The human cytomegalovirus ul11 protein interacts with the receptor tyrosine phosphatase cd45, resulting in functional paralysis of t cells

Human cytomegalovirus (CMV) exerts diverse and complex effects on the immune system, not all of which have been attributed to viral genes. Acute CMV infection results in transient restrictions in T cell proliferative ability, which can impair the control of the virus and increase the risk of secondary infections in patients with weakened or immature immune systems. In a search for new immunomodulatory proteins, we investigated the UL11 protein, a member of the CMV RL11 family. This protein family is defined by the RL11 domain, which has homology to immunoglobulin domains and adenoviral immunomodulatory proteins. We show that pUL11 is expressed on the cell surface and induces intercellular interactions with leukocytes. This was demonstrated to be due to the interaction of pUL11 with the receptor tyrosine phosphatase CD45, identified by mass spectrometry analysis of pUL11-associated proteins. CD45 expression is sufficient to mediate the interaction with pUL11 and is required for pUL11 binding to T cells, indicating that pUL11 is a specific CD45 ligand. CD45 has a pivotal function regulating T cell signaling thresholds; in its absence, the Src family kinase Lck is inactive and signaling through the T cell receptor (TCR) is therefore shut off. In the presence of pUL11, several CD45-mediated functions were inhibited. The induction of tyrosine phosphorylation of multiple signaling proteins upon TCR stimulation was reduced and T cell proliferation was impaired. We therefore conclude that pUL11 has immunosuppressive properties, and that disruption of T cell function via inhibition of CD45 is a previously unknown immunomodulatory strategy of CMV

Transport costs in the distribution of HKScan : A study of the factors that drive transport costs and how they can be affected

Denna rapport innehåller en fallstudie av företaget HKScan och fokuserar på deras interna hantering av transporter ut till kunderna. Eftersom HKScan verkar i en konkurrensutsatt bransch med små marginaler så är det viktigt att varenda krona används på ett bra sätt. Transporter är en aktivitet som sällan undersöks eftersom det är en operativ aktivitet som är fristående från övrig verksamhet. Det har dock visat sig att även om olika funktioner i ett företag traditionellt styrs separat så finns det starka kopplingar mellan transporter och funktioner som sälj, marknad, inköp, ekonomi, personaladministration och produktion. Denna studies syfte var därför att undersöka vilka faktorer som påverkar transportkostnaderna och ge förslag på hur transportkostnaderna på sikt kan minskas. Undersökningen av vilka faktorer som påverkar transportkostnaderna genomfördes i flera steg. Först sammanställdes de faktorer som nämns i teorin vilket kompletterades med de faktorer som Supply Chain-funktionen på HKScan trodde påverkade transportkostnaderna. Detta resulterade i en modell med 18 möjliga påverkande faktorer som sedan avgränsades beroende på vad HKScan mäter och vad som ansågs relevant att undersöka. Denna avgränsade lista bestod av sju drivare som sedan undersöktes med hjälp av en multipel regressionsanalys. I denna analys kunde det matematiskt bevisas att faktorerna vikt per transportkolli, transporttemperatur, kvantitet, avstånd samt vilken typ av kund som transporten gick till påverkar transportkostnaden både på sändningsnivå och per transportkolli. Efter att dessa drivare identifierats så hölls intervjuer för att undersöka vilka funktioner som har störst möjlighet att påverka dem och därför i förlängningen även kan påverka transportkostnaden direkt. Dessa intervjuer visade att det främst är funktionerna för sälj och Supply Chain som direkt kan påverka transportkostnaden. Även marknad och produktion har möjlighet att påverka transportkostnaden på ett indirekt sätt. Slutligen genomfördes intervjuer med personal från de berörda funktionerna för att undersöka på vilket sätt medvetenheten och styrningen av transportkostnaderna kan förbättras. Detta resulterade i ett stort antal förslag där det mest frekvent förekommande var en kontinuerlig uppföljning av transportkostnaderna. Denna uppföljning ska inte bara vara på nivån att transportkostnaderna varit dyra utan gå djupare och peka på vilka mönster i beställningar och transporter som gett upphov till den högre kostnaden. Om denna uppföljning ska ske manuellt eller med hjälp av ett automatiserat verktyg finns det olika åsikter om men personalen känner genomgående de behöver öka medvetenheten om vad som påverkar transportkostnaderna för att kunna sänka dem.This report contains a case study of the company HKScan and focuses on their internal handling of transports to customers. As HKScan operates in a competitive industry with small margins, it is important that all money is used in the best way. An activity that costs money but rarely is investigated is the transportation since it is seen as a very operative activity. It has, however, been found that although different functions of a company are traditionally controlled separately, there are strong links between transports and functions such as sales, marketing, purchasing, finance, human resource management and production. The purpose of this study was therefore to investigate which factors that affect transport costs and provide suggestions on how transport costs can be reduced. The study of which factors that affect transport costs was carried out in several stages. First, factors mentioned in the theory were compiled and complemented by the factors that the Supply Chain department at HKScan believed could affect the cost. This resulted in a list of 18 possible influencing factors that were then demarcated depending on what HKScan measures and which was considered relevant to investigate. This demarcated list consisted of seven factors, which were then investigated using a multiple regression analysis. From this analysis, it could be mathematically proven that the parameters quantity, distance, weight per transport package, temperature, and the type of customer to which the transport went, affects the transport cost both at the shipping level and per transport package. After these drivers had been identified, interviews were held to investigate which departments have the greatest potential to influence them and, in the long run, affect transport costs. These interviews showed that it was primarily the sales and Supply Chain departments that affect the shipping costs, even though market and production have a more indirect impact. Finally, interviews were conducted with staff from the relevant departments to investigate how awareness and management of transport costs can be improved. This resulted in a large number of proposals where the most frequent one mentioned was a continuous follow-up on transport costs. This follow-up should point out which patterns in orders and shipments that gave rise to the higher cost. If this follow-up is to be done manually or by means of an automated tool, there are different views, but the staff feels that in order to reduce transport costs, they need increased awareness of what affects them.Observera att alla siffror och resultat i rapporten är modifierade och speglar inte det verkliga resultatet.</p

Integrated modeling, finite-element analysis, and engineering design for thin-shell structures using subdivision

Many engineering des98 applications require geometric modeling and mechanical s imulation of thin flexibles tructures ,s uchas thos e found in the automotive and aerosH ce indus ries Traditionally, geometric modeling, mechanical s mulation, and engineering des ign are treated as s eparate modules requiring di#erent methods and represR tations Due to the incompatibility of the involved repres9 tations the trans ition from geometric modeling to mechanicals imulation,as wellas in the oppos ite direction, requires s ubs tantial e#ort. However, for engineering des ign purpos es e#- cient trans ition between geometric modeling and mechanicalsa ulationis esio tial. We propos e the us ofs ubdivis ons5AP ces as a common foundation for modeling, s mulation, and des gn in a unified framework. Subdivis ons686 ces provide a flexible and e#cient tool for arbitrary topology free-forms urface modeling, avoiding many of the problems inherent in traditionals pline patch bas d approaches The underlying bass functions are als ideallys5 ted for a finite-element treatment of thes o-called thins hell equations , which des cribe the mechanical behavior of the modeleds tructures The res ulting s lvers are highly s alable, providing an e#cient computational foundation for des ign exploration and optimization. We demons rate our claims withs everal des5R examples s howing the versH6P64 y and high accuracy of the propos d method. Key words: Subdivis on Surfaces Finite-Elements Shells ;