19 research outputs found

    Angle of repose of snow: An experimental study on cohesive properties

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    The angle of repose is a measure reflecting the internal friction and cohesion properties of a granular material. In this paper, we present an experimental setup and measurements for the angle of repose of snow for seven different snow samples over a large range of temperatures. The results show that the angle of repose is dependent on the fall height, the temperature, and the grain size of the snow. These variables are quantified, and their interdependencies are separately studied. With increased snow temperature, the angle of repose increases, and this can be explained by the presence of a liquid layer on ice that can be thermodynamically stable at temperatures below the melting point of water. With decreasing grain size the angle of repose also increases which is expected since the cohesive energy decreases more slowly than the grain mass. For increasing fall height, the snow grains generally accelerate to larger collisional velocities, yielding a smaller angle of repose. In general, the dimensionless cohesion number was found to largely reflect the dependencies of the variables and is therefore useful for understanding what affects the angle of repose. The results demonstrate that the drag force and collision dynamics of ice grains are important for understanding how snow accumulates on a surface, for example if one desires predicting snow accretion by simulating a dispersed cloud of snow

    Transcription factor regulation can be accurately predicted from the presence of target gene signatures in microarray gene expression data

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    Deciphering transcription factor networks from microarray data remains difficult. This study presents a simple method to infer the regulation of transcription factors from microarray data based on well-characterized target genes. We generated a catalog containing transcription factors associated with 2720 target genes and 6401 experimentally validated regulations. When it was available, a distinction between transcriptional activation and inhibition was included for each regulation. Next, we built a tool (www.tfacts.org) that compares submitted gene lists with target genes in the catalog to detect regulated transcription factors. TFactS was validated with published lists of regulated genes in various models and compared to tools based on in silico promoter analysis. We next analyzed the NCI60 cancer microarray data set and showed the regulation of SOX10, MITF and JUN in melanomas. We then performed microarray experiments comparing gene expression response of human fibroblasts stimulated by different growth factors. TFactS predicted the specific activation of Signal transducer and activator of transcription factors by PDGF-BB, which was confirmed experimentally. Our results show that the expression levels of transcription factor target genes constitute a robust signature for transcription factor regulation, and can be efficiently used for microarray data mining

    Entanglement negativity in a two dimensional harmonic lattice: Area law and corner contributions

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    We study the logarithmic negativity and the moments of the partial transpose in the ground state of a two dimensional massless harmonic square lattice with nearest neighbour interactions for various configurations of adjacent domains. At leading order for large domains, the logarithmic negativity and the logarithm of the ratio between the generic moment of the partial transpose and the moment of the reduced density matrix at the same order satisfy an area law in terms of the length of the curve shared by the adjacent regions. We give numerical evidence that the coefficient of the area law term in these quantities is related to the coefficient of the area law term in the R\ue9nyi entropies. Whenever the curve shared by the adjacent domains contains vertices, a subleading logarithmic term occurs in these quantities and the numerical values of the corner function for some pairs of angles are obtained. In the special case of vertices corresponding to explementary angles, we provide numerical evidence that the corner function of the logarithmic negativity is given by the corner function of the R\ue9nyi entropy of order 1/2

    Modulering av PDGF receptorsignalering via fosfataset SHP-2 och dockingproteinet Gab1

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    xPlatelet-derived growth factors (PDGF), a family of potent mitogens and chemoattractants for cells of mesenchymal origin, elicit their biological effects through the binding of two related receptor tyrosine kinases, denoted α- and β-receptors. The binding of PDGF to the receptors causes receptor dimerization and autophosphorylation on tyrosine residues. Src homology 2 (SH2) domain-containing proteins then bind the phosphorylated receptors, mediating further propagation of the signal. This thesis describes how the interaction between the PDGF receptors and some of their downstream targets can modify the cellular response to PDGF. The tyrosine phosphatase SHP-2 has been implicated in activation of the Ras/MAPK pathway downstream of several receptor tyrosine kinases. We found that SHP-2 binds to phosphorylated Y763 in the PDGF β-receptor, in addition to the already reported binding to Y1009. Cells expressing PDGF β-receptors with Y763 and Y1009 mutated to phenylalanine exhibited decreased Ras-GTP loading and reduced activation of Erk2 in response to PDGF. Whereas these cells did not show any change in the mitogenic response to PDGF, the PDGF-induced chemotaxis was significantly reduced in cells expressing mutant compared to wild-type receptor. The phosphorylation of Y771 of the PDGF β-receptor had been shown to be significantly lower in the αβ-heterodimeric receptor compared to in the ββ-homodimer, causing reduced binding of RasGAP to the heterodimer and increased Ras/MAPK activation. We could demonstrate that the reduced phosphorylation of Y771 is due to dephosphorylation by tyrosine phosphatases, including SHP-2. SHP-2 had been shown to associate with the docking protein Gab1 after growth factor stimulation. We showed that the adaptor protein Grb2 was required for PDGF mediated phosphorylation of Gab1, and that phosphorylated Gab1, Grb2 and SHP-2 create a complex upon PDGF stimulation. Using a cell system with an inducible Gab1 expression, we further demonstrated that Gab1 increased SHP-2 activity in response to PDGF, without affecting the interaction between SHP-2 and the b-receptor. Induction of Gab1 correlated with an increase in both PDGF-induced Erk and p38 MAPK activation, whereas Akt activation was unaffected. The latter finding was in line with our observation that PDGF had no effect on the interaction between Gab1 and p85 of PI3’-kinase. The increase in MAPK activity after Gab1 induction and PDGF treatment did not correlate with an increase in PDGF-induced mitogenicity; instead these cells displayed more pronounced actin reorganization in response to PDGF. In conclusion, our data indicate that SHP-2 regulates the PDGF response both through direct dephosphorylation of the receptor and through its interaction with Gab1. PDGF stimulated activation of SHP-2 seems to be correlated not only with mitogenesis, but also with reorganization of the actin cytoskeleton and cell migration

    Den militära professionens förändring i dagens Sverige med särskilt fokus på Försvarsmaktens framtida internationalisering

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    Syftet med uppsatsen har varit att beskriva hur attityder avseende internationell tjänstgöring ochutbildningen av officerare har förändrats och anpassats till det framtida kravet på internationellaåtaganden. Utifrån syfte och problemformulering skulle uppsatsen ge svar på om officerens attitydoch vilja att tjänstgöra internationellt förändrats och om utbildningen av officerare på bästa sätthar anpassats till den utökade uppgiften att bidra till fred och säkerhet i omvärlden. Inledningsvishar den utveckling som skett sedan 1989 av Försvarsmaktens internationella uppgifter beskrivits.Därefter har en översiktlig bild av viljan och synen på internationell tjänst bland officerarebeskrivits. Detta har kompletterats med Officersförbundets syn på internationell tjänst.Avslutningsvis har en analys gjorts av det insamlade materialet där de huvudsakliga slutsatserna äratt Försvarsmakten tidigt måste analysera vilka kompetens- och utbildningsbehov som finns för attmatcha den utökade internationaliseringen som i framtiden kommer att krävas av Försvarsmakten.Detta för att implementera behoven i utbildningen av officerare så att kompetensgapet mellanpersonal och uppgifter inte skall öka.The main purpose of this essay has been to describe if the education of officershas changed and whether it has been adapted due to the future demand oninternational commitment that the Swedish government has given to the ArmedForces. Another purpose has been to answer the question if the attitude and willto serve abroad among the officers has changed during the last couple of years.The main sources that have been used come from the Swedish government, theArmed forces headquarter, and official books. The method used in the essay isa qualitative, investigational and textual analysis. The overall conclusions arethat the Armed forces must early identify and analyse what competence andeducational requirements, both practical and theoretical that are needed in thefuture to match the escalating internationalisation that is required of theSwedish officers. These requirements are most important to implement inmilitary schools and to reduce the “gap” between the officer’s profession andthe overall international tasks.Avdelning: ALB - Slutet Mag 3 C-upps.Hylla: Upps. ChP 01-0

    Lära ut mjukvarutestning i en modern utvecklingsmiljö

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    All developers understand the benefits of testing their code to ensure its functionality. Today’s market is moving further towards design principles where testing is a central or driving force during development. This puts a certain pressure on academia to supply these skills to their students.Recently the course II1302 Projects and project methods at the Royal Institute of Technology in Kista made a concerted effort to introduce the students of the course to these modern concepts. This thesis investigates how areas of testing can effectively be introduced to the students in the course, utilizing a tailored example that takes the area of testing into particular consideration and how to automate it via DevOps-tools provided by a cloud-based service. Further, it also makes an attempt to provide additional material to be used for teaching testing in conjunction with the example provided.The case study covers the development of an example application, meant to mirror a typical student project. It also covers how this was used for teaching the students about the testing areas considered. The covered testing areas include unit testing, integration testing and UI testing. With these given testing areas, the application and an associated learning module was developed for each area in question. Relevant standards, strategies and approaches was also identified for each of these areas.The thesis also presents important properties to take into consideration when developing similar examples in the future, based on the experiences obtained during the study. These include needs such as understandable by inexperienced students, applicability outside the course, adherence to established standards, tools that are simple to use and an architectural structure that allows for testing.Some improvements are also recommended: the students would benefit from learning software testing from an early stage of their studies. The content of the learning modules should also be brought to the students earlier in the course, so it can be applied in their projects at an early stage as well.Further research is also recommended to evaluate the suitability of using other cloud-based environments instead, and to evaluate the applicability of the learning modules for students of varying disabilities.Alla utvecklare förstår fördelarna med att testa kod för att garantera dess funktionalitet. Dagens industri går i en riktning där testning spelar en central del av design under utveckling av mjukvara. Denna tendens lägger en viss press på högskolan att lära ut dessa erfarenheter till dess studenter.På senare tid har kursen II1302 Projekt och projektmetoder på Kungliga Tekniska Högskolan i Kista tagit en stor ansats för att introducera sina studenter inför dessa moderna koncept. Denna uppsats undersöker hur testningsområdet effektivt kan introduceras till studenterna inom denna kurs, genom att utnyttja ett egengjort exempel som har området i fokus, samt att automatisera detta via DevOps-verktyg tillhandahållna av molnbaserade tjänster. Dessutom görs även en ansats för att tilldela ytterligare material som kan användas för att lära ut testning av mjukvara i samband med det givna exemplet.Fallstudien omfattar utvecklingen av en exempelapplikation, som var avsedd att likna ett typiskt studentprojekt. Den täcker även hur denna användes för att lära ut de betraktade testningsområdena till studenterna. De täckta områdena av testning inkluderar enhetstestning, integrationstestning och testning av användargränssnitt. Med dessa givna testningsområden utvecklades både applikationen och dess associerade lärmoduler för vardera testningområde i fråga. Relevanta standarder, strategier och metoder var också identifierade för vardera av dessa områden.Denna uppsats presenterar även ett antal viktiga egenskaper att hålla i åtanke vid utveckling av liknande exempel i framtiden, baserat på erfarenheterna från studien. Detta inkluderar behov som tillgänglighet för mindre erfarna studenter, applicerbarhet utanför själva kursen, tillämpning av etablerade standarder, utnyttjande av lättanvända verktyg och en arkitektur som tillåter testning.Några förbättringar föreslås även: studenterna skulle gynnas av att lära sig om mjukvarutestning i ett tidigt skede av sina studier. Innehållet i lärmodulerna bör även presenteras för studenterna tidigare i kursen för att kunna appliceras i deras projekt.Ytterligare forskning rekommenderas även för att utvärdera andra lämpliga molnbaserade miljöer, samt för att utvärdera tillämpbarheten av lärmodulerna hos studenter med inlärningssvårigheter

    Lära ut mjukvarutestning i en modern utvecklingsmiljö

    No full text
    All developers understand the benefits of testing their code to ensure its functionality. Today’s market is moving further towards design principles where testing is a central or driving force during development. This puts a certain pressure on academia to supply these skills to their students.Recently the course II1302 Projects and project methods at the Royal Institute of Technology in Kista made a concerted effort to introduce the students of the course to these modern concepts. This thesis investigates how areas of testing can effectively be introduced to the students in the course, utilizing a tailored example that takes the area of testing into particular consideration and how to automate it via DevOps-tools provided by a cloud-based service. Further, it also makes an attempt to provide additional material to be used for teaching testing in conjunction with the example provided.The case study covers the development of an example application, meant to mirror a typical student project. It also covers how this was used for teaching the students about the testing areas considered. The covered testing areas include unit testing, integration testing and UI testing. With these given testing areas, the application and an associated learning module was developed for each area in question. Relevant standards, strategies and approaches was also identified for each of these areas.The thesis also presents important properties to take into consideration when developing similar examples in the future, based on the experiences obtained during the study. These include needs such as understandable by inexperienced students, applicability outside the course, adherence to established standards, tools that are simple to use and an architectural structure that allows for testing.Some improvements are also recommended: the students would benefit from learning software testing from an early stage of their studies. The content of the learning modules should also be brought to the students earlier in the course, so it can be applied in their projects at an early stage as well.Further research is also recommended to evaluate the suitability of using other cloud-based environments instead, and to evaluate the applicability of the learning modules for students of varying disabilities.Alla utvecklare förstår fördelarna med att testa kod för att garantera dess funktionalitet. Dagens industri går i en riktning där testning spelar en central del av design under utveckling av mjukvara. Denna tendens lägger en viss press på högskolan att lära ut dessa erfarenheter till dess studenter.På senare tid har kursen II1302 Projekt och projektmetoder på Kungliga Tekniska Högskolan i Kista tagit en stor ansats för att introducera sina studenter inför dessa moderna koncept. Denna uppsats undersöker hur testningsområdet effektivt kan introduceras till studenterna inom denna kurs, genom att utnyttja ett egengjort exempel som har området i fokus, samt att automatisera detta via DevOps-verktyg tillhandahållna av molnbaserade tjänster. Dessutom görs även en ansats för att tilldela ytterligare material som kan användas för att lära ut testning av mjukvara i samband med det givna exemplet.Fallstudien omfattar utvecklingen av en exempelapplikation, som var avsedd att likna ett typiskt studentprojekt. Den täcker även hur denna användes för att lära ut de betraktade testningsområdena till studenterna. De täckta områdena av testning inkluderar enhetstestning, integrationstestning och testning av användargränssnitt. Med dessa givna testningsområden utvecklades både applikationen och dess associerade lärmoduler för vardera testningområde i fråga. Relevanta standarder, strategier och metoder var också identifierade för vardera av dessa områden.Denna uppsats presenterar även ett antal viktiga egenskaper att hålla i åtanke vid utveckling av liknande exempel i framtiden, baserat på erfarenheterna från studien. Detta inkluderar behov som tillgänglighet för mindre erfarna studenter, applicerbarhet utanför själva kursen, tillämpning av etablerade standarder, utnyttjande av lättanvända verktyg och en arkitektur som tillåter testning.Några förbättringar föreslås även: studenterna skulle gynnas av att lära sig om mjukvarutestning i ett tidigt skede av sina studier. Innehållet i lärmodulerna bör även presenteras för studenterna tidigare i kursen för att kunna appliceras i deras projekt.Ytterligare forskning rekommenderas även för att utvärdera andra lämpliga molnbaserade miljöer, samt för att utvärdera tillämpbarheten av lärmodulerna hos studenter med inlärningssvårigheter

    Lära ut mjukvarutestning i en modern utvecklingsmiljö

    No full text
    All developers understand the benefits of testing their code to ensure its functionality. Today’s market is moving further towards design principles where testing is a central or driving force during development. This puts a certain pressure on academia to supply these skills to their students.Recently the course II1302 Projects and project methods at the Royal Institute of Technology in Kista made a concerted effort to introduce the students of the course to these modern concepts. This thesis investigates how areas of testing can effectively be introduced to the students in the course, utilizing a tailored example that takes the area of testing into particular consideration and how to automate it via DevOps-tools provided by a cloud-based service. Further, it also makes an attempt to provide additional material to be used for teaching testing in conjunction with the example provided.The case study covers the development of an example application, meant to mirror a typical student project. It also covers how this was used for teaching the students about the testing areas considered. The covered testing areas include unit testing, integration testing and UI testing. With these given testing areas, the application and an associated learning module was developed for each area in question. Relevant standards, strategies and approaches was also identified for each of these areas.The thesis also presents important properties to take into consideration when developing similar examples in the future, based on the experiences obtained during the study. These include needs such as understandable by inexperienced students, applicability outside the course, adherence to established standards, tools that are simple to use and an architectural structure that allows for testing.Some improvements are also recommended: the students would benefit from learning software testing from an early stage of their studies. The content of the learning modules should also be brought to the students earlier in the course, so it can be applied in their projects at an early stage as well.Further research is also recommended to evaluate the suitability of using other cloud-based environments instead, and to evaluate the applicability of the learning modules for students of varying disabilities.Alla utvecklare förstår fördelarna med att testa kod för att garantera dess funktionalitet. Dagens industri går i en riktning där testning spelar en central del av design under utveckling av mjukvara. Denna tendens lägger en viss press på högskolan att lära ut dessa erfarenheter till dess studenter.På senare tid har kursen II1302 Projekt och projektmetoder på Kungliga Tekniska Högskolan i Kista tagit en stor ansats för att introducera sina studenter inför dessa moderna koncept. Denna uppsats undersöker hur testningsområdet effektivt kan introduceras till studenterna inom denna kurs, genom att utnyttja ett egengjort exempel som har området i fokus, samt att automatisera detta via DevOps-verktyg tillhandahållna av molnbaserade tjänster. Dessutom görs även en ansats för att tilldela ytterligare material som kan användas för att lära ut testning av mjukvara i samband med det givna exemplet.Fallstudien omfattar utvecklingen av en exempelapplikation, som var avsedd att likna ett typiskt studentprojekt. Den täcker även hur denna användes för att lära ut de betraktade testningsområdena till studenterna. De täckta områdena av testning inkluderar enhetstestning, integrationstestning och testning av användargränssnitt. Med dessa givna testningsområden utvecklades både applikationen och dess associerade lärmoduler för vardera testningområde i fråga. Relevanta standarder, strategier och metoder var också identifierade för vardera av dessa områden.Denna uppsats presenterar även ett antal viktiga egenskaper att hålla i åtanke vid utveckling av liknande exempel i framtiden, baserat på erfarenheterna från studien. Detta inkluderar behov som tillgänglighet för mindre erfarna studenter, applicerbarhet utanför själva kursen, tillämpning av etablerade standarder, utnyttjande av lättanvända verktyg och en arkitektur som tillåter testning.Några förbättringar föreslås även: studenterna skulle gynnas av att lära sig om mjukvarutestning i ett tidigt skede av sina studier. Innehållet i lärmodulerna bör även presenteras för studenterna tidigare i kursen för att kunna appliceras i deras projekt.Ytterligare forskning rekommenderas även för att utvärdera andra lämpliga molnbaserade miljöer, samt för att utvärdera tillämpbarheten av lärmodulerna hos studenter med inlärningssvårigheter

    JAK1 and Tyk2 activation by the homologous polycythemia vera JAK2 V617F mutation - Cross-talk with IGF1 receptor

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    The majority of polycythemia vera (PV) patients harbor a unique somatic mutation (V617F) in the pseudokinase domain of JAK2, which leads to constitutive signaling. Here we show that the homologous mutations in JAK1 (V658F) and in Tyk2 (V678F) lead to constitutive activation of these kinases. Their expression induces autonomous growth of cytokine-dependent cells and constitutive activation of STAT5, STAT3, mitogen-activated protein kinase, and Akt signaling in Ba/F3 cells. The mutant JAKs exhibit constitutive signaling also when expressed in fibrosarcoma cells deficient in JAK proteins. Expression of the JAK2 V617F mutant renders Ba/F3 cells hypersensitive to insulin-like growth factor 1 (IGF1), which is a hallmark of PV erythroid progenitors. Upon selection of Ba/F3 cells for autonomous growth induced by the JAK2 V617F mutant, cells respond to IGF1 by activating STAT5, STAT3, Erk1/2, and Akt on top of the constitutive activation characteristic of autonomous cells. The synergic effect on proliferation and STAT activation appears specific to the JAK2 V617F mutant. Our results show that the homologous V617F mutation induces activation of JAK1 and Tyk2, suggesting a common mechanism of activation for the JAK1, JAK2, and Tyk2 mutants. JAK3 is not activated by the homologous mutation M592F, despite the presence of the conserved GVC preceding sequence. We suggest that mutations in the JAK1 and Tyk2 genes may be identified as initial molecular defects in human cancers and autoimmune diseases

    Gab1 Contributes to Cytoskeletal Reorganization and Chemotaxis in Response to Platelet-derived Growth Factor

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    Gab1 is a scaffolding/docking protein that has been suggested to play a role in signal transduction down-stream of certain plasma membrane receptors, including platelet-derived growth factor (PDGF) receptors. We found that PDGF induced a rapid Gab1 phosphorylation, which depended on the recruitment of Grb2, indicating that Grb2 acts as a bridge between Gab1 and the PDGF β-receptor. PDGF also enhanced the binding of Gab1 to the phosphatase SHP-2, but not to p85. To further study the role of Gab1 in PDGF signaling, we transfected porcine aortic endothelial cells with a doxycycline-inducible Gab1 construct. Increased Gab1 expression enhanced the recruitment and activation of SHP-2, as well as the phosphorylation of the mitogen-activated protein kinases Erk and p38 by PDGF. Gab1 expression also enhanced the formation of lamellipodia and cellular protrusions. In Gab1-deficient mouse embryonic fibroblasts, the same phenotype was induced by restoring the expression of wild-type Gab1, but not a mutant Gab1 that was unable to associate with SHP-2. These effects of PDGF on the actin cytoskeleton were not altered by the inhibition of p38 or Erk, but could be blocked by a dominant-negative form of Rac (Asn17). Finally, Gab1-deficient fibroblasts showed a decreased chemotactic response toward gradients of PDGF as compared with wild-type cells. In conclusion, Gab1 plays a selective role in the regulation of the mitogen-activated protein kinases Erk and p38 downstream of the PDGF β-receptor, and contributes to cytoskeletal reorganization and chemotaxis in response to PDGF
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