analyze-Improve-Control); to implement and pinpoint a strategy for corporations adopting the Six Sigma while deploying VOC (voice of customer) to transform operations into the CTQ (Critical to Quality) stage. The concept of performance management is the nexus where balanced scorecard and Six Sigma can join to produce a formidable weapon that aligns strategic intent with tactical execution. Balanced scorecard is a comprehensive collection of financial and non-financial data and information supplied to the managers of an entity in order to help them achieve the entity¡¦s objectives. This case study uses surveys on the targeted company for further research on how to drive a powerful management tool through the unification of these two proven strategies. An approach that combines the targeted performance indicators of a Balanced Scorecard with the statistical rigor of Six Sigma to be used to effectively focus an organization on the achievement of long-term strategic goals. Based on the statistical result from the surveys on the targeted company, it meets the strategic priorities for various business processes that create customer and shareholder satisfaction (i.e. Internal Business Process). However, it deviates from three other perspectives, financial, customer, and learning and growth. This reveals the company¡¦s needs to be improvised to drive the long-term value and competitive performance.