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3. |
- Daas, Piet, et al.
(författare)
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Guidelines on the usage of the prototype of the computerized version of QRCA, and Report on the overall evaluation results. (Deliverable WP8.2)
- 2013
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Rapport (refereegranskat)abstract
- In this report the findings of the evaluation of various administrative data sources used by Dutch, Italian and Swedish National Statistical Institutes are reported. Administrative data sources were studied from both the data source quality and input oriented output quality point of view (deliverable 4.2). Since not all of the institutes were able to directly apply the statistical measurement methods implemented in the R-package developed in WP 4 (deliverable 4.3), the measurement methods required were implemented in the (standard) programming language of choice for each institute. The experiences and results obtained by the NSIs involved are generally discussed in this report. In the appendices, the findings of each source foreach individual NSI are included. This report also contains the manual for the methods implemented in the dataquality R-package and the most recent version of the Quality Report Card for Administrative data (QRCA).
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9. |
- Wallgren, Anders, 1942-, et al.
(författare)
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Register-based statistics : administrative data for statistical purposes
- 2007
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Bok (övrigt vetenskapligt/konstnärligt)abstract
- There is a growing interest in developing register-based surveys; that is surveys based upon already available administrative data. Since huge amounts of such data are generated within various administrative systems, the opportunity exists to use the data for statistical analysis without any of the costs involved in data collection. Register-based surveys require their own methodology and the development of these methods is an important challenge to statistical science. Instead of methods on how to collect data, methods for integrating data from different sources are necessary. How should administrative data be transformed to meet the statistical needs? Register-based Statistics offers readers a detailed account of the principles and practices of this increasingly popular area of statistics. Provides a comprehensive overview of register-based statistics, both in terms of theory and advanced application. Uses real life examples taken from Statistics Sweden to illustrate fundamental global principles. Proposes a much-needed systematic terminology for the field. Describes how to create statistical registers and a methodology for integration of data from many sources as a key tool for the future. Develops estimation methods and quality concepts for register-based surveys. Discusses statistical systems consisting of many statistical registers and surveys, highlighting the importance of consistency and coherence. Register-based Statistics provides a unique guide for all those working in statistical agencies. It will also prove invaluable for academic researchers and teachers in statistics, and statisticians working with administrative systems in government institutions and enterprises.
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- Berg, Lotta, et al.
(författare)
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Yttrande från SLUs vetenskapliga råd för djurskydd om djurskydd inom grisuppfödning
- 2019
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Detta yttrande svarar på följande fråga av Djurskyddet Sverige, Svenska Djurskyddsföreningen, Djurens Rätt, World Animal Protection Sverige, Compassion in World Farming Sverige och Vi Konsumenter, som vänt sig till det vetenskapliga rådet med anledning av Jordbruksverkets ändring av djurskyddsbestämmelserna för gris, Statens jordbruksverks föreskrifter och allmänna råd m ( SJVFS 2017:25) om grishållning inom lantbruket m.m., saknr. L 106: Är det förenat med bättre, likvärdig eller sämre djurvälfärd, vid en sammantagen bedömning av såväl smågrisens välfärd som suggans, om smågrisar avvänjs från suggan vid 21 dagars ålder i stället för vid 28 dagars ålder? Rådet ombads att belysa frågan utifrån ett brett perspektiv innefattande såväl psykisk som fysisk hälsa och välbefinnande.
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- Böhm, Johann, et al.
(författare)
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Mutation spectrum in the large GTPase dynamin 2, and genotype-phenotype correlation in autosomal dominant centronuclear myopathy.
- 2012
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Ingår i: Human mutation. - : Hindawi Limited. - 1098-1004 .- 1059-7794. ; 33:6, s. 949-59
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Tidskriftsartikel (refereegranskat)abstract
- Centronuclear myopathy (CNM) is a genetically heterogeneous disorder associated with general skeletal muscle weakness, type I fiber predominance and atrophy, and abnormally centralized nuclei. Autosomal dominant CNM is due to mutations in the large GTPase dynamin 2 (DNM2), a mechanochemical enzyme regulating cytoskeleton and membrane trafficking in cells. To date, 40 families with CNM-related DNM2 mutations have been described, and here we report 60 additional families encompassing a broad genotypic and phenotypic spectrum. In total, 18 different mutations are reported in 100 families and our cohort harbors nine known and four new mutations, including the first splice-site mutation. Genotype-phenotype correlation hypotheses are drawn from the published and new data, and allow an efficient screening strategy for molecular diagnosis. In addition to CNM, dissimilar DNM2 mutations are associated with Charcot-Marie-Tooth (CMT) peripheral neuropathy (CMTD1B and CMT2M), suggesting a tissue-specific impact of the mutations. In this study, we discuss the possible clinical overlap of CNM and CMT, and the biological significance of the respective mutations based on the known functions of dynamin 2 and its protein structure. Defects in membrane trafficking due to DNM2 mutations potentially represent a common pathological mechanism in CNM and CMT.
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16. |
- De Ambrogi, Marco, et al.
(författare)
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Effect of storage in short- and long-term commercial semen extenders on the motility, plasma membrane and chromatin integrity of boar spermatozoa
- 2006
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Ingår i: International Journal of Andrology. - : Wiley-Blackwell. - 0105-6263 .- 1365-2605. ; 29:5, s. 543-552
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Tidskriftsartikel (refereegranskat)abstract
- For artificial insemination (AI) in pigs, preservation of liquid boar semen at 16-20 degrees C is still common practice as sperm cryopreservation remains suboptimal in this species. To meet the different needs of the swine industry, several extenders have been developed to preserve semen in liquid form for short- and long-term storage. In the present study, three different commercial extenders devised for short-term (BTS+) or long-term preservation (MR-A and X-Cell), were used to test whether storage of semen from four mature, fertile boars at 17 degrees C for 96 h would affect sperm characteristics relevant for fertility, such as motility, membrane integrity and chromatin stability. Computer-assisted sperm analysis, and stainings with the acylated membrane dye SYBR-14/propidium iodide, and acridine orange in connection with flow cytometry were used to evaluate these variables. Percentages of total motile spermatozoa decreased slightly, but significantly, after 72-96 h. While membrane integrity values varied during the period of study, no significant changes in either membrane integrity or chromatin stability were, however, registered. This suggests a customary 96-day storage at 17 degrees C in these extenders was too short an interval to cause losses of integrity in nuclear DNA in the boar population studied.
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17. |
- Deori, Sourabh, et al.
(författare)
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Comparison of single layer centrifugation and magnetic activated cell sorting for selecting viable boar spermatozoa after thawing
- 2022
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Ingår i: Livestock Science. - : Elsevier BV. - 1871-1413 .- 1878-0490. ; 257
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Tidskriftsartikel (refereegranskat)abstract
- Sperm selection techniques, such as magnetic activated cell sorting (MACS) and colloid centrifugation, are reported to select good quality spermatozoa from semen samples of various species. Although the sperm quality of fresh boar semen is usually good, cryopreservation has a negative effect on parameters such as plasma membrane integrity and mitochondrial activity. Therefore, the objective of the present study was to determine whether MACS or centrifugation through a single layer of colloid (Single Layer Centrifugation, SLC) would be beneficial in enriching thawed boar sperm samples for viable spermatozoa with active mitochondria and good chromatin integrity. Frozen samples from three boars, three ejaculates per boar, were thawed and split. One part was selected by MACS, one was prepared by SLC, and the remainder served as the control. Controls and the selected sperm samples were evaluated for sperm quality (plasma membrane integrity, chromatin integrity, mitochondrial membrane potential and production of reactive oxygen species). Although several aspects of sperm quality were improved in the SLC-selected sperm samples compared to control, the flow-through MACS samples were only improved in having a lower proportion of spermatozoa with immature chromatin (Hi green fluorescence) compared to the labeled control. Sperm quality in the SLC samples was better than in the flow-through samples from MACS. Therefore, despite promising reports of the use of MACS for selecting good quality spermatozoa from semen in other species, the method was not useful for improving sperm quality in the thawed boar sperm samples in this experiment.
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18. |
- Essving, Per, et al.
(författare)
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Reduced hospital stay, morphine consumption, and pain intensity with local infiltration analgesia after unicompartmental knee arthroplasty
- 2009
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Ingår i: ACTA ORTHOPAEDICA. - : Medical Journals Sweden AB. - 1745-3674 .- 1745-3682. ; 80:2, s. 213-219
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose The degree of postoperative pain is usually moderate to severe following knee arthroplasty. We investigated the efficacy of local administration of analgesics into the operating area, both intraoperatively and postoperatively. Methods 40 patients undergoing unicompartmental knee arthroplasty (UKA) were randomized into 2 groups in a double-blind study (ClinicalTrials.gov identifier: NCT00653926). In group A (active), 200 mg ropivacaine, 30 mg ketorolac, and 0.5 mg epinephrine (total volume 106 mL) were infiltrated intraoperatively into the soft tissue, while in group P (placebo), no injections were given. 21 hours postoperatively, 150 mg ropivacain, 30 mg ketorolac, and 0.1 mg epinephrine were injected intraarticularly via a catheter in group A, whereas patients in group P were injected with the same volume of saline (22 mL). Results Median hospital stay was shorter in group A than in group P: 1 (1-6) days as opposed to 3 (1-6) days (p 0.001). Postoperative pain in group A was statistically significantly lower at rest after 6 h and 27 h and on movement after 6, 12, 22, and 27 h. Morphine consumption was statistically significantly lower in group A for the first 48 h, resulting in a lower frequency of nausea, pruritus, and sedation. Postoperatively, there were improved functional scores (Oxford knee score and EQ-5D) in both groups relative to the corresponding preoperative values. Interpretation Local injection of analgesics periarticularly at the end of the operation and intraarticularly at 21 h postoperatively provided excellent pain relief and earlier home discharge following UKA. There was a high degree of patient satisfaction in both groups after 6 months.
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19. |
- Essving, Per, et al.
(författare)
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Reduced hospital stay, morphine consumption, and pain intensity with local infiltration analgesia after unicompartmental knee arthroplasty : a randomized double-blind study of 40 patients
- 2009
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Ingår i: Acta Orthopaedica. - Lund : Taylor & Francis. - 1745-3674 .- 1745-3682. ; 80:2, s. 213-219
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: The degree of postoperative pain is usually moderate to severe following knee arthroplasty. We investigated the efficacy of local administration of analgesics into the operating area, both intraoperatively and postoperatively. METHODS: 40 patients undergoing unicompartmental knee arthroplasty (UKA) were randomized into 2 groups in a double-blind study (ClinicalTrials.gov identifier: NCT00653926). In group A (active), 200 mg ropivacaine, 30 mg ketorolac, and 0.5 mg epinephrine (total volume 106 mL) were infiltrated intraoperatively into the soft tissue, while in group P (placebo), no injections were given. 21 hours postoperatively, 150 mg ropivacain, 30 mg ketorolac, and 0.1 mg epinephrine were injected intraarticularly via a catheter in group A, whereas patients in group P were injected with the same volume of saline (22 mL). RESULTS: Median hospital stay was shorter in group A than in group P: 1 (1-6) days as opposed to 3 (1-6) days (p < 0.001). Postoperative pain in group A was statistically significantly lower at rest after 6 h and 27 h and on movement after 6, 12, 22, and 27 h. Morphine consumption was statistically significantly lower in group A for the first 48 h, resulting in a lower frequency of nausea, pruritus, and sedation. Postoperatively, there were improved functional scores (Oxford knee score and EQ-5D) in both groups relative to the corresponding preoperative values. INTERPRETATION: Local injection of analgesics periarticularly at the end of the operation and intraarticularly at 21 h postoperatively provided excellent pain relief and earlier home discharge following UKA. There was a high degree of patient satisfaction in both groups after 6 months (Clinical Trials.gov: NCT 00653926).
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20. |
- Essving, Per, 1960-, et al.
(författare)
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Reduced morphine consumption and pain intensity with local infiltration analgesia (LIA) following total knee arthroplasty : a randomized double-blind study involving 48 patients
- 2010
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Ingår i: Acta Orthopaedica. - : Medical Journals Sweden AB. - 1745-3674 .- 1745-3682. ; 81:3, s. 354-360
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: Postoperative pain is often severe following total knee arthroplasty (TKA). We investigated the efficacy of local infiltration analgesia (LIA) technique, intra- and postoperatively.Methods: 48 patients undergoing TKA were randomized into 2 groups in a double-blind study. In group A, 400 mg ropivacaine, 30 mg ketorolac and 0.5 mg epinephrine were infiltrated periarticularly intra-operatively. In group P, no injections were given. At 21 hours postoperatively, 200 mg ropivacaine, 30 mg ketorolac and 0.1 mg epinephrine were injected intraarticularly in group A, and the same volume of saline was injected in group P. Patients were followed up for 3 months.Results: Median morphine consumption was lower in group A during 0-48 h: 18 (1-74) mg vs. 87 (36-160) mg in group P. Postoperative pain was lower at rest in group A during the first 27 h, and on movement during the first 48 h, except at 21 h. Time to fulfilling discharge criteria was shorter in group A than in group P; 3 (1-7) vs. 5 (2-8) days. Patient satisfaction was higher in group A compared to group P on day 1 and 7. The unbound venous blood concentration of ropivacaine was below systemic toxic blood concentrations. Interpretation: Local infiltration analgesia (LIA) technique provides excellent pain relief and lower morphine consumption following TKA, resulting in shorter time to home readiness and higher patient satisfaction. Side effects were few and systemic LA concentrations low.
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23. |
- Johannisson, Anders, et al.
(författare)
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Single Layer Centrifugation with Androcoll-P can be scaled-up to process larger volumes of boar semen
- 2011
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Ingår i: ISRN Veterinary Science. - : Hindawi Limited. - 2090-4452 .- 2090-4460. ; 2011
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Tidskriftsartikel (refereegranskat)abstract
- The objective of this study was to scale-up the procedure for Single Layer Centrifugation (SLC) through AndrocollTM-P, as a preliminary step towords processing the whole ejaculate. The first experiment compared Single Layer Centrifugation using 4.5 mL and 15 mL extended ejaculate (SLC-4.5 and SLC-15, resp.), assessing sperm quality by objective motility analysis, morphology, viability, and the production of reactive oxygen species (ROS). In the second experiment, SLC-4.5 was compared to Single Layer Centrifugation with 25 mL extended ejaculate (SLC-25) using motility analysis and morphology. In both experiments, normal morphology and linear motility were significantly higher in the SLC-selected samples than in the uncentrifuged controls (P<.001), whereas total motility and membrane integrity were unchanged. Although ROS production was higher in the SLC-selected samples than in the controls (P<.01), this might have been due to the presence of antioxidants in seminal plasma in the latter. In conclusion, there was no difference in sperm quality between SLC-4.5 and SLC-15 samples, or between SLC-4.5 and SLC-25 samples, indicating that the SLC method can be scaled-up successfully.
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24. |
- Johannisson, Anders, et al.
(författare)
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Spermatozoa in the sperm-peak-fraction of the boar ejaculate show a lower flow of Ca2+ under capacitation conditions post-thaw which might account for their higher membrane stability after cryopreservation
- 2011
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Ingår i: Animal Reproduction Science. - : Elsevier BV. - 0378-4320 .- 1873-2232. ; 128, s. 37-44
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Tidskriftsartikel (refereegranskat)abstract
- Boar spermatozoa collected in the ejaculate sperm peak-portion (P1, first 10 mL of the sperm-rich fraction, SRF), had shown a higher resilience to freezing and thawing compared to spermatozoa from the rest of the ejaculate (2nd portion of the SRF plus the post-sperm-rich fraction, PSRF), even when using a simplified freezing technique, as long as spermatozoa were incubated in their own seminal plasma (SP). This experiment studied the stability of P1- and SRF-P1 boar spermatozoa frozen in MiniFlatPacks (MFP), post-thaw, using flow cytometry. Since spermatozoa from either portion showed similar cryosurvival and low proportions of unstable membranes (<3%, annexin-V/propidium iodide staining), and only a tendency for SRF-P1 live spermatozoa to depict acrosome exocytosis (FITC-PNA/PI/H33342); they were explored for Ca2+ contents using a Fluo-4 probe under in vitro capacitating conditions (mBO+ medium), as well they were tested for their ability to sustain a short Ca2+-ionophore (A23187) in vitro challenge. The proportions of live spermatozoa depicting high Ca2+-levels were initially <2% but increased over incubation time, particularly in SRF-P1(P < 0.05), while proportions of live spermatozoa with low Ca2+-levels were basically constant over incubation time (similar to 11-14%), for either portion. Incubation in capacitation medium did not modify the proportions of low-Ca2+ but dramatically increased the proportions of high-Ca2+ spermatozoa (P < 0.001) already after 15 min exposure, highest for SRF-P1 spermatozoa. While the proportion of live spermatozoa with intact acrosome was significantly decreased among SRF-P1 (P < 0.001), that of P1-spermatozoa remained unchanged, probably owing to the lowest relative content of cytosolic Ca2+. The results suggest that spermatozoa in the P1-portion are more resilient to express acrosome exocytosis post-thaw compared to those bathing in the rest of the SRF-fraction when cryopreserved using a simplified technique, in MFPs. (C) 2011 Elsevier B.V. All rights reserved.
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25. |
- Juvany, Laura, et al.
(författare)
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From simple metrics to cervid forage : Improving predictions of ericaceous shrub biomass
- 2023
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Ingår i: Forest Ecology and Management. - Amsterdam : Elsevier. - 0378-1127 .- 1872-7042. ; 544
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Tidskriftsartikel (refereegranskat)abstract
- Common understory vegetation species such as the ericaceous shrubs bilberry (Vaccinium myrtillus), cowberry (V. vitis-idaea) and heather (Calluna vulgaris), are key forage plant species for moose and other large herbivores, as well as fulfilling many additional ecosystem functions and services. Here we developed models to predict above-ground biomass of these ericaceous species in coniferous forests, using data on their percentage cover, height, and different stand characteristics. We also built models to understand how the aforementioned variables affect the proportion of the shrubs commonly utilized as forage by large herbivores. We found that the percentage cover of shrubs was the most important explanatory variable when predicting above-ground biomass, explaining 51%, 47% and 71% of the variation (marginal R2) in bilberry, cowberry and heather biomass, respectively. By adding ramet height to the model with percentage cover, the variation explained increased to 77% for bilberry, 75% for cowberry and 87% for heather. The best outcome for candidate models was obtained by adding stand site index and spruce basal area to the model, improving the variation explained in bilberry to 83%, to 81% for cowberry, and 91% for heather. When modelling the proportion of the shrubs commonly utilized as forage by large herbivores, stand site index and spruce basal area often played important roles. Some of the best fitting models for forage biomass explained 51% of the variation in bilberry, 59% in cowberry and 30% in heather. Site location did not have a major role in improving the variability explained in either type of model, which indicated the applicability of the models regardless of study location. Our models therefore have a high potential to be implemented in forestry decision support systems. Their inclusion should provide better large-scale estimations of forage resources, aiding forest management, and thereby taking an important step forward to determine the ecosystem carrying capacity of large herbivores. © 2023 The Author(s)
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26. |
- Kumaresan, A., et al.
(författare)
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Quantification of kinetic changes in protein tyrosine phosphorylation and cytosolic Ca2+ concentration in boar spermatozoa during cryopreservation
- 2012
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Ingår i: Reproduction, Fertility and Development. - 1031-3613 .- 1448-5990. ; 24:4, s. 531-542
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Tidskriftsartikel (refereegranskat)abstract
- Protein tyrosine phosphorylation in sperm is associated with capacitation in several mammalian species. Although tyrosine phosphorylated proteins have been demonstrated in cryopreserved sperm, indicating capacitation-like changes during cryopreservation, these changes have not yet been quantified objectively. We monitored tyrosine phosphorylation, intracellular calcium and sperm kinematics throughout the cryopreservation process, and studied the relationships among them in boar spermatozoa. Sperm kinetics changed significantly during cryopreservation: curvilinear velocity, average path velocity and straight line velocity all decreased significantly (P < 0.05). While the percentage of sperm with high intracellular calcium declined (P < 0.05), global phosphorylation increased significantly (P < 0.01). Specifically, cooling to 5 degrees C induced phosphorylation in the spermatozoa. After cooling, a 32-kDa protein not observed in fresh semen appeared and was consistently present throughout the cryopreservation process. While the level of expression of this phosphoprotein decreased after addition of the second extender, frozen-thawed spermatozoa showed an increased expression. The proportion of sperm cells with phosphorylation in the acrosomal area also increased significantly (P < 0.05) during cryopreservation, indicating that phosphorylation might be associated with capacitation-like changes. These results provide the first quantitative evidence of dynamic changes in the subpopulation of boar spermatozoa undergoing tyrosine phosphorylation during cryopreservation.
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27. |
- Laurell, Anna, et al.
(författare)
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Intratumorally injected pro-inflammatory allogeneic dendritic cells as immune enhancers: a first-in-human study in unfavourable risk patients with metastatic renal cell carcinoma
- 2017
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Ingår i: Journal for Immunotherapy of Cancer. - : BMJ. - 2051-1426. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Background: Accumulating pre-clinical data indicate that the efficient induction of antigen-specific cytotoxic CD8+ T cells characterizing viral infections is caused by cross-priming where initially infected DCs produce an unique set of inflammatory factors that recruit and activate non-infected bystander DCs. Our DC-based immunotherapy concept is guided by such bystander view and accordingly, we have developed a cellular adjuvant consisting of pre-activated allogeneic DCs producing high levels of DC-recruiting and DC-activating factors. This concept doesn't require MHC-compatibility between injected cells and the patient and therefore introduces the possibility of using pre-produced and freeze-stored DCs from healthy blood donors as an off-the-shelf immune enhancer. The use of MHC-incompatible allogeneic DCs will further induce a local rejection process at the injection site that is expected to further enhance recruitment and maturation of endogenous bystander DCs. Methods: Twelve intermediate and poor risk patients with newly diagnosed metastatic renal cell carcinoma (mRCC) where included in a phase I/II study. Pro-inflammatory allogeneic DCs were produced from a leukapheresis product collected from one healthy blood donor and subsequently deep-frozen. A dose of 5-20 x 106 DCs (INTUVAX) was injected into the renal tumor twice with 2 weeks interval before planned nephrectomy and subsequent standard of care. Results: No INTUVAX-related severe adverse events were observed. A massive infiltration of CD8+ T cells was found in 5 out of 12 removed kidney tumors. No objective tumor response was observed and 6 out of 11 evaluable patients have subsequently received additional treatment with standard tyrosine kinase inhibitors (TKI). Three of these 6 patients experienced an objective tumor response including one sunitinib-treated patient who responded with a complete and durable regression of 4 brain metastases. Median overall survival (mOS) is still not reached (currently 42.5 months) but has already passed historical mOS in patients with unfavourable risk mRCC on standard TKI therapy. Conclusions: Our findings indicate that intratumoral administration of proinflammatory allogeneic DCs induces an antitumor immune response that may prolong survival in unfavourable risk mRCC-patients given subsequent standard of care. A randomized, multi-center, phase II mRCC trial (MERECA) with INTUVAX in conjuction with sunitinib has been initiated.
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28. |
- Ljung Aust, Mikael, 1973, et al.
(författare)
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Final measures (Deliverable 5.5)
- 2020
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The main objective of WP5 has been to run a set of field trials with naïve users (i.e. not experts involved in the development of the measures) for all nudging and coaching measures developed in WP2-4. Then, given the outcome of the field trials, the task has been to analyse which impacts these measures may have on road safety along with the cost of implementing them in vehicle fleets and/or infrastructure. All these activities have taken place in Tasks 5.4 (Data collection) and 5.6 (Data analysis).
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29. |
- Ljung Aust, Mikael, 1973, et al.
(författare)
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Results of field trials (Deliverable 5.4)
- 2020
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The main objective of WP5 is to run a set of field trials with naïve users (i.e. not experts involved in the development of the measures) for all nudging and coaching measures developed in WP2-4. Field trials with naïve users are necessary in order to validate the estimated effectiveness of each measure. The field trials were set up in as realistic settings as possible, given the possibilities to implement/distribute each measure. This deliverable gives a short description of the field trial setup for each measure, and then reports the effects of the nudge on road user behaviour.
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30. |
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31. |
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33. |
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34. |
- Nicot, A. S., et al.
(författare)
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Mutations in amphiphysin 2 (BIN1) disrupt interaction with dynamin 2 and cause autosomal recessive centronuclear myopathy
- 2007
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Ingår i: Nat Genet. - : Springer Science and Business Media LLC. ; 39:9, s. 1134-1139
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Tidskriftsartikel (refereegranskat)abstract
- Centronuclear myopathies are characterized by muscle weakness and abnormal centralization of nuclei in muscle fibers not secondary to regeneration. The severe neonatal X-linked form (myotubular myopathy) is due to mutations in the phosphoinositide phosphatase myotubularin (MTM1), whereas mutations in dynamin 2 (DNM2) have been found in some autosomal dominant cases. By direct sequencing of functional candidate genes, we identified homozygous mutations in amphiphysin 2 (BIN1) in three families with autosomal recessive inheritance. Two missense mutations affecting the BAR (Bin1/amphiphysin/RVS167) domain disrupt its membrane tubulation properties in transfected cells, and a partial truncation of the C-terminal SH3 domain abrogates the interaction with DNM2 and its recruitment to the membrane tubules. Our results suggest that mutations in BIN1 cause centronuclear myopathy by interfering with remodeling of T tubules and/or endocytic membranes, and that the functional interaction between BIN1 and DNM2 is necessary for normal muscle function and positioning of nuclei.
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35. |
- Pedersen, Anders, 1976, et al.
(författare)
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Expression and purification of full-length anti-apoptotic Bcl-2 using cell-free protein synthesis
- 2011
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Ingår i: Protein Expression and Purification. - : Elsevier Inc. - 1046-5928 .- 1096-0279. ; 77:2, s. 220-223
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Tidskriftsartikel (refereegranskat)abstract
- The anti-apoptotic B cell CLL/lymphoma-2 (Bcl-2) protein is a key player in the regulation of programmed cell death and is linked to various types of cancer and their resistance to drug treatment. Biophysical and structural studies of the full-length intact Bcl-2 have been hampered due to difficulties in expression and severe solubility problems, precluding isolation of this hydrophobic membrane protein. Therefore, previous work has so far mainly been carried out using structurally modified Bcl-2 variants, lacking the transmembrane region. Thus, biophysical information regarding the full-length protein is still missing. Here, a protocol is presented for expression and purification of preparative amounts of the full-length human isoform 2 of Bcl-2 (Bcl-2(2)). A batch-based cell-free expression system, using extract isolated from Escherichia coli (E. coli) was employed to produce recombinant protein encoded by an optimized gene sequence. Presence of polyoxyethylene-(20)-cetyl-ether (Brij-58) in the reaction mixture and subsequently in the immobilized metal-affinity purification steps was crucial to keep Bcl-2(2) soluble. The obtained yield was 0.25-0.3mg per ml of cell-free reaction. Far-UV circular dichroism (CD) spectroscopy confirmed the α-helical structure of the purified protein, characteristic for members of the Bcl-2 protein family.
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36. |
- Rodriguez, Heriberto, et al.
(författare)
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The physiological roles of the boar ejaculate
- 2009
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Ingår i: Society of Reproduction and Fertility Supplement. - 1747-3403. ; 66, s. 1-21
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Tidskriftsartikel (refereegranskat)abstract
- During ejaculation in the boar, sperm cohorts emitted in epididymal cauda fluid are sequentially exposed and resuspended in different mixtures of accessory sex gland secretion. This paper reviews the relevance of such unevenly composed fractions of seminal plasma (SP) in vivo on sperm transport and sperm function and how this knowledge could benefit boar semen processing for artificial insemination (AI). The firstly ejaculated spermatozoa (first 10 ml of the sperm-rich fraction, SRF [P1]) remain mainly exposed to epididymal cauda fluid and its specific proteins i.e. various lipocalins, including the fertility-related prostaglandin D synthase; than to prostatic and initial vesicular gland secretions. P1-spermatozoa are hence exposed to less bicarbonate, zinc or fructose and mainly to PSP-I spermadhesin; than if they were in the rest of the SRF and the post-SRF (P2). Since the P1-SP is less destabilizing for sperm membrane and chromatin, P1-spermatozoa sustain most in vitro procedures, including cryopreservation, the best. Moreover, ejaculated firstly, the P1-spermatozoa seem also those deposited by the boar as a vanguard cohort, thus becoming overrepresented in the oviductal sperm reservoir (SR). This vanguard SR-entry occurs before the endometrial signalling of SP components (as PSP-I/PSP-II and cytokines) causes a massive influx of the innate defensive PMNs to cleanse the uterus from eventual pathogens, superfluous spermatozoa and the allogeneic SP. The SP also conditions the mucosal immunity of the female genital tract, to tolerate the SR-spermatozoa and the semi-allogeneic conceptus. These in vivo gathered data can be extrapolated into procedures for handling boar spermatozoa in vitro for AI and other biotechnologies, including simplified cryopreservation.
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37. |
- Saravia-Ramos, Fernando, et al.
(författare)
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Exposure to the seminal plasma of different portions of the boar ejaculate modulates the survival of spermatozoa cryopreserved in MiniFlatPacks
- 2009
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Ingår i: Theriogenology. - : Elsevier. - 0093-691X .- 1879-3231. ; 71:4, s. 662-675
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Tidskriftsartikel (refereegranskat)abstract
- Spermatozoa present in the first collectable 10 mL of the sperm-rich fraction (SRF) of the boar ejaculate (portion 1, PI I have higher documented viability during and after cryopreservation than spermatozoa in the rest of the ejaculate (portion 2, P2). probably in relation to different features of the surrounding seminal plasma (SP). In the present study. We investigated whether the SP from these ejaculate portions (SP1 or SP2) was able to differently influence sperm viability and chromatin structure of the P1- or P2-contained spermatozoa from individual boars primarily or secondarily exposed (e.g., following cleansing and re-exposure) to pooled SP1 or SP2 from the same males during 60 min. Spermatozoa were subjected to controlled cooling and thawing in MiniFlatPacks (MFPs) and examined for motility (using computer-assisted sperm analysis, CASA) at selected stages of processing Moreover, sperm plasma membrane intactness (investigated using, SYBR-14/propidium iodide, PI), plasma membrane architecture (examined using Annexin-V-PI staining), and chromatin (deoxyribonucleic acid, DNA) integrity (tested using sperm chromatin structure assay, SCSA) were assessed post-thaw (PT). A higher proportion of PI spermatozoa than of P2 spermatozoa incubated in their native SP portion were confirmed to be motile from collection to PT. When P1 spermatozoa were cleansed from their original SP and re-exposed to pooled P2-SP. sperm kinematics deteriorated from extension to PT. By contrast, cleansed P2 spermatozoa increased motility to P1 levels, especially PT when re-exposed to pooled P1-SP. Such differential effects on motility were not clearly accompanied by biologically related modifications of sperm membrane or chromatin structure. This influence of the SP on sperm kinematics was not sire-dependent and it Was presumably related to different concentrations or either SP proteins or bicarbonate in the different ejaculate portions. (C) 2009 Elsevier Inc. All rights reserved.
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38. |
- Sharoare Hossain, Md, et al.
(författare)
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Flow cytometry for the assessment of animal sperm integrity and functionality: state of the art
- 2011
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Ingår i: ASIAN JOURNAL OF ANDROLOGY. - : Blackwell Publishing Ltd. - 1008-682X .- 1745-7262. ; 13:3, s. 406-419
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Forskningsöversikt (refereegranskat)abstract
- Flow cytometry is now a recognized methodology within animal spermatology, and has moved from being a research tool to become routine in the assessment of animal semen destined to breeding. The availability of bench-top flow cytometers and of newer and versatile markers for cell structure and function had allowed the instrumentation to measure more sperm parameters, from viability to reactiveness when exposed to exogenous stimuli, and to increase our capabilities to sort spermatozoa for potential fertilizing capacity, or chromosomal sex. The present review summarizes the state of the art regarding flow cytometry applied to animal andrology, albeit keeping an open comparative intent. It critically evaluates the present and future capabilities of flow cytometry for the diagnostics of potential fertility and for the development of current reproductive technologies such as sperm freezing, sperm selection and sperm sorting. The flow cytometry methods will probably further revolutionize our understanding of the sperm physiology and their functionality, and will undoubtedly extend its application in isolating many uncharacterized features of spermatozoa. However, continuous follow-up of the methods is a necessity owing to technical developments and the complexity of mapping spermatozoa.
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39. |
- Sharoare Hossain, Md., et al.
(författare)
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Spermatozoa in the sperm-peak-fraction of the boar ejaculate show a lower flow of Ca(2+) under capacitation conditions post-thaw which might account for their higher membrane stability after cryopreservation
- 2011
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Ingår i: Animal Reproduction Science. - : Elsevier Masson. - 0378-4320 .- 1873-2232. ; 128:1-4, s. 37-44
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Tidskriftsartikel (refereegranskat)abstract
- Boar spermatozoa collected in the ejaculate sperm peak-portion (P1, first 10 mL of the sperm-rich fraction, SRF), had shown a higher resilience to freezing and thawing compared to spermatozoa from the rest of the ejaculate (2nd portion of the SRF plus the post-sperm-rich fraction, PSRF), even when using a simplified freezing technique, as long as spermatozoa were incubated in their own seminal plasma (SP). This experiment studied the stability of P1- and SRF-P1 boar spermatozoa frozen in MiniFlatPacks (MFP), post-thaw, using flow cytometry. Since spermatozoa from either portion showed similar cryosurvival and low proportions of unstable membranes (less than3%, annexin-V/propidium iodide staining), and only a tendency for SRF-P1 live spermatozoa to depict acrosome exocytosis (FITC-PNA/PI/H33342); they were explored for Ca(2+) contents using a Fluo-4 probe under in vitro capacitating conditions (mBO+ medium), as well they were tested for their ability to sustain a short Ca(2+)-ionophore (A23187) in vitro challenge. The proportions of live spermatozoa depicting high Ca(2+)-levels were initially less than2% but increased over incubation time, particularly in SRF-P1(P less than 0.05), while proportions of live spermatozoa with low Ca(2+)-levels were basically constant over incubation time (similar to 11-14%), for either portion. Incubation in capacitation medium did not modify the proportions of low-Ca(2+) but dramatically increased the proportions of high-Ca(2+) spermatozoa (P less than 0.001) already after 15 min exposure, highest for SRF-P1 spermatozoa. While the proportion of live spermatozoa with intact acrosome was significantly decreased among SRF-P1 (P less than 0.001), that of P1-spermatozoa remained unchanged, probably owing to the lowest relative content of cytosolic Ca(2+). The results suggest that spermatozoa in the P1-portion are more resilient to express acrosome exocytosis post-thaw compared to those bathing in the rest of the SRF-fraction when cryopreserved using a simplified technique, in MFPs.
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40. |
- Siqueira, A P, et al.
(författare)
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Quality of boar spermatozoa from the sperm-peak portion of the ejaculate after simplified freezing in MiniFlatpacks compared to the remaining spermatozoa of the sperm-rich fraction
- 2011
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Ingår i: THERIOGENOLOGY. - : Elsevier Science B.V., Amsterdam.. - 0093-691X .- 1879-3231. ; 75:7, s. 1175-1184
-
Tidskriftsartikel (refereegranskat)abstract
- Boar sperm viability post-thaw differs depending on the ejaculate fraction used, with spermatozoa present in the first 10 mL of the sperm-rich fraction (SRF) (portion 1, P1, sperm-peak portion) displaying the best cryosurvival in vitro compared with that of spermatozoa from the rest of the ejaculate (portion 2 of the SRF plus the post-spermatic fraction), even when using simplified freezing routines. This viability apparently relates to the specific profile of seminal plasma in P1 (i.e., glycoprotein and bicarbonate concentrations, and pH). However, spermatozoa from PI have not been compared with spermatozoa from the rest of the SRF (SRF P1, usually 30-40 mL of the SRF), which is routinely used for freezing. We compared P1 with SRF P I in terms of sperm kinematics (using the QualiSperm (TM) system), while membrane integrity (SYBR-14/PI), acrosome integrity (FITC PNA/PI), and sperm membrane stability (Annexin-V) were explored using flow cytomety. As well, total protein concentration and the proteomics of the seminal plasma (SP) of both portions of the SRF were studied using two-dimensional electrophoresis (2DE), mass fingerprinting (MALDI-TOF), and collision-induced dissociation tandem mass spectrometry (CID-MS/MS) on selected peptides. The SRF portions were collected weekly from four mature boars (4-5 replicates per boar, sperm concentration: P1, 1.86 +/- 0.20; SRF P1, 1.25 +/- 0.14 x 10(9) spz/mL) and processed using a quick freezing method in MiniFlatPacks. Post-thaw sperm motility reached 50%, without differences between SRF portions, but with clear inter-boar variation. Neither plasma membrane nor acrosome integrity differed (ns) between fractions. These results indicate that there are no differences in cryosurvival after quick freezing of boar spermatozoa derived from either of the two SRF portions. While P1 and SRF-P1 clearly differed in relative total protein contents, as expected, they displayed very similar protein profiles as assessed using 2DE and mass spectrometry (tryptic peptide mass fingerprint analysis and CID-MS/MS), indicating a similar emission of epididymal protein content.
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41. |
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42. |
- Toussaint, Anne, et al.
(författare)
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Defects in amphiphysin 2 (BIN1) and triads in several forms of centronuclear myopathies.
- 2011
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Ingår i: Acta neuropathologica. - : Springer Science and Business Media LLC. - 1432-0533 .- 0001-6322. ; 121:2, s. 253-266
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Tidskriftsartikel (refereegranskat)abstract
- Myotubular myopathy and centronuclear myopathies (CNM) are congenital myopathies characterized by generalized muscle weakness and mislocalization of muscle fiber nuclei. Genetically distinct forms exist, and mutations in BIN1 were recently identified in autosomal recessive cases (ARCNM). Amphiphysins have been implicated in membrane remodeling in brain and skeletal muscle. Our objective was to decipher the pathogenetic mechanisms underlying different forms of CNM, with a focus on ARCNM cases. In this study, we compare the histopathological features from patients with X-linked, autosomal recessive, and dominant forms, respectively, mutated in myotubularin (MTM1), amphiphysin 2 (BIN1), and dynamin 2 (DNM2). We further characterize the ultrastructural defects in ARCNM muscles. We demonstrate that the two BIN1 isoforms expressed in skeletal muscle possess the phosphoinositide-binding domain and are specifically targeted to the triads close to the DHPR-RYR1 complex. Cardiac isoforms do not contain this domain, suggesting that splicing of BIN1 regulates its specific function in skeletal muscle. Immunofluorescence analyses of muscles from patients with BIN1 mutations reveal aberrations of BIN1 localization and triad organization. These defects are also observed in X-linked and autosomal dominant forms of CNM and in Mtm1 knockout mice. In addition to previously reported implications of BIN1 in cancer as a tumor suppressor, these findings sustain an important role for BIN1 skeletal muscle isoforms in membrane remodeling and organization of the excitation-contraction machinery. We propose that aberrant BIN1 localization and defects in triad structure are part of a common pathogenetic mechanism shared between the three forms of centronuclear myopathies.
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43. |
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44. |
- Wallgren, Erik, 1942-
(författare)
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Essays on Capability Indices for Autocorrelated Data
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The use of process capability indices in the industry is traditionally based on the assumptions that a sample from a process are observations on independently, identically and normally distributed random variables, IIN. However, all three assumptions are open to discussion and in this thesis, the estimation of the indices is studied when the assumption of independence is not fulfilled.In five reports, the indices Cpk and Cpm are studied, and instead of random samples, samples are regarded as observations on a time series.In the first four reports, each index is studied for either an AR(1) or an MA(1) process and the fifth report, both indices are studied for a general ARMA(p,q) process.In all reports, alternatives to Cpk and Cpm are suggested as well as point and interval estimators for the suggested indices. The accuracy of interval estimators are evaluated through large Monte Carlo simulations and the difference between empirical coverage rates and nominal confidence limits are calculated.It was found in all reports that a dependency among observations has a great impact on the coverage rates. The coverage rate difference depends on both the size of the autocorrelation and the type of time series model and for the original Cpk and Cpm the difference can be large. With the suggested alternative indices, however, the differences are always reduced and unless the autocorrelations are close to ±1, the sizes of differences are of little consequence.
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45. |
- Wallgren, Jakob, et al.
(författare)
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Concise Synthesis of Potential 4-Hydroxy-5-fluoropentyl Side-Chain Metabolites of Four Synthetic Cannabinoids
- 2020
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Ingår i: Synlett. - : GEORG THIEME VERLAG KG. - 0936-5214 .- 1437-2096. ; 31:5, s. 517-520
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Tidskriftsartikel (refereegranskat)abstract
- Synthetic cannabinoids are a group of compounds that act on the CB1 receptor and are used illicitly as substitutes for cannabis. Given the rapid and extensive metabolism of synthetic cannabinoids, urinary biomarkers are essential if proof of drug intake is to be obtained in forensic laboratories. To identify good biomarker candidates, the metabolism of synthetic cannabinoids must be studied and reference standards need to be acquired. Studies on the metabolism of synthetic cannabinoids containing a terminally fluorinated pentyl side chain have shown that hydroxylation can occur at the four position of the side chain. This makes the 4-hydroxy-5-fluoropentyl side-chain metabolite a good urinary biomarker for proving intake of the corresponding parent drug, as this compound cannot be formed from its nonfluorinated analogue. Here, a concise synthetic route to the 4-hydroxy-5-fluoropentyl side-chain metabolites of the synthetic cannabinoids STS-135, MAM-2201, AM-2201, and XLR-11 is reported.
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46. |
- Wallgren, Jakob, et al.
(författare)
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Synthesis and identification of an important metabolite of AKB-48 with a secondary hydroxyl group on the adamantyl ring
- 2017
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Ingår i: Tetrahedron Letters. - : PERGAMON-ELSEVIER SCIENCE LTD. - 0040-4039 .- 1359-8562. ; 58:15, s. 1456-1458
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Tidskriftsartikel (refereegranskat)abstract
- Studies on the metabolism of bioactive substances containing the adamantyl moiety have shown that hydroxylation is likely to occur at a tertiary carbon of adamantane. Herein, we report the synthesis and identification of one major metabolite of AKB-48, a new illicit psychoactive substance with a hydroxyl group at a secondary carbon of the adamantyl ring. (C) 2017 Elsevier Ltd. All rights reserved.
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47. |
- Wallgren, Marcus, 1978-, et al.
(författare)
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Reconstitution of the Anti-Apoptotic Bcl-2 Protein into Lipid Membranes and Biophysical Evidence for Its Detergent-Driven Association with the Pro-Apoptotic Bax Protein
- 2013
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 8:4
-
Tidskriftsartikel (refereegranskat)abstract
- The anti-apoptotic B-cell CLL/lymphoma-2 (Bcl-2) protein and its counterpart, the pro-apoptotic Bcl-2-associated X protein (Bax), are key players in the regulation of the mitochondrial pathway of apoptosis. However, how they interact at the mitochondrial outer membrane (MOM) and there determine whether the cell will live or be sentenced to death remains unknown. Competing models have been presented that describe how Bcl-2 inhibits the cell-killing activity of Bax, which is common in treatment-resistant tumors where Bcl-2 is overexpressed. Some studies suggest that Bcl-2 binds directly to and sequesters Bax, while others suggest an indirect process whereby Bcl-2 blocks BH3-only proteins and prevents them from activating Bax. Here we present the results of a biophysical study in which we investigated the putative interaction of solubilized full-length human Bcl-2 with Bax and the scope for incorporating the former into a native-like lipid environment. Far-UV circular dichroism (CD) spectroscopy was used to detect direct Bcl-2-Bax-interactions in the presence of polyoxyethylene-(23)-lauryl-ether (Brij-35) detergent at a level below its critical micelle concentration (CMC). Additional surface plasmon resonance (SPR) measurements confirmed this observation and revealed a high affinity between the Bax and Bcl-2 proteins. Upon formation of this protein-protein complex, Bax also prevented the binding of antimycin A(2) (a known inhibitory ligand of Bcl-2) to the Bcl-2 protein, as fluorescence spectroscopy experiments showed. In addition, Bcl-2 was able to form mixed micelles with Triton X-100 solubilized neutral phospholipids in the presence of high concentrations of Brij-35 (above its CMC). Following detergent removal, the integral membrane protein was found to have been fully reconstituted into a native-like membrane environment, as confirmed by ultracentrifugation and subsequent SDS-PAGE experiments.
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48. |
- Wallgren-Pettersson, Carina, et al.
(författare)
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Distal myopathy caused by homozygous missense mutations in the nebulin gene
- 2007
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Ingår i: Brain. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 130:Pt 6, s. 1465-1476
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Tidskriftsartikel (refereegranskat)abstract
- We describe a novel, recessively inherited distal myopathy caused by homozygous missense mutations in the nebulin gene (NEB), in which other combinations of mutations are known to cause nemaline (rod) myopathy (NM). Two different missense mutations were identified in homozygous form in seven Finnish patients from four unrelated families with childhood or adult-onset foot drop. Both mutations, when combined in compound heterozygous form with more disruptive mutations in NEB, are known to cause NM. Hitherto, no patients with NM have been found to have two missense mutations in NEB. Muscle weakness predominantly affected ankle dorsiflexors, finger extensors and neck flexors, a distribution different both from the patterns of weakness seen in NM caused by NEB mutations, and those of the known recessively inherited distal myopathies. Singleton cases need to be distinguished from the Laing type of distal myopathy. Histologically, this myopathy differs from NM in that nemaline bodies were not detectable with routine light microscopy, and they were inconspicuous or absent even with electron microscopy. Rimmed vacuoles, commonly seen in other distal myopathies, were not a feature. We conclude that homozygous missense mutations in NEB cause a novel distal myopathy, predominantly involving lower leg extensor muscles, finger extensors and neck flexors.
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49. |
- Wallgren, Sara, et al.
(författare)
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A single sequential snake saphenous vein graft versus separate left and right vein grafts in coronary artery bypass surgery: a population-based cohort study from the SWEDEHEART registry
- 2019
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Ingår i: European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery. - : Oxford University Press (OUP). - 1873-734X. ; 56:3, s. 518-525
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Tidskriftsartikel (refereegranskat)abstract
- Our goal was to compare short- and midterm outcomes after coronary artery bypass grafting (CABG) using 2 different revascularization strategies.A total of 6895 patients were included who had CABG in Sweden from 2009 to 2015 using the left internal mammary artery to the left anterior descending artery and either a single sequential saphenous vein graft connecting the left and right coronary territories to the aorta (snake graft, n=2122) or separate vein grafts to both territories (n=4773). Data were obtained from the Swedish Web System for Enhancement of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART) and the Swedish Patient Registry. The groups were compared using adjusted logistic regression for short-term (30-day) and Cox regression and flexible parametric survival models for midterm outcomes. Primary outcome was a composite of all-cause mortality, myocardial infarction (MI), reangiography and new revascularization. The median follow-up time was 35months.At 30days, the incidences of the composite end point [odds ratio (OR) 1.31, 95% confidence interval (CI) 1.03-1.68; P=0.03] and reangiography (OR 1.51, 95% CI 1.07-2.14; P=0.02) were higher in the snake group. There was also a trend towards higher mortality (OR 1.47, 95% CI 0.97-2.22; P=0.07). The event rates during the complete follow-up period were 6.5 (5.9-7.2) and 5.7 (5.3-6.1) per 100 person-years for the snake group and the separate vein group, respectively. At the midterm follow-up, no significant difference between the groups could be shown for the composite end point [hazard ratio (HR) 1.08, 95% CI 0.95-1.22; P=0.24], mortality (HR 0.95, 95% CI 0.79-1.14; P=0.56), MI (HR 1.11, 95% CI 0.88-1.41; P=0.39) or new revascularization (HR 1.19, 95% CI 0.94-1.50; P=0.15), whereas reangiography remained more common in the snake group (HR 1.25, 95% CI 1.05-1.48; P=0.01).Snake grafts were associated with a higher rate of early postoperative complications, possibly reflecting a more demanding surgical technique, whereas midterm outcomes were comparable. Based on these data, one strategy cannot be recommended over the other.
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50. |
- Wikenros, Camilla, et al.
(författare)
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Fear or food - Abundance of red fox in relation to occurrence of lynx and Wolf
- 2017
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Ingår i: Scientific Reports. - London : Nature Publishing Group. - 2045-2322. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Apex predators may affect mesopredators through intraguild predation and/or supply of carrion from their prey, causing a trade-off between avoidance and attractiveness. We used wildlife triangle snow-tracking data to investigate the abundance of red fox (Vulpes vulpes) in relation to lynx (Lynx lynx) and wolf (Canis lupus) occurrence as well as land composition and vole (Microtus spp.) density. Data from the Swedish wolf-monitoring system and VHF/GPS-collared wolves were used to study the effect of wolf pack size and time since wolf territory establishment on fox abundance. Bottom-up processes were more influential than top-down effects as the proportion of arable land was the key indicator of fox abundance at the landscape level. At this spatial scale, there was no effect of wolf abundance on fox abundance, whereas lynx abundance had a positive effect. In contrast, at the wolf territory level there was a negative effect of wolves on fox abundance when including detailed information of pack size and time since territory establishment, whereas there was no effect of lynx abundance. This study shows that different apex predator species may affect mesopredator abundance in different ways and that the results may be dependent on the spatiotemporal scale and resolution of the data. © 2017 The Author(s).
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