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| 2. |
- Zieba, Agata, et al.
(författare)
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Molecular tools for companion diagnostics
- 2012
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Ingår i: New Biotechnology. - : Elsevier BV. - 1871-6784 .- 1876-4347. ; 29:6, s. 634-640
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Forskningsöversikt (refereegranskat)abstract
- The heterogeneous nature of cancer results in highly variable therapeutic responses even among patients with identical stages and grades of a malignancy. The move towards personalised medicine in cancer therapy has therefore been motivated by a need to customise therapy according to molecular features of individual tumours. Companion diagnostics serves to support early drug development, it can provide surrogate markers in clinical trials, and also guide selection of individual therapies and monitoring of responses in routine clinical care. The era of companion diagnostics can be said to have begun with the introduction of the HercepTest - a first-of-a-kind diagnostic tool developed by DakoCytomation in 1998 to select patients for therapy with the anticancer drug Herceptin (trastuzumab). Herceptin and the paired test proved that companion diagnostics can help guide patient-tailored therapies. We will discuss herein technologies to analyse companion diagnostics markers at the level of DNA, RNA or protein, focusing on a series of methods developed in our laboratory that can facilitate drug development and help stratify patients for therapy.
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| 3. |
- Adolfo, Eldridge Vigil, et al.
(författare)
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Electoral Violence in Africa
- 2012
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- In the time period 2012–2013, over 20 national elections and two constitutional referendums are scheduled in Africa. In several of these elections, violence is anticipated to play a prominent role. There is great urgency to support the establishment of effective and legitimate electoral institutions and electoral frameworks; institute reforms aimed at lowering the stakes of elections; encourage the devolution of powers; improve the socio-economic standing of the populace; and devise strategies to prevent and manage electoral violence.
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| 4. |
- Boij, Mats, et al.
(författare)
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Betti numbers of graded modules and the multiplicity conjecture in the non-Cohen-Macaulay case
- 2012
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Ingår i: Algebra & Number Theory. - : Mathematical Sciences Publishers. - 1937-0652 .- 1944-7833. ; 6:3, s. 437-454
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Tidskriftsartikel (refereegranskat)abstract
- We use results of Eisenbud and Schreyer to prove that any Betti diagram of a graded module over a standard graded polynomial ring is a positive linear combination of Betti diagrams of modules with a pure resolution. This implies the multiplicity conjecture of Herzog, Huneke, and Srinivasan for modules that are not necessarily Cohen-Macaulay and also implies a generalized version of these inequalities. We also give a combinatorial proof of the convexity of the simplicial fan spanned by pure diagrams.
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| 5. |
- Castegren, Markus, et al.
(författare)
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Differences in Organ Dysfunction in Endotoxin Tolerant Pigs Under Intensive Care Exposed to a Second Hit of Endotoxin
- 2012
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Ingår i: Shock. - 1073-2322 .- 1540-0514. ; 37:5, s. 501-510
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Tidskriftsartikel (refereegranskat)abstract
- Endotoxin tolerance is a well-studied phenomenon associated with a reduced inflammatory response. In the switch from an inflammatory to an anti-inflammatory response in clinical sepsis the concept of endotoxin tolerance is of obvious interest. However, only limited data exist regarding the effect of endotoxin tolerance on organ dysfunction and, therefore, this was investigated in a porcine intensive care sepsis model. Twenty-seven healthy pigs, including nine control animals, were included in the study. Twelve pigs pre-exposed to 24 h of intravenous endotoxin infusion and intensive care and six unexposed pigs were given either a high- or low-dose endotoxin challenge for 6 h. Inflammatory, circulatory, hypoperfusion and organ dysfunction parameters were followed. The inflammatory responses as well as parameters representing circulation, hypoperfusion, cardiac and renal function were all markedly attenuated in animals pre-exposed to endotoxin and intensive care as compared with animals not pre-exposed. In animals pre-exposed to endotoxin and given the high-dose of endotoxin challenge, deterioration in pulmonary function was equal to or even worse than in animals not pre-exposed.In contrast to the overall protective effect of endotoxin tolerance observed in other organ systems, the lungs of endotoxin tolerant animals demonstrated an increased responsiveness to high-dose endotoxin challenge.
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| 6. |
- Clausson, Carl-Magnus, et al.
(författare)
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Methods for analysis of the cancer microenvironment and their potential for disease prediction, monitoring and personalized treatments
- 2012
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Ingår i: The EPMA journal. - : Springer Science and Business Media LLC. - 1878-5085 .- 1878-5077. ; 3:7
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Forskningsöversikt (refereegranskat)abstract
- A tumor does not consist of a homogenous population of cancer cells. Therefore, to understand cancer, the tumor microenvironment and the interplay between the different cell types present in the tumor has to be taken into account, and how this regulates the growth and survival of the cancer cells. To achieve a full picture of this complex interplay, analysis of tumor tissue should ideally be performed with cellular resolution, providing activity status of individual cells in this heterogeneous population of different cell-types. In addition, in situ analysis provides information on the architecture of the tissue wherein the cancer cells thrive, providing information of the identity of neighboring cells that can be used to understand cell-cell communication. Herein we describe how padlock probes and in situ PLA can be used for visualization of nucleic acids and protein activity, respectively, directly in tissue sections, and their potential future role in personalized medicine.
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| 7. |
- Conze, Tim, 1977-
(författare)
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Ligation-mediated Molecular Analysis of Influenza Subtypes, Splicing and Protein Glycosylation
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Binder-based assays are employed throughout the life sciences. Powerful signal amplification techniques have enabled detection of very rare molecule species diluted in simple buffers. Unspecific binding of primary binders leads to increased background in more complex samples. By requiring two recognition events, ligation-based molecular analyses provide highly specific detection of biomolecules in complex samples. We developed a highly multiplexed padlock-ligation assay targeting signature sequences in the hemagglutinin and neuraminidase genes. From a panel of 77 avian influenza isolates of all major serotypes, 97% were genotyped correctly in accordance with previous classifications by classical diagnostic methods (Paper I). Alternative splicing is an important mechanism expanding the proteome. Current analysis techniques fail to provide sequences of complete transcripts beyond the read length of sequencing instruments. We devised and implemented a strategy to compress the sequence information contained in the splicing pattern of a transcript into the presence or absence of sequence-blocks. We demonstrate that this assay yields information about the splicing patterns in thousands of transcripts from cellular cDNA (Paper II). Expression changes of mucin proteins and glycosylation structures are frequently observed from the early stages of cancer development. Expression of mucin 2 and sialyl-Tn are common features of intestinal metaplasia and gastric cancer, and are known to co-locate. Here we have developed an in situ proximity ligation assay (PLA) directed against mucin 2 and sialyl-Tn. Our study on intestinal metaplasia and gastric cancer tissue sections identified mucin 2 as a major carrier of sialyl-Tn in these conditions, and demonstrated how conveniently glycosylation of proteins can be studied by in situ PLA (Paper III). This thesis shows how the dual recognition requirement of ligation-based assays can be employed to detect target molecules with high specificity, to analyze several sequence features of nucleic acids or to study the proximity of two antigens in situ.
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| 8. |
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| 9. |
- Enström Öst, Cecilia, 1971-, et al.
(författare)
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High house prices and homeownership rates
- 2013
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Earlier research have concluded that high house prices, relative to household income and wealth, and a tax on imputed rent are the most important causes of a countries low ownership rate. Given these findings, it is challenging to apply a similar analysis to a housing market characterized by comparatively high homeownership rates. One candidate for such a comparison is Sweden, where homeownership rates have exceeded 80% for at least the last two decades. From a particularly rich database covering all inhabitants of Sweden, we use observations of some 790,000 households (corresponding to some 2.9 million inhabitants) to analyze the Stockholm region housing market in 2008. The results suggest that high house prices relative to rents are unlikely to be the only key variable explaining the general ownership rate pattern in a housing market.
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| 10. |
- Enström Öst, Cecilia, et al.
(författare)
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Household allocation and spatial distribution in a market under ("soft") rent control
- 2014
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Ingår i: Journal of Policy Modeling. - : Elsevier BV. - 0161-8938 .- 1873-8060. ; 36:2, s. 353-372
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Tidskriftsartikel (refereegranskat)abstract
- We analyse whether segregation exists in the rental housing market in Stockholm, Sweden, a market under persistent and all-embracing, yet "soft", rent control. We use segregation measures for the uncontrolled cooperative housing segment as benchmarks for analysing whether rent control counteracts segregation. We apply the analyses to a rich dataset encompassing some 400,000 households. We find that income segregation is significantly lower in the rent control segment than in the free market benchmark. However, when analysing segregation with respect to other segregation measures, the rental housing market is more segregated in these respects than in the non-regulated market for cooperatives. Rent control has arguably led to a comparatively flat rent gradient over the city and thus the comparatively low rents in the central, and most attractive, areas of the city provide a general subsidy to those who live in these areas. But according to our results this subsidy does not efficiently benefit households with low educated level, households with children, young households or households with a migrant background.
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