An efficient new route to dihydropyranobenzimidazole inhibitors of HCV replication.

A class of dihydropyranobenzimidazole inhibitors was recently discovered that acts against the hepatitis C virus (HCV) in a new way, binding to the IRES-IIa subdomain of the highly conserved 5' untranslated region of the viral RNA and thus preventing the ribosome from initiating translation. However, the reported synthesis of these compounds is lengthy and low-yielding, the intermediates are troublesome to purify, and the route is poorly structured for the creation of libraries. We report a streamlined route to this class of inhibitors in which yields are far higher and most intermediates are crystalline. In addition, a key variable side chain is introduced late in the synthesis, allowing analogs to be easily synthesized for optimization of antiviral activity

Dynamically Scaled Model Experiment of a Mooring Cable

The dynamic response of mooring cables for marine structures is scale-dependent, and perfect dynamic similitude between full-scale prototypes and small-scale physical model tests is difficult to achieve. The best possible scaling is here sought by means of a specific set of dimensionless parameters, and the model accuracy is also evaluated by two alternative sets of dimensionless parameters. A special feature of the presented experiment is that a chain was scaled to have correct propagation celerity for longitudinal elastic waves, thus providing perfect geometrical and dynamic scaling in vacuum, which is unique. The scaling error due to incorrect Reynolds number seemed to be of minor importance. The 33 m experimental chain could then be considered a scaled 76 mm stud chain with the length 1240 m, i.e., at the length scale of 1:37.6. Due to the correct elastic scale, the physical model was able to reproduce the effect of snatch loads giving rise to tensional shock waves propagating along the cable. The results from the experiment were used to validate the newly developed cable-dynamics code, MooDy, which utilises a discontinuous Galerkin FEM formulation. The validation of MooDy proved to be successful for the presented experiments. The experimental data is made available here for validation of other numerical codes by publishing digitised time series of two of the experiments

List of Doctoral Thesis Titles (March 2019)

Radio Frequency Identification är en relativt gammal teknik (sedan andra världskriget), som upplevt en renässans. Då som nu användes RFID för att identifiera föremål, dock med vissa tekniska skillnader. Ökade krav på industrier och samhället i övrigt har lett till den ”informa-tionsålder” vi nu lever i. Som ett steg i denna utveckling ställs allt högre krav på insamlingen av den information som många processer och beslut baseras på. Förenklat kan kommunika-tionen förklaras som en radiosignal som skickas från en RFID-läsare till en RFID-tagg. Taggen sitter på objektet som skall identifieras och information om objektet finns lagrad i taggen. Radiosignalen väcker taggen som skickar den information som finns lagrad i dess mikrochip tillbaka till läsaren. RFID kan användas i en stor mängd olika områden och applikationer där två av dessa är inom transportnätverk och försörjningskedjor. Anledningen till att detta projekt initierades var att logistikföretaget Schenker AB såg ett behov i att undersöka hur tekniken kan användas inom deras verksamhet. För Schenkers del var det viktigt att få utreda eventuella möjligheter med tekniken, och dess kostnader innan kunderna kom med krav eller önskemål om användning. Tre förslag på hur RFID kan användas i verksamheten har utarbetats för att få en bra bild av hur användningen kan gå till och vad som krävs. Studien visar att det krävs en hel del av Schenker i form av utrustning och även datasystem. De slutsatser som kan dras efter att projektet är genomfört är att det finns potential för förbättringar vid användning av RFID-teknik inom Schenkers verksamhet. Dock är dessa förknippade med relativt höga initiala kostnader. Vidare finns även en del tekniska begränsningar vilket gör att systemet måste planeras och konstrueras noggrant för full funktionalitet. Ytterligare undersökningar måste göras för att få mer underlag för hur pass väl RFID kan användas inom Schenker. Tester och försök i mindre flöden hos Schenker vore ett bra sätt för att få erfarenhet och kunskap om teknikens funktionalitet, möjligheter och begränsningar

Crisis or Struggle? A Language of Natality as a Struggle for Education

Taking its point of departure in the connotations to war and violence inherent in what is here called the ‘language of crisis’ (Jantzen), the purpose of this article is to explore what it might mean to reassess the language of educational change and policy reform in the imagery of natality and birth (Arendt). If the task in a ‘crisis’ is to fi ght against the crisis, eff ectively and forcefully, the argument of the paper is that the root metaphors of natality and birth puts into play an imagery that makes possible a relational language for educational change and reform. If the language we use has performative consequences, the question explored is what a ‘language of natality’ can make possible as a language of struggle for education

Tyre Pressure Monitoring using Sensors

This thesis presents an implementation of a positioning and navigation system for a mobile robot using ultrasonic pulses and passive sensors that are part of a sensor network. The system uses the Telos Tmote Sky sensor-boards running Contiki. In addition to the Tmote Sky the mobile robot consists of a number of processors and is equipped with position encoders for the wheels in order to be able to accurately estimate the position using dead-reckoning. It is also equipped with an ultrasound transmitter. The sensor nodes are equipped with ultrasound receivers

Simulaatio moduulien valmistuksesta teollisessa rakentamisessa

This bachelor’s thesis examines industrialized construction (IC) and its various phases. The thesis is divided into two parts, where the first part is a literature review, and the second part focuses on simulation modelling. The literature review explores the industrialized construction process through five different phases that include planning, procurement, production, logistics, and siteworks. Each phase is analysed based on its characteristics using academic literature. The main advantages of industrialized construction include improved productivity, better quality management, and cost-efficiency. However, it also presents challenges such as high initial investments and the need to manage resistance to change. The second part of the thesis focuses on building a simulation model using the AnyLogic software. The model is part of a larger model Siculogic, which represents competition in the industrialized construction sector from the perspective of construction companies. The developed model focuses only on the first three phases and includes three types of agents. The simulation illustrates how a construction project progresses through the phases of industrialized construction. Each project consists of one hundred modules that go through the manufacturing process. The model is used for educational purposes and as a tool for visualizing the phases of industrialized construction. It also provides a foundation for further development with a more detailed model.Tässä kandidaatintyössä tarkastellaan teollista rakentamista (industrialized construction, IC) ja sen eri vaiheita. Työ on jaettu kahteen osaan, joista ensimmäinen on kirjallisuuskatsaus ja toinen on simulaatiomallinnus. Työn kirjallisuuskatsaus käsittelee teollisen rakentamisen prosessia viiden eri vaiheen näkökulmasta. Nämä vaiheet ovat suunnittelu, hankinta, tuotanto, logistiikka ja työmaa. Eri vaiheita analysoidaan niiden ominaispiirteiden pohjalta kirjallisuuden avulla. Teollisen rakentamisen etuina korostuvat muun muassa tuottavuuden parantuminen, laadunhallinta ja kustannustehokkuus. Siihen liittyy kuitenkin myös haasteita, kuten korkeat investointitarpeet ja muutosvastarinnan huomioiminen. Työn toinen osa keskittyy simulaatiomallin rakentamiseen Anylogic-ohjelmistolla. Tehty malli on osa isompaa Siculogic -mallia, joka simuloi teollisen rakentamisen kilpailua yritysten näkökulmasta. Tehty malli keskittyy erityisesti kolmeen ensimmäiseen vaiheeseen ja se käsittelee kolmea eri agenttia. Simulaatio kuvaa rakennusprojektia, joka kulkee teollisen rakentamisen vaiheiden läpi. Jokainen projekti koostuu sadasta moduulista, jotka kulkevat tuotantoprosessin läpi. Malli toimii opetuskäytössä, sekä työkaluna teollisen rakentamisen vaiheiden visualisointiin. Se tarjoaa myös pohjan jatkokehitykselle yksityiskohtaisempaa mallinnusta varten

Cellular Processes and Mechanisms in Saccharomyces cerevisiae Influencing Anaerobic Xylose Fermentation

In 2009 the EU approved two directives as a first initiative towards reducing greenhouse gas emissions and becoming independent of fossil fuels: the Renewable Energy Directive and the Fuel Quality Directive. As a result, the demand for biofuels will increase enormously over the next decade, both nationally and in the entire EU. This huge demand will require a more advanced type of biofuels, produced from cellulosic and lignocellulosic raw materials that do not compete with the supply of food crops. These biofuels are referred to as second generation (2G) fuels. The production of 2G bioethanol at a commercial scale requires yeast strains capable of producing ethanol at high yield and high productivity from all sugars (hexoses and pentoses) extracted from the raw material. The aim of the work presented in this thesis has been to increase the ethanol productivity of recombinant xylose-fermenting strains of the yeast Saccharomyces cerevisiae during batch fermentation of a glucose/xylose mixture. A parameter that has a big influence on productivity is cellular growth and the yeast strains currently used today grow rather poorly on xylose. Many of the signals cells use to regulate growth originate from changes in the concentrations of metabolites inside the cells. To increase our knowledge of xylose metabolism the dynamic changes in intracellular metabolite concentrations were measured during batch fermentation of a glucose/xylose mixture using LC-MS/MS. This study gave meaningful insights about important intracellular signals, biological phenomena and mechanism. The analysis of the metabolite data pointed toward limitations in the folding of proteins inside the ER, which might be the underlying cause of the slow growth on xylose. Another important factor is the regulation of expression of genes required for sugar transport and those related to fermentative metabolism. Hexokinase 2 (Hxk2p) is an important bi-functional protein that acts both as a catalytic enzyme and a global transcription factor. This protein plays a role in the regulation of the above mentioned genes and becomes inactivated in the presence of xylose. As a consequence it loses its’ regulatory function. In an effort to improve repression signals during xylose fermentation this protein was engineered to become immune towards inactivation by xylose. By combining methods for protein and genetic engineering with fermentation technology a mutation in the gene was identified which increased the catalytic activity by 64% in the presence of xylose. The new variant allowed faster glucose consumption in the presence of xylose, but had no obvious impact on xylose fermentation. These results indicate that Hxk2p does not act alone and other proteins are involved in the regulation. These proteins remain to be identified. This thesis describes the cellular processes required for balanced anaerobic microbial growth and the intracellular signals that regulate them. The aim has been to identify biochemical mechanisms that limit anaerobic growth of recombinant S. cerevisiae strains on xylose

Crisis or Struggle? A Language of Natality as a Struggle for Education

Taking its point of departure in the connotations to war and violence inherent in what is here called the ‘language of crisis’ (Jantzen), the purpose of this article is to explore what it might mean to reassess the language of educational change and policy reform in the imagery of natality and birth (Arendt). If the task in a ‘crisis’ is to fi ght against the crisis, eff ectively and forcefully, the argument of the paper is that the root metaphors of natality and birth puts into play an imagery that makes possible a relational language for educational change and reform. If the language we use has performative consequences, the question explored is what a ‘language of natality’ can make possible as a language of struggle for education