23 research outputs found

    Intrinsic investigation of sales and operations monitoring and planning in a challenging and complex project-based organization: A case study

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    S&OP has gained extensive admiration from companies recently due to its potential benefits, such as reduced inventory levels, improved forecast accuracy, better resource utilization, and increased customer satisfaction. A S&OP process is one of the fundamental components for companies to survive and sustain a competitive edge in today’s challenging and complex business environment. Considering the recent recognition of S&OP, this master’s thesis explores how an S&OP pro-cess can be designed and executed in a challenging and complex business environment. The objectives of the thesis were to map and describe how the case company currently performs its S&OP process, identify gained benefits, current process challenges, and the roles and re-sponsibilities of the process. Based on the key findings, suggested improvement proposals were developed, for the case company as remedies to take the process to the next level. A qualitative case study was conducted to answer the research questions and reach the goal and objectives of the thesis. Data was collected and analyzed through interviews, observa-tions, and secondary company material. Based on the findings and observations, a compari-son was made against existing literature, theories, and frameworks to find similarities and gaps. The findings indicate that the case company follows a five-step S&OP process initially de-signed for high volumes businesses and not for companies characterized by high complexity, demand fluctuations, and weak forecasting precision. That can be one of the reasons why the case company struggles to acquire all expected benefits from S&OP. Related to this, an-other key finding was that there are no existing theories or frameworks available for S&OP in an engineer-to-order environment. Through S&OP, the case company has achieved many benefits like improved alignment, communication, teamwork, visibility, accountability, deci-sion-making capacity utilization, risk reduction, enabled bundling opportunities in project purchasing and logistics, and reduced inventory levels. Many S&OP-related challenges were also identified, through the empirical study. The main challenges identified are limited sup-plier collaboration, systems connectivity, missing performance management, and data avail-ability and accuracy. The study provides many managerial implications, and suggested im-provement areas in the case company’s S&OP process. All these recommendations are in-tended to support the case company and eventually, other companies to overcome typical challenges. The key enablers of S&OP in a complex and challenging project-based environ-ment are highlighted. Even though the findings generated from this study are based on the case company, other companies operating in a similar environment can acquire beneficial insights and guidelines that might be relevant to them. Finally, future research could investi-gate how an advanced planning system can support organizations operating in a challenging and complex project-based environment and investigate how to measure the performance of the overall S&OP process.FörsĂ€ljning och verksamhetsplanering har pĂ„ senare tid fĂ„tt ett ökat intresse frĂ„n företag pĂ„ grund av dess potentiella fördelar, sĂ„som minskade lagernivĂ„er, förbĂ€ttrad prognosnoggrannhet, bĂ€ttre resursanvĂ€ndning och ökad kundnöjdhet. Processen Ă€r en av de grundlĂ€ggande komponenterna för företag att överleva och upprĂ€tthĂ„lla sin konkurrenskraft i dagens utmanande och komplexa affĂ€rsmiljö. Detta magisterarbete redogör för hur en sĂ„dan process kan utformas och tillĂ€mpas i en utmanande och komplex affĂ€rsmiljö. Uppsatsens mĂ„l var att kartlĂ€gga och beskriva hur det aktuella fallföretaget genomför sin S&OP-process, identifiera uppnĂ„dda fördelar, aktuella processutmaningar samt rollerna och ansvarsomrĂ„den. Resultaten utvecklades pĂ„ basen av förbĂ€ttringsförslag för fallföretaget och Ă„tgĂ€rder för att ta processen till nĂ€sta nivĂ„. En kvalitativ fallstudie genomfördes för att besvara forskningsfrĂ„gorna och uppnĂ„ uppsatsens mĂ„l och syften. Data samlades in och analyserades genom intervjuer, observationer och sekundĂ€rt företagsmaterial. Baserat pĂ„ resultaten gjordes en jĂ€mförelse mot befintlig litteratur, teorier och ramverk för att hitta likheter och möjliga luckor i existerande litteratur. Resultaten visar att fallföretaget följer en femstegs S&OP-process som ursprungligen utformades för företag med höga volymer och inte för företag som kĂ€nnetecknas av hög komplexitet, efterfrĂ„gefluktuationer och svag prognosprecision. Detta kan vara en av anledningarna till att fallföretaget kĂ€mpar med att uppnĂ„ alla förvĂ€ntade fördelar. Ett annat nyckelfynd var att det inte finns nĂ„gra befintliga teorier eller ramverk tillgĂ€ngliga för företag med skrĂ€ddarsydda produkter och lösningar. Fallföretaget har uppnĂ„tt mĂ„nga fördelar med processen sĂ„som förbĂ€ttrad samordning, kommunikation, synlighet, besparingar i logistik- och inköpskostnader samt minskade lagernivĂ„er. Företaget har ocksĂ„ flera utmaningar med processen, var de huvudsakliga utmaningarna Ă€r begrĂ€nsat samarbete med leverantörer, systemanslutning, prestationsstyrning samt tillgĂ€nglighet och noggrannhet av data. Studien ger mĂ„nga ledningsmĂ€ssiga implikationer och föreslagna förbĂ€ttringsomrĂ„den i fallföretagets S&OP-process. Alla dessa rekommendationer Ă€r avsedda att stödja fallföretaget och eventuellt Ă€ven andra företag att övervinna dessa utmaningar. Även om resultaten frĂ„n denna studie Ă€r baserade pĂ„ fallföretaget kan andra företag som verkar i en liknande miljö erhĂ„lla gynnsamma insikter och riktlinjer som kan vara relevanta för dem. Slutligen kan framtida forskning undersöka hur ett avancerat planeringssystem kan stödja organisationer som verkar i en utmanande och komplex projektbaserad miljö samt undersöka hur man mĂ€ter prestandan för den övergripande S&OP-processen

    Microglia : health promoting pathways and therapeutic targets in ageing and neuroinflammation

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    Microglia are the innate immune cells of the CNS with an embryonic origin and self-renew with a slow turnover throughout life. The health-promoting capacities of this cell are being acknowledged through updated and specific tools separating microglia from bone marrow-derived macrophages. Knowing that microglia depends on TGF-ÎČ signaling in acquiring a mature homeostatic phenotype, we also found this cytokine to mediate the integration of monocyte-derived cells into an empty myeloid CNS niche. Microglia or the integrated monocyte-derived macrophages, absent in TGF-ÎČ signaling, developed a damaging phenotype causing spontaneous de-myelination, clinical motor deficits, and death of experimental mice. Multiple sclerosis (MS) is a de-myelinating autoimmune CNS disease, commonly with onset in young adults as a relapsing-remitting disease that over time converts to a progressive accumulation of clinical deficits. The etiology of MS is partly inherited but, in many aspects, unknown, although we have successful treatments targeting the adaptive immune system reducing relapses and likely delay progression. However, the progressive MS disease, believed to emanate from the cells residing in the CNS, is very limited in treatment options. Genetic association studies imply that the microglial cell harness a substantial part of the MS-pathogenicity. How this relates to disease phenotypes offering treatment targets is sparsely explored. As the human CNS is rather inaccessible, the use of the rodent animal model experimental autoimmune encephalomyelitis (EAE) has been instrumental in deciphering the MS pathology. In the recovery phase of this disease, the microglial clearance of myelin is of substantial importance. We found this process to depend on a lysosomal degradation process referred to as autophagy- or LC3- associated phagocytosis. During EAE, microglia lacking the autophagy gene Atg7 accumulated myelin debris and had reduced recirculation of scavenger receptors, causing a secondary impairment in tissue myelin-clearance. These cells also acquired an altered transcriptome associated with inflammatory microglia/macrophage phenotypes found in, e.g., MS, neurodegenerative disease, and stroke, while the genes of the homeostatic signature were downregulated. Autophagy is known to alter with age, and we targeted this by increasing autophagy-associated phagocytosis in aged microglia by treatment with the sugar molecule trehalose, which ameliorated EAE. Of note, trehalose metabolism and some autophagy-associated phagocytosis pathway components are associated with MS through risk allele analysis. Microglial proliferation and survival rely on CSF-1 (M-CSF) or IL-34 mediated activation of the CSF-1 receptor (CSF1R). While microglial CSF-1 expression is elevated during inflammation, CSF1R associate with the homeostatic microglia. In the healthy CNS, neurons are the main source of IL-34, but a specific role of this cytokine in neuroinflammation remains to be evaluated. The ageing CNS is challenging for microglia in terms of adaptations to aid in health-promoting capacities in functions that, together with CSF1R signaling, engage canonical-autophagy. This degradation pathway controls the quality and quantity of, e.g., inflammatory mediators, receptors, and organelles. By deleting the key canonical-autophagy gene Ulk1, we found an age-associated subpopulation of microglia with highly activated ERK1/2 upon CSF1R engagement to be diminished, a loss not compensated by other microglia or myeloid cells. The loss of this population in aged mice caused neural and glial cell death and high mortality in EAE. In autophagy-competent aged mice, we could expand this CNS protective population specifically by IL-34 treatment and thereby ameliorate disease. In this thesis, I present TGF-ÎČ as an essential factor in establishing a homeostatic CNS myeloid cell and a demand in aged microglia for canonical-autophagy to maintain a neuroprotective phenotype. The myelin processing by microglia through autophagyassociated phagocytosis is dissected in detail, and we can show how a decline in this pathway can be restored in aged microglia

    Microglial autophagy-associated phagocytosis is essential for recovery from neuroinflammation

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    Multiple sclerosis (MS) is a leading cause of incurable progressive disability in young adults caused by inflammation and neurodegeneration in the central nervous system (CNS). The capacity of microglia to clear tissue debris is essential for maintaining and restoring CNS homeostasis. This capacity diminishes with age, and age strongly associates with MS disease progression, although the underlying mechanisms are still largely elusive. Here, we demonstrate that the recovery from CNS inflammation in a murine model of MS is dependent on the ability of microglia to clear tissue debris. Microglia-specific deletion of the autophagy regulator Atg7, but not the canonical macroautophagy protein Ulk1, led to increased intracellular accumulation of phagocytosed myelin and progressive MS-like disease. This impairment correlated with a microglial phenotype previously associated with neurodegenerative pathologies. Moreover, Atg7-deficient microglia showed notable transcriptional and functional similarities to microglia from aged wild-type mice that were also unable to clear myelin and recover from disease. In contrast, induction of autophagy in aged mice using the disaccharide trehalose found in plants and fungi led to functional myelin clearance and disease remission. Our results demonstrate that a noncanonical form of autophagy in microglia is responsible for myelin degradation and clearance leading to recovery from MS-like disease and that boosting this process has a therapeutic potential for age-related neuroinflammatory conditions.Swedish Research CouncilSwedish Brain FoundationSwedish Association for Persons with Neurological DisabilitiesStockholm County Council (ALF project)AstraZeneca (AstraZeneca-Science for Life Laboratory collaboration)European Union Horizon 2020/European Research Council Consolidator Grant (Epi4MS)Knut and Alice Wallenbergs FoundationMargeretha af Ugglas FoundationAlltid Litt SterkereFoundation of Swedish MS researchNEURO SwedenKarolinska InstitutetAccepte

    Reconstruction of Genome-Scale Active Metabolic Networks for 69 Human Cell Types and 16 Cancer Types Using INIT

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    Development of high throughput analytical methods has given physicians the potential access to extensive and patient-specific data sets, such as gene sequences, gene expression profiles or metabolite footprints. This opens for a new approach in health care, which is both personalized and based on system-level analysis. Genome-scale metabolic networks provide a mechanistic description of the relationships between different genes, which is valuable for the analysis and interpretation of large experimental data-sets. Here we describe the generation of genome-scale active metabolic networks for 69 different cell types and 16 cancer types using the INIT (Integrative Network Inference for Tissues) algorithm. The INIT algorithm uses cell type specific information about protein abundances contained in the Human Proteome Atlas as the main source of evidence. The generated models constitute the first step towards establishing a Human Metabolic Atlas, which will be a comprehensive description (accessible online) of the metabolism of different human cell types, and will allow for tissue-level and organism-level simulations in order to achieve a better understanding of complex diseases. A comparative analysis between the active metabolic networks of cancer types and healthy cell types allowed for identification of cancer-specific metabolic features that constitute generic potential drug targets for cancer treatment

    Acute treatment with valproic acid and L-thyroxine ameliorates clinical signs of experimental autoimmune encephalomyelitis and prevents brain pathology in DA rats

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    This work was supported by grants from the Swedish Research Council (MJ (K2008-66X-20776-01-4 and K2012-99X-20776-05-3)), OH (2011-3457) and GCB (K2011-80P-21816-01-4 and K2011-80X- 21817-01-4)), Harald and Greta Jeanssons Foundation (MJ), Swedish Association for Persons with Neurological Disabilities (MJ), ÅkeWibergs Foundation (MJ), Åke Löwnertz Foundation (MJ), Swedish Brain Foundation (MJ and GCB), David and Astrid HagĂ©len Foundation (GCB), Swedish Society for Medical Research (GCB), Swedish Society of Medicine (GCB), Socialstyrelsen (MJ), Karolinska Institutet funds (MJ and GCB), Marie Curie Integration Grant, Seventh Framework Programme, European Union (GCB, PCIG12-GA-2012-333713)), Neuropromise LSHM-CT-2005-018637 (MZA, HL) and Theme Center for Regenerative Medicine at Karolinska Institutet (OH)

    Pupils areas of interest, self-confidence, space for action and gender conceptions in music production courses at a upper secondary school : - in relation to the gender norms in the music industry

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    Denna studies syfte Ă€r att undersöka hur intresseomrĂ„den, sjĂ€lvförtroende, platstagande och genusförestĂ€llningar skiljer sig Ă„t mellan elever med olika kön i kurserna Musikproduktion 1 och 2 pĂ„ gymnasiet i relation till musikbranschens könsnormer. Studiens data samlades in genom fyra kvalitativa semistrukturerade intervjuer med informanter som gĂ„r kurserna Musikproduktion 1 och Musikproduktion 2 pĂ„ gymnasiet. Empirin analyserades sedan med tematisk analys och utifrĂ„n ett genusteoretiskt ramverk. I resultatet framkommer det att kursernas könsfördelning skiljer sig mot normen inom musikbranschen - det Ă€r alltsĂ„ fler tjejer Ă€n killar. Även teknikintresset skiljer sig dĂ€r tjejerna i kurserna generellt sett Ă€r mer intresserade av teknik Ă€n de som identifierar sig som kille respektive icke-binĂ€r. I andra situationer, dĂ€r grupparbete Ă€r i fokus, Ă€r genusordningen mer likt normen. I dessa situationer vĂ€ljer tjejerna att positionera sig i en supportande roll till killarna för att slippa bli dömda utifrĂ„n deras kunskap inom teknik. Hos en av informanterna som identifierar sig som tjej, följs den norm som enligt tidigare forskning finns gĂ€llande dĂ„ligt sjĂ€lvförtroende. UtifrĂ„n studiens bakgrund, tidigare forskning och genusteoretiskt perspektiv diskuteras sedan resultatet

    When is congestion tax socioeconomically viable?

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    Det sker en ökad trafik i Sverige, vilket medför konsekvenser som t.ex. ökad trĂ€ngsel pĂ„ vĂ€garna samt utslĂ€pp som pĂ„verkar miljön. Dessa Ă€r exempel pĂ„ negativa externa effekter, vilka kan motverkas genom en optimal prissĂ€ttning av gatuutrymme. Sverige har olika miljömĂ„l, för att uppnĂ„ dessa mĂ„l Ă€r eventuellt förĂ€ndringar i motortrafik ett tillvĂ€gagĂ„ngssĂ€tt. UtslĂ€pp i stĂ€der Ă€r ett hĂ€lsoproblem, för att kunna förbĂ€ttra hĂ€lsan och förĂ€ndra trafikmönster behövs det att nĂ„gon/nĂ„gra Ă„tgĂ€rder genomförs. Ett exempel pĂ„ en sĂ„dan Ă„tgĂ€rd som har för avsikt att motverka trafik i stadskĂ€rnor samt bidra till renare luft Ă€r trĂ€ngselskatt.Uppsatsens syfte Ă€r att analysera och undersöka vilka faktorer som krĂ€vs för att ett införande av trĂ€ngselskatt ska vara samhĂ€llsekonomiskt lönsamt i en stad. För att kunna undersöka detta har vi valt att genomföra samhĂ€llsekonomiska lönsamhetskalkyler för trĂ€ngselskatt i Malmö, Uppsala och Linköping.Med hjĂ€lp av en lönsamhetskalkyl och teorier bakom optimal prissĂ€ttning genomför vi undersökningar för att besvara huruvida det Ă€r samhĂ€llsekonomiskt lönsamhet med trĂ€ngselskatt. Vi anvĂ€nder av Stockholmsförsöket som en utgĂ„ngspunkt och kompletterar med uppgifter frĂ„n trafikverket.För att vi ska hĂ„lla oss inom ramen för en kandidatuppsats har vissa avgrĂ€nsningar behövt göras. Vi har valt att avgrĂ€nsa oss till att studera Sverige. För att genomföra studien har vi anvĂ€nt oss av Stockholm och Göteborg, dĂ„ de infört trĂ€ngselskatt. Ännu en avgrĂ€nsning vi gör Ă€r att endast undersöka direkta effekter inom transportsektorn och inte ta hĂ€nsyn till t.ex. turismens pĂ„verkan vid ett införande av trĂ€ngselskatt.Vi drar slutsatsen utifrĂ„n vĂ„ra kalkyler att det ej verkar vara samhĂ€llsekonomiskt lönsamt att införa trĂ€ngselskatt i Malmö, Uppsala eller Linköping. VĂ„ra studier tyder pĂ„ att en specifik faktor pĂ„verkar det samhĂ€llsekonomiska utfallet. Denna faktor verkar vara befolkningsmĂ€ngden i stĂ€derna

    What characterizes the typical consumer of ecological products in Sweden?

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    PĂ„ livsmedelsmarknaden finns det olika produkter som konsumenten kan vĂ€lja mellan. Valensom görs inom dagligvaruhandeln kan pĂ„verka individen och samhĂ€llet pĂ„ olika sĂ€tt, dĂ„produkter har olika nĂ€ringsinnehĂ„ll och de har producerats under olika förutsĂ€ttningar. För attkonsumenten ska veta hur olika produkter pĂ„verkar individen och samhĂ€llet finns det olikamĂ€rkningar sĂ„som Fairtrade och KRAV. Ekologiska produkter marknadsförs som hĂ€lsosammasamtidigt som de ska vara bĂ€ttre för miljön Ă€n icke ekologiska produkter. Den ekologiskamarknaden har ökat de senaste 5 Ă„ren. Av den anledningen finner vi det intressant att analyseravem som vĂ€ljer att konsumera ekologiska produkter och varför.Syftet med studien Ă€r att analysera vilka faktorer som pĂ„verkar konsumenternas val attkonsumera ekologiska produkter. För att kunna analysera de olika faktorerna anvĂ€ndskvantitativa ansatser. Data samlas in genom en enkĂ€tundersökning och analyseras medekonometriska tekniker. Resultatet analyseras Ă€ven med hjĂ€lp av ekonomiska teorier.EnkĂ€tundersökningen genomförs pĂ„ den svenska marknaden, i de tvĂ„ kommunerna Norrköpingoch Ockelbo.Studiens resultat indikerar att utbildning, kön, upplevd kunskap om ekologiska mĂ€rkningar,upplevd mediepĂ„verkan, hĂ€rkomst och kommun Ă€r signifikanta variabler för att förklaraekologisk konsumtion. Resultatet indikerar Ă€ven att de tvĂ„ viktigaste argumenten för attkonsumera ekologiska produkter Ă€r ur hĂ€lso- och miljösynpunkt.The consumer can choose between different products at the market of groceries. These choicescan affect the human being and society in different ways, because products do not have thesame nutritional value and they may not have been produced in the same way. Therefore, it isimportant for the consumer to have knowledge about brands like Fairtrade and KRAV. InSweden, the products that are marketed as healthy and environmentally friendly alternatives arecalled ecological products. In the last 5 years, the market of ecological products has increased,because the market shows that the demand of ecological alternatives has increased. For thisreason, we think it is interesting to analyze who the typical consumer of ecological products isand why.The purpose of this study is to analyze which factors that affects the consumer’s choice ofecological products. To analyze the different factors the study is using quantitative methods.The data will be collected from surveys and then analyzed by using econometrical techniques,and the results will be analyzed and examined using economic theories. The survey is beingperformed on the Swedish market, where the municipalities Norrköping and Ockelbo has beenchosen. Norrköping has a substantially larger population than Ockelbo, which we consider is abenefit for the study.The results of the study shows us that education, gender, perceived knowledge about ecologicalbrands, experienced influence from media, a Nordic heritage and municipality are significantvariables to explain ecological consumption. The results also indicate the two most importantarguments for consuming ecological products are those of health and environmentalperspectives
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