| 1. |
- Falconer, D., et al.
(författare)
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New Air-interface Technologies and Deployment Concepts
- 2006
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Ingår i: Technologies for the Wireless Future: Wireless World Research Forum (WWRF). - Chichester, UK : John Wiley & Sons. - 0470029056 - 9780470029053 ; , s. 131-226
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 2. |
- Pervjakova, Natalia, et al.
(författare)
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Multi-ancestry genome-wide association study of gestational diabetes mellitus highlights genetic links with type 2 diabetes
- 2022
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 31:19, s. 3377-3391
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Tidskriftsartikel (refereegranskat)abstract
- Gestational diabetes mellitus (GDM) is associated with increased risk of pregnancy complications and adverse perinatal outcomes. GDM often reoccurs and is associated with increased risk of subsequent diagnosis of type 2 diabetes (T2D). To improve our understanding of the aetiological factors and molecular processes driving the occurrence of GDM, including the extent to which these overlap with T2D pathophysiology, the GENetics of Diabetes In Pregnancy (GenDIP) Consortium assembled genome-wide association studies (GWAS) of diverse ancestry in a total of 5485 women with GDM and 347 856 without GDM. Through multi-ancestry meta-analysis, we identified five loci with genome-wide significant association (p < 5x10-8) with GDM, mapping to/near MTNR1B (p = 4.3x10-54), TCF7L2 (p = 4.0x10-16), CDKAL1 (p = 1.6 × 10-14), CDKN2A-CDKN2B (p = 4.1x10-9) and HKDC1 (p = 2.9x10-8). Multiple lines of evidence pointed to the shared pathophysiology of GDM and T2D: (i) four of the five GDM loci (not HKDC1) have been previously reported at genome-wide significance for T2D; (ii) significant enrichment for associations with GDM at previously reported T2D loci; (iii) strong genetic correlation between GDM and T2D; and (iv) enrichment of GDM associations mapping to genomic annotations in diabetes-relevant tissues and transcription factor binding sites. Mendelian randomisation analyses demonstrated significant causal association (5% false discovery rate) of higher body mass index on increased GDM risk. Our results provide support for the hypothesis that GDM and T2D are part of the same underlying pathology but that, as exemplified by the HKDC1 locus, there are genetic determinants of GDM that are specific to glucose regulation in pregnancy.
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| 3. |
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| 4. |
- Rämö, JT, et al.
(författare)
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Genome-wide screen of otosclerosis in population biobanks: 27 loci and shared associations with skeletal structure
- 2023
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 14:1, s. 157-
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Tidskriftsartikel (refereegranskat)abstract
- Otosclerosis is one of the most common causes of conductive hearing loss, affecting 0.3% of the population. It typically presents in adulthood and half of the patients have a positive family history. The pathophysiology of otosclerosis is poorly understood. A previous genome-wide association study (GWAS) identified a single association locus in an intronic region of RELN. Here, we report a meta-analysis of GWAS studies of otosclerosis in three population-based biobanks comprising 3504 cases and 861,198 controls. We identify 23 novel risk loci (p < 5 × 10−8) and report an association in RELN and three previously reported candidate gene or linkage regions (TGFB1, MEPE, and OTSC7). We demonstrate developmental stage-dependent immunostaining patterns of MEPE and RUNX2 in mouse otic capsules. In most association loci, the nearest protein-coding genes are implicated in bone remodelling, mineralization or severe skeletal disorders. We highlight multiple genes involved in transforming growth factor beta signalling for follow-up studies.
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| 5. |
- Andersson, K, et al.
(författare)
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Kinetic characterization of the interaction of the Z-fragment of protein A with mouse-IgG3 in a volume in chemical space.
- 1999
-
Ingår i: Proteins. - 0887-3585 .- 1097-0134. ; 37:3
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Tidskriftsartikel (refereegranskat)abstract
- The kinetic rate parameters for the interaction between a single domain analogue of staphylococcal protein A (Z) and a mouse-IgG3 monoclonal antibody (MAb) were measured in Hepes buffer with different chemical additives. Five buffer ingredients (pH, NaCl, DMSO, EDTA, and KSCN) were varied simultaneously in 16 experiments following a statistical experimental plan. The 16 buffers thus spanned a volume in chemical space. A mathematical model, using data from the buffer composition, was developed and used to predict apparent kinetic parameters in five new buffers within the spanned volume. Association and dissociation parameters were measured in the new buffers, and these agreed with the predicted values, indicating that the model was valid within the spanned volume. The pattern of variation of the kinetic parameters in relation to buffer composition was different for association and dissociation, such that pH influenced both association and dissociation and NaCl influenced only dissociation. This indicated that the recognition mechanism (association) and the stability of the formed complex (dissociation) involve different binding forces, which can be further investigated by kinetic studies in systematically varied buffers.
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| 6. |
- Bradley, E. L., et al.
(författare)
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The BIOSAFEPAPER project for in vitro toxicity assessments : Preparation, detailed chemical characterisation and testing of extracts from paper and board samples
- 2008
-
Ingår i: Food and Chemical Toxicology. - : Elsevier BV. - 0278-6915 .- 1873-6351. ; 46:7, s. 2498-2509
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Tidskriftsartikel (refereegranskat)abstract
- Nineteen food contact papers and boards and one non-food contact board were extracted following test protocols developed within European Union funded project BIOSAFEPAPER. The extraction media were either hot or cold water, 95% ethanol or Tenax, according to the end use of the sample. The extractable dry matter content of the samples varied from 1200 to 11,800 mg/kg (0.8-35.5 mg/dm2). According to GC-MS the main substances extracted into water were pulp-derived natural products such as fatty acids, resin acids, natural wood sterols and alkanols. Substances extracted into ethanol particularly, were diisopropylnaphthalenes, alkanes and phthalic acid esters. The non-food contact board showed the greatest number and highest concentrations of GC-MS detectable compounds. The extracts were subjected to a battery of in vitro toxicity tests measuring both acute and sublethal cytotoxicity and genotoxic effects. None of the water or Tenax extracts was positive in cytotoxicity or genotoxicity assays. The ethanol extract of the non-food contact board gave a positive response in the genotoxicity assays, and all four ethanol extracts gave positive response(s) in the cytotoxicity assays to some extent. These responses could not be pinpointed to any specific compound, although there appeared a correlation between the total amount of extractables and toxicity.
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| 7. |
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| 8. |
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| 9. |
- Honkalampi-Hämäläinen, U., et al.
(författare)
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Safety evaluation of food contact paper and board using chemical tests and in vitro bioassays : Role of known and unknown substances
- 2010
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Ingår i: Food Additives and Contaminants. - : Informa UK Limited. - 0265-203X .- 1464-5122. ; 27:3, s. 406-115
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Tidskriftsartikel (refereegranskat)abstract
- In vitro toxicological tests have been proposed as an approach to complement the chemical safety assessment of food contact materials, particularly those with a complex or unknown chemical composition such as paper and board. Among the concerns raised regarding the applicability of in vitro tests are the effects of interference of the extractables on the outcome of the cytotoxicity and genotoxicity tests applied and the role of known compounds present in chemically complex materials, such as paper and board, either as constituents or contaminants. To answer these questions, a series of experiments were performed to assess the role of natural substances (wood extracts, resin acids), some additives (diisopropylnaphthalene, phthalates, acrylamide, fluorescent whitening agents) and contaminants (2,4-diaminotoluene, benzo[a]pyrene) in the toxicological profile of paper and board. These substances were individually tested or used to spike actual paper and board extracts. The toxic concentrations of diisopropylnaphthalenes and phthalates were compared with those actually detected in paper and board extracts showing conspicuous toxicity. According to the results of the spiking experiments, the extracts did not affect the toxicity of tested chemicals nor was there any significant metabolic interference in the cases where two compounds were used in tests involving xenobiotic metabolism by the target cells. While the identified substances apparently have a role in the cytotoxicity of some of the project samples, their presence does not explain the total toxicological profile of the extracts. In conclusion, in vitro toxicological testing can have a role in the safety assessment of chemically complex materials in detecting potentially harmful activities not predictable by chemical analysis alone.
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| 10. |
- Hämäläinen, Jari, et al.
(författare)
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Multiobjective Decision Making for Papermaking
- 2004
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Ingår i: CD-Proceedings of MCDM2004, the 17th International Conference on Multiple Criteria Decision Making.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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| 11. |
- Lim, Elaine T, et al.
(författare)
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Distribution and Medical Impact of Loss-of-Function Variants in the Finnish Founder Population.
- 2014
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 10:7
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Tidskriftsartikel (refereegranskat)abstract
- Exome sequencing studies in complex diseases are challenged by the allelic heterogeneity, large number and modest effect sizes of associated variants on disease risk and the presence of large numbers of neutral variants, even in phenotypically relevant genes. Isolated populations with recent bottlenecks offer advantages for studying rare variants in complex diseases as they have deleterious variants that are present at higher frequencies as well as a substantial reduction in rare neutral variation. To explore the potential of the Finnish founder population for studying low-frequency (0.5-5%) variants in complex diseases, we compared exome sequence data on 3,000 Finns to the same number of non-Finnish Europeans and discovered that, despite having fewer variable sites overall, the average Finn has more low-frequency loss-of-function variants and complete gene knockouts. We then used several well-characterized Finnish population cohorts to study the phenotypic effects of 83 enriched loss-of-function variants across 60 phenotypes in 36,262 Finns. Using a deep set of quantitative traits collected on these cohorts, we show 5 associations (p<5×10-8) including splice variants in LPA that lowered plasma lipoprotein(a) levels (P = 1.5×10-117). Through accessing the national medical records of these participants, we evaluate the LPA finding via Mendelian randomization and confirm that these splice variants confer protection from cardiovascular disease (OR = 0.84, P = 3×10-4), demonstrating for the first time the correlation between very low levels of LPA in humans with potential therapeutic implications for cardiovascular diseases. More generally, this study articulates substantial advantages for studying the role of rare variation in complex phenotypes in founder populations like the Finns and by combining a unique population genetic history with data from large population cohorts and centralized research access to National Health Registers.
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| 12. |
- Nygård, K, et al.
(författare)
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Isotope quantum effects in the electron momentum density of water.
- 2007
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Ingår i: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 126:15, s. 154508-
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Tidskriftsartikel (refereegranskat)abstract
- The isotope quantum effects in the ground-state electron momentum density of water are studied at temperatures ranging from 5 to 90 degrees C by combining Compton scattering experiments utilizing synchrotron radiation and computational analysis within density functional theory. We observe clear differences in the momentum density between normal and heavy water at room temperature, which are interpreted as predominantly reflecting intramolecular structural differences. The changes in the momentum density upon increasing the temperature are found to be larger for heavy than for normal water, which is attributed primarily to temperature-induced intramolecular structural effects. Both model computations and an ab initio approach qualitatively reproduce the changes in the momentum density as a function of temperature.
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| 13. |
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| 14. |
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Fieldwork Education in Social Work as One Way of Building Bridges between China and Europe : In Rajendra Baikady, Sajid S.M., Varoshini Nadesan, and M. Rezaul Islam (eds) The Routledge Handbook of Field Work Education in Social Work
- 2022
-
Samlingsverk (redaktörskap) (övrigt vetenskapligt/konstnärligt)abstract
- The Routledge Handbook of Field Work Education in Social Work is a welcome addition to the lit- erature on social work education and comparative research. It offers a wealth of contributions on field education across four continents.The book comes at a time of increased interest in international social work and in learning from others. It is also a time when educators in diverse contexts are struggling to provide quality field education for students, as field education across the globe is facing both old and new challenges. As the editors point out early in their introduction, field education is an essential part of the preparation of social workers; indeed, it is now sometimes referred to by the US Council on Social Work Education and others as the ‘signature pedagogy’ of the field. From the earliest days, educators have recognised that practical experience must accompany academic learning to prepare social work practitioners.This differentiates a profession from a purely academic subject. A review of the history of social work education bears this out. Between 1950 and 1972, the United Nations (UN) conducted five world surveys of social work education. In the very first of these, issues and variations in ‘practical training’ were dis- cussed (UN, 1950). Supervision, the need to integrate theory and practice, and the balance between observation and learning by doing were highlighted in the overview and in country summaries.The International Association of Schools of Social Work continued the global survey of educational programmes,issuing the World Guide to SocialWork Education in 1984.The crite- ria for inclusion as a social work programme were few in number and quite modest. It clearly stated, however, that ‘The course of study should include theoretical study as well as substantial continuing field practicum with an arrangement for appropriate instruction in both class and field’ (p. ix).This volume profiled social work programs in 61 countries across six continents, an expansion from the 46 countries listed in the 1950 UN publication. In 2004, the International Association of Schools of Social Work and the International Federation of Social Workers issued the first ever Global Standards for the Education and Training of the Social Work Profession. The standards were revised in 2020 (IASSW/IFSW, 2020). Both versions include lengthy sections on field education under curricula and state that field education must ‘be sufficient in duration and complexity of tasks and learning opportunities to ensure that students are prepared for professional practice’ (IASSW/IFSW, 2020, p. 13). Other standards include pro- viding qualified supervision, training for field instructors, a field manual with clear policies, and methods of evaluating students and field settings. New to the 2020 version is an aspirational stand- ard that programmes should ‘Create practice placement opportunities that correspond to at least 25% of the overall education activity within the courses (counted in either credits, days, or hours)’ (p. 14).This is clearly an effort to reduce the variability in attention paid to the field component. Organising and delivering quality field education continues to be a challenge for schools of social work. Many of the issues identified 70 years ago continue, including providing regular, xxvii Downloaded By: 10.3.98.104 At: 20:32 15 Jun 2022; For: 9781032164946, Prelims, 10.4324/9781032164946 Foreword professionally competent supervision and the need to help students integrate their classwork with field education. Over the past three decades, social work has expanded to numerous new locales,most notably to the countries of the former Soviet Union and China.The 2020 world census of social work education identified more than 3,500 programs in 159 countries (IASSW, 2021). In some places, social work is a completely new subject, and educators have had to initiate placements in areas without trained supervisors or even settings that defined them- selves as social work settings (Healy & Thomas, 2021). In other countries, including such diverse places as Jamaica and Ethiopia, expansion in the number of schools of social work and increases in the number of students enrolled has outpaced the availability of suitable field placements (Kebede, 2019). Mentoring students into the profession is less likely to occur if experienced social work supervision is missing. The Routledge Handbook of Field Work Education in Social Work includes overviews of field education and treatment of special subjects in 26 countries ranging from the United Kingdom to China, Slovenia,Turkey, Canada, and New Zealand. Several chapters provide student perspec- tives on their learning in the field. Special topics addressed include the experiences of indig- enous students in field placement and considerations for ensuring that international placements are optimally designed and supported. Reflexivity as a component of learning and way of inte- grating learning is addressed by several authors. Finally, the impact of the COVID-19 pandemic is covered in three chapters at the end of the volume. Field education faced disruptions and unusual challenges, in terms of the needs and demands of service users, threats to the health of students and field instructors, and widespread closures of in-person services. Learning from these experiences will inform education in future emergencies. In their conclusion, the editors lament that the topic of technology is not adequately addressed in the present book. Presumably, the expansion of virtual service delivery during the pandemic will offer lessons for future considera- tion of technologies in field education. In concluding the book, the editors remind readers that ‘Competency of students and graduates from a school of social work largely depends on the quality of the field education agency, availability of faculty support, competent supervisors, and expertise in introducing an innovative fieldwork practicum’. In the United States, and perhaps other contexts, increased pressures for research and publication have diminished the involvement of full-time faculty in field liaison and engagement, widening the divide between classroom instruction and field learning and severing what was, in earlier times, a close collaboration between academia and the field. At the same time, neoliberal pressures push agencies to meet higher efficiency stand- ards through increased caseloads and outputs.This leaves less time for field instruction and is resulting in fewer available placements for the growing social work student population.These trends may heighten the stresses on the dominant model of field education for social work and call out for creative solutions. Comparative study and increased sharing across borders can help in developing new models.This volume is an excellent start and a most welcome addition to the literature. Lynne M. Healy, MSW, PhD Board ofTrustees Distinguished Professor Emerita University of Connecticut School of Social Work, USA
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| 15. |
- Knuuttila, M., et al.
(författare)
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Applying mass spectrometric methods to study androgen biosynthesis and metabolism in prostate cancer
- 2019
-
Ingår i: Journal of molecular endocrinology. - 1479-6813. ; 62:4
-
Tidskriftsartikel (refereegranskat)abstract
- Recent development of gas chromatography and liquid chromatography-tandem mass spectrometry (GC-MS/MS, LC-MS/MS) has provided novel tools to define sex steroid concentrations. These new methods overcome several of the problems associated with immunoassays for sex steroids. With the novel MS-based applications we are now able to measure small concentrations of the steroid hormones reliably and with high accuracy in both body fluids and tissue homogenates. The sensitivity of the tandem mass spectrometry assays allows us also for the first time to reliably measure picomolar or even femtomolar concentrations of estrogens and androgens. Furthermore, due to a high sensitivity and specificity of MS technology, we are also able to measure low concentrations of steroid hormones of interest in the presence of pharmacological concentration of other steroids and structurally closely related compounds. Both of these features are essential for multiple preclinical models for prostate cancer. The MS assays are also valuable for the simultaneous measurement of multiple steroids and their metabolites in small sample volumes in serum and tissue biopsies of prostate cancer patients before and after drug interventions. As a result, novel information about steroid hormone synthesis and metabolic pathways in prostate cancer has been obtained. In our recent studies, we have extensively applied a GC-MS/MS method to study androgen biosynthesis and metabolism in VCaP prostate cancer xenografts in mice. In the present review, we shortly summarize some of the benefits of the GC-MS/MS and novel LC-MS/MS assays, and provide examples of their use in defining novel mechanisms of androgen action in prostate cancer.
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| 16. |
- Kostic, Aleksandar D., et al.
(författare)
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The dynamics of the human infant gut microbiome in development and in progression toward type 1 diabetes
- 2015
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Ingår i: Cell Host and Microbe. - : Cell Press. - 1931-3128 .- 1934-6069. ; 17:2, s. 260-273
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Tidskriftsartikel (refereegranskat)abstract
- Colonization of the fetal and infant gut microbiome results in dynamic changes in diversity, which can impact disease susceptibility. To examine the relationship between human gut microbiome dynamics throughout infancy and type 1 diabetes (T1D), we examined a cohort of 33 infants genetically predisposed to T1D. Modeling trajectories of microbial abundances through infancy revealed a subset of microbial relationships shared across most subjects. Although strain composition of a given species was highly variable between individuals, it was stable within individuals throughout infancy. Metabolic composition and metabolic pathway abundance remained constant across time. A marked drop in alpha-diversity was observed in T1D progressors in the time window between seroconversion and T1D diagnosis, accompanied by spikes in inflammation-favoring organisms, gene functions, and serum and stool metabolites. This work identifies trends in the development of the human infant gut microbiome along with specific alterations that precede T1D onset and distinguish T1D progressors from nonprogressors.
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| 17. |
- Libard, Sylwia, et al.
(författare)
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Human cytomegalovirus tegument protein pp65 is detected in all intra- and extra-axial brain tumours independent of the tumour type or grade
- 2014
-
Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:9, s. e108861-
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Tidskriftsartikel (refereegranskat)abstract
- Human cytomegalovirus (HCMV) has been indicated being a significant oncomodulator. Recent reports have suggested that an antiviral treatment alters the outcome of a glioblastoma. We analysed the performance of commercial HCMV-antibodies applying the immunohistochemical (IHC) methods on brain sample obtained from a subject with a verified HCMV infection, on samples obtained from 14 control subjects, and on a tissue microarray block containing cores of various brain tumours. Based on these trials, we selected the best performing antibody and analysed a cohort of 417 extra- and intra-axial brain tumours such as gliomas, medulloblastomas, primary diffuse large B-cell lymphomas, and meningiomas. HCMV protein pp65 immunoreactivity was observed in all types of tumours analysed, and the IHC expression did not depend on the patient's age, gender, tumour type, or grade. The labelling pattern observed in the tumours differed from the labelling pattern observed in the tissue with an active HCMV infection. The HCMV protein was expressed in up to 90% of all the tumours investigated. Our results are in accordance with previous reports regarding the HCMV protein expression in glioblastomas and medulloblastomas. In addition, the HCMV protein expression was seen in primary brain lymphomas, low-grade gliomas, and in meningiomas. Our results indicate that the HCMV protein pp65 expression is common in intra- and extra-axial brain tumours. Thus, the assessment of the HCMV expression in tumours of various origins and pathologically altered tissue in conditions such as inflammation, infection, and even degeneration should certainly be facilitated.
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| 18. |
- Murtoniemi, Katja, et al.
(författare)
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Longitudinal changes in plasma hemopexin and alpha-1-microglobulin concentrations in women with and without clinical risk factors for pre-eclampsia
- 2019
-
Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 14:12
-
Tidskriftsartikel (refereegranskat)abstract
- Recent studies have shown increased concentration of fetal hemoglobin (HbF) in pre-eclamptic women. Plasma hemopexin (Hpx) and alpha-1-microglobulin (A1M) are hemoglobin scavenger proteins that protect against toxic effects of free heme released in the hemoglobin degradation process. We used an enzyme-linked immunosorbent assay to analyze maternal plasma Hpx and A1M concentrations at 12–14, 18–20 and 26–28 weeks of gestation in three groups: 1) 51 women with a low risk for pre-eclampsia (LRW), 2) 49 women with a high risk for pre-eclampsia (PE) who did not develop PE (HRW) and 3) 42 women with a high risk for PE who developed PE (HRPE). The study had three aims: 1) to investigate whether longitudinal differences exist between study groups, 2) to examine if Hpx and A1M concentrations develop differently in pre-eclamptic women with small for gestational age (SGA) fetuses vs. pre-eclamptic women with appropriate for gestational age fetuses, and 3) to examine if longitudinal Hpx and A1M profiles differ by PE subtype (early-onset vs. late-onset and severe vs. non-severe PE). Repeated measures analysis of variance was used to analyze differences in Hpx and A1M concentrations between the groups. We found that the differences in longitudinal plasma Hpx and A1M concentrations in HRW compared to HRPE and to LRW may be associated with reduced risk of PE regardless of clinical risk factors. In women who developed PE, a high A1M concentration from midgestation to late second trimester was associated with SGA. There were no differences in longitudinal Hpx and A1M concentrations from first to late second trimester in high-risk women who developed early-onset or. late-onset PE or in women who developed severe or. non-severe PE.
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| 19. |
- Nwaru, Bright I, 1978, et al.
(författare)
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Vitamin D intake during the first 4years and onset of asthma by age 5: A nested case-control study.
- 2017
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Ingår i: Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology. - : Wiley. - 1399-3038. ; , s. 1-8
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Tidskriftsartikel (refereegranskat)abstract
- Early-life vitamin D intake has been linked to asthma risk in childhood, but the role of longitudinal vitamin D exposure has not been previously evaluated. We investigated the association between vitamin D intake during the first 4years of life and asthma risk by age 5.Within a Finnish population-based birth cohort, 182 incident asthma cases were matched to 728 controls on sex, genetic risk for type 1 diabetes, delivery hospital, and time of birth. Vitamin D intake was assessed by age-specific 3day food records. Parents completed a validated version of the International Study of Asthma and Allergies in Childhood questionnaire at 5years.At 3months, supplements were the main source of vitamin D intake; intake from foods increased from 3months on, mainly from fortified milk products. Vitamin D intake at each specific age was associated with an increased risk of any asthma, atopic, and non-atopic asthma, but only intake at 1 and 2years was statistically significantly associated with asthma. Longitudinal vitamin D intake was associated with an increased risk of asthma (OR 1.24; 95%CI 1.00-1.53).Increased vitamin D intake in childhood, particularly intake at 1 and 2years of age, may increase risk of childhood asthma. This might reflect a true effect or residual confounding by lifestyle or environmental factors. Repeated assessment of vitamin D intake allowed evaluation of the longitudinal and age-dependent impact of vitamin D on the risk of asthma. Further longitudinal studies are required to confirm or question these findings.
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| 20. |
- Oksanen, Minna, et al.
(författare)
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NF-E2-related factor 2 activation boosts antioxidant defenses and ameliorates inflammatory and amyloid properties in human Presenilin-1 mutated Alzheimer's disease astrocytes
- 2020
-
Ingår i: GLIA. - : Wiley. - 0894-1491 .- 1098-1136. ; 68:3, s. 589-599
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer's disease (AD) is a common dementia affecting a vast number of individuals and significantly impairing quality of life. Despite extensive research in animal models and numerous promising treatment trials, there is still no curative treatment for AD. Astrocytes, the most common cell type of the central nervous system, have been shown to play a role in the major AD pathologies, including accumulation of amyloid plaques, neuroinflammation, and oxidative stress. Here, we show that inflammatory stimulation leads to metabolic activation of human astrocytes and reduces amyloid secretion. On the other hand, the activation of oxidative metabolism leads to increased reactive oxygen species production especially in AD astrocytes. While healthy astrocytes increase glutathione (GSH) release to protect the cells, Presenilin-1-mutated AD patient astrocytes do not. Thus, chronic inflammation is likely to induce oxidative damage in AD astrocytes. Activation of NRF2, the major regulator of cellular antioxidant defenses, encoded by the NFE2L2 gene, poses several beneficial effects on AD astrocytes. We report here that the activation of NRF2 pathway reduces amyloid secretion, normalizes cytokine release, and increases GSH secretion in AD astrocytes. NRF2 induction also activates the metabolism of astrocytes and increases the utilization of glycolysis. Taken together, targeting NRF2 in astrocytes could be a potent therapeutic strategy in AD.
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| 21. |
- Pöllänen, E., et al.
(författare)
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Differential influence of peripheral and systemic sex steroids on skeletal muscle quality in pre- and postmenopausal women
- 2011
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Ingår i: Aging Cell. - : Wiley. - 1474-9718. ; 10:4, s. 650-660
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Tidskriftsartikel (refereegranskat)abstract
- Aging is associated with gradual decline of skeletal muscle strength and mass often leading to diminished muscle quality. This phenomenon is known as sarcopenia and affects about 30% of the over 60-year-old population. Androgens act as anabolic agents regulating muscle mass and improving muscle performance. The role of female sex steroids as well as the ability of skeletal muscle tissue to locally produce sex steroids has been less extensively studied. We show that despite the extensive systemic deficit of sex steroid hormones in postmenopausal compared to premenopausal women, the hormone content of skeletal muscle does not follow the same trend. In contrast to the systemic levels, muscle tissue of post- and premenopausal women had similar concentrations of dehydroepiandrosterone and androstenedione, while the concentrations of estradiol and testosterone were significantly higher in muscle of the postmenopausal women. The presence of steroidogenetic enzymes in muscle tissue indicates that the elevated postmenopausal steroid levels in skeletal muscle are because of local steroidogenesis. The circulating sex steroids were associated with better muscle quality while the muscle concentrations reflected the amount of infiltrated fat within muscle tissue. We conclude that systemically delivered and peripherally produced sex steroids have distinct roles in the regulation of neuromuscular characteristics during aging.
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| 22. |
- Sönksen, C. P., et al.
(författare)
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Capture and analysis of low molecular weight ligands by surface plasmon resonance combined with mass spectrometry
- 2001
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Ingår i: European journal of mass spectrometry. - : SAGE Publications. - 1469-0667 .- 1751-6838. ; 7:4-5, s. 385-391
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Tidskriftsartikel (refereegranskat)abstract
- The combination of biomolecular interaction analysis (BIA)by surface plasmon resonance (SPR)and nano-electrospray ionization ion trap mass spectrometry (nanoESI-Ion Trap MS)as well as matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-ToF MS)is demonstrated for the binding of low molecular weight inhibitors (∼ 600 Da) to HIV-1 protease. Inhibitors were captured on sensor chips of a manual or an automated SPR biosensor, to which HIV-1 protease was immobilized. Compounds and buffer components that bound unspecifically to the sensor surface were removed and the inhibitors were eluted in a minimal volume (3 μL), between air bubbles, in order to prevent dispersion of analyte into buffer eluent. Molecular weights were subsequently determined by mass spectrometry, structural information was obtained by MALDI-ToF post-source decay as well as by electrospray ionization tandem mass spectrometry (MS/MS)analysis. Furthermore, competition experiments, using a mixture of different ligands, demonstrated that the peak intensities in the MALDI-ToF spectrum could be used for relative quantification of the amount of the different ligands bound to the immobilized target. Methodology for automated capture and elution of analytes was developed and evaluated.
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| 23. |
- Valkonen, J., et al.
(författare)
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Formal Verification of Safety I&C System Designs : Two Nuclear Power Plant Related Applications
- 2008
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Ingår i: Proceedings Man-Technology-Organisation Session, Enlarged Halden Programme Group Meeting. - Norway : Institt for energiteknikk.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Instrumentation and control (I&C) systems play a crucial role in the operation of nuclear power plants(NPP) and other safety critical processes. An important change is the replacement of the old analogue I&Csystems with new digitalised ones. The programmable digital logic controllers enable more complicatedcontrol tasks than the old analogue systems and thus the validation of the control logic designs against safetyrequirements has become more important. In order to diminish the subjective component of the evaluationthere is a need to develop new formal verification methods. A promising approach is a method called modelchecking, which enables the complete verification of requirements when a finite state machine model of thesystem is available. The use of model checking to verify two nuclear power plant related systems isdescribed: an arc protection system and a reactor emergency cooling system. For the verification, it was alsonecessary to model the operation environment of the device and the larger system it is part of. Theenvironment models could be kept relatively simple, but it is important that the essential behaviour of theenvironment is covered. The reactor emergency cooling system is in use in an operating nuclear power plantand the arc protection system model included a typical realistic operation environment. The results showedthat it was possible to reliably verify the presence of desired behaviour as well as the absence of anundesired behaviour of the system. The possibility for complete verification makes model checking differentfrom simulation-based testing where only a number of selected scenarios can be simulated and one can neverbe sure that all the possible behaviour is covered. The challenges for future research are to develop morededicated methods for the verification of safety critical automation and safety critical embedded software.
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| 24. |
- Xie, Minshu, 1988, et al.
(författare)
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Benchmarking for On-Scalp MEG Sensors
- 2017
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Ingår i: IEEE Transactions on Biomedical Engineering. - : Institute of Electrical and Electronics Engineers (IEEE). - 0018-9294 .- 1558-2531. ; 64:6, s. 1270-1276
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Tidskriftsartikel (refereegranskat)abstract
- Objective: We present a benchmarking protocol for quantitatively comparing emerging on-scalp magnetoencephalography (MEG) sensor technologies to their counterparts in state-of-the-art MEG systems. Methods: As a means of validation, we compare a high-critical-temperature superconducting quantum interference device (high T-c SQUID) with the low-T-c SQUIDs of an Elekta Neuromag TRIUX system in MEG recordings of auditory and somatosensory evoked fields (SEFs) on one human subject. Results: We measure the expected signal gain for the auditory-evoked fields (deeper sources) and notice some unfamiliar features in the on-scalp sensor-based recordings of SEFs (shallower sources). Conclusion: The experimental results serve as a proof of principle for the benchmarking protocol. This approach is straightforward, general to various on-scalp MEG sensors, and convenient to use on human subjects. The unexpected features in the SEFs suggest on-scalp MEG sensors may reveal information about neuromagnetic sources that is otherwise difficult to extract from state-of-the-art MEG recordings. Significance: As the first systematically established on-scalp MEG benchmarking protocol, magnetic sensor developers can employ this method to prove the utility of their technology in MEG recordings. Further exploration of the SEFs with on-scalp MEG sensors may reveal unique information about their sources.
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| 25. |
- Åkerblom, Hans, et al.
(författare)
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Dietary manipulation of beta cell autoimmunity in infants at increased risk of type 1 diabetes : A pilot study
- 2005
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 48:5, s. 829-837
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis: We aimed to assess the feasibility of a dietary intervention trial with weaning to hydrolysed formula in infants at increased risk of type 1 diabetes and to study the effect of the intervention on the emergence of diabetes-associated autoantibodies in early childhood. Methods: We studied 242 newborn infants who had a first-degree relative with type 1 diabetes and carried risk-associated HLA-DQB1 alleles. After exclusive breastfeeding, the infants underwent a double-blind, randomised pilot trial of either casein hydrolysate (Nutramigen, Mead Johnson) or conventional cow's milk-based formula until the age of 6-8 months. During a mean observation period of 4.7 years, autoantibodies to insulin, anti-glutamic acid decarboxylase and insulinoma-associated antigen-2 were measured by radiobinding assays, and islet cell antibodies (ICA) by immunofluorescence. Results: The feasibility of screening and identifying a cohort of first-degree relatives with HLA-conferred disease susceptibility, enrolling them in a dietary intervention trial and following them for seroconversion to autoantibody positivity is established. The cumulative incidence of autoantibodies was somewhat smaller in the casein hydrolysate vs control formula group, suggesting the need for a larger well-powered study. After adjustment for duration of study formula feeding, life-table analysis showed a significant protection by the intervention from positivity for ICA (p=0.02) and at least one autoantibody (p=0.03). Conclusions/interpretation: The present study provides the first evidence ever in man, despite its limited power, that it may be possible to manipulate spontaneous beta cell autoimmunity by dietary intervention in infancy. © Springer-Verlag 2005.
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