| 1. |
- Liu, Meng, 1976, et al.
(författare)
-
Targeting the protein prenyltransferases efficiently reduces tumor development in mice with K-RAS-induced lung cancer
- 2010
-
Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 107:14, s. 6471-6476
-
Tidskriftsartikel (refereegranskat)abstract
- RAS and RHO proteins, which contribute to tumorigenesis and metastasis, undergo posttranslational modification with an isoprenyl lipid by protein farnesyltransferase (FTase) or protein geranylgeranyltransferase-I (GGTase-I). Inhibitors of FTase and GGTase-I were developed to block RAS-induced malignancies, but their utility has been difficult to evaluate because of off-target effects, drug resistance, and toxicity. Moreover, the impact of FTase deficiency and combined FTase/GGTase-I deficiency has not been evaluated with genetic approaches. We found that inactivation of FTase eliminated farnesylation of HDJ2 and H-RAS, prevented H-RAS targeting to the plasma membrane, and blocked proliferation of primary and K-RAS(G12D)-expressing fibroblasts. FTase inactivation in mice with K-RAS-induced lung cancer reduced tumor growth and improved survival, similar to results obtained previously with inactivation of GGTase-I. Simultaneous inactivation of FTase and GGTase-I markedly reduced lung tumors and improved survival without apparent pulmonary toxicity. These data shed light on the biochemical and therapeutic importance of FTase and suggest that simultaneous inhibition of FTase and GGTase-I could be useful in cancer therapeutics.
|
|
| 2. |
- Öhlén, Mats, 1977-, et al.
(författare)
-
Ideologisk konvergens mellan öst och väst? : de europeiska partifamiljerna 1990-2013
- 2015
-
Ingår i: Nordisk Østforum. - : Universitetsforlaget. - 0801-7220 .- 1891-1773. ; 29:2, s. 167-189
-
Tidskriftsartikel (refereegranskat)abstract
- In this paper we compare ideological positions of political parties in Eastern and Western Europe. As the Communist regimes collapsed and new democracies began to emerge in Eastern Europe, it became obvious that historical and cultural differences existed in relation to Western Europe. This was not least visible among the political parties. When the West European parties initiated contacts with potential sister parties in the East, noticeable differences were revealed in several issues. In general, the eastern parties appeared to be more nationalist, more populist and less tolerant towards minorities than their Western sister parties. The question raised in this paper is whether these differences, have faded or not during the 25-year period after 1989. In order to perform this analysis, the three largest and most influential party families are selected: the Christian Democratic EPP, the Social Democratic PES and the Liberal ALDE. Departing from election manifesto data compiled by the Comparative Manifesto Project, we have performed a time series analysis ranging from 1990 to 2013. Here, the Eastern parties are compared to their Western sister parties within each party family. Firstly, they are compared along the general left-right dimension, and secondly they are compared in specific issues, which have been conceived as delicate matter: the view on the EU, nationalism and view on multiculturalism.
|
|
| 3. |
- Dalin, Martin, 1982, et al.
(författare)
-
Myocardial KRASG12D expression does not cause cardiomyopathy in mice
- 2014
-
Ingår i: Cardiovascular Research. - : Oxford University Press (OUP). - 0008-6363 .- 1755-3245. ; 101:2, s. 229-235
-
Tidskriftsartikel (refereegranskat)abstract
- AimsGerm-line mutations in genes encoding components of the RAS/mitogen-activated protein kinase (MAPK) pathway cause developmental disorders called RASopathies. Hypertrophic cardiomyopathy (HCM) is the most common myocardial pathology and a leading cause of death in RASopathy patients. KRAS mutations are found in Noonan and cardio-facio-cutaneous syndromes. KRAS mutations, unlike mutations of RAF1 and HRAS, are rarely associated with HCM. This has been attributed to the fact that germ-line KRAS mutations cause only a moderate up-regulation of the MAPK pathway. Highly bioactive KRAS mutations have been hypothesized to cause severe cardiomyopathy incompatible with life. The aim of this study was to define the impact of KRASG12D expression in the heart.Methods and resultsTo generate mice with endogenous cardiomyocyte-specific KRASG12D expression (cKRASG12D mice), we bred mice with a Cre-inducible allele expressing KRASG12D from its endogenous promoter (Kras2LSL) to mice expressing Cre under control of the cardiomyocyte-specific α-myosin heavy chain promoter (αMHC-Cre). cKRASG12D mice showed high levels of myocardial ERK and AKT signalling. However, surprisingly, cKRASG12D mice were born in Mendelian ratios, appeared healthy, and had normal function, size, and histology of the heart.ConclusionMice with cardiomyocyte-specific KRAS G12D expression do not develop heart pathology. These results challenge the view that the level of MAPK activation correlates with the severity of HCM in RASopathies and suggests that MAPK-independent strategies may be of interest in the development of new treatments for these syndromes. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2013.
|
|
| 4. |
- Karlsson, Fredrik, 1974-, et al.
(författare)
-
Information security culture : state-of-the-art review between 2000 and 2013
- 2015
-
Ingår i: Information and Computer Security. - : Emerald. - 2056-4961. ; 23:3, s. 246-285
-
Forskningsöversikt (refereegranskat)abstract
- Purpose – The aim of this paper is to survey existing information security culture research to scrutinise the kind of knowledge that has been developed and the way in which this knowledge has been brought about.Design/methodology/approach – Results are based on a literature review of information security culture research published between 2000 and 2013 (December).Findings – This paper can conclude that existing research has focused on a broad set of research topics, but with limited depth. It is striking that the effects of different information security cultures have not been part of that focus. Moreover, existing research has used a small repertoire of research methods, a repertoire that is more limited than in information systems research in general. Furthermore, an extensive part of the research is descriptive, philosophical or theoretical – lacking a structured use of empirical data – which means that it is quite immature.Research limitations/implications – Findings call for future research that: addresses the effects of different information security cultures; addresses the identified research topics with greater depth; focuses more on generating theories or testing theories to increase the maturity of this subfield of information security research; and uses a broader set of research methods. It would be particularly interesting to see future studies that use intervening or ethnographic approaches because, to date, these have been completely lacking in existing research.Practical implications – Findings show that existing research is, to a large extent, descriptive, philosophical or theoretical. Hence, it is difficult for practitioners to adopt these research results, such as frameworks for cultivating or assessment tools, which have not been empirically validated.Originality/value – Few state-of-the-art reviews have sought to assess the maturity of existing research on information security culture. Findings on types of research methods used in information security culture research extend beyond the existing knowledge base, which allows for a critical discussion about existing research in this sub-discipline of information security.
|
|
| 5. |
- Karlsson, Fredrik, 1974-, et al.
(författare)
-
Measuring employees’ compliance : The importance of value pluralism
- 2017
-
Ingår i: Information and Computer Security. - : Emerald Group Publishing Limited. - 2056-4961. ; 25:3, s. 279-299
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: This paper aims to investigate two different types of compliance measures: the first measure is a value-monistic compliance measure, whereas the second is a value-pluralistic measure, which introduces the idea of competing organisational imperatives.Design/methodology/approach: A survey was developed using two sets of items to measure compliance. The survey was sent to 600 white-collar workers and analysed through ordinary least squares.Findings: The results suggest that when using the value-monistic measure, employees' compliance was a function of employees' intentions to comply, their self-efficacy and awareness of information security policies. In addition, compliance was not related to the occurrence of conflicts between information security and other organisational imperatives. However, when the dependent variable was changed to a value-pluralistic measure, the results suggest that employees' compliance was, to a great extent, a function of the occurrence of conflicts between information security and other organisational imperatives, indirect conflicts with other organisational values.Research limitations/implications: The results are based on small survey; yet, the findings are interesting and justify further investigation. The results suggest that relevant organisational imperatives and value systems, along with information security values, should be included in measures for employees' compliance with information security policies.Practical implications: Practitioners and researchers should be aware that there is a difference in measuring employees' compliance using value monistic and value pluralism measurements.Originality/value: Few studies exist that critically compare the two different compliance measures for the same population.
|
|
| 6. |
- Karlsson, Martin, 1982-, et al.
(författare)
-
Organisationskulturens påverkan på informationssäkerhetsarbetet
- 2017. - 1
-
Ingår i: Informationssäkerhet och organisationskultur. - Lund : Studentlitteratur AB. - 9789144121406 ; , s. 25-40
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Organisationskulturen sägs ofta vara en central del i att styra en modern organisation. I detta kapitel resonerar vi kring sambandet mellan den kultur som enligt svenska tjänstemän finns i deras organisationer och informationssäkerheten i dessa organisationer. Denna kunskap är viktig dels för att kunna använda förändring av organisationskulturen som ett sätt att åstadkomma ökad informationssäkerhet, dels för att kunna förutse konsekvenserna av att allt fler organisationer idag förändras i riktning mot vad som enligt vår studie skapar sämre förutsättningar för informationssäkerhet.
|
|
| 7. |
- Karlsson, Martin, 1982-, et al.
(författare)
-
Phenoxazine dyes in solid-state dye-sensitized solar cells
- 2012
-
Ingår i: Journal of Photochemistry and Photobiology A. - : Elsevier BV. - 1010-6030 .- 1873-2666. ; 239, s. 55-59
-
Tidskriftsartikel (refereegranskat)abstract
- Several structural modifications have been made to a sensitizer dye based on the phenoxazine core. which was tested in a solid-state dye-sensitized solar cell configuration based on the hole transporting material 2,2',7,7'-tetrakis(N,N-di-p-methoxyphenyl-amine)-9,9'-spirofluorene. Light-to-power conversion efficiencies between 2.5% and 4.1% are reported herein. The difference in device performance is significantly related to the variations of dye molecular structure, with dye molecules having surface protecting alkoxy-groups yielding better solar cell devices. The phenoxazine dyes were characterized by their light harvesting capabilities and electronic properties such as electron recombination lifetime and chemical dipole moment.
|
|
| 8. |
- Karlsson, Martin, 1982-, et al.
(författare)
-
The effect of perceived organizational culture on employees’ information security compliance
- 2022
-
Ingår i: Information and Computer Security. - : Emerald Group Publishing Limited. - 2056-4961. ; 30:3, s. 382-401
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: This paper aims to investigate the connection between different perceived organizational cultures and information security policy compliance among white-collar workers.Design/methodology/approach: The survey using the Organizational Culture Assessment Instrument was sent to white-collar workers in Sweden (n = 674), asking about compliance with information security policies. The survey instrument is an operationalization of the Competing Values Framework that distinguishes between four different types of organizational culture: clan, adhocracy,market and bureaucracy.Findings: The results indicate that organizational cultures with an internal focus are positively related to employees’ information security policy compliance. Differences in organizational culture with regards to control and flexibility seem to have less effect. The analysis shows that a bureaucratic form of organizational culture is most fruitful for fostering employees’ information security policy compliance.Research limitations/implications: The results suggest that differences in organizational culture are important for employees’ information security policy compliance. This justifies further investigating the mechanisms linking organizational culture to information security compliance.Practical implications: Practitioners should be aware that the different organizational cultures do matter for employees’ information security compliance. In businesses and the public sector, the authors see a development toward customer orientation and marketization, i.e. the opposite an internal focus, that may have negative ramifications for the information security of organizations.Originality/value: Few information security policy compliance studies exist on the consequences of different organizational/information cultures.
|
|
| 9. |
- Le Gal, Kristell, et al.
(författare)
-
Antioxidants can increase melanoma metastasis in mice.
- 2015
-
Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6242 .- 1946-6234. ; 7:308
-
Tidskriftsartikel (refereegranskat)abstract
- Antioxidants in the diet and supplements are widely used to protect against cancer, but clinical trials with antioxidants do not support this concept. Some trials show that antioxidants actually increase cancer risk and a study in mice showed that antioxidants accelerate the progression of primary lung tumors. However, little is known about the impact of antioxidant supplementation on the progression of other types of cancer, including malignant melanoma. We show that administration of N-acetylcysteine (NAC) increases lymph node metastases in an endogenous mouse model of malignant melanoma but has no impact on the number and size of primary tumors. Similarly, NAC and the soluble vitamin E analog Trolox markedly increased the migration and invasive properties of human malignant melanoma cells but did not affect their proliferation. Both antioxidants increased the ratio between reduced and oxidized glutathione in melanoma cells and in lymph node metastases, and the increased migration depended on new glutathione synthesis. Furthermore, both NAC and Trolox increased the activation of the small guanosine triphosphatase (GTPase) RHOA, and blocking downstream RHOA signaling abolished antioxidant-induced migration. These results demonstrate that antioxidants and the glutathione system play a previously unappreciated role in malignant melanoma progression.
|
|
| 10. |
- Sjögren, Anna-Karin, 1980, et al.
(författare)
-
GGTase-I deficiency reduces tumor formation and improves survival in mice with K-RAS-induced lung cancer
- 2007
-
Ingår i: J Clin Invest. - 0021-9738. ; 117:5, s. 1294-304
-
Tidskriftsartikel (refereegranskat)abstract
- Protein geranylgeranyltransferase type I (GGTase-I) is responsible for the posttranslational lipidation of CAAX proteins such as RHOA, RAC1, and cell division cycle 42 (CDC42). Inhibition of GGTase-I has been suggested as a strategy to treat cancer and a host of other diseases. Although several GGTase-I inhibitors (GGTIs) have been synthesized, they have very different properties, and the effects of GGTIs and GGTase-I deficiency are unclear. One concern is that inhibiting GGTase-I might lead to severe toxicity. In this study, we determined the effects of GGTase-I deficiency on cell viability and K-RAS-induced cancer development in mice. Inactivating the gene for the critical beta subunit of GGTase-I eliminated GGTase-I activity, disrupted the actin cytoskeleton, reduced cell migration, and blocked the proliferation of fibroblasts expressing oncogenic K-RAS. Moreover, the absence of GGTase-I activity reduced lung tumor formation, eliminated myeloproliferative phenotypes, and increased survival of mice in which expression of oncogenic K-RAS was switched on in lung cells and myeloid cells. Interestingly, several cell types remained viable in the absence of GGTase-I, and myelopoiesis appeared to function normally. These findings suggest that inhibiting GGTase-I may be a useful strategy to treat K-RAS-induced malignancies.
|
|
