| 1. |
|
|
| 2. |
- Alwin, Jenny, et al.
(author)
-
Utvärdering av försöksverksamhet med service- och signalhundar
- 2014
-
Reports (other academic/artistic)abstract
- Denna rapport redovisar utvärderingen av en försöksverksamhet med ser-vice- och signalhundar som bedrevs mellan år 2009 och 2014. Utvärderingen inkluderar servicehundar, signalhundar samt alarmerande servicehundar (epilepsihundar och diabeteshundar). Totalt 56 ekipage (förare samt hund) ingick i utvärderingsstudien. Data i studien samlades in före samt efter genomgången service- och signalhundsutbildning. Syftet med utvärderingen är att studera hur certifierade service- och signalhundar påverkar förarnas behov av offentliga stödinsatser och de totala samhällskostnaderna. Dessutom studerades hur service- och signalhundar påverkar förarna med avseende på hälsorelaterad livskvalitet, välbefinnande, självförtroende och fysisk aktivitet samt om användningen av service- och signalhundar är kostnadseffektiv ur ett samhällsperspektiv. Resultat och slutsatserService- och signalhundar minskar i genomsnitt förarnas behov av offentliga stödinsatser med 197 000 kronor (6 procent) under en tioårsperiod.Livskvaliteten för personer med behov av service- och signalhundar är låg jämfört med den allmänna populationen i Sverige. Studien visar på en förbättring i livskvaliteten och välbefinnandet för förare med en certifierad hund.Förarnas grad av fysisk aktivitet ökade med en certifierad hund och majoriteten av dem angav att de ökat sin tid utanför hemmet samt att de även ökat sin tid för att delta i sociala aktiviteter tack vare hunden.Förarnas negativa emotionella upplevelser minskar med en certifierad hund.Förarna beskriver själva den certifierade hunden som ett viktigt verktyg för ökad självständighet och trygghet.Den hälsoekonomiska modellen som analyserar kostnadseffektiviteten visar att ett innehav av en certifierad hund är ett dominant alternativ jämfört med att inte ha en certifierad hund. Detta innebär att kostnaderna ur ett samhällsperspektiv under en tioårsperiod är lägre (-103 000 kronor) samtidigt som effekterna i form av vunna QALY (kvalitetsjusterade levnadsår) är högre (+0,15).Finansieringsanalysen visar att förare som har certifierade hundar sparar resurser åt alla aktörer (stat, kommun och landsting) men får själva ökade utgifter på grund av hunden.Studien baseras på ett lågt antal observationer (56 ekipage). Det i kombination med att det är en stor spridning i resursförbrukningen mellan ekipagen medför att det finns en statistisk osäkerhet i resultaten. Slutsatserna bedöms dock som rimliga eftersom de är samstämmiga.
|
|
| 3. |
- Fredenberg, Erik, PhD, 1979-, et al.
(author)
-
A photon-counting detector for dual-energy breast tomosynthesis
- 2009
-
In: Medical Imaging 2009. - : SPIE. ; , s. 72581-
-
Conference paper (peer-reviewed)abstract
- We present the first evaluation of a recently developed silicon-strip detector for photon-counting dual-energy breast tomosynthesis. The detector is well suited for tomosynthesis with high dose efficiency and intrinsic scatter rejection. A method was developed for measuring the spatial resolution of a system based on the detector in terms of the three-dimensional modulation transfer function (MTF). The measurements agreed well with theoretical expectations, and it was seen that depth resolution was won at the cost of a slightly decreased lateral resolution. This may be a justifiable trade-off as clinical images acquired with the system indicate improved conspicuity of breast lesions. The photon-counting detector enables dual-energy subtraction imaging with electronic spectrumsplitting. This improved the detectability of iodine in phantom measurements, and the detector was found to be stable over typical clinical acquisition times. A model of the energy resolution showed that further improvements are witn reach by optimization of the detector.
|
|
| 4. |
- Zamani, Leila, et al.
(author)
-
High cell density perfusion culture has a maintained exoproteome and metabolome
-
Other publication (other academic/artistic)abstract
- Chinese hamster ovary (CHO) cells are the workhorse to produce recombinant proteins in the biopharmaceutical industry using mammalian cells and are commonly cultured in either fed-batch or perfusion mode. The optimization of the complex biological systems used in such processes is extremely challenging. Multi-omics approaches can reveal otherwise unknown characteristics of these systems and identify culture parameters that can be manipulated to optimize the cultivation process. Here we have ap- plied both metabolomic and proteomic profiling to a monoclonal antibody (mAb) production operated in perfusion mode to explore how cell biology and reactor environment change as the cell density reaches ≥ 200 x 106 cells/mL. The extracellular metabolic composition obtained in perfusion mode was also com- pared to fed-batch, which showed a more stable profile for perfusion despite a far larger range of viable cell densities. The proteomics data showed an increase of structural proteins as the cell density increased, and both the proteomic and metabolic results showed signs of oxidative stress and changes in glutathione metabolism at very high cell densities. The methodology presented herein could be a powerful tool for optimizing cultivation processes and recombinant protein production.
|
|
| 5. |
- Zamani, Leila, et al.
(author)
-
High Cell Density Perfusion Culture has a Maintained Exoproteome and Metabolome
- 2018
-
In: Biotechnology Journal. - : Wiley. - 1860-6768 .- 1860-7314. ; 13:10
-
Journal article (peer-reviewed)abstract
- The optimization of bioprocesses for biopharmaceutical manufacturing by Chinese hamster ovary (CHO) cells can be a challenging endeavor and, today, heavily relies on empirical methods treating the bioreactor process and the cells as black boxes. Multi-omics approaches have the potential to reveal otherwise unknown characteristics of these systems and identify culture parameters to more rationally optimize the cultivation process. Here, the authors have applied both metabolomic and proteomic profiling to a perfusion process, using CHO cells for antibody production, to explore how cell biology and reactor environment change as the cell density reaches 200x10(6)cellsmL(-1). The extracellular metabolic composition obtained in perfusion mode shows a markedly more stable profile in comparison to fed-batch, despite a far larger range of viable cell densities in perfusion. This stable profile is confirmed in the extracellular proteosome. Furthermore, the proteomics data shows an increase of structural proteins as cell density increases, which could be due to a higher shear stress and explain the decrease in cell diameter at very high cell densities. Both proteomic and metabolic results shows signs of oxidative stress and changes in glutathione metabolism at very high cell densities. The authors suggest the methodology presented herein to be a powerful tool for optimizing processes of recombinant protein production.
|
|
| 6. |
- Ahmadi, Elena, 1978-
(author)
-
Managers’ Work, Working Conditions and Wellbeing in Small Companies with Profitable Growth
- 2024
-
Doctoral thesis (other academic/artistic)abstract
- Background Managers’ work, working conditions and wellbeing are important determinants of occupational health in organizations. Nevertheless, little research has investigated these factors in the context of small growing businesses, which are known to contribute to employment, economic growth and social stability. The aim of this thesis was to explore managers’ work, working conditions and wellbeing in the context of small businesses with profitable growth. Methods Study I used a cross-sectional design to assess patterns in managerial work activities and leadership behaviours. Studies II–IV used qualitative interviews with managers (II–IV) and employees (II) to explore the effects of managers’ wellbeing on their leadership (II), their working conditions (III), and changes in their working conditions and wellbeing in the context of growing small businesses (IV).Results Managers worked long hours, posing risks for occupational health, but also adopted work practices that bolster occupational health. Firm size matters for managerial work. Managers’ wellbeing reflected in their mood and energy levels and influenced their leadership behaviours and performance, and the company’s work environment. Managers were more constructive when they felt well, and more passively destructive when they felt unwell. Certain factors mitigated the consequences of their negative behaviours in the organization. Five types of managers’ demands and resources (daily managerial work; achievement of results; and social; organizational; and individual factors) were identified, where the specificity of the small business context revealed unique characteristics. Company growth changed managers’ experiences of working conditions and wellbeing.Conclusions The specific context of small growing businesses shaped managers’ work, working conditions and wellbeing and the interplay between them. Dynamism in the organizational context due to growth had implications for managers’ work, working conditions and wellbeing.
|
|
| 7. |
- Almby, Kristina E., et al.
(author)
-
Effects of Gastric Bypass Surgery on the Brain : Simultaneous Assessment of Glucose Uptake, Blood Flow, Neural Activity, and Cognitive Function During Normo- and Hypoglycemia
- 2021
-
In: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 70:6, s. 1265-1277
-
Journal article (peer-reviewed)abstract
- While Roux-en-Y gastric bypass (RYGB) surgery in obese individuals typically improves glycemic control and prevents diabetes, it also frequently causes asymptomatic hypoglycemia. Previous work showed attenuated counterregulatory responses following RYGB. The underlying mechanisms as well as the clinical consequences are unclear. In this study, 11 subjects without diabetes with severe obesity were investigated pre- and post-RYGB during hyperinsulinemic normo-hypoglycemic clamps. Assessments were made of hormones, cognitive function, cerebral blood flow by arterial spin labeling, brain glucose metabolism by F-18-fluorodeoxyglucose (FDG) positron emission tomography, and activation of brain networks by functional MRI. Post- versus presurgery, we found a general increase of cerebral blood flow but a decrease of total brain FDG uptake during normoglycemia. During hypoglycemia, there was a marked increase in total brain FDG uptake, and this was similar for post- and presurgery, whereas hypothalamic FDG uptake was reduced during hypoglycemia. During hypoglycemia, attenuated responses of counterregulatory hormones and improvements in cognitive function were seen postsurgery. In early hypoglycemia, there was increased activation post- versus presurgery of neural networks in brain regions implicated in glucose regulation, such as the thalamus and hypothalamus. The results suggest adaptive responses of the brain that contribute to lowering of glycemia following RYGB, and the underlying mechanisms should be further elucidated.
|
|
| 8. |
- Almby, Kristina E., et al.
(author)
-
Effects of GLP-1 on counter-regulatory responses during hypoglycemia after GBP surgery
- 2019
-
In: European Journal of Endocrinology. - : Bioscientifica. - 0804-4643 .- 1479-683X. ; 181:2, s. 161-171
-
Journal article (peer-reviewed)abstract
- Objectives: The aim of the study was to explore the role of GLP-1 receptor activation on the counter-regulation and symptoms of hypoglycemia in subjects who have undergone gastric bypass surgery (GBP).Design: Experimental hyperinsulinemic–hypoglycemic clamp study.Methods: Twelve post-GBP subjects participated in a randomized cross-over study with two hyperinsulinemic, hypoglycemic clamps (glucose nadir 2.7 mmol/L) performed on separate days with concomitant infusions of the GLP-1 analog exenatide or with saline, respectively. Continuous measurements of metabolites and counter-regulatory hormones as well as assessments of heart rate variability and symptoms of hypoglycemia were performed throughout the clamps.Results: No effect of GLP-1 receptor activation on counter-regulatory hormones (glucagon, catecholamines, cortisol, GH) or glucose infusion rate was seen, but we found indications of a downregulation of the sympathetic relative to the parasympathetic nerve activity, as reflected in heart rate variability. No significant differences in symptom of hypoglycemia were observed.Conclusions/interpretation: Short-term exposure to a GLP-1 receptor agonist does not seem to impact the counter-regulatory hormonal and metabolic responses in post-GBP subjects during hypoglycemic conditions, suggesting that the improvement in symptomatic hypoglycemia post-GBP seen following treatment with GLP-1 receptor agonists may be mediated by mechanism not directly involved in counter-regulation.
|
|
| 9. |
- Alsterholm, Mikael, 1977, et al.
(author)
-
Establishment and utility of SwedAD : a nationwide Swedish registry for patients with atopic dermatitis receiving systemic pharmacotherapy
- 2023
-
In: Acta Dermato-Venereologica. - : Medical Journals Sweden AB. - 0001-5555 .- 1651-2057. ; 103
-
Journal article (peer-reviewed)abstract
- SwedAD, a Swedish nationwide registry for patients with atopic dermatitis receiving systemic pharmacotherapy, was launched on 1 September 2019. We describe here the establishment of a user-friendly registry to the benefit of patients with atopic dermatitis. By 5 November 2022, 38 clinics had recorded 931 treatment episodes in 850 patients with an approximate national coverage rate of 40%. Characteristics at enrolment included median Eczema Area and Severity Index (EASI) 10.2 (interquartile range 4.0, 19.4), Patient-Oriented Eczema Measure (POEM) 18.0 (10.0, 24.0), Dermatology Life Quality Index (DLQI) 11.0 (5.0, 19.0) and Peak Itch Numerical Rating Scale-11 (NRS-11) 6.0 (3.0, 8.0). At 3 months, median EASI was 3.2 (1.0, 7.3) and POEM, DLQI, and NRS-11 were improved. Regional coverage varied, reflecting the distribution of dermatologists, the ratio of public to private healthcare, and difficulties in recruiting certain clinics. This study highlights the importance of a nationwide registry when managing systemic pharmacotherapy of atopic dermatitis.
|
|
| 10. |
- Andersson, Josefina, et al.
(author)
-
Visible men and elusive women
- 2011
-
In: International Journal of Historical Archaeology. - : Springer Science and Business Media LLC. - 1092-7697 .- 1573-7748. ; 15:1, s. 10-29
-
Journal article (peer-reviewed)abstract
- Early gender archaeology formulated two statements: men are visible, women are invisible, and men work in hard materials, women work in soft materials. We discuss these dichotomies in connection with nineteenth-century folklore and an excavated eighteenth-century cottage at a summer-farm. We conclude that much of the gendered order-of-work tasks broke down in pragmatic day-to-day life, especially by women crossing the gender border. However, social chaos was held at bay by ritual acts and magic objects.
|
|
| 11. |
- Andersson, Mattias, et al.
(author)
-
Editor's Choice – Structured Computed Tomography Analysis can Identify the Majority of Patients at Risk of Post-Endovascular Aortic Repair Rupture
- 2022
-
In: European Journal of Vascular and Endovascular Surgery. - : Elsevier BV. - 1078-5884 .- 1532-2165. ; 64, s. 166-174
-
Journal article (peer-reviewed)abstract
- Objective: The main objective was to report mechanisms and precursors for post-endovascular aneurysm repair (EVAR) rupture. The second was to apply a structured protocol to explore whether these factors were identifiable on follow up computed tomography (CT) prior to rupture. The third objective was to study the incidence, treatment, and outcome of post-EVAR rupture. Methods: This was a multicentre, retrospective study of patients treated with standard EVAR at five Swedish hospitals from 2008 to 2018. Patients were identified from the Swedvasc registry. Medical records were reviewed up to 2020. Index EVAR and follow up data were recorded. The primary endpoint was post-EVAR rupture. CT at follow up and at post-EVAR rupture were studied, using a structured protocol, to determine rupture mechanisms and identifiable precursors. Results: In 1 805 patients treated by EVAR, 45 post-EVAR ruptures occurred in 43 patients. The cumulative incidence was 2.5% over a mean follow up of 5.2 years. The incidence rate was 4.5/1 000 person years. Median time to post-EVAR rupture was 4.1 years. A further six cases of post-EVAR rupture in five patients found outside the main cohort were included in the analysis of rupture mechanisms only. The rupture mechanism was type IA in 20 of 51 cases (39%), IB in 20 of 51 (39%) and IIIA/B in 11 of 51 (22%). One of these had type IA + IB combined. One patient had an aortoduodenal fistula without another mechanism being identified. Precursors had been noted on CT follow up prior to post-EVAR rupture in 16 of 51 (31%). Retrospectively, using the structured protocol, precursors could be identified in 43 of 51 (84%). In 17 of 27 (63%) cases missed on follow up but retrospectively identifiable, the mechanisms were type IB/III. Overall, the 30 day mortality rate after post-EVAR rupture was 47% (n = 24/51) and the post-operative mortality rate was 21% (n = 7/33). Conclusions: Most precursors of post-EVAR rupture are underdiagnosed but identifiable before rupture using a structured follow up CT protocol. Precursors of type IB and III failures caused the majority of post-EVAR ruptures.
|
|
| 12. |
- Andersson, Magnus, et al.
(author)
-
Vortex liquid properties in optimally doped and oxygen-deficient YBa2Cu3O7-delta single crystals
- 2000
-
In: Physica. C, Superconductivity. - 0921-4534 .- 1873-2143. ; 332:1-4, s. 86-92
-
Journal article (peer-reviewed)abstract
- The electrical anisotropy, gamma = (m(c)/m(ab))(1/2), can easily be varied by changing the oxygen content in single crystals of YBa2Cu3O7-delta (YBCO); thus making this system useful as a test system For vortex dynamics in high-temperature superconductors (HTSC). Here, some recent results are reviewed. Measurements of the c-axis resistivity with the magnetic field B II ab-plane is shown to be a powerful tool in studying vortex velocity correlations both parallel and perpendicular to the applied field. In optimally doped crystals, we iind evidence that the in-plane vortex lattice melts at T-m into a disentangled vortex liquid, which looses its correlation along the c-axis at a higher temperature T-br > T-m. For weakly disordered crystals and magnetic fields B \\ c-axis, a relation between the vortex glass line and the magnetic field dependence of the characteristic energy, U*, in the pinned vortex liquid is proposed. This approach is shown to give support to our idea of describing the vortex glass resistivity in the liquid regime by a modified glass correlation Length, xi(g) = xi(0)\k(B)T/U-0 - 1\(-nu) which depends on the average pinning energy, Lr,, in the system [A. Rydh, O. Rapp, M. Andersson, Phys. Rev. Lett. 83 (1999) 1850].
|
|
| 13. |
- Andersson, Magnus, et al.
(author)
-
Vortex liquid-to-solid transition in underdoped YBa2Cu3O7-delta single crystals with B parallel to ab
- 2003
-
In: Physica. C, Superconductivity. - 0921-4534 .- 1873-2143. ; 388, s. 691-692
-
Journal article (peer-reviewed)abstract
- A nearly magnetic field independent vortex liquid-to-solid transition has been observed in both the ab-plane and in the c-axis resistivity of underdoped YBa2Cu3O7-delta single crystals for magnetic fields Bparallel toab-plane. These observations suggest that intrinsic pinning caused by the superconducting layers do neither lead to a system of completely decoupled superconducting layers nor to a smectic vortex phase at high fields. A possible explanation may include a transition driven by changes in elastic properties (e.g., the shear modulus) of the vortex system.
|
|
| 14. |
- Austeng, Dordi, et al.
(author)
-
Incidence of and risk factors for neonatal morbidity after active perinatal care : extremely preterm infants study in Sweden (EXPRESS)
- 2010
-
In: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 99:7, s. 978-992
-
Journal article (peer-reviewed)abstract
- Aims: The aim of this study was to determine the incidence of neonatal morbidity in extremely preterm infants and to identify associated risk factors. Methods: Population based study of infants born before 27 gestational weeks and admitted for neonatal intensive care in Sweden during 2004-2007. Results: Of 638 admitted infants, 141 died. Among these, life support was withdrawn in 55 infants because of anticipation of poor long-term outcome. Of 497 surviving infants, 10% developed severe intraventricular haemorrhage (IVH), 5.7% cystic periventricular leucomalacia (cPVL), 41% septicaemia and 5.8% necrotizing enterocolitis (NEC); 61% had patent ductus arteriosus (PDA) and 34% developed retinopathy of prematurity (ROP) stage >= 3. Eighty-five per cent needed mechanical ventilation and 25% developed severe bronchopulmonary dysplasia (BPD). Forty-seven per cent survived to one year of age without any severe IVH, cPVL, severe ROP, severe BPD or NEC. Tocolysis increased and prolonged mechanical ventilation decreased the chances of survival without these morbidities. Maternal smoking and higher gestational duration were associated with lower risk of severe ROP, whereas PDA and poor growth increased this risk. Conclusion: Half of the infants surviving extremely preterm birth suffered from severe neonatal morbidities. Studies on how to reduce these morbidities and on the long-term health of survivors are warranted.
|
|
| 15. |
- Bengtsson, Magnus, et al.
(author)
-
Remote laser-induced breakdown spectroscopy for the detection and removal of salt on metal and polymeric surfaces
- 2006
-
In: Applied Spectroscopy. - : SAGE Publications. - 1943-3530 .- 0003-7028. ; 60:10, s. 1188-1191
-
Journal article (peer-reviewed)abstract
- The detection of contamination such as salt in outdoor high-voltage insulator systems and its subsequent removal are vital for a reliable transmission of electric power. Remote detection of salt on a copper metal surface was carried out by using a mobile laser-induced breakdown spectroscopy (LIBS) Lidar system with a laser wavelength of 355 nm. Detection of salt on a polymeric high-voltage insulator was obtained when an additional lens was inserted into the beam path, and the number of photons that was detected could be calculated by using a calibrated white light source. Ablative cleaning could readily be carried out with LIBS and was verified by observing the disappearance of the sodium D-line emission.
|
|
| 16. |
|
|
| 17. |
|
|
| 18. |
|
|
| 19. |
|
|
| 20. |
- Carlsson, Katrin, et al.
(author)
-
Fear and the Amygdala : Manipulation of Awareness Generates Differential Cerebral Responses to Phobic and Fear-Relevant (but Nonfeared) Stimuli
- 2004
-
In: Emotion. - : American Psychological Association (APA). - 1528-3542 .- 1931-1516. ; 4:4, s. 340-353
-
Journal article (peer-reviewed)abstract
- Rapid response to danger holds an evolutionary advantage. In this positron emission tomography study, phobics were exposed to masked visual stimuli with timings that either allowed awareness or not of either phobic, fear-relevant (e.g., spiders to snake phobics), or neutral images. When the timing did not permit awareness, the amygdala responded to both phobic and fear-relevant stimuli. With time for more elaborate processing, phobic stimuli resulted in an addition of an affective processing network to the amygdala activity, whereas no activity was found in response to fear-relevant stimuli. Also, right prefrontal areas appeared deactivated, comparing aware phobic and fear-relevant conditions. Thus, a shift from top-down control to an affectively driven system optimized for speed was observed in phobic relative to fear-relevant aware processing. (PsycINFO Database Record (c) 2006 APA, all rights reserved) (journal abstract)
|
|
| 21. |
- Cederström, Björn, et al.
(author)
-
Observer-model optimization of X-ray system in photon-counting breast imaging
- 2011
-
In: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 648:Supplement 1, s. S54-S57
-
Journal article (peer-reviewed)abstract
- An ideal-observer model is applied to optimize the design of an X-ray tube intended for use in a multi-slit scanning photon-counting mammography system. The design is such that the anode and the heel effect are reversed and the projected focal spot is smallest at the chest wall. Using linear systems theory, detectability and dose efficiency for a 0.1-mm disk are calculated for different focal spot sizes and anode angles. It is shown that the image acquisition time can be reduced by about 25% with spatial resolution and dose efficiency improved near the chest wall and worsened further away. The image quality is significantly more homogeneous than for the conventional anode orientation, both with respect to noise and detectability of a small object. With the tube rotated 90°, dose efficiency can be improved by 20% for a fixed image acquisition time.
|
|
| 22. |
- Dahlman, Nils, et al.
(author)
-
Evaluation of photon-counting spectral breast tomosynthesis
- 2011
-
In: Medical Imaging 2011. - : SPIE.
-
Conference paper (peer-reviewed)abstract
- We have designed a mammography system that for the first time combines photon-counting spectral imaging with tomosynthesis. The present study is a comprehensive physical evaluation of the system; tomosynthesis, spectral imaging, and the combination of both are compared using an ideal-observer model that takes anatomical noise into account. Predictions of signal and noise transfer through the system are verified by contrast measurements on a tissue phantom and 3D measurements of MTF and NPS. Clinical images acquired with the system are discussed in view of the model predictions.
|
|
| 23. |
|
|
| 24. |
|
|
| 25. |
- Danielsson, Henrik, et al.
(author)
-
A Systematic Review of Longitudinal Trajectories of Mental Health Problems in Children with Neurodevelopmental Disabilities
- 2024
-
In: Journal of Developmental and Physical Disabilities. - : Springer. - 1056-263X .- 1573-3580. ; 36, s. 203-242
-
Research review (peer-reviewed)abstract
- To review the longitudinal trajectories - and the factors influencing their development - of mental health problems in children with neurodevelopmental disabilities. Systematic review methods were employed. Searches of six databases used keywords and MeSH terms related to children with neurodevelopmental disabilities, mental health problems, and longitudinal research. After the removal of duplicates, reviewers independently screened records for inclusion, extracted data (outcomes and influencing factors), and evaluated the risk of bias. Findings were tabulated and synthesized using graphs and a narrative. Searches identified 94,662 unique records, from which 49 publications were included. The median publication year was 2015. Children with attention deficit hyperactivity disorder were the most commonly included population in retrieved studies. In almost 50% of studies, trajectories of mental health problems changed by < 10% between the first and last time point. Despite multiple studies reporting longitudinal trajectories of mental health problems, greater conceptual clarity and consideration of the measures included in research is needed, along with the inclusion of a more diverse range of populations of children with neurodevelopmental disabilities.
|
|
| 26. |
- de Almeida Cadorin, Eduardo, 1976-
(author)
-
Science Parks and talent attraction : a study on the development of Science Parks
- 2021
-
Doctoral thesis (other academic/artistic)abstract
- This dissertation investigates the development of Science Parks (SPs) from the perspective of talent attraction activities. Studies on SPs often address only traditional services that parks provide tenant firms. Thus, few studies have focused on activities organised by SPs to attract talent, and even fewer studies have considered the perspective of SP management (supply-side) rather than tenant firms (demand-side). This dissertation argues that the characteristics of the talent attracted to tenant firms and the SP’s structure, processes, characteristics, and stakeholder relationships influence SP performance. In addition, the talent attraction activities developed by the SP mediate this influence.This thesis relies on five papers, both qualitative and quantitative, written in collaboration with other scholars. This study shows that SPs organise talent attraction activities according to the characteristics of the desired talent and park configurations, such as their collaborations with stakeholders and the level of maturity of the tenant firms. These activities provide tenant firms with access to human resources suitable for their growth, contributing to the performance of the SP.This study contributes to research on the development of SPs by shedding light on how talent attraction activities organised by SPs influence their development. Furthermore, this thesis presents talent attraction as a conceptual element and proposes a model that includes the influence of talent attraction in a supply-side perspective and as a mediator of SP performance.Finally, this thesis recommends that SP managers support tenant firms of all maturity in the search for qualified professionals, facilitate the entry process of talents and firms from abroad, strengthen ties with the local university and student community and promote a creative, enterprising and innovative environment.
|
|
| 27. |
- Ding, Mei, et al.
(author)
-
Secretome screening reveals immunomodulating functions of IFNα-7, PAP and GDF-7 on regulatory T-cells
- 2021
-
In: Scientific Reports. - : Springer Nature. - 2045-2322. ; , s. 16767-
-
Journal article (peer-reviewed)abstract
- Regulatory T cells (Tregs) are the key cells regulating peripheral autoreactive T lymphocytes. Tregs exert their function by suppressing effector T cells. Tregs have been shown to play essential roles in the control of a variety of physiological and pathological immune responses. However, Tregs are unstable and can lose the expression of FOXP3 and suppressive functions as a consequence of outer stimuli. Available literature suggests that secreted proteins regulate Treg functional states, such as differentiation, proliferation and suppressive function. Identification of secreted proteins that affect Treg cell function are highly interesting for both therapeutic and diagnostic purposes in either hyperactive or immunosuppressed populations. Here, we report a phenotypic screening of a human secretome library in human Treg cells utilising a high throughput flow cytometry technology. Screening a library of 575 secreted proteins allowed us to identify proteins stabilising or destabilising the Treg phenotype as suggested by changes in expression of Treg marker proteins FOXP3 and/or CTLA4. Four proteins including GDF-7, IL-10, PAP and IFNα-7 were identified as positive regulators that increased FOXP3 and/or CTLA4 expression. PAP is a phosphatase. A catalytic-dead version of the protein did not induce an increase in FOXP3 expression. Ten interferon proteins were identified as negative regulators that reduced the expression of both CTLA4 and FOXP3, without affecting cell viability. A transcriptomics analysis supported the differential effect on Tregs of IFNα-7 versus other IFNα proteins, indicating differences in JAK/STAT signaling. A conformational model experiment confirmed a tenfold reduction in IFNAR-mediated ISG transcription for IFNα-7 compared to IFNα-10. This further strengthened the theory of a shift in downstream messaging upon external stimulation. As a summary, we have identified four positive regulators of FOXP3 and/or CTLA4 expression. Further exploration of these Treg modulators and their method of action has the potential to aid the discovery of novel therapies for both autoimmune and infectious diseases as well as for cancer.
|
|
| 28. |
- Engvall, Kristina, et al.
(author)
-
Impact of persistent peripheral neuropathy on health-related quality of life among early-stage breast cancer survivors : a population-based cross-sectional study
- 2022
-
In: Breast Cancer Research and Treatment. - : Springer. - 0167-6806 .- 1573-7217. ; 195, s. 379-391
-
Journal article (peer-reviewed)abstract
- Background We explored the impact of persistent sensory and motor taxane-induced peripheral neuropathy (TIPN) symptoms on health-related quality of life (HRQL) among early-stage breast cancer survivors (ESBCS). Methods A population-based cohort of 884 residual-free ESBCS received a postal questionnaire, including the EORTC chemotherapy-induced PN (CIPN20) and the EORTC QLQ-C30 instruments. Mean scores of QLQ-C30 scales among ESBCS with and without TIPN were calculated and adjusted for confounding factors (age, lifestyle factors, co-morbidities; linear regression analyses). Interpretation of QLQ-C30 results were based on guidelines. Results Response rate was 79%, and 646 survivors were included in the analysis. In median, 3.6 (1.5-7.3) years had elapsed post-taxane treatment. All TIPN symptoms had a significant impact on global QoL, which worsened with increased severity of TIPN. Between 29.5% and 93.3% of ESBCS with moderate-severe TIPN reported a clinical important impairment of functioning and personal finances, 64.3-85.7% reporting "difficulty walking because of foot drop," and 53.1-81.3% reporting "problems standing/walking because of difficulty feeling ground under feet" had impaired functioning/finances. The difference in mean scores between affected and non-affected survivors was highest for "numbness in toes/feet" and "difficulty walking because of foot drop." Moderate-severe "difficulty climbing stairs or getting out of chair because of weakness of legs" and "problems standing/walking because of difficulty feeling ground under feet" were associated with the largest clinically important differences on all scales. Conclusion Persistent sensory and motor TIPN is associated with clinically relevant impairment of global QoL, functioning, and personal finances among ESBCS, which increased with level of TIPN severity.
|
|
| 29. |
- Fellman, Vineta, et al.
(author)
-
One-year survival of extremely preterm infants after active perinatal care in Sweden.
- 2009
-
In: JAMA : the journal of the American Medical Association. - : American Medical Association (AMA). - 1538-3598 .- 0098-7484. ; 301:21, s. 2225-33
-
Journal article (peer-reviewed)abstract
- Up-to-date information on infant survival after extremely preterm birth is needed for assessing perinatal care services, clinical guidelines, and parental counseling.
|
|
| 30. |
- Forsberg, Håkan, et al.
(author)
-
Early Results and Ideas for Enhancements of the Master of Engineering Programme in Dependable Aerospace Systems
- 2017
-
In: The 6th Development Conference for Swedish Engineering USIU2017.
-
Conference paper (peer-reviewed)abstract
- The five-year Master of Engineering Programme in Dependable Aerospace Systems, with dependability as its silver thread, started at Mälardalen University (MDH) in 2015. This paper presents selected ideas behind the creation of the programme, together with some preliminary analysis of current results and suggested enhancements for the programme’s fourth and fifth years.
|
|
| 31. |
- Fredenberg, Erik, PhD, 1979-, et al.
(author)
-
Contrast-enhanced dual-energy subtraction imaging using electronic spectrum-splitting and multi-prism x-ray lenses
- 2008
-
In: Medical Imaging 2008 - Physics of Medical Imaging. - San Diego, CA, USA : SPIE. - 9780819470973 ; , s. 91310-91310
-
Conference paper (peer-reviewed)abstract
- Dual-energy subtraction imaging (DES) is a method to improve the detectability of contrast agents over a lumpy background. Two images, acquired at x-ray energies above and below an absorption edge of the agent material, are logarithmically subtracted, resulting in suppression of the signal from the tissue background and a relative enhancement of the signal from the agent. Although promising, DES is still not widely used in clinical practice. One reason may be the need for two distinctly separated x-ray spectra that are still close to the absorption edge, realized through dual exposures which may introduce motion unsharpness. In this study, electronic spectrum-splitting with a silicon-strip detector is theoretically and experimentally investigated for a mammography model with iodinated contrast agent. Comparisons are made to absorption imaging and a near-ideal detector using a signal-to-noise ratio that includes both statistical and structural noise. Similar to previous studies, heavy absorption filtration was needed to narrow the spectra at the expense of a large reduction in x-ray flux. Therefore, potential improvements using a chromatic multi-prism x-ray lens (MPL) for filtering were evaluated theoretically. The MPL offers a narrow tunable spectrum, and we show that the image quality can be improved compared to conventional filtering methods.
|
|
| 32. |
- Fredenberg, Erik, PhD, 1979-, et al.
(author)
-
Energy resolution of a photon-counting silicon strip detector
- 2010
-
In: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; , s. 156-162
-
Journal article (peer-reviewed)abstract
- A photon-counting silicon strip detector with two energy thresholds was investigated for spectral X-ray imaging in a mammography system. Preliminary studies already indicate clinical benefit of the detector, and the purpose of the present study is optimization with respect to energy resolution. Factors relevant for the energy response were measured, simulated, or gathered from previous studies, and used as input parameters to a cascaded detector model. Threshold scans over several X-ray spectra were used to calibrate threshold levels to energy, and to validate the model. The energy resolution of the detector assembly was assessed to range over ΔE/E=0.12–0.26 in the mammography region. Electronic noise dominated the peak broadening, followed by charge sharing between adjacent detector strips, and a channel-to-channel threshold spread. The energy resolution may be improved substantially if these effects are reduced to a minimum. Anti-coincidence logic mitigated double counting from charge sharing, but erased the energy resolution of all detected events, and optimization of the logic is desirable. Pile-up was found to be of minor importance at typical mammography rates.
|
|
| 33. |
- Fredenberg, Erik, PhD, 1979-, et al.
(author)
-
Imaging with multi-prism x-ray lenses
- 2008
-
In: Medical Imaging 2008 - Physics of Medical Imaging. - : SPIE. - 9780819470973 ; , s. 91308-91308
-
Conference paper (peer-reviewed)abstract
- The multi-prism lens (MPL) is a refractive x-ray lens consisting of two rows of prisms facing each other at an angle. Rays entering the lens at the periphery will encounter a larger number of prisms than will central ones, hence experiencing a greater refraction. The focusing effect of the MPL can be used to gather radiation from a large aperture onto a smaller detector, and accordingly to make better use of the available x-ray flux in medical x-ray imaging. Potential advantages of a better photon economy include shorter acquisition times, a reduced tube loading, or an improved resolution. Since the focusing effect is one-dimensional it matches the design of scanning systems. In this study we present the first images acquired with an MPL instead of the pre-breast slit collimator in a scanning mammography system. According to the measurements, the MPL is able to increase the flux 32% at equal resolution compared to the slit collimator, or to improve the resolution 2.4 mm(-1) at equal flux. If used with a custom-made absorption filter in a clinical set-up, the gain of flux of the MPL is expected to be at least 45%, and the corresponding improvement in resolution to be 3 mm(-1).
|
|
| 34. |
- Fredenberg, Erik, PhD, 1979-, et al.
(author)
-
Observer model optimization of a spectral mammography system
- 2010
-
In: Medical Imaging 2010. - : SPIE. - 9780819480231
-
Conference paper (peer-reviewed)abstract
- Spectral imaging is a method in medical x-ray imaging to extract information about the object constituents by the material-specific energy dependence of x-ray attenuation. Contrast-enhanced spectral imaging has been thoroughly investigated, but unenhanced imaging may be more useful because it comes as a bonus to the conventional non-energy-resolved absorption image at screening; there is no additional radiation dose and no need for contrast medium. We have used a previously developed theoretical framework and system model that include quantum and anatomical noise to characterize the performance of a photon-counting spectral mammography system with two energy bins for unenhanced imaging. The theoretical framework was validated with synthesized images. Optimal combination of the energy-resolved images for detecting large unenhanced tumors corresponded closely, but not exactly, to minimization of the anatomical noise, which is commonly referred to as energy subtraction. In that case, an ideal-observer detectability index could be improved close to 50% compared to absorption imaging. Optimization with respect to the signal-to-quantum-noise ratio, commonly referred to as energy weighting, deteriorated detectability. For small microcalcifications or tumors on uniform backgrounds, however, energy subtraction was suboptimal whereas energy weighting provided a minute improvement. The performance was largely independent of beam quality, detector energy resolution, and bin count fraction. It is clear that inclusion of anatomical noise and imaging task in spectral optimization may yield completely different results than an analysis based solely on quantum noise.
|
|
| 35. |
- Ghorbani, Shaban Reza, et al.
(author)
-
Thermoelectric power and resistivity of Nd1-xCaxBa2Cu3Oy and Nd1-xLaxBa2Cu3Oy
- 2000
-
In: Physica. C, Superconductivity. - 0921-4534 .- 1873-2143. ; 339:4, s. 245-252
-
Journal article (peer-reviewed)abstract
- The structural and transport properties of Nd1-xCaxBa2Cu3Oy (x = 0.0, 0.03, 0.06, and 0.10) and Nd1-xLax- Ba2Cu3Oy. (x nominally 0.0, 0.05, 0.10, and 0.15) have been studied by X-ray powder diffraction, electrical resistivity, and thermoelectric power measurements. In both series, the a- and b-axis lattice parameters decrease with increasing doping while the c-axis lattice parameter increases. The transport properties suggest improved metallic behaviour with increasing Ca doping in contrast to La doping. An anomalous sharp peak in the thermoelectric power close to T-c was observed, which depended on the doping content. We analysed the thermoelectric power as a function of temperature with a two-band model with an additional linear T term. An excellent agreement between model and data was obtained.
|
|
| 36. |
- Ghorbani, Shaban Reza, et al.
(author)
-
Thermoelectric power and resistivity of Nd1-xPrxBa2Cu3O7-delta
- 2001
-
In: Physica. C, Superconductivity. - 0921-4534 .- 1873-2143. ; 353:1-2, s. 77-84
-
Journal article (peer-reviewed)abstract
- The structural and transport properties of Nd1-xPrxBa2Cu3O7-delta (x = 0.0, 0.05, 0.10, and 0.15), have been studied by X-ray powder diffraction, electrical resistivity measurements, and thermoelectric power measurements. The decrease of the superconducting critical temperature with doping is described by a parabolic term and a linear term. The c-axis lattice parameter and the cell volume decrease with doping up to x = 0.10. Analyses of the thermoelectric power, critical temperature, c-axis lattice parameter, and the cell volume suggest that the Pr ions have a valence close to +4 at low doping concentration. The room temperature resistivity indicates that hole concentration decreases with increasing Pr doping. The room temperature thermoelectric power is positive for all samples and increases with increasing Pr doping due to a decrease in the carrier concentration. We analyzed the thermoelectric power as a function of temperature with a two-band model with an additional linear T term. An excellent agreement between model and data was obtained. The band width of the narrow band increases and its peak position moves away from the Fermi energy with increasing doping concentration.
|
|
| 37. |
- Gram, Magnus, et al.
(author)
-
Up-Regulation of A1M/α(1)-Microglobulin in Skin by Heme and Reactive Oxygen Species Gives Protection from Oxidative Damage.
- 2011
-
In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:11
-
Journal article (peer-reviewed)abstract
- During bleeding the skin is subjected to oxidative insults from free heme and radicals, generated from extracellular hemoglobin. The lipocalin α(1)-microglobulin (A1M) was recently shown to have reductase properties, reducing heme-proteins and other substrates, and to scavenge heme and radicals. We investigated the expression and localization of A1M in skin and the possible role of A1M in the protection of skin tissue from damage induced by heme and reactive oxygen species. Skin explants, keratinocyte cultures and purified collagen I were exposed to heme, reactive oxygen species, and/or A1M and investigated by biochemical methods and electron microscopy. The results demonstrate that A1M is localized ubiquitously in the dermal and epidermal layers, and that the A1M-gene is expressed in keratinocytes and up-regulated after exposure to heme and reactive oxygen species. A1M inhibited the heme- and reactive oxygen species-induced ultrastructural damage, up-regulation of antioxidation and cell cycle regulatory genes, and protein carbonyl formation in skin and keratinocytes. Finally, A1M bound to purified collagen I (K(d) = 0.96×10(-6) M) and could inhibit and repair the destruction of collagen fibrils by heme and reactive oxygen species. The results suggest that A1M may have a physiological role in protection of skin cells and matrix against oxidative damage following bleeding.
|
|
| 38. |
- Granlund, Mats, 1954-, et al.
(author)
-
Definitions and operationalization of mental health problems, wellbeing and participation constructs in children with ndd : Distinctions and clarifications
- 2021
-
In: International Journal of Environmental Research and Public Health. - : MDPI. - 1661-7827 .- 1660-4601. ; 18:4, s. 1-19
-
Journal article (peer-reviewed)abstract
- Children with impairments are known to experience more restricted participation than other children. It also appears that low levels of participation are related to a higher prevalence of mental health problems in children with neurodevelopmental disorders (NDD). The purpose of this conceptual paper is to describe and define the constructs mental health problems, mental health, and participation to ensure that future research investigating participation as a means to mental health in children and adolescents with NDD is founded on conceptual clarity. We first discuss the difference between two aspects of mental health problems, namely mental disorder and mental illness. This discussion serves to highlight three areas of conceptual difficulty and their consequences for understanding the mental health of children with NDD that we then consider in the article: (1) how to define mental health problems, (2) how to define and assess mental health problems and mental health, i.e., wellbeing as separate constructs, and (3) how to describe the relationship between participation and wellbeing. We then discuss the implications of our propositions for measurement and the use of participation interventions as a means to enhance mental health (defined as wellbeing). Conclusions: Mental disorders include both diagnoses related to impairments in the developmental period, i.e., NDD and diagnoses related to mental illness. These two types of mental disorders must be separated. Children with NDD, just like other people, may exhibit aspects of both mental health problems and wellbeing simultaneously. Measures of wellbeing defined as a continuum from flourishing to languishing for children with NDD need to be designed and evaluated. Wellbeing can lead to further participation and act to protect from mental health problems.
|
|
| 39. |
- Grip, Carl-Erik, et al.
(author)
-
Determination of thermal stratification and emptying flow in ladles by continuous temperature measurement and tracer addition
- 1996
-
In: ISIJ International. - 0915-1559 .- 1347-5460. ; 36:Supplement, s. S211-S214
-
Journal article (peer-reviewed)abstract
- If we want to control and predict the temperature of steel in the tundish we must know the thermal stratification in the ladle before and during casting, as well as the interaction with the steel flow through the nozzle. A group project, with participation of SSAB (Luleå and Oxelo̊sund), Luleå University and MEFOS, has been carried out to study these phenomenon. The stratification in the ladle was measured by thermo-couples penetrating into the melt at different levels. Such measurements were carried out before and during casting. To get information about the drainage flow, studies were made with tracer elements added at different points in the ladle. The response, defined as the tracer concentration in the outlet stream from the ladle, was measured by frequent sampling. Model work by numerical simulation and with tanks in series is discussed briefly.
|
|
| 40. |
- Grönlund, Rasmus, et al.
(author)
-
Remote LIBS and Raman imaging for assessment of cultural heritage
- 2005
-
In: 2005 Conference on Lasers and Electro-Optics Europe. - 0780389743 ; , s. 684-684
-
Conference paper (peer-reviewed)abstract
- In this paper, we propose to perform remote laser-induced breakdown spectroscopy (LIBS) and Raman imaging of historical monuments to assess the state of a building. The lidar system is equipped with a Nd:YAG pumped optical parametrical oscillator (OPO) system, allowing laser radiation in the wavelength range 220 nm-4 μm. The laser radiation can be sent through a roof-top dome which can steer the radiation onto the point of interest
|
|
| 41. |
- Hansen, Henning Gram, et al.
(author)
-
Versatile microscale screening platform for improving recombinant protein productivity in Chinese hamster ovary cells
- 2015
-
In: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 5
-
Journal article (peer-reviewed)abstract
- Chinese hamster ovary (CHO) cells are widely used as cell factories for the production of biopharmaceuticals. In contrast to the highly optimized production processes for monoclonal antibody (mAb)-based biopharmaceuticals, improving productivity of non-mAb therapeutic glycoproteins is more likely to reduce production costs significantly. The aim of this study was to establish a versatile target gene screening platform for improving productivity for primarily non-mAb glycoproteins with complete interchangeability of model proteins and target genes using transient expression. The platform consists of four techniques compatible with 96-well microplates: lipid-based transient transfection, cell cultivation in microplates, cell counting and antibody-independent product titer determination based on split-GFP complementation. We were able to demonstrate growth profiles and volumetric productivity of CHO cells in 96-half-deepwell microplates comparable with those obtained in shake flasks. In addition, we demonstrate that split-GFP complementation can be used to accurately measure relative titers of therapeutic glycoproteins. Using this platform, we were able to detect target gene-specific increase in titer and specific productivity of two non-mAb glycoproteins. In conclusion, the platform provides a novel miniaturized and parallelisable solution for screening target genes and holds the potential to unravel genes that can enhance the secretory capacity of CHO cells.
|
|
| 42. |
- Harrysson, Lars, et al.
(author)
-
Student Centred Learning in a Flexible Blended Mode Environment
- 2009
-
Conference paper (peer-reviewed)abstract
- The Faculty of Sciences at Lund University has developed online courses to enhance physical as well as virtual exchange and promote joint delivery of courses among partner universities. The purpose is to increase the flexibility of studies within joint programmes. As part of the development of a blended mode course we have included an online research tool, “Global Research Gateway”.
|
|
| 43. |
- Hellqvist, Magnus, 1964-, et al.
(author)
-
Developing Earth Science education research
- 2014
-
In: 31st Nordic Geological Winter Meeting. Lund, Sweden, January 8-10 2014. Scientific program. - Lund : Geologiska Föreningen. ; , s. 167-167
-
Conference paper (peer-reviewed)abstract
- This paper presents an attempt to build up research within the field earth science education, presenting results from interview studies on the student’s experience of participation to Earth science (1st year earth science students), inventory on previous research, interviews of primary school pupils and a public survey of knowledge in earth science. In Sweden, there is almost no research on Earth science education, the field within science education concerning Earth Science. In both European and international perspective this is in opposite to Physics, Computer science, Chemistry and Biology. Also in an international perspective the published research on Earth science education is very low, with one exceptional exception in North America where there is a lot of research in science education of different subjects. The largest number of publications is, therefore, also published in North America. The subjects of highest interest in previous earth science education research are on questions about misconceptions, concept inventories and field related education, where virtual field studies is of special interest.In the attempt to build up research, focus is primarily on education and teaching in university studies, but pre-university studies (primary & secondary school; upper secondary school) and the public knowledge on Earth science are also of interest. The studies focus on: experience of participation (i.e. identity); managing difficult and/or advanced questions; misconceptions; education in particular fields, especially field studies and laboratory work. Methodological the research is mainly performed through quantitative and qualitative data analysis, case study research and phenomenographic approaches.
|
|
| 44. |
- Hellqvist, Magnus, 1964-, et al.
(author)
-
Missuppfattningar och ovetande som mått på kunskapen betydelse - en undersökning av ”geovetenskaplig analfabetism” hos allmänheten och beslutsfattare
- 2014
-
Conference paper (other academic/artistic)abstract
- Den ämnesknutna didaktiken, som geovetenskaplig didaktik, diskuterar frågor kring uppfattningar, åsikter och värden som är bundna till den innehållsmässiga delen av undervisningen för ett ämnesområde (Sjöberg, 2010), vilket även kan vändas till kunskap hos allmänhet och beslutsfattare. I Sverige finns ämnet geovetenskap bara som fristående ämne på akademisk nivå, utan grundkunskaper i ämnet skapas en kunskapsbrist inför exempelvis frågor om klimatförändringar och naturresursutnyttjande. En studie undersöktes det geovetenskapliga kunskapsläget och om frånvaron av undervisning i skolan kan orsaka ”geovetenskaplig analfabetism”. Undersökningen genomfördes med internetbaserade enkäter till allmänhet och beslutsfattare. Resultaten visar på kunskapsbrist i båda undersökningsgrupperna. Det går dock att utläsa en liten skillnad i kunskapsnivå, då beslutsfattare har en något högre kunskapsnivå än allmänheten. Resultaten visar också att det finns en oro bland allmänheten för exempelvis klimatförändringar. För att kunna förbättra de geovetenskapliga kunskapsnivåerna krävs dels utbildning och dels utveckling av geovetenskaplig didaktik i Sverige.
|
|
| 45. |
- Hu, Francis Jingxin, 1986-, et al.
(author)
-
SAMURAI (Solid-phase Assisted Mutagenesis by Uracil Restricted Ablation In vitro) for Antibody Affinity Maturation and Paratope Mapping
-
Other publication (other academic/artistic)abstract
- Mutagenesis libraries are essential for combinatorial protein engineering. Despite improve- ments in gene synthesis and directed mutagenesis, current methodologies still have limitations regarding the synthesis of intact antibody scFv genes and simultaneous diversification of all six CDRs. Here, we de- scribe the generation of mutagenesis libraries for antibody affinity maturation, using a cell-free solid-phase technique for annealing of single-strand mutagenic oligonucleotides. This procedure consists of PCR-based incorporation of uracil into a wild-type template, bead-based capture, and elution of single-strand DNA, and in vitro uracil excision enzyme based degradation of the template DNA. Our approach enabled rapid (8 hours) mutagenesis and automated cloning of 50 position specific alanine mutants for mapping of a scFv antibody paratope. We further exemplify our method by generating affinity maturation libraries with di- versity introduced in critical, nonessential, or all CDR positions randomly. Assessment with Illumina deep sequencing showed >99% functional diversity in two libraries and the ability to diversify all CDR positions simultaneously. Selections of the libraries with bacterial display and deep sequencing evaluation of the selection output showed that diversity introduced in non-essential positions allowed quicker enrichment of improved binders compared to the other two diversification strategies.
|
|
| 46. |
- Hu, Francis Jingxin, 1986-, et al.
(author)
-
SAMURAI (Solid-phase Assisted Mutagenesis by Uracil Restriction for Accurate Integration) for antibody affinity maturation and paratope mapping
- 2019
-
In: Nucleic Acids Research. - : OXFORD UNIV PRESS. - 0305-1048 .- 1362-4962. ; 47:6
-
Journal article (peer-reviewed)abstract
- Mutagenesis libraries are essential for combinatorial protein engineering. Despite improvements in gene synthesis and directed mutagenesis, current methodologies still have limitations regarding the synthesis of complete antibody single-chain variable fragment (scFv) genes and simultaneous diversification of all six CDRs. Here, we describe the generation of mutagenesis libraries for antibody affinity maturation using a cell-free solid-phase technique for annealing of single-strand mutagenic oligonucleotides. The procedure consists of PCR-based incorporation of uracil into a wild-type template, bead-based capture, elution of single-strand DNA, and in vitro uracil excision enzyme based degradation of the template DNA. Our approach enabled rapid (8 hours) mutagenesis and automated cloning of 50 position-specific alanine mutants for mapping of a scFv antibody paratope. We further exemplify our method by generating affinity maturation libraries with diversity introduced in critical, nonessential, or all CDR positions randomly. Assessment with Illumina deep sequencing showed less than 1% wild-type in two libraries and the ability to diversify all CDR positions simultaneously. Selections of the libraries with bacterial display and deep sequencing evaluation of the selection output showed that diversity introduced in non-essential positions allowed for a more effective enrichment of improved binders compared to the other two diversification strategies.
|
|
| 47. |
- Hu, Francis Jingxin, 1986-, et al.
(author)
-
SPUX - A Solid Phase Uracil Excision Method for Antibody Affinity Maturation and Paratope Mapping
-
Other publication (other academic/artistic)abstract
- Mutagenesis libraries are the heart of combinatorial protein engineering where proteins such as antibodies are evolved for improved functionality. Despite recent improvements in gene synthesis and selection methodologies, current methods still fail to provide practical means for synthesis of complete antibody scFv and screening of theoretical diversities, hence forcing the user to focused diversity screening and assembly of shorter oligos to avoid synthesis errors and maximize library functionality. Here we demonstrate a way to generate highly functional tailored mutagenesis libraries for efficient antibody affinity maturation using a rapid cell-free solid phase cloning method with single strand diversity oligonucleotides. For this we are utilizing a combination of a high-fidelity polymerase for PCR-based incorporation of Uracil into a wild-type template, bead-based solid-phase technology for elution of single strand DNA, oligonucleotide annealing, extension and automation, and an uracil excision enzyme cocktail for in vitro degradation of template DNA to minimize background. Our method allowed for fast (8 hours) mutagenesis and automated cloning of a complete set of 50 position specific alanine-mutations for mapping of the paratope of a scFv antibody in a single robot run. We further exemplify our method by generating and stratifying a set of antibody scFv affinity maturation libraries with targeted diversity into critical or nonessential paratope positions, as well as by a complete randomization in all positions. The libraries were subjected to bacterial surface display selections and output was followed by Illumina deep sequencing and binding analysis by SPR. The functional quality of our libraries were high, with a yield of >99% functional diversity in the case for two of our libraries. We were further able to target all positions in all loops with diversity, and we could show the ability to target all six loops with diversity at the same time. The comparison of different library focus showed us that scFv libraries with diversity targeted to non-essential enhancing paratope positions more quickly rendered enrichment of improved binders compared to random diversity or paratope-targeted libraries. Surprisingly several of the improved binders from the random library had beneficial mutations in the same positions targeted by the smaller focused non-essential enhancing residue focused library indicating a possible benefit of focusing diversity to these spots. We believe our method for construction of libraries with site directed mutagenesis to be a viable way for generation of functional and diverse genetic libraries, particularly suitable for affinity maturation and paratope mapping of antibodies.
|
|
| 48. |
|
|
| 49. |
- Jordal, Kristin, et al.
(author)
-
Legal and regulatory framework for Swedish/Norwegian CCS cooperation
- 2022
-
Reports (other academic/artistic)abstract
- A description is provided of the legal/regulatory situation, as of early December 2021, for CO2 transport from Sweden/Preem AB to Norway/Northern Lights. CO2 transport from Sweden to Norway for the purpose of geological storage under the seabed is since 2019 legal, thanks to the provisional application of the amended Article 6 of the London Protocol, provided that the necessary unilateral declarations are deposited from Norway and Sweden to IMO and that Sweden and Norway enter a bilateral agreement on the matter. Economic incentives for CCS include the EU-ETS for fossil CO2 and the Swedish support for Bio-CCS through reverse auctioning.
|
|
| 50. |
- Joshi, Peter K, et al.
(author)
-
Directional dominance on stature and cognition in diverse human populations
- 2015
-
In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 523:7561, s. 459-462
-
Journal article (peer-reviewed)abstract
- Homozygosity has long been associated with rare, often devastating, Mendelian disorders, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 × 10(-300), 2.1 × 10(-6), 2.5 × 10(-10) and 1.8 × 10(-10), respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months' less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been.
|
|
