| 1. |
- Eriksson, Daniel, et al.
(author)
-
Cytokine Autoantibody Screening in the Swedish Addison Registry Identifies Patients With Undiagnosed APS1
- 2018
-
In: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 103:1, s. 179-186
-
Journal article (peer-reviewed)abstract
- Context: Autoimmune polyendocrine syndrome type 1 (APS1) is a monogenic disorder that features autoimmune Addison disease as a major component. Although APS1 accounts for only a small fraction of all patients with Addison disease, early identification of these individuals is vital to prevent the potentially lethal complications of APS1.Objective: To determine whether available serological and genetic markers are valuable screening tools for the identification of APS1 among patients diagnosed with Addison disease.Design: We systematically screened 677 patients with Addison disease enrolled in the Swedish Addison Registry for autoantibodies against interleukin-22 and interferon-α4. Autoantibody-positive patients were investigated for clinical manifestations of APS1, additional APS1-specific autoantibodies, and DNA sequence and copy number variations of AIRE.Results: In total, 17 patients (2.5%) displayed autoantibodies against interleukin-22 and/or interferon-α4, of which nine were known APS1 cases. Four patients previously undiagnosed with APS1 fulfilled clinical, genetic, and serological criteria. Hence, we identified four patients with undiagnosed APS1 with this screening procedure.Conclusion: We propose that patients with Addison disease should be routinely screened for cytokine autoantibodies. Clinical or serological support for APS1 should warrant DNA sequencing and copy number analysis of AIRE to enable early diagnosis and prevention of lethal complications.
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| 2. |
- Eriksson, D, et al.
(author)
-
Extended exome sequencing identifies BACH2 as a novel major risk locus for Addison's disease
- 2016
-
In: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 286:6, s. 595-608
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Autoimmune disease is one of the leading causes of morbidity and mortality worldwide. In Addison's disease, the adrenal glands are targeted by destructive autoimmunity. Despite being the most common cause of primary adrenal failure, little is known about its aetiology.METHODS: To understand the genetic background of Addison's disease, we utilized the extensively characterized patients of the Swedish Addison Registry. We developed an extended exome capture array comprising a selected set of 1853 genes and their potential regulatory elements, for the purpose of sequencing 479 patients with Addison's disease and 1394 controls.RESULTS: We identified BACH2 (rs62408233-A, OR = 2.01 (1.71-2.37), P = 1.66 × 10(-15) , MAF 0.46/0.29 in cases/controls) as a novel gene associated with Addison's disease development. We also confirmed the previously known associations with the HLA complex.CONCLUSION: Whilst BACH2 has been previously reported to associate with organ-specific autoimmune diseases co-inherited with Addison's disease, we have identified BACH2 as a major risk locus in Addison's disease, independent of concomitant autoimmune diseases. Our results may enable future research towards preventive disease treatment.
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| 3. |
- Locke, Adam E, et al.
(author)
-
Genetic studies of body mass index yield new insights for obesity biology.
- 2015
-
In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401
-
Journal article (peer-reviewed)abstract
- Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
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| 4. |
- Baldwin, Alexander, et al.
(author)
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Bus Runner : Using Contextual Cues for Procedural Generation of Game Content on Public Transport
- 2017
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In: HCI 2017. - Cham : Springer. ; , s. 21-34
-
Conference paper (peer-reviewed)abstract
- With the support of the regional public transport operator, this paper explores the potential for mobile games to make journeys on public transport more enjoyable. To this end we have developed a game called Bus Runner which is a context-aware endless runner, based on open and shared data. By blending features of the physical world, such as recognisable landmarks, with the game’s virtual world, we situate and enhance passengers’ experience of travelling on public transport. We identify a set of challenges and opportunities based on the development and evaluation of Bus Runner. These are of relevance not only for game development purposes, but also impact context-driven content generation of infotainment services as a whole.
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| 5. |
- Berg Doukkali, Eva, et al.
(author)
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Adolescents and Young Adults Experiences of Childhood Cancer: Descriptions of Daily Life 5 Years After Diagnosis
- 2013
-
In: Cancer Nursing. - : Lippincott, Williams and Wilkins. - 0162-220X .- 1538-9804. ; 36:5, s. 400-407
-
Journal article (peer-reviewed)abstract
- Background: less thanbrgreater than less thanbrgreater thanSurvivors of childhood cancer are a growing population in society. These young people have a high risk of developing chronic health problems with a potential strong impact on their lives. How a childhood cancer experience affects survivors in adolescence has been studied to a limited extent; an increased understanding of this young group is needed to improve follow-up care. less thanbrgreater than less thanbrgreater thanObjective: less thanbrgreater than less thanbrgreater thanThe aim of this study was to gain a deeper understanding of how childhood cancer affects the lives of survivors by exploring adolescents and young adults views of what it is like living with this experience. less thanbrgreater than less thanbrgreater thanMethods: less thanbrgreater than less thanbrgreater thanFifty-nine 11- to 22-year-olds were interviewed a median of 5 years after a cancer diagnosis (response rate, 66%). Data were collected through telephone interviews and were analyzed using qualitative content analysis techniques. less thanbrgreater than less thanbrgreater thanResults: less thanbrgreater than less thanbrgreater thanThree groups of informants were identified according to their descriptions of the influence of cancer treatment on their daily life: feeling like anyone else (informants who described that the cancer experience had almost no influence on current life) (49%), feeling almost like others (those who described some influence) (44%), and feeling different (those describing a great influence on current life) (7%). less thanbrgreater than less thanbrgreater thanConclusions: less thanbrgreater than less thanbrgreater thanMost of the adolescents and young adults appear to get along well, although many informants described that life was affected to some extent by having had cancer. less thanbrgreater than less thanbrgreater thanImplications for Practice: less thanbrgreater than less thanbrgreater thanFollow-up care is needed that can identify those young survivors of childhood cancer having trouble with daily life and offer them support to strengthen their resources in managing difficulties in relation to having had cancer.
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| 6. |
- Berndt, Sonja I., et al.
(author)
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Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture
- 2013
-
In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:5, s. 501-U69
-
Journal article (peer-reviewed)abstract
- Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.
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| 7. |
- Blomberg, Jeanette, et al.
(author)
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Inhibition of cellular FLICE-like inhibitory protein abolishes insensitivity to interferon-α in a resistant variant of the human U937 cell line
- 2011
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In: Apoptosis (London). - : Springer Science and Business Media LLC. - 1360-8185 .- 1573-675X. ; 16:8, s. 783-794
-
Journal article (peer-reviewed)abstract
- Type I interferons constitute a family of pleiotropic cytokines that have a key role in both adaptive and innate immunity. The interferon signalling pathways mediate transcriptional regulation of hundreds of genes, which result in mRNA degradation, decreased protein synthesis, cell cycle inhibition and induction of apoptosis. To elucidate regulatory networks important for interferon induced cell death, we generated interferon resistant U937 cells by selection in progressively increasing concentrations of interferon-α (IFN-α). The results show that IFN-α activates the death receptor signalling pathway and that IFN resistance was associated with cross-resistance to several death receptor ligands in a manner similar to previously described Fas resistant U937 cell lines. Increased expression of the long splice variant of the cellular FLICE-like inhibitor protein (cFLIP-L) was associated with the resistance to death receptor and IFN-α stimulation. Accordingly, inhibition of cFLIP-L expression with cycloheximide or through cFLIP short harpin RNA interference restored sensitivity to Fas and/or IFN-α. Thus, we now show that selection for interferon resistance can generate cells with increased expression of cFLIP, which protects the cells from both IFN-α and death receptor mediated apoptosis.
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| 8. |
- Blomberg, Jeanette, 1977-
(author)
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Regulation of apoptosis during treatment and resistance development in tumour cells
- 2008
-
Doctoral thesis (other academic/artistic)abstract
- Induction of apoptosis is the most studied cell death process and it is a tightly regulated physiological event that enables elimination of damaged and unwanted cells. Apoptosis can be induced via activation of either the intrinsic or the extrinsic signalling pathway. The intrinsic pathway involves activation of the mitochondria by stress stimuli, whereas the extrinsic pathway is triggered by ligand induced activation of death receptors such as Fas. Apoptosis induction via Fas activation plays an important role in the function of cytotoxic T lymphocytes and in the control of immune cell homeostasis. Several studies have shown that anticancer therapies require functional cell death signalling pathways. Irradiation based therapy has been successful in treatment of several malignancies but the usage of high doses has been associated with side effects. Therefore, low dose therapies, that either is optimized for specific delivery or administrated in combination with other treatments, are promising modalities. However, in order to achieve high-quality effects of such treatments, the death effector mechanisms involved in tumour eradication needs to be further explored. Importantly, tumour cells frequently acquire resistance to apoptosis, which consequently allows tumour cells to escape from elimination by the immune system and/or treatment. Interferons constitute a large family of pleotrophic cytokines that are important for the immune response against viruses and other microorganisms. The interferon signalling pathway mediates transcriptional regulation of hundreds of genes, which result in mRNA degradation, decreased protein synthesis, cell cycle inhibition and induction of apoptosis. Interferon has successfully been used in therapy against some tumours. However, several drawbacks have been reported, such as reduced sensitivity to interferon during treatment. The aim of this thesis was to elucidate mechanisms that mediate resistance to death receptor or interferon induced apoptosis in human tumour cell models, as well as investigate what molecular events that underlie cell death following radiation therapy of tumour cells. In order to elucidate mechanisms involved in acquired resistance to Fas- or interferon-induced apoptosis, a Fas- and interferon-sensitive human cell line, U937, was subjected to conditions where resistance to either Fas- or interferon induced apoptosis was acquired. Characterization of the Fas resistant cells showed that multiple resistant mechanisms had been acquired. Reduced Fas expression and increased cFLIP expression, which is an inhibitor of death receptor signalling, were two important changes found. To further examine the importance of these two alterations, clones from the Fas resistant population were established. The reduced Fas expression was determined to account for the resistant phenotype in approximately 70% of the clones. In the Fas resistant clones with normal Fas expression, the importance of an increased amount of the cFLIP protein was confirmed with shRNA interference. A cross-resistance to death receptor induced apoptosis was detected in the interferon resistant variant, which illustrates that a connection between death receptor and interferon induced apoptosis exists. Notably, interferon resistant cells also contained increased cFLIP expression, which were determined to mediate resistance to both interferon and death receptor mediated apoptosis. Finally, when cell death induced by irradiation treatment was investigated in HeLa Hep2 cells we could demonstrate that cell death was mediated by centrosome hyperamplification and mitotic aberrations, which forced the cells into mitotic catastrophes and delayed apoptosis. In conclusion, we have described model systems where selection for resistance to Fas or interferon induced apoptosis generated a heterogeneous population, where several signalling molecules were altered. Furthermore, we have shown that a complex cell death network was activated by irradiation based therapy.
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| 9. |
- Bäcklund, Nils, et al.
(author)
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Salivary cortisol and cortisone in diagnosis of Cushing's syndrome - a comparison of six different analytical methods
- 2023
-
In: Clinical Chemistry and Laboratory Medicine. - : Walter de Gruyter. - 1434-6621 .- 1437-4331. ; 61:10, s. 1780-1791
-
Journal article (peer-reviewed)abstract
- Objectives: Salivary cortisol and cortisone at late night and after dexamethasone suppression test (DST) are increasingly used for screening of Cushing's syndrome (CS). We aimed to establish reference intervals for salivary cortisol and cortisone with three liquid chromatography-tandem mass spectrometry (LC-MS/MS) techniques and for salivary cortisol with three immunoassays (IAs), and evaluate their diagnostic accuracy for CS.Methods: Salivary samples at 08:00 h, 23:00 h and 08:00 h after a 1-mg DST were collected from a reference population (n=155) and patients with CS (n=22). Sample aliquots were analyzed by three LC-MS/MS and three IA methods. After establishing reference intervals, the upper reference limit (URL) for each method was used to calculate sensitivity and specificity for CS. Diagnostic accuracy was evaluated by comparing ROC curves.Results: URLs for salivary cortisol at 23:00 h were similar for the LC-MS/MS methods (3.4-3.9 nmol/L), but varied between IAs: Roche (5.8 nmol/L), Salimetrics (4.3 nmol/L), Cisbio (21.6 nmol/L). Corresponding URLs after DST were 0.7-1.0, and 2.4, 4.0 and 5.4 nmol/L, respectively. Salivary cortisone URLs were 13.5-16.6 nmol/L at 23:00 h and 3.0-3.5 nmol/L at 08:00 h after DST. All methods had ROC AUCs =0.96.Conclusions: We present robust reference intervals for salivary cortisol and cortisone at 08:00 h, 23:00 h and 08:00 h after DST for several clinically used methods. The similarities between LC-MS/MS methods allows for direct comparison of absolute values. Diagnostic accuracy for CS was high for all salivary cortisol and cortisone LC-MS/MS methods and salivary cortisol IAs evaluated.
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| 10. |
- Church, Timothy W., et al.
(author)
-
AKAP79 enables calcineurin to directly suppress protein kinase A activity
- 2021
-
In: eLIFE. - : eLIFE SCIENCES PUBL LTD. - 2050-084X. ; 10
-
Journal article (peer-reviewed)abstract
- Interplay between the second messengers cAMP and Ca2+ is a hallmark of dynamic cellular processes. A common motif is the opposition of the Ca2+-sensitive phosphatase calcineurin and the major cAMP receptor, protein kinase A (PKA). Calcineurin dephosphorylates sites primed by PKA to bring about changes including synaptic long-term depression (LTD). AKAP79 supports signaling of this type by anchoring PKA and calcineurin in tandem. In this study, we discovered that AKAP79 increases the rate of calcineurin dephosphorylation of type II PKA regulatory subunits by an order of magnitude. Fluorescent PKA activity reporter assays, supported by kinetic modeling, show how AKAP79-enhanced calcineurin activity enables suppression of PKA without altering cAMP levels by increasing PKA catalytic subunit capture rate. Experiments with hippocampal neurons indicate that this mechanism contributes toward LTD. This non-canonical mode of PKA regulation may underlie many other cellular processes.
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| 11. |
- Dalin, Frida, 1984-, et al.
(author)
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Clinical and immunological characteristics of Autoimmune Addison's disease : a nationwide Swedish multicenter study
- 2017
-
In: Journal of Clinical Endocrinology and Metabolism. - : Oxford University Press. - 0021-972X .- 1945-7197. ; 102:2, s. 379-389
-
Journal article (peer-reviewed)abstract
- CONTEXT: Studies on clinical and immunological features of Autoimmune Addison's disease (AAD) are needed to understand the disease burden and increased mortality.OBJECTIVE: To provide upgraded data on autoimmune comorbidities, replacement therapy, autoantibody profiles and cardiovascular risk factors.DESIGN, SETTING AND PARTICIPANTS: Cross sectional, population-based study. 660 AAD patients were included utilizing the Swedish Addison Registry (SAR) 2008-2014. When analyzing cardiovascular risk factors, 3,594 individuals from the population-based survey in Northern Sweden, MONICA (MONItoring of Trends and Determinants of CArdiovascular Disease), served as controls.MAIN OUTCOME MEASURE: Prevalence of autoimmune comorbidities and cardiovascular risk factors. Autoantibodies against 13 autoantigens were determined.RESULTS: Sixty percent of the SAR cohort consisted of females. Mean age at diagnosis was significantly higher for females than for males (36.8 vs. 31.1 years). The proportion of 21-hydroxylase autoantibody positive patients was 83% and 62% of patients had one or more associated autoimmune diseases, more frequently coexisting in females (p<0.0001). AAD patients had lower BMI (p<0.0001) and prevalence of hypertension (p=0.027) compared with controls. Conventional hydrocortisone tablets were used by 89% of patients; with the mean dose 28.1±8.5 mg/day. The mean hydrocortisone equivalent dose normalized to body surface was 14.8±4.4 mg/m(2)/day. Higher hydrocortisone equivalent dose was associated with higher incidence of hypertension (p=0.046).CONCLUSIONS: Careful monitoring of AAD patients is warranted to detect associated autoimmune diseases. Contemporary Swedish AAD patients do not have increased prevalence of overweight, hypertension, T2DM or hyperlipidemia. However, high glucocorticoid replacement doses may be a risk factor for hypertension.
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| 12. |
- Dittrich, Yvonne, et al.
(author)
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Co-Operative Method Development revisited
- 2005
-
Conference paper (peer-reviewed)abstract
- During the last five years, we applied a research approach we call 'Co-operative Method Development' formulated on first experience with empirical research focusing especially on the social side of software engineering. This position paper summarizes the experiences and discusses the improvement and further development of this research approach based on our experiences in different research projects in co-operation with industrial partners.
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| 13. |
- Dittrich, Yvonne, et al.
(author)
-
Cooperative method development : Combining qualitative empirical research with method, techniqueand process improvement
- 2008
-
In: Empirical Software Engineering. - : Springer Netherlands. - 1382-3256 .- 1573-7616. ; 13:3, s. 231-260
-
Journal article (peer-reviewed)abstract
- The development of methods tools and process improvements is best to be based on the understanding of the development practice to be supported. Qualitative research has been proposed as a method for understanding the social and cooperative aspects of software development. However, qualitative research is not easily combined with the improvement orientation of an engineering discipline. During the last 6 years, we have applied an approach we call ‘cooperative method development’, which combines qualitative social science fieldwork, with problem-oriented method, technique and process improvement. The action research based approach focusing on shop floor software development practices allows an understanding of how contextual contingencies influence the deployment and applicability of methods, processes and techniques. This article summarizes the experiences and discusses the further development of this approach based on several research projects in cooperation with industrial partners.
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| 14. |
- Dittrich, Yvonne, et al.
(author)
-
End User Development and Infrastructuring : Sustaining Organizational Innovation Capabilities
- 2017
-
In: New Perspectives in End-User Development. - Cham : Springer. - 9783319602905 - 9783319602912 ; , s. 165-206
-
Book chapter (peer-reviewed)abstract
- Today, both businesses and public organizations need to be able to innovate and continuously develop their services and processes along with the underpinning IT infrastructure. We argue that End-User Development (EUD) becomes a necessary part of the innovation capability that underpins such service and process innovation. The book chapter presents a meta-analysis of two case studies. The analysis shows how the need for change in both cases brought about an organizationally established sustainable practice of EUD, where empowered employees cooperated with IT professionals in the development and evolution of an IT infrastructure based on flexible technologies. The chapter further discusses how such practices are supported by (participatory) organizational IT management structures and processes. Finally, it discusses how EUD in this way contributes to the innovation capability of the organization. The conclusion points to transferability of the insights gained and provides suggestions for future research.
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| 15. |
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| 16. |
- Eckerblad, Jeanette, et al.
(author)
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Nurses conceptions of facilitative strategies of weaning patients from mechanical ventilation-A phenomenographic study
- 2009
-
In: Intensive and Critical Care Nursing. - : Elsevier BV. - 0964-3397. ; 25:5, s. 225-232
-
Journal article (peer-reviewed)abstract
- Background: Mechanical ventilator withdrawal can amount up to 40% of total ventilator time. Being on a mechanical ventilator is associated with risk of anxiety, post-traumatic stress syndrome, nosocomial pneumonia and premature mortality. Purpose: The purpose of the present study was to describe different conceptions of nurses facilitating decision-making strategies regarding weaning patients from mechanical ventilations cared for in intensive care unit (ICU). Method: Semi-structured interviews were analysed within the phenomenographic framework. Twenty ICU nurses were interviewed. Findings: The findings revealed three main categories of nurses facilitating decision-making strategies: "The intuitive and interpretative strategy" featured nurses pre-understandings. "The instrumental strategy" involved analysis and assessment of technological and physiological parameters. "The cooperative strategy" was characterised by interpersonal relationships in the work situation. Absence of a common strategy and lack of understanding of others strategies were a source of frustration. The main goals were to end mechanical ventilator support, create a sense of security, and avoid further complications. Conclusion: Although these findings need to be confirmed by further studies we suggest that nurses variable use of individual strategies more likely complicate an efficient and safe weaning process of the patients from mechanical ventilation.
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| 17. |
- Eriksson, Daniel, et al.
(author)
-
Common genetic variation in the autoimmune regulator (AIRE) locus is associated with autoimmune Addison’s disease in Sweden
- 2018
-
In: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 8:1
-
Journal article (peer-reviewed)abstract
- Autoimmune Addison's disease (AAD) is the predominating cause of primary adrenal failure. Despite its high heritability, the rarity of disease has long made candidate-gene studies the only feasible methodology for genetic studies. Here we conducted a comprehensive reinvestigation of suggested AAD risk loci and more than 1800 candidate genes with associated regulatory elements in 479 patients with AAD and 2394 controls. Our analysis enabled us to replicate many risk variants, but several other previously suggested risk variants failed confirmation. By exploring the full set of 1800 candidate genes, we further identified common variation in the autoimmune regulator (AIRE) as a novel risk locus associated to sporadic AAD in our study. Our findings not only confirm that multiple loci are associated with disease risk, but also show to what extent the multiple risk loci jointly associate to AAD. In total, risk loci discovered to date only explain about 7% of variance in liability to AAD in our study population.
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| 18. |
- Eriksson, Daniel, et al.
(author)
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GWAS for autoimmune Addison’s disease identifies multiple risk loci and highlights AIRE in disease susceptibility
- 2021
-
In: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 12:1
-
Journal article (peer-reviewed)abstract
- Autoimmune Addison's disease (AAD) is characterized by the autoimmune destruction of the adrenal cortex. Low prevalence and complex inheritance have long hindered successful genetic studies. We here report the first genome-wide association study on AAD, which identifies nine independent risk loci (P < 5 × 10-8). In addition to loci implicated in lymphocyte function and development shared with other autoimmune diseases such as HLA, BACH2, PTPN22 and CTLA4, we associate two protein-coding alterations in Autoimmune Regulator (AIRE) with AAD. The strongest, p.R471C (rs74203920, OR = 3.4 (2.7-4.3), P = 9.0 × 10-25) introduces an additional cysteine residue in the zinc-finger motif of the second PHD domain of the AIRE protein. This unbiased elucidation of the genetic contribution to development of AAD points to the importance of central immunological tolerance, and explains 35-41% of heritability (h2).
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| 19. |
- Eriksson, David, et al.
(author)
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Iodine-131 induces mitotic catastrophes and activates apoptotic pathways in HeLa Hep2 cells
- 2008
-
In: Cancer Biotherapy and Radiopharmaceuticals. - : Mary Ann Liebert Inc. - 1084-9785 .- 1557-8852. ; 23:5, s. 541-549
-
Journal article (peer-reviewed)abstract
- Iodine-131 (131I) has been used both in unconjugated form and conjugated to antibody derivates (i.e., radioimmunotherapy; RIT) to treat malignant diseases. The mechanisms by which 131I-irradiation causes growth retardation are, however, inadequately understood. The aim of this study was to elucidate the sequential molecular and cellular events that initiate cell death in HeLa Hep2 cells exposed to 131I. In this paper, HeLa Hep2 cells were found to display a transient G2-M arrest following irradiation, but then reentered the cell cycle still containing unrepaired cellular damage. An increase of multipolar mitotic spindles, as well as a significant increase in centrosome numbers from 8.8% +/- 1.9% in controls to 54.7% +/- 2.2% in irradiated cells, was observed (p < 0.0001). A subsequent failure of cytokinesis caused the cells to progress into mitotic catastrophe. This was accompanied by the formation of giant cells with multiple nuclei, multilobulated nuclei, and an increased frequency of polyploidy cells. A fraction of the cells also displayed apoptotic features, including the activation of initiator caspases-2, -8, -9, and effector caspase-3, as well as cleavage of poly(ADP-ribose) polymerase, a cell-death substrate for active caspase-3. These findings demonstrate that mitotic catastrophes and the activation of a delayed type of apoptosis might be important mechanisms involved in cell death following the RIT of solid tumors with -emitting radionuclides, such as 131I.
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| 20. |
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| 21. |
- Eriksson, Jeanette, et al.
(author)
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Beyond 'Happy Apps' : Using the Internet of Things to Support Emotional Health
- 2016
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In: HealthyIoT 2016: Internet of Things Technologies for HealthCare. - Cham : Springer. - 9783319512334 - 9783319512341 ; , s. 95-100
-
Conference paper (peer-reviewed)abstract
- Emotions and physical health are strongly related. A first step towards emotional well-being is to monitor, understand and reflect upon one’s feelings and emotions. A number of personal emotion-tracking applications are available today. In this paper we describe an examination of these applications which indicates that many of the applications do not provide sufficient support for monitoring a full spectrum of emotional data or for analyzing or using the data that is provided. To design applications that better support emotional well-being, the full capabilities of the Internet of Things should be utilized. The paper concludes with a description of how Internet of Things technologies can enable the development of systems that can more accurately capture emotional data and support personal learning in the area of emotional health.
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| 22. |
- Eriksson, Jeanette
(author)
-
Bridging the Gap between Development and Use : Support of Tailorability in Software Evolution
- 2005
-
Licentiate thesis (other academic/artistic)abstract
- The intention of tailorable systems is to make it possible for end users to evolve an application to better fit altered requirements and tasks, and to make the system more endurable. This thesis discusses tailorable systems in the context of a rapidly changing business environment. The objective was to determine what is necessary for a tailorable business system to continuously adapt to expanding requirements and thereby live up to the intention of the system. The thesis includes five different studies, of which one is a literature study. The other four studies were conducted in three projects; one technical project exploring the possibility to use Metaobject Protocol in tailorable systems, one project in an explorative environment concerned with physical interfaces and one project, that also embraced user participation and user evaluation, regarded the possibility for end users to manage system infrastructure. The projects began with field studies (including participant observations and interviews) and workshops with users and developers. In each project, based on the outcome, an end-user tailorable prototype was developed. The prototypes were used for evaluating possibilities and problems with tailorable systems. Taken together the evaluations revealed what was required to make a tailorable system work as intended in a rapidly changing business environment. It could be concluded that tailoring is a good way to evolve a system to meet altered needs, because people who already possess the required domain knowledge can make changes quickly. Tailoring is not however enough, because the tailoring capabilities are always limited, meaning that tailoring cannot support completely unanticipated changes. In such cases the tailoring capabilities must be extended. Since such changes are only concerned with the system itself, and not the business task, it is hard to motivate even skilled users to make these types of changes. Tailoring activities must therefore be coordinated with software evolution activities performed by professional developers. This allows the system to adapt continuously to a rapidly changing business environment and thereby live up to the intention of the system. The final conclusion is that there is a need for close collaboration between end users, tailors and developers to make tailorable information systems adaptable to rapid changes in the business environment as well as being endurable. The collaboration has to be supported in the structure of the system by providing support for the work of users, tailors and developers.
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| 23. |
- Eriksson, Jeanette
(author)
-
Förskolans hall : en kommunikativ möjlighet?
- 2017
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In: Förskolans kommunikationsmiljö. - Gävle : Gävle University Press. - 9789197489386 - 9789197489393 ; , s. 161-180
-
Book chapter (pop. science, debate, etc.)
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| 24. |
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| 25. |
- Eriksson, Jeanette, et al.
(author)
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Leaving Variability Management to the End User; A Comparison Between Different Tailoring Approaches
- 2003
-
Reports (other academic/artistic)abstract
- To enable software to fulfill user requirements over time and meet changes in, for example, business environments, software variability is needed. One way to achieve variability is through tailoring. However, some kind of variability management is needed in order to take advantage of variability. With a tailorable system we mean a system that is designable when it is in use. This means that some design decisions are postponed until the system is up and running. It is the end-user who will adjust the program to fit altered requirements through, for example, run-time configuration. In other words, tailoring requires that the variability management of the system is left to the end user. In this article we present three different examples of tailoring and in the form of a comparison between the three approaches we identify and discuss some issues which must be considered when variability management is left to the end user.
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