| 1. |
- Birkinshaw, Julian M., et al.
(författare)
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Why Do Some Multinational Corporations Relocate Their Headquarters Overseas?
- 2006
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Ingår i: Strategic Management Journal. - : Wiley. - 0143-2095 .- 1097-0266. ; 27:7, s. 681-700
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Tidskriftsartikel (refereegranskat)abstract
- This paper examines the decision by a multinational corporation (MNC) to relocate its business unit and/or corporate HQ overseas. We argue that business unit HQs move overseas in response to changes in the internal configuration of their unit's activities and the demands of the product markets in which they operate, whereas corporate HQs move overseas in response to the demands of external stakeholders, in particular global financial markets and shareholders. Using data on 125 business unit HQs and 35 corporate HQs, we test and find support for these arguments. The research highlights important differences between corporate- and business-level strategy, and it suggests ways in which the theory of the MNC needs to be reconsidered.
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| 2. |
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| 3. |
- Holm, Pontus, et al.
(författare)
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Loss- and gain-of-function analyses reveal targets of Pax6 in the developing mouse telencephalon.
- 2007
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Ingår i: Molecular and Cellular Neuroscience. - : Elsevier BV. - 1044-7431 .- 1095-9327. ; 34:1, s. 99-119
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Forskningsöversikt (refereegranskat)abstract
- Appropriate neurogenesis and patterning of the forebrain requires the transcription factor Pax6, yet it is largely unknown how Pax6 exerts its effects at the molecular level. To characterize Pax6-mediated regulation of gene expression during murine forebrain neurogenesis, we performed microarray analysis with tissue from the dorsal Pax6-dependent telencephalon and the ventral Pax6-negative telencephalon at the onset of neurogenesis (E12) and at mid-neurogenesis (E15) in wild-type and Pax6-deficient mutant littermates. In the Pax6-deficient cortex the expression levels of various transcription factors involved in neurogenesis (like Satb2, Nfia, AP-2 gamma, NeuroD6, Ngn2, Tbr2, Bhlhb5) and the retinoic acid signalling molecule Rlbp1 were reduced. Regulation by Pax6 could be confirmed upon electroporation of a Pax6- and a dominant-negative Pax6-containing vector into embryonic cortex. Taken together, our data reveal novel insights into the molecular pathways regulated by Pax6 during cortical neurogenesis. Most intriguingly, this analysis revealed time- and region-specific differences in Pax6-mediated transcription, explaining the specific function of Pax6 at early and later stages of neurogenesis. (c) 2006 Elsevier Inc. All rights reserved.
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| 4. |
- Holm, Pontus
(författare)
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Survival and differentiation of central noradrenergic neurons
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- About half of all central noradrenergic (NA) neurons reside in the locus coeruleus (LC). Projections from the LC reach target regions throughout the entire brain and regulate a variety of functions, such as mood, vigilance, arousal, sleep, attention and memory acquisition. The development of LC noradrenergic neurons is severely affected by reductions in the availability of BMPs in vivo, and by the lack of the basic helix-loophelix protein Mash1, or the Phox2a, Phox2b or Rnx homeodomain proteins, as shown in null mutant mice. To produce NA neurons we generated neural stem cell clones with stable overexpression of Mash1 or Phox2b and treated them with combinations of BDNF, NT-4, BMPs and FGF to induce a noradrenergic phenotype, but no TH expression was detected. To characterize the survival requirements of developing LC neurons, we examined the involvement of rhombomere I patterning proteins. FGF8, BMP2, BMP5 and BMP7 were able to increase the number of TH positive LC neurons in E13.5 LC cultures. Of all the Writs expressed in the first rhombomere by E12.5 in mice, Wnt5a was the only one that was expressed in the vicinity of the LC and Wnt5a increased the survival of TH positive neurons in LC cultures. These results suggest that patterning signals of rhombomere I may work as survival factors in the LC at later stages of development. Analysis of GDNF and NT-3 double null mutant mice revealed no LC abnormalities, just as in the individual knockouts. Treatment of E13.5 LC cultures with GDNF, NTN and NT-3 did not affect LC neuron survival, suggesting that these molecules are not essential for embryonic LC development. However, we show, both in vivo and in vitro, that GDNF and NTN are neuritogenic factors for LC noradrenergic neurons. The two neurotrophins NT-4 and BDNF and their preferred receptor, TrkB, were studied for their role in LC development. We conclude that they play critical roles for the survival and phenotypic differentiation of developing LC noradrenergic neurons, possibly by linking the CREB and the Mash1-Phox2 pathways of catecholaminergic phenotype induction. TrkB is expressed in the developing mouse LC and TrkB knockout mice suffer deficient LC development. BDNF and NT-4 dramatically increase the number of TH and Phox2a immunoreactive neurons in E 13.5 rat LC primary cultures. Examination of more mature LC neurons (E15) treated with BMP2 and/or forskolin suggested that stimulation of these cells by BMPs and cAMP plays an important role in conferring NA neurons responsiveness to several trophic factors.
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| 5. |
- Holm, Tina, et al.
(författare)
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Studying the uptake of cell-penetrating peptides
- 2006
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Ingår i: Nature Protocols. - : Springer Science and Business Media LLC. - 1754-2189 .- 1750-2799. ; 1:2, s. 1001-1005
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Tidskriftsartikel (refereegranskat)abstract
- More than a decade ago, it was discovered that cationic peptides could traverse the cellular plasma membrane without specific transporter proteins or membrane damage. Subsequently, it was found that these peptides, known as cell-penetrating peptides (CPPs), were also capable of delivering cargos into cells, hence the great potential of these vectors was acknowledged. Today, many different research groups are working with CPPs, which necessitates efforts to develop unified assays enabling the comparison of data. Here we contribute three protocols for evaluation of CPPs which, if used in conjunction, provide complementary data about the amount and mechanism of uptake (fluorometric analysis and confocal microscopy, respectively), as well as the extent of degradation (HPLC analysis of cell lysates). All three protocols are based on the use of fluorescently labeled peptides and can be performed on the same workday.
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| 6. |
- Närman, Per, et al.
(författare)
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Data accuracy assessment using enterprise architecture
- 2011
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Ingår i: Enterprise Information Systems. - : Informa UK Limited. - 1751-7575 .- 1751-7583. ; 5:1, s. 37-58
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Tidskriftsartikel (refereegranskat)abstract
- Errors in business processes result in poor data accuracy. This article proposes an architecture analysis method which utilises ArchiMate and the Probabilistic Relational Model formalism to model and analyse data accuracy. Since the resources available for architecture analysis are usually quite scarce, the method advocates interviews as the primary data collection technique. A case study demonstrates that the method yields correct data accuracy estimates and is more resource-efficient than a competing sampling-based data accuracy estimation method.
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| 7. |
- Närman, Per, et al.
(författare)
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Using enterprise architecture and technology adoption models to predict application usage
- 2012
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Ingår i: Journal of Systems and Software. - : Elsevier BV. - 0164-1212 .- 1873-1228. ; 85:8, s. 1953-1967
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Tidskriftsartikel (refereegranskat)abstract
- Application usage is an important parameter to consider in application portfolio management. This paper presents an enterprise architecture analysis framework which can be used to assess application usage. The framework, in the form of an architecture metamodel, incorporates variables from the previously published Technology Acceptance Model (TAM) and the Task-Technology Fit (TTF) model. The paper describes how the metamodel has been tailored for a specific domain, viz, industry maintenance management. The metamodel was tested in the maintenance management domain through a survey with 55 respondents at five companies. Data collected in the survey showed that the domain-specific metamodel is able to explain variations in maintenance management application usage. Integrating the TAM and TTF variables with an architecture metamodel allows architects to reuse research results smoothly, thereby aiding them in producing good application portfolio decision-support.
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| 8. |
- Tengryd, Christoffer, et al.
(författare)
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The proteoglycan mimecan is associated with carotid plaque vulnerability and increased risk of future cardiovascular death
- 2020
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Ingår i: Atherosclerosis. - : Elsevier BV. - 0021-9150. ; 313, s. 88-95
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims: A vulnerable plaque is an atherosclerotic plaque that is rupture-prone with a higher risk to cause cardiovascular symptoms such as myocardial infarction or stroke. Mimecan or osteoglycin is a small leucine-rich proteoglycan, important for collagen fibrillogenesis, that has been implicated in atherosclerotic disease, yet the role of mimecan in human atherosclerotic disease remains unknown. Methods: 196 human atherosclerotic carotid plaques were immunostained for mimecan. Smooth muscle cells, macrophages and intraplaque haemorrhage were also measured with immunohistochemistry. Neutral lipids were stained with Oil Red O and calcium deposits were quantified. Plaque homogenate levels of MCP-1, IL-6 and MIP-1β were measured using a Proximity Extension Assay and MMP-9 levels were measured using Mesoscale. Glycosaminoglycans, collagen and elastin were assessed by colorimetric assays and TGF-β1, β2 and β3 were measured using a multiplex assay. Mimecan gene expression in THP-1 derived macrophages was quantified by qPCR and protein expression in vitro was visualized with immunofluorescence. Cardiovascular events were registered using medical charts and national registers during follow-up. Results: Mimecan correlated positively with plaque area of lipids, macrophages, intraplaque haemorrhage and inversely with smooth muscle cell staining. Mimecan also correlated positively with plaque levels of MMP-9 and MCP-1. Mimecan was upregulated in THP-1 derived macrophages upon stimulation with MCP-1. Patients with high levels of mimecan (above median) had higher risk for cardiovascular death. Conclusions: This study indicates that mimecan is associated with a vulnerable plaque phenotype, possibly regulated by plaque inflammation. In line, plaque levels of mimecan independently predict future cardiovascular death.
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| 9. |
- Xie, Haiyan, et al.
(författare)
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Drug quantification in turbid media by fluorescence imaging combined with light-absorption correction using white Monte Carlo simulations.
- 2011
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Ingår i: Journal of Biomedical Optics. - : SPIE-Intl Soc Optical Eng. - 1083-3668. ; 16:6
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Tidskriftsartikel (refereegranskat)abstract
- Accurate quantification of photosensitizers is in many cases a critical issue in photodynamic therapy. As a noninvasive and sensitive tool, fluorescence imaging has attracted particular interest for quantification in pre-clinical research. However, due to the absorption of excitation and emission light by turbid media, such as biological tissue, the detected fluorescence signal does not have a simple and unique dependence on the fluorophore concentration for different tissues, but depends in a complex way on other parameters as well. For this reason, little has been done on drug quantification in vivo by the fluorescence imaging technique. In this paper we present a novel approach to compensate for the light absorption in homogeneous turbid media both for the excitation and emission light, utilizing time-resolved fluorescence white Monte Carlo simulations combined with the Beer-Lambert law. This method shows that the corrected fluorescence intensity is almost proportional to the absolute fluorophore concentration. The results on controllable tissue phantoms and murine tissues are presented and show good correlations between the evaluated fluorescence intensities after the light-absorption correction and absolute fluorophore concentrations. These results suggest that the technique potentially provides the means to quantify the fluorophore concentration from fluorescence images.
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