| 1. |
- De Leoz, M. L. A., et al.
(författare)
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NIST Interlaboratory Study on Glycosylation Analysis of Monoclonal Antibodies: Comparison of Results from Diverse Analytical Methods
- 2020
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Ingår i: Molecular & Cellular Proteomics. - 1535-9476. ; 19:1, s. 11-30
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Tidskriftsartikel (refereegranskat)abstract
- A broad-based interlaboratory study of glycosylation profiles of a reference and modified IgG antibody involving 103 reports from 76 laboratories. Glycosylation is a topic of intense current interest in the development of biopharmaceuticals because it is related to drug safety and efficacy. This work describes results of an interlaboratory study on the glycosylation of the Primary Sample (PS) of NISTmAb, a monoclonal antibody reference material. Seventy-six laboratories from industry, university, research, government, and hospital sectors in Europe, North America, Asia, and Australia submitted a total of 103 reports on glycan distributions. The principal objective of this study was to report and compare results for the full range of analytical methods presently used in the glycosylation analysis of mAbs. Therefore, participation was unrestricted, with laboratories choosing their own measurement techniques. Protein glycosylation was determined in various ways, including at the level of intact mAb, protein fragments, glycopeptides, or released glycans, using a wide variety of methods for derivatization, separation, identification, and quantification. Consequently, the diversity of results was enormous, with the number of glycan compositions identified by each laboratory ranging from 4 to 48. In total, one hundred sixteen glycan compositions were reported, of which 57 compositions could be assigned consensus abundance values. These consensus medians provide community-derived values for NISTmAb PS. Agreement with the consensus medians did not depend on the specific method or laboratory type. The study provides a view of the current state-of-the-art for biologic glycosylation measurement and suggests a clear need for harmonization of glycosylation analysis methods.
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| 4. |
- Falck-Ytter, Terje, et al.
(författare)
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The Babytwins Study Sweden (BATSS): A Multi-Method Infant Twin Study of Genetic and Environmental Factors Influencing Infant Brain and Behavioral Development
- 2021
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Ingår i: Twin Research and Human Genetics. - : Cambridge University Press (CUP). - 1832-4274 .- 1839-2628. ; 24:4, s. 217-227
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Tidskriftsartikel (refereegranskat)abstract
- Twin studies can help us understand the relative contributions of genes and environment to phenotypic trait variation, including attentional and brain activation measures. In terms of applying methodologies such as electroencephalography (EEG) and eye tracking, which are key methods in developmental neuroscience, infant twin studies are almost nonexistent. Here, we describe the Babytwins Study Sweden (BATSS), a multi-method longitudinal twin study of 177 MZ and 134 DZ twin pairs (i.e., 622 individual infants) covering the 5-36 month time period. The study includes EEG, eye tracking and genetics, together with more traditional measures based on in-person testing, direct observation and questionnaires. The results show that interest in participation in research among twin parents is high, despite the comprehensive protocol. DNA analysis from saliva samples was possible in virtually all participants, allowing for both zygosity confirmation and polygenic score analyses. Combining a longitudinal twin design with advanced technologies in developmental cognitive neuroscience and genomics, BATSS represents a new approach in infancy research, which we hope to have impact across multiple disciplines in the coming years.
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| 6. |
- Pijl, M. K. J., et al.
(författare)
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Parent-child interaction during the first year of life in infants at elevated likelihood of autism spectrum disorder
- 2021
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Ingår i: Infant Behavior and Development. - : Elsevier. - 0163-6383 .- 1879-0453 .- 1934-8800. ; 62
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Tidskriftsartikel (refereegranskat)abstract
- Autism spectrum disorder (ASD) likely emerges from a complex interaction between pre-existing neurodevelopmental vulnerabilities and the environment. The interaction with parents forms a key aspect of an infant’s social environment, but few prospective studies of infants at elevated likelihood (EL) for ASD (who have an older sibling with ASD) have examined parent-child interactions in the first year of life. As part of a European multisite network, parent-child dyads of free play were observed at 5 months (62 EL infants, 47 infants at typical likelihood (TL)) and 10 months (101 EL siblings, 77 TL siblings). The newly-developed Parent-Infant/Toddler Coding of Interaction (PInTCI) scheme was used, focusing on global characteristics of infant and parent behaviors. Coders were blind to participant information. Linear mixed model analyses showed no significant group differences in infant or parent behaviors at 5 or 10 months of age (all ps≥0.09, d≤0.36), controlling for infant’s sex and age, and parental educational level. However, without adjustments, EL infants showed fewer and less clear initiations at 10 months than TL infants (p = 0.02, d = 0.44), but statistical significance was lost after controlling for parental education (p = 0.09, d = 0.36), which tended to be lower in the EL group. Consistent with previous literature focusing on parent-infant dyads, our findings suggest that differences between EL and TL dyads may only be subtle during the first year of life. We discuss possible explanations and implications for future developmental studies.
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| 11. |
- Sekine, Takuya, et al.
(författare)
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TOX is expressed by exhausted and polyfunctional human effector memory CD8(+) T cells
- 2020
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Ingår i: Science immunology. - : American Association for the Advancement of Science (AAAS). - 2470-9468. ; 5:49
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Tidskriftsartikel (refereegranskat)abstract
- CD8(+) T cell exhaustion is a hallmark of many cancers and chronic infections. In mice, T cell factor 1 (TCF-1) maintains exhausted CD8(+) T cell responses, whereas thymocyte selection-associated HMG box (TOX) is required for the epigenetic remodeling and survival of exhausted CD8(+) T cells. However, it has remained unclear to what extent these transcription factors play analogous roles in humans. In this study, we mapped the expression of TOX and TCF-1 as a function of differentiation and specificity in the human CD8(+) T cell landscape. Here, we demonstrate that circulating TOX+ CD8(+) T cells exist in most humans, but that TOX is not exclusively associated with exhaustion. Effector memory CD8(+) T cells generally expressed TOX, whereas naive and early-differentiated memory CD8(+) T cells generally expressed TCF-1. Cytolytic gene and protein expression signatures were also defined by the expression of TOX. In the context of a relentless immune challenge, exhausted HIV-specific CD8(+) T cells commonly expressed TOX, often in clusters with various activation markers and inhibitory receptors, and expressed less TCF-1. However, polyfunctional memory CD8(+) T cells specific for cytomegalovirus (CMV) or Epstein-Barr virus (EBV) also expressed TOX, either with or without TCF-1. A similar phenotype was observed among HIV-specific CD8(+) T cells from individuals who maintained exceptional immune control of viral replication. Collectively, these data demonstrate that TOX is expressed by most circulating effector memory CD8(+) T cell subsets and not exclusively linked to exhaustion.
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| 17. |
- Bartl-Pokorny, K. D., et al.
(författare)
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Eye Tracking in Basic Research and Clinical Practice
- 2013
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Ingår i: Klinische Neurophysiologie. - : Georg Thieme Verlag KG. - 1434-0275 .- 1439-4081. ; 44:3, s. 193-198
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Tidskriftsartikel (refereegranskat)abstract
- Eye tracking is a non-invasive technique based on infrared video technology that is used to analyse eye movements. Such analyses might provide insights into perceptual and cognitive capacities. It is a method widely used in various disciplines, such as ophthalmology, neurology, psychiatry and neuropsychology for basic science, but also clinical practice. For example, recent studies on children who were later diagnosed with autism spectrum disorders revealed early abnormal eye movement patterns in socio-communicative settings; children with dyslexia appeared also to have peculiar eye movement patterns, expressed in longer fixation durations and smaller saccades while reading. Current research using eye tracking systems in combination with neurophysiological and brain imaging techniques will add to a better understanding of cognitive, linguistic and socio-communicative development and in the near future possibly also lead to a broader clinical application of this method.
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| 18. |
- Falck, Felicitas A O K, et al.
(författare)
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Subjective Experiences of Pregnancy, Delivery, and Nursing in Transgender Men and Non-Binary Individuals : A Qualitative Analysis of Gender and Mental Health Concerns
- 2024
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Ingår i: Archives of Sexual Behavior. - 0004-0002 .- 1573-2800. ; 53:5, s. 1981-2002
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Tidskriftsartikel (refereegranskat)abstract
- Studies of how gender-diverse individuals experience pregnancy, childbirth, and nursing remain few, mainly focus on the US and contain scarce information about mental health concerns peri-partum. This hinders informed reproductive health decisions and counseling. We used in-depth interviews to examine how gestational gender-diverse individuals in Sweden experience the process of planning and undergoing pregnancy, delivery, and nursing. In total, 12 participants, identifying on the masculine side of the gender spectrum or as non-binary, who had attended Swedish antenatal care and delivered a live birth, were included in the study. Data were analyzed using qualitative thematic content analysis. The analysis resulted in one overarching theme: sustaining gender congruence during pregnancy and three main categories: (1) considering pregnancy; (2) undergoing pregnancy and childbirth; and (3) postnatal reflections. The association between childbearing and being regarded as female permeated narratives. Participants renegotiated the feminine connotations of pregnancy, accessed gender-affirming treatment, and concealed their pregnancy to safeguard their gender congruence. Mis-gendering and breast enlargement triggered gender dysphoria. Social judgment, loneliness, information shortages, hormonal influence and cessation of testosterone increased gender dysphoria and strained their mental health. Depression exacerbated gender dysphoria and made it harder to claim one's gender identity. Dissociation was used to handle a feminized body, vaginal delivery, and nursing. Pregnancy was easier to envision and handle after masculinizing gender-affirming treatments. The results deepen the understanding of gender dysphoria and may be used to inform reproductive counseling and healthcare development. Research outcomes on mental health concerns provide a basis for further research.
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| 19. |
- Falck, Tillmann, et al.
(författare)
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Least-Squares Support Vector Machines for the identification of Wiener-Hammerstein systems
- 2012
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Ingår i: Control Engineering Practice. - : Elsevier BV. - 0967-0661 .- 1873-6939. ; 20:11, s. 1165-1174
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Tidskriftsartikel (refereegranskat)abstract
- This paper considers the identification of Wiener-Hammerstein systems using Least-Squares Support Vector Machines based models. The power of fully black-box NARX-type models is evaluated and compared with models incorporating information about the structure of the systems. For the NARX models it is shown how to extend the kernel-based estimator to large data sets. For the structured model the emphasis is on preserving the convexity of the estimation problem through a suitable relaxation of the original problem. To develop an empirical understanding of the implications of the different model design choices, all considered models are compared on an artificial system under a number of different experimental conditions. The obtained results are then validated on the Wiener-Hammerstein benchmark data set and the final models are presented. It is illustrated that black-box models are a suitable technique for the identification of Wiener-Hammerstein systems. The incorporation of structural information results in significant improvements in modeling performance.
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| 20. |
- Falck, Tillmann, et al.
(författare)
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Segmentation of Time Series from Nonlinear Dynamical Systems
- 2011
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Ingår i: Proceedings of the 18th IFAC World Congress. - 9783902661937 ; , s. 13209-13214
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Konferensbidrag (refereegranskat)abstract
- Segmentation of time series data is of interest in many applications, as for example in change detection and fault detection. In the area of convex optimization, the sum-of-norms regularization has recently proven useful for segmentation. Proposed formulations handle linear models, like ARX models, but cannot handle nonlinear models. To handle nonlinear dynamics, we propose integrating the sum-of-norms regularization with a least squares support vector machine (LS-SVM) core model. The proposed formulation takes the form of a convex optimization problem with the regularization constant trading off the fit and the number of segments.
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