Att byta styrdokument: En studie om hur Läroplan för gymnasieskola 2011 påverkar undervisningen och betygsättningen i och statusen för kursen Instrument eller sång

The aim of this essay is to study how the teaching and grading of the course instrument or singing correspond with the curriculum for upper secondary school 2011 and if it has meant that the teachers have changed their pedagogical work. My aim is also to find out if the new curriculum brought any change to the status of the course and the teacher’s role. I have made qualitative interviews with three instumental teachers of the arts programme, of whom two work at two different public schools and one at a free school. The current curriculum and the governments bills, together with other researchers’ categorizations of different kinds of teachers, learning and grading, are this essay’s theoretical approach. The results of the interviews and the theoretical background have led to my conclusion which implies that if you change your pedagogical work because of the curriculum for upper secondary school 2011, you can choose to focus on which parts of the renewal that best suit your pedagogical ideology, since the new curriculum allows you to personally interpret it.Denna studie har som syfte att undersöka hur undervisningen och betygsättningen ser ut i kursen instrument eller sång i förhållande till läroplan för gymnasieskola 2011 och om den inneburit att lärarna förändrat sitt pedagogiska arbete. Jag vill dessutom ta reda på om den nya läroplanen medfört någon statusförändring av kursen eller lärarrollen. Jag har genomfört kvalitativa intervjuer med tre instrumentallärare på det estetiska programmet, av vilka två arbetar på två olika kommunala skolor och en på en friskola. Studiens teoretiska utgångspunkter är ,dels de nu rådande styrdokumenten, dels de regeringspropositioner som ligger till grund för förändringarna, men även andra forskares kategoriseringar av olika typer av lärare, lärande och bedömning inom musikundervisningen. Resultatet av mina intervjusvar tillsammans med den teoretiska bakgrunden ligger till grund för mina slutsatser som innebär att om man förändrar sitt pedagogiska arbete på grund av Läroplan för gymnasieskola 2011 så kan man välja att fokusera på den del av förnyelsen som bäst stämmer överens med ens pedagogiska ideologi, eftersom den nya läroplanen ger utrymme för personliga tolkningar

Power Consumption of Hybrid EDFA/Raman Amplified Systems

We analyze the power consumption in hybrid EDFA/Raman amplified links along with the trade-off of span distance and the use of FEC. A simple model provides some guidelines for the choices to be made

Relevance of the N-terminal NLS-like sequence of the prion protein for membrane perturbation effects

AbstractWe investigated the nuclear localization-like sequence KKRPKP, corresponding to the residues 23–28 in the mouse prion protein (mPrP), for its membrane perturbation activity, by comparing effects of two mPrP-derived peptides, corresponding to residues 1–28 (mPrPp(1–28)) and 23–50 (mPrPp(23–50)), respectively. In erythrocytes, mPrPp(1–28) induced ∼60% haemoglobin leakage after 30 min, whereas mPrPp(23–50) had negligible effects. In calcein-entrapping, large unilamellar vesicles (LUVs), similar results were obtained. Cytotoxicity estimated by lactate dehydrogenase leakage from HeLa cells, was found to be ∼12% for 50 μM mPrPp(1–28), and ∼1% for 50 μM mPrPp(23–50). Circular dichroism spectra showed structure induction of mPrPp(1–28) in the presence of POPC:POPG (4:1) and POPC LUVs, while mPrPp(23–50) remained a random coil. Membrane translocation studies on live HeLa cells showed mPrPp(1–28) co-localizing with dextran, suggesting fluid-phase endocytosis, whereas mPrPp(23–50) hardly translocated at all. We conclude that the KKRPKP-sequence is not sufficient to cause membrane perturbation or translocation but needs a hydrophobic counterpart

Long-term observation reveals high-frequency engraftment of human acute myeloid leukemia in immunodeficient mice

Repopulation of immunodeficient mice remains the primary method for functional assessment of human acute myeloid leukemia. Published data report engraftment in ~40-66% of cases, mostly of intermediate- or poor-risk subtypes. Here we report that extending follow-up beyond the standard analysis endpoints of 10 to 16 weeks after transplantation permitted leukemic engraftment from nearly every case of xenotransplanted acute myeloid leukemia (18/19, ~95%). Xenogeneic leukemic cells showed conserved immune pheno-types and genetic signatures when compared to corresponding pre-transplant cells and, furthermore, were able to induce leukemia in re-transplantation assays. Importantly, bone marrow biopsies taken at standardized time points failed to detect leukemic cells in 11/18 of cases that later showed robust engraftment (61%, termed "long-latency engrafters"), indicating that leukemic cells can persist over months at undetectable levels without losing disease-initiating properties. Cells from favorable-risk leukemia subtypes required longer to become detectable in NOD/SCID/IL2Rγ; null; mice (27.5±9.4 weeks) than did cells from intermediate-risk (21.9±9.4 weeks,; P; <0.01) or adverse-risk (17±7.6 weeks;; P; <0.0001) subtypes, explaining why the engraftment of the first was missed with previous protocols. Mechanistically, leukemic cells engrafting after a prolonged latency showed inferior homing to the bone marrow. Finally, we applied our model to favorable-risk acute myeloid leukemia with inv(16); here, we showed that CD34; +; (but not CD34; -; ) blasts induced robust, long-latency engraftment and expressed enhanced levels of stem cell genes. In conclusion, we provide a model that allows; in vivo; mouse studies with a wide range of molecular subtypes of acute myeloid leukemia subtypes which were previously considered not able to engraft, thus enabling novel insights into leukemogenesis

The sympathomimetic agonist mirabegron did not lower JAK2-V617F allele burden, but restored nestin-positive cells and reduced reticulin fibrosis in patients with myeloproliferative neoplasms: results of phase II study SAKK 33/14

The β-3 sympathomimetic agonist BRL37344 restored nestin-positive cells within the stem cell niche, and thereby normalized blood counts and improved myelofibrosis in a mouse model of JAK2-V617F positive myeloproliferative neoplasms. We therefore tested the effectiveness of mirabegron, a β-3 sympathomimetic agonist, in a phase II trial including 39 JAK2-V617F positive MPN with a mutant allele burden >20%. Treatment consisted of mirabegron 50 mg daily for 24 weeks. The primary endpoint, reduction of the JAK2-V617F allele burden ≥50%, was not reached in any of the patients. One patient achieved a 25% reduction in JAK2-V617F allele burden by 24 weeks. A small subgroup of patients showed hematological improvement. As a side study, bone marrow biopsies were evaluated in 20 patients.We found an increase in the nestin+ cells from a median of 1.09 (interquartile range 0.38-3.27)/mm2 to 3.95 (interquartile range 1.98-8.79)/mm2 (p<0.0001) and a slight decrease of reticulin fibrosis from a median grade of 1.0 (interquartile range 0-3) to 0.5 (interquartile range 0-2) (p=0.01) between start and end of mirabegron treatment. Despite the fact that the primary endpoint of reducing JAK2-V617F allele burden was not reached, the observed effects on nestin+ MSCs and reticulin fibrosis is encouraging and shows that mirabegron can modify the microenvironment where the JAK2-mutant stem cells are maintained

Effects of lenalidomide on the bone marrow microenvironment in acute myeloid leukemia: Translational analysis of the HOVON103 AML/SAKK30/10 Swiss trial cohort.

This translational study aimed at gaining insight into the effects of lenalidomide in acute myeloid leukemia (AML). Forty-one AML patients aged 66 or older of the Swiss cohort of the HOVON-103 AML/SAKK30/10 study were included. After randomization, they received standard induction chemotherapy with or without lenalidomide. Bone marrow biopsies at diagnosis and before the 2nd induction cycle were obtained to assess the therapeutic impact on leukemic blasts and microenvironment. Increased bone marrow angiogenesis, as assessed by microvessel density (MVD), was found at AML diagnosis and differed significantly between the WHO categories. Morphological analysis revealed a higher initial MVD in AML with myelodysplasia-related changes (AML-MRC) and a more substantial decrease of microvascularization after lenalidomide exposure. A slight increase of T-bet-positive TH1-equivalents was identifiable under lenalidomide. In the subgroup of patients with AML-MRC, the progression-free survival differed between the two treatment regimens, showing a potential but not significant benefit of lenalidomide. We found no correlation between the cereblon genotype (the target of lenalidomide) and treatment response or prognosis. In conclusion, addition of lenalidomide may be beneficial to elderly patients suffering from AML-MRC, where it leads to a reduction of microvascularization and, probably, to an intensified specific T cell-driven anti-leukemic response

Designing Polymers for Biological Interfaces - From Antifouling to Drug Delivery

Unspecific interactions, at the interface between a synthetic material and an aqueous biological environment, leading to irreversible protein adsorption can cause to undesired consequences. These include fouling of a boat hull or a triggered immune response. Thus, stealthy materials are a topic that has generated a great deal of interest in the scientific community. This work deals with the design of networks, nanoparticles, and surfaces containing poly(ethylene glycol) (PEG), known for its resistance to protein adsorption and non-toxic nature. Initially, PEG-based networks, hydrogels, were synthesized using photoinduced thiol-ene chemistry in order to afford coatings targeted for marine antifouling applications. By varying the length of the PEG chain, curing chemistry, cross-linker as well as hydrolytical stability, a library of hydrogel coatings was produced. The coatings were subsequently characterized with respect to curing efficiency, thermal and mechanical properties, and aqueous stability. Furthermore, the antifouling properties of coatings were evaluated using in vitro tests with proteins, marine bacteria, and diatoms. As a final test the coatings were evaluated in a four month field test. It was found that coatings comprising longer PEG chains displayed enhanced antifouling performance, compared to shorter PEGs. In addition, the choice of cross-linker, curing chemistry, and hydrolytical stability also affected the properties to a great extent. This thesis further deals with the design of amphiphilic linear dendritic hybrids, with PEG as the hydrophilic block. Using non-toxic 2,2-bis(methylol) propionic acid (bis-MPA) based dendrons, bearing click functional cores (alkyne or allyl) and peripheral hydroxyl groups, as macrointitiators for ring-opening polymerization of ε-caprolactone, a library of star branched materials was afforded. As a final step, click functional (azide or thiol) PEGs were attached using copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) or thiol-ene click chemistry. The size of the dendrons was varied from generation 0-4, along with variation of both poly(ε-caprolactone) (PCL) length and PEG length. The materials were designed in order to allow a study of the impact of the dendron generation. Finally, the hybrid materials were used for the preparation of micelles, as well as for the formation of honeycomb membranes. The micelles critical micelle concentration, size and drug loading capacity were shown to be highly dependent on the generation of the dendron. The generation of the dendron also had a profound effect on the ability of the hybrid materials to form ordered honeycomb membranes, and hybrid materials of the 3rd generation yielded the most highly ordered membranes.Ickespecifika interaktioner vid gränsytan, mellan ett syntetiskt material och en vattenbaserad biologisk miljö, kan leda till irreversibel adsorption av proteiner. Detta kan i sin tur leda till oönskade följdeffekter, såsom beväxning på båtskrov eller trigga en immunologisk reaktion. För att motverka dessa effekter har forskare utvecklat så kallade smygmaterial. Denna avhandling behandlar design av nätverk, nanopartiklar och ytor innehållande poly(etylenglykol) (PEG), som är känt för sina smygegenskaper och för att vara icke-toxiskt. Initialt behandlar avhandlingen PEG-baserade nätverk, hydrogeler, syntetiserade med fotoinitierad tiol-enekemi, för användning som beväxningsavvisande beläggningar för marina applikationer. Genom att variera olika parametrar, såsom längden på PEG-kedjan, härdningskemin, tvärbindaren samt den hydrolytiska stabiliteten, byggdes ett bibliotek av hydrogelbeläggningar upp. Hydrogelbeläggningarna karaktäriserades sedan med avseende på härdningseffektivitet, termiska och mekaniska egenskaper, samt hydrolytisk stabilitet. Vidare studerades beläggningarnas avvisande förmåga mot proteiner, bakterier samt kiselalger. Slutligen studerades ytbeläggningarna i ett fyra månader långt fälttest. Av testerna framgick att längre PEG-kedjor gav beläggningar med bättre avvisande förmåga. Dessutom framgick att valet av tvärbindare, härdningskemi samt hydrolytisk stabilitet var av betydelse för beläggningarnas effektivitet. Denna avhandling behandlar vidare design av amfifila linjära dendritiska hybridmaterial, med PEG som den hydrofila delen. Genom att använda icke-toxiska 2,2-bis(metylol)propionsyrabaserade dendroner, med en klickfunktionalitet i kärnan (alkyne eller allyl) och perifera hydroxylgrupper, som makroinitiatorer för ringöppningspolymerisation av ε-kaprolakton byggdes ett bibliotek av material upp. För att göra materialen amfifila, kopplades klickfunktionella PEG-kedjor (azid eller tiol) till kärnan med koppar(I)-katalyserad azid-alkyn cykloadditionskemi alternativt tiol-enekemi. Storleken på dendronerna varierades från generation 0-4, dessutom varierades längden på både poly(ε-kaprolakton)- och PEG-kedjorna. Materialen designades så att inverkan av dendrongenerationen kunde studeras. Slutligen användes dessa hybridmaterial för att framställa miceller samt isoporösa filmer. Micellernas kritiska micellbildningskoncentration, storlek samt förmåga att laddas med läkemedel visade sig vara mycket beroende av dendrongenerationen. Dendrongenerationen visade sig vidare även ha stor inverkan i hybridmaterialens förmåga att självorganisera sig till en isoporös struktur och material av tredje generationen gav de mest välordnade filmerna.QC 2010112

Naturally derived cell-penetrating peptides and applications in gene regulation : A study on internalization mechanisms and endosomal escape

Cell-penetrating peptides are a class of peptides which have achieved a lot of recognition due to their vector abilities. Since their discovery over a decade ago, there has been an uncertainty concerning the mechanism by which they are internalized into the cells. Early studies claimed the uptake to be receptor- and energy independent, whereas more recent studies have shifted the general view to a more endocytotic belief, without prior binding to a receptor. As an increasing amount of reports emerges claiming the uptake to be endocytic, there is still a discrepancy concerning which endocytic mechanism that is responsible for the internalization and how to exploit the endocytic machinery for improved delivery. The main aim of this thesis was to elucidate the internalization mechanism for a series of cell-penetrating peptides derived from naturally occurring proteins, such as the prion protein which is thought to be the infectious particle in prion disorders. Furthermore, applications in gene regulation and improvement of delivery efficacy by induction of endosomolysis were examined. The results obtained confirm the uptake of cell-penetrating peptides to be endocytic; however the internalization mechanism appears to be peptide dependent where macropinocytosis is the most widespread endocytic component responsible for the internalization. The results further demonstrate that the biological response can be increased manifold by the induction of endosomolysis, either by using lysosomotropic agents or peptides able to alter their secondary structure upon protonation with concomitant endosomolysis. Altogether the results prove that enhanced delivery using cell-penetrating peptides can be achieved by exploiting the intrinsic endocytic mechanisms involved in the translocation process

Instructions via Augmented Reality for Industrial Maintenance

Förstärkt verklighet (hädanefter förkortat AR efter engelskans augmented reality) är när virtuellt blandas med verkligt, och används till exempel för mobilspel och inom det militära. Utvecklingen av AR-applikationer har under de senaste åren förenklats, vilket gett upphov till nya möjligheter för tillämpning av AR-tekniken. Syftet med vårt arbete är att undersöka om instruktioner givna via AR bidrar till att användare gör färre fel när de utför industriellt underhåll. Vi har valt att jämföra AR-instruktioner med pappersmanualer, då det senare är det som oftast används inom industrin idag. Det finns ett intresse inom industrin för att integrera AR-lösningar i deras verksamhet, inte minst för att det potentiellt kan minska tiden det tar att åtgärda driftstopp, men även för att kunna hjälpa oerfarna och nya operatörer. Idag finns det ett flertal hjälpmedel och programmeringsbibliotek som har gjort utveckling av AR-applikationer enklare, vilket öppnar upp för fler möjligheter när det gäller AR:s tillämpningsområden. För att undersöka om AR-instruktioner kan bidra till att användare gör färre fel har vi utvecklat en AR-applikation till mobiltelefon. I ett experiment jämför vi applikationen mot en pappersmanual på en egen-konstruerad industriell underhållsuppgift. Vi har visat att med hjälp av vår AR-applikation gjorde an-vändare i snitt drygt 60% färre fel. Vi genomförde även ett test för användarvänlighet där applikationen fick ett resultat som var ett poäng under det som anses vara helt tillfredställande.Augmented reality (AR) is when the virtual is mixed with the real, AR is used in for example mobile games and the military. The development of AR-applications has been simplified during recent years, which has opened possibilities for new applications of the AR-technology. The purpose of our work is to research whether instructions given via AR leads to the users making fewer errors when performing industrial maintenance. We chose to compare AR-instructions to paper manuals since this is the most commonly used instruction medium today. Companies have shown interest in the development of AR-solutions for industrial maintenance in their day-to-day operations. Particularly since it can potentially lead to decreased downtime and help new or inexperienced operators. Today there exists several aids and programming libraries that has simplified the development of AR-applications, which opens for more possibilities when it comes to the areas of application for AR. To examine if AR-instructions leads to fewer errors made by the users, we have developed an AR-application for mobile phones. In our experiment we compare the AR-application with a paper manual on a custom-built maintenance task. Our results show that the users with the AR-application perform just over 60% fewer errors. To verify the usability of the application we conducted a usability test, the results from this test puts our application one point below the acceptable limit