76 research outputs found

    TAOK2 Kinase Mediates PSD95 Stability and Dendritic Spine Maturation through Septin7 Phosphorylation

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    Abnormalities in dendritic spines are manifestations of several neurodevelopmental and psychiatric diseases. TAOK2 is one of the genes in the 16p11.2 locus, copy number variations of which are associated with autism and schizophrenia. Here, we show that the kinase activity of the serine/threonine kinase encoded by TAOK2 is required for spine maturation. TAOK2 depletion results in unstable dendritic protrusions, mislocalized shaft-synapses, and loss of compartmentalization of NMDA receptor-mediated calcium influx. Using chemical-genetics and mass spectrometry, we identified several TAOK2 phosphorylation targets. We show that TAOK2 directly phosphorylates the cytoskeletal GTPase Septin7, at an evolutionary conserved residue. This phosphorylation induces translocation of Septin7 to the spine, where it associates with and stabilizes the scaffolding protein PSD95, promoting dendritic spine maturation. This study provides a mechanistic basis for postsynaptic stability and compartmentalization via TAOK2-Sept7 signaling, with implications toward understanding the potential role of TAOK2 in neurological deficits associated with the 16p11.2 region

    Control and follow-up of contracts - part 2, condition development,measurement errors and risks : Road surface measurement

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    Trafikverket har som mĂ„l att öka antalet totalentreprenader. För att fĂ„ en fungerande kontrollapparat kring entreprenaderna krĂ€vs metoder för att verifiera att stĂ€llda krav uppfylls under vĂ€gens garantitid. I denna undersökning riktar vi in oss pĂ„ funktionella krav som stĂ€lls vid totalentreprenader och som kan kontrolleras med vĂ€gytemĂ€tning. Rapporten belyser mĂ€tfel vid objektmĂ€tning (kontrollmĂ€tning). MĂ€tfelet delas upp i olika komponenter: slumpmĂ€ssiga, systematiska och variation mellan olika leverantörer. Även riskbedömning berörs dĂ€r berĂ€kningar av risken för felbedömning av en strĂ€cka presenteras. Slutligen presenteras hur jĂ€mnheten vid anlĂ€ggningen av en entreprenad pĂ„verkar vĂ€gens framtida tillstĂ„ndsutveckling och vilka initialvĂ€rden vi kan förvĂ€nta oss pĂ„ en totalentreprenad och underhĂ„llsbelĂ€ggning. Vi ser att en vĂ€g med god jĂ€mnhet lĂ€ngs och tvĂ€rs fĂ€rdriktningen ger lĂ€gre utvecklingstakt under belĂ€ggningens livslĂ€ngd.The Swedish Transport Administration aims to increase the number of design build contracts. To get a functioning control device around the contracts, well defined requirements must be set for the warranty period of the road. In this survey we focus on functional requirements that are set for design build contracts and which can be checked by means of a road surface testing. In the report, measurement errors are highlighted in object measurement (control measurement). The measurement error is divided into different components: random, systematic and variation between different suppliers. Risk assessment is also discussed where calculations of the risk of error assessment of a section are presented. Finally, it is presented how the results of the condition (evenness) affect the future development of the road and what initial values we can expect from a design build contract and maintenance work. We see that a road of good evenness, longitudinally and transversally, gives a lower development rate during the life of the road

    Control and follow-up of contracts - part 2, condition development,measurement errors and risks : Road surface measurement

    No full text
    Trafikverket har som mĂ„l att öka antalet totalentreprenader. För att fĂ„ en fungerande kontrollapparat kring entreprenaderna krĂ€vs metoder för att verifiera att stĂ€llda krav uppfylls under vĂ€gens garantitid. I denna undersökning riktar vi in oss pĂ„ funktionella krav som stĂ€lls vid totalentreprenader och som kan kontrolleras med vĂ€gytemĂ€tning. Rapporten belyser mĂ€tfel vid objektmĂ€tning (kontrollmĂ€tning). MĂ€tfelet delas upp i olika komponenter: slumpmĂ€ssiga, systematiska och variation mellan olika leverantörer. Även riskbedömning berörs dĂ€r berĂ€kningar av risken för felbedömning av en strĂ€cka presenteras. Slutligen presenteras hur jĂ€mnheten vid anlĂ€ggningen av en entreprenad pĂ„verkar vĂ€gens framtida tillstĂ„ndsutveckling och vilka initialvĂ€rden vi kan förvĂ€nta oss pĂ„ en totalentreprenad och underhĂ„llsbelĂ€ggning. Vi ser att en vĂ€g med god jĂ€mnhet lĂ€ngs och tvĂ€rs fĂ€rdriktningen ger lĂ€gre utvecklingstakt under belĂ€ggningens livslĂ€ngd.The Swedish Transport Administration aims to increase the number of design build contracts. To get a functioning control device around the contracts, well defined requirements must be set for the warranty period of the road. In this survey we focus on functional requirements that are set for design build contracts and which can be checked by means of a road surface testing. In the report, measurement errors are highlighted in object measurement (control measurement). The measurement error is divided into different components: random, systematic and variation between different suppliers. Risk assessment is also discussed where calculations of the risk of error assessment of a section are presented. Finally, it is presented how the results of the condition (evenness) affect the future development of the road and what initial values we can expect from a design build contract and maintenance work. We see that a road of good evenness, longitudinally and transversally, gives a lower development rate during the life of the road.Objektiv kontroll vid funktionsĂ„taganden, tillstĂ„ndsvĂ€rdering av vĂ€gyta

    Control and follow-up of contracts - Part 1, current requirements and methods : Road surface measurement

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    Trafikverket har som mÄl att öka antalet totalentreprenader. För att fÄ en fungerande kontrollapparat kring entreprenaderna krÀvs metoder för att verifiera att stÀllda krav uppfylls under vÀgens garantitid. I denna undersökning riktar vi in oss pÄ funktionella krav som stÀlls vid totalentreprenader och som kan kontrolleras med vÀgytemÀtning. Rapporten belyser vilka krav som finns och hur de kontrolleras men den tar Àven upp subjektivt bedömda krav som borde ersÀttas med en objektiv metod. Vidare beskrivs viktiga aspekter vid genomförandet av en entreprenad, bl.a. Àr kontakten mellan mÀtleverantören och entreprenören ytterst viktig för att avgöra nÀr, hur och var kontrollerna ska göras. En totalentreprenad innehÄller ofta flera vÀgar, ramper och dylikt som krÀver sin speciella planering och kontroll. En genomgÄng görs av defekter som kan upptrÀda pÄ totalentreprenader och i vilket skede de upptrÀder (byggskede/bruksskede). För mÄnga av de defekter som identifieras finns ingen etablerad objektiv mÀtmetod och dÀrför sammanfattas möjliga metoder som kan anvÀndas men som bör utvecklas och verifieras. Ytterligare en viktig aspekt vid totalentreprenader Àr hur kraven stÀlls och följs upp. Tydliga riktlinjer för kravstÀllningen bör arbetas fram dÀr det framgÄr vilken hÀnsyn som ska tas till exempelvis trafikmÀngd, dubbdÀcksandel, hastighet och klimat.The Swedish Transport Administration aims to increase the number of design build contracts. To get a functioning control device around the contracts, well defined requirements must be set for the warranty period of the road. In this survey we focus on functional requirements that are set for design build contracts and which can be checked by means of a road surface testing. The report highlights what requirements are used and how they are checked, but it also takes up subjectively assessed requirements that should be replaced by an objective method. Furthermore, important aspects of the implementation of a contract are described. The contact between the measuring supplier and the contractor is extremely important for determining when, how and where the controls are to be performed. A total contract often contains several roads, ramps and so forth, which requires its special planning and control routines. A review is made of defects that can occur on design build contracts and at what stage they occur (construction stage/use stage). For many of the defects identified there is no established objective measurement method. Therefore, usable methods need to be further developed and verified. Another important aspect of design build contract is how the requirements are set and followed up. Clear guidelines for the requirement setting should be worked out where it is decided which consideration should be taken, for example, for traffic volume, studded tires, signed speed and climate.Objektiv kontroll vid funktionsÄtaganden, tillstÄndsvÀrdering av vÀgyta

    Control and follow-up of contracts - Part 1, current requirements and methods : Road surface measurement

    No full text
    Trafikverket har som mÄl att öka antalet totalentreprenader. För att fÄ en fungerande kontrollapparat kring entreprenaderna krÀvs metoder för att verifiera att stÀllda krav uppfylls under vÀgens garantitid. I denna undersökning riktar vi in oss pÄ funktionella krav som stÀlls vid totalentreprenader och som kan kontrolleras med vÀgytemÀtning. Rapporten belyser vilka krav som finns och hur de kontrolleras men den tar Àven upp subjektivt bedömda krav som borde ersÀttas med en objektiv metod. Vidare beskrivs viktiga aspekter vid genomförandet av en entreprenad, bl.a. Àr kontakten mellan mÀtleverantören och entreprenören ytterst viktig för att avgöra nÀr, hur och var kontrollerna ska göras. En totalentreprenad innehÄller ofta flera vÀgar, ramper och dylikt som krÀver sin speciella planering och kontroll. En genomgÄng görs av defekter som kan upptrÀda pÄ totalentreprenader och i vilket skede de upptrÀder (byggskede/bruksskede). För mÄnga av de defekter som identifieras finns ingen etablerad objektiv mÀtmetod och dÀrför sammanfattas möjliga metoder som kan anvÀndas men som bör utvecklas och verifieras. Ytterligare en viktig aspekt vid totalentreprenader Àr hur kraven stÀlls och följs upp. Tydliga riktlinjer för kravstÀllningen bör arbetas fram dÀr det framgÄr vilken hÀnsyn som ska tas till exempelvis trafikmÀngd, dubbdÀcksandel, hastighet och klimat.The Swedish Transport Administration aims to increase the number of design build contracts. To get a functioning control device around the contracts, well defined requirements must be set for the warranty period of the road. In this survey we focus on functional requirements that are set for design build contracts and which can be checked by means of a road surface testing. The report highlights what requirements are used and how they are checked, but it also takes up subjectively assessed requirements that should be replaced by an objective method. Furthermore, important aspects of the implementation of a contract are described. The contact between the measuring supplier and the contractor is extremely important for determining when, how and where the controls are to be performed. A total contract often contains several roads, ramps and so forth, which requires its special planning and control routines. A review is made of defects that can occur on design build contracts and at what stage they occur (construction stage/use stage). For many of the defects identified there is no established objective measurement method. Therefore, usable methods need to be further developed and verified. Another important aspect of design build contract is how the requirements are set and followed up. Clear guidelines for the requirement setting should be worked out where it is decided which consideration should be taken, for example, for traffic volume, studded tires, signed speed and climate

    Objective measurement of surface defects and cracks in the road surface : road surface condition measurement with scanning laser technique

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    Den tillstĂ„ndsmĂ€tning av de statliga vĂ€garna som görs i Sverige idag ger inte en tillrĂ€ckligt allsidig beskrivning av skadelĂ€get för att kunna vĂ€lja strĂ€ckor som Ă€r i behov av underhĂ„ll. Den information som vi saknar rör vĂ€gytans skick. Det kan vara sprickor eller andra ytskador som t.ex. stenslĂ€pp. I denna studie har 27 dubbelriktade strĂ€ckor valts ut. StrĂ€ckorna har i olika grad ett skadelĂ€ge i ytskiktet som identifierats som ”i behov av underhĂ„ll” av Trafikverkets belĂ€ggningsingenjörer. StrĂ€ckorna Ă€r mĂ€tta med ett mĂ€tsystem som Ă€r heltĂ€ckande (HTL, heltĂ€ckande lasermĂ€tning) över körfĂ€ltet och som jĂ€mförelsegrund har ocksĂ„ en okulĂ€r inventering gjorts av skadelĂ€get. Vi ser att den objektiva HTL-mĂ€tningen har god upprepbarhet avseende sprickor och stenslĂ€pp. Vid jĂ€mförelse med den subjektiva bedömningen finns det strĂ€ckor dĂ€r identifieringen av ytskadorna stĂ€mmer vĂ€l överens men Ă€ven motsatsen. För att en HTL-mĂ€tning ska ge anvĂ€ndbar information om sprickor och ytskador krĂ€vs erfarenhet och arbete med att trimma in parametrar i analysprogramvaran.As condition measurements carried out on the Swedish national road network currently do not provide a sufficiently comprehensive description of all types of distress, it is difficult to select the sections most in need of maintenance. This lack of information concerns mainly pavement surface condition parameters such as cracking and ravelling. In this study, twenty-seven two-way road sections with varying degrees of pavement surface distress were selected. All sections were identified as "in need of maintenance" by engineers from the Swedish Transport Administration. The sections were objectively measured using a system that covered the full lane width. For comparison purposes, a subjective condition inventory was also done. We found that the objective lane-wide measurements had good repeatability with respect to cracking and ravelling. When comparing the objective and subjective inventories, some sections correlated well whereas some hardly correlated at all. In order for a lane-wide measurement to provide useful information on cracking and other forms of surface distress, our conclusion is that more experience and a better understanding of how to adjust the parameters in the analysis software is needed
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