| 1. |
- Arver, Brita, et al.
(författare)
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Bilateral Prophylactic Mastectomy in Swedish Women at High Risk of Breast Cancer: A National Survey.
- 2011
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Ingår i: Annals of surgery. - : Lippincott Williams and Wilkins; 1999. - 1528-1140 .- 0003-4932. ; 253:6, s. 1147-1154
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND/OBJECTIVE:: This study attempted a national inventory of all bilateral prophylactic mastectomies performed in Sweden between 1995 and 2005 in high-risk women without a previous breast malignancy. The primary aim was to investigate the breast cancer incidence after surgery. Secondary aims were to describe the preoperative risk assessment, operation techniques, complications, histopathological findings, and regional differences. METHODS:: Geneticists, oncologists and surgeons performing prophylactic breast surgery were asked to identify all women eligible for inclusion in their region. The medical records were reviewed in each region and the data were analyzed centrally. The BOADICEA risk assessment model was used to calculate the number of expected/prevented breast cancers during the follow-up period. RESULTS:: A total of 223 women operated on in 8 hospitals were identified. During a mean follow-up of 6.6 years, no primary breast cancer was observed compared with 12 expected cases. However, 1 woman succumbed 9 years post mastectomy to widespread adenocarcinoma of uncertain origin. Median age at operation was 40 years. A total of 58% were BRCA1/2 mutation carriers. All but 3 women underwent breast reconstruction, 208 with implants and 12 with autologous tissue. Four small, unifocal, invasive cancers and 4 ductal carcinoma in situ were found in the mastectomy specimens. The incidence of nonbreast related complications was low (3%). Implant loss due to infection/necrosis occurred in 21 women (10%) but a majority received a new implant later. In total, 64% of the women underwent at least 1unanticipated secondary operation. CONCLUSIONS:: Bilateral prophylactic mastectomy is safe and efficacious in reducing future breast cancer in asymptomatic women at high risk. Unanticipated reoperations are common. Given the small number of patients centralization seems justified.
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| 2. |
- Barra, Mathias, et al.
(författare)
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Do not despair about severity—yet
- 2020
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Ingår i: Journal of Medical Ethics. - : BMJ Publishing Group Ltd. - 0306-6800 .- 1473-4257. ; 46:8, s. 557-558
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- In a recent extended essay, philosopher Daniel Hausman goes a long way towards dismissing severity as a morally relevant attribute in the context of priority setting in healthcare. In this response, we argue that although Hausman certainly points to real problems with how severity is often interpreted and operationalised within the priority setting context, the conclusion that severity does not contain plausible ethical content is too hasty. Rather than abandonment, our proposal is to take severity seriously by carefully mapping the possibly multiple underlying accounts to well-established ethical theories, in a way that is both morally defensible and aligned with the term’s colloquial uses.
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| 3. |
- Berglund, Eva C, et al.
(författare)
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Accurate detection of subclonal single nucleotide variants in whole genome amplified and pooled cancer samples using HaloPlex target enrichment
- 2013
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Ingår i: BMC Genomics. - : BioMed Central. - 1471-2164. ; 14, s. 856-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Target enrichment and resequencing is a widely used approach for identification of cancer genes and genetic variants associated with diseases. Although cost effective compared to whole genome sequencing, analysis of many samples constitutes a significant cost, which could be reduced by pooling samples before capture. Another limitation to the number of cancer samples that can be analyzed is often the amount of available tumor DNA. We evaluated the performance of whole genome amplified DNA and the power to detect subclonal somatic single nucleotide variants in non-indexed pools of cancer samples using the HaloPlex technology for target enrichment and next generation sequencing. Results: We captured a set of 1528 putative somatic single nucleotide variants and germline SNPs, which were identified by whole genome sequencing, with the HaloPlex technology and sequenced to a depth of 792-1752. We found that the allele fractions of the analyzed variants are well preserved during whole genome amplification and that capture specificity or variant calling is not affected. We detected a large majority of the known single nucleotide variants present uniquely in one sample with allele fractions as low as 0.1 in non-indexed pools of up to ten samples. We also identified and experimentally validated six novel variants in the samples included in the pools. Conclusion: Our work demonstrates that whole genome amplified DNA can be used for target enrichment equally well as genomic DNA and that accurate variant detection is possible in non-indexed pools of cancer samples. These findings show that analysis of a large number of samples is feasible at low cost, even when only small amounts of DNA is available, and thereby significantly increases the chances of indentifying recurrent mutations in cancer samples.
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| 4. |
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| 5. |
- Borgå, Olof, et al.
(författare)
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Maximum Tolerated Dose and Pharmacokinetics of Paclitaxel Micellar in Patients with Recurrent Malignant Solid Tumours : A Dose-Escalation Study
- 2019
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Ingår i: Advances in Therapy. - : Springer. - 0741-238X .- 1865-8652. ; 36:5, s. 1150-1163
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: A water-soluble Cremophor EL-free formulation of paclitaxel, in which retinoic acid derivates solubilize paclitaxel by forming micelles (paclitaxel micellar), was studied for the first time in man to establish the maximum tolerated dose (MTD) and to characterize the pharmacokinetics (PK).Methods: This was an open-label, one-arm, dose-escalating study in patients with advanced solid malignant tumours, for which no standard therapy was available or had failed. Paclitaxel micellar was given as 1-h intravenous infusion every 21 days for 3 cycles, mainly without premedication. Plasma samples were collected during 24 h at the first cycle and paclitaxel concentrations were assayed by high-performance liquid chromatography. PK was evaluated using a two-compartment model.Results: Thirty-four patients received paclitaxel micellar at doses ranging between 90 and 275 mg/m2. MTD was established as 250 mg/m2. Fatigue and neuropathy were the most frequent dose-limiting toxicities. No hypersensitivity reactions were observed. PK of paclitaxel was evaluated in 25 data sets. Paclitaxel micellar had a rapid initial distribution phase, mean half-life 0.55 h, estimated to be completed 3 h after dosing and a mean terminal half-life of 8.8 h. Mean clearance was 13.4 L/h/m2 with fivefold interindividual variability. The residual areas after 10 h and 24 h were 15.7 ± 8.6% and 5.7 ± 3.9% of the area under the plasma concentration–time curve to infinite time (AUCinf), respectively.Conclusion: No new side effects unknown for paclitaxel were observed. Maximum plasma concentration (Cmax) and AUCinf showed a tendency to increase linearly with dose within the 150–275 mg/m2dose range. The possibility to administer paclitaxel micellar without steroid premedication makes it an attractive candidate for further studies in combination with immunotherapy.Trial Registration: EudraCT no: 2004-001821-54.
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| 6. |
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| 7. |
- Burström, Kristina, et al.
(författare)
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Swedish experience-based value sets for EQ-5D health states
- 2014
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Ingår i: Quality of Life Research. - : Springer Science and Business Media LLC. - 1573-2649 .- 0962-9343. ; 23:2, s. 431-442
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Tidskriftsartikel (refereegranskat)abstract
- PurposeTo estimate Swedish experience-based value sets for EQ-5D health states using general population health survey data.MethodsApproximately 45,000 individuals valued their current health status by means of time trade off (TTO) and visual analogue scale (VAS) methods and answered the EQ-5D questionnaire, making it possible to model the association between the experience-based TTO and VAS values and the EQ-5D dimensions and severity levels. The association between TTO and VAS values and the different severity levels of respondents’ answers on a self-rated health (SRH) question was assessed.ResultsAlmost all dimensions (except usual activity) and severity levels had less impact on TTO valuations compared with the UK study based on hypothetical values. Anxiety/depression had the greatest impact on both TTO and VAS values. TTO and VAS values were consistently related to SRH. The inclusion of age, sex, education and socioeconomic group affected the main effect coefficients and the explanatory power modestly.ConclusionsA value set for EQ-5D health states based on Swedish valuations has been lacking. Several authors have recently advocated the normative standpoint of using experience-based values. Guidelines of economic evaluation for reimbursement decisions in Sweden recommend the use of experience-based values for QALY calculations. Our results that anxiety/depression had the greatest impact on both TTO and VAS values underline the importance of mental health for individuals’ overall HRQoL. Using population surveys is in line with recent thinking on valuing health states and could reduce some of the focusing effects potentially appearing in hypothetical valuation studies.
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| 8. |
- Gad, Helge, et al.
(författare)
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MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool
- 2014
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 508:7495, s. 215-221
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Tidskriftsartikel (refereegranskat)abstract
- Cancers have dysfunctional redox regulation resulting in reactive oxygen species production, damaging both DNA and free dNTPs. The MTH1 protein sanitizes oxidized dNTP pools to prevent incorporation of damaged bases during DNA replication. Although MTH1 is non-essential in normal cells, we show that cancer cells require MTH1 activity to avoid incorporation of oxidized dNTPs, resulting in DNA damage and cell death. We validate MTH1 as an anticancer target in vivo and describe small molecules TH287 and TH588 as first-in-class nudix hydrolase family inhibitors that potently and selectively engage and inhibit the MTH1 protein in cells. Protein co-crystal structures demonstrate that the inhibitors bindin the active site of MTH1. The inhibitors cause incorporation of oxidized dNTPs in cancer cells, leading to DNA damage, cytotoxicity and therapeutic responses in patient-derived mouse xenografts. This study exemplifies the non-oncogene addiction concept for anticancer treatment and validates MTH1 as being cancer phenotypic lethal.
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| 9. |
- Gineste, Charlotte, et al.
(författare)
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Enzymatically dissociated muscle fibers display rapid dedifferentiation and impaired mitochondrial calcium control
- 2022
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Ingår i: iScience. - : Elsevier. - 2589-0042. ; 25:12
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Tidskriftsartikel (refereegranskat)abstract
- Cells rapidly lose their physiological phenotype upon disruption of their extracellular matrix (ECM)-intracellular cytoskeleton interactions. By comparing adult mouse skeletal muscle fibers, isolated either by mechanical dissection or by collagenase-induced ECM digestion, we investigated acute effects of ECM disruption on cellular and mitochondrial morphology, transcriptomic signatures, and Ca2+ handling. RNA-sequencing showed striking differences in gene expression patterns between the two isolation methods with enzymatically dissociated fibers resembling myopathic phenotypes. Mitochondrial appearance was grossly similar in the two groups, but 3D electron microscopy revealed shorter and less branched mitochondria following enzymatic dissociation. Repeated contractions resulted in a prolonged mitochondrial Ca2+ accumulation in enzymatically dissociated fibers, which was partially prevented by cyclophilin inhibitors. Of importance, muscle fibers of mice with severe mitochondrial myopathy show pathognomonic mitochondrial Ca2+ accumulation during repeated contractions and this accumulation was concealed with enzymatic dissociation, making this an ambiguous method in studies of native intracellular Ca2+ fluxes.
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| 10. |
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| 11. |
- Henriksson, Niklas, 1976-
(författare)
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Poly(A)-specific Ribonuclease (PARN) : Structural and Functional Studies of Poly(A) Recognition and Degradation
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Regulation of mRNA degradation is a powerful way for the cell to regulate gene expression. A critical step in eukaryotic mRNA degradation is the removal of the poly(A) tail at the 3'-end of the mRNA. Poly(A)-specific ribonuclease (PARN) is an oligomeric, processive and cap-interacting 3'-5' exoribonuclease that efficiently degrades eukaryotic mRNA poly(A) tails. In addition to the exonuclease domain, PARN harbors two RNA-binding domains, a classical RNA recognition motif (RRM) and an R3H-domain. In this project we have studied mechanisms by which PARN specifically recognizes and degrades poly(A). We investigated the RNA binding properties of PARN by using electrophoretic mobility shift assays and filter-binding analysis and we could show that PARN binds poly(A) with high affinity and specificity. Furthermore, we showed that the RRM and R3H domains of PARN separately could bind to poly(A). To investigate specificity for and recognition of poly(A) in the active site of PARN, we performed a kinetic analysis on a repertoire of trinucleotide substrates in vitro. We showed that PARN harbors affinity for adenosines in the active site and that both the penultimate and the 3' end located nucleotide play an important role for providing adenosine-specificity in the active site of PARN. Moreover, we solved a crystal structure of PARN in complex with m7GpppG cap analogue and showed that the cap binding and active sites overlap both structurally and functionally. By mutational analysis we identified residues in the active site that specifically recognize adenosines. Furthermore, biochemical data showed that the adenosine specificity in the active site is lost when Mn2+ is used instead of Mg2+ as divalent metal ion. Taken together, these results demonstrate that both RNA-binding properties of the RRM and R3H-domains in addition to base recognition in the active site contributes to PARN poly(A)-specificity.
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| 12. |
- Henriksson, Niklas, et al.
(författare)
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Poly(A)-specific ribonuclease (PARN) loses specificity for recognition of adenosine residues in the presence of Mn2
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Poly(A)-specific ribonuclease (PARN) is an oligomeric, processive and cap-interacting 3'-5' exoribonuclease that efficiently degrades eukaryotic mRNA poly(A) tails. PARN is a member of the DEDD superfamily of exonucleases and is dependent on divalent metal ions for its activity. Here, we have investigated how PARN poly(A) specificity can be modulated by using Mn2+ instead of Mg2+ as the divalent metal ion. In the presence of Mn2+ PARN lost specificity for poly(A) degradation. By using homotrinucleotides as substrates we could demonstrate that the loss in specificity was an intrinsic property of the active site in the presence of Mn2+ and not caused by changes in the RNA binding properties of PARN. We conclude that Mn2+ can be used as a probe to understand mechanisms behind poly(A) specificity in the active site of PARN.
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| 13. |
- Henriksson, Niklas, et al.
(författare)
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Recognition of Adenosine Residues by the Active Site of Poly(A)-specific Ribonuclease
- 2010
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 285:1, s. 163-170
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Tidskriftsartikel (refereegranskat)abstract
- Poly(A)-specific ribonuclease (PARN) is a mammalian 3′-exoribonuclease that degrades poly(A) with high specificity. To reveal mechanisms by which poly(A) is recognized by the active site of PARN, we have performed a kinetic analysis using a large repertoire of trinucleotide substrates. Our analysis demonstrated that PARN harbors specificity for adenosine recognition in its active site and that the nucleotides surrounding the scissile bond are critical for adenosine recognition. We propose that two binding pockets, which interact with the nucleotides surrounding the scissile bond, play a pivotal role in providing specificity for the recognition of adenosine residues by the active site of PARN. In addition, we show that PARN, besides poly(A), also quite efficiently degrades poly(U), ∼10-fold less efficiently than poly(A). The poly(U)-degrading property of PARN could be of biological significance as oligo(U) tails recently have been proposed to play a role in RNA stabilization and destabilization.
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| 14. |
- Henriksson, Niklas, et al.
(författare)
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RNA binding properties of the R3H domain of poly(A)-specific ribonuclease (PARN)
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Poly(A)-specific ribonuclease (PARN) is an oligomeric, processive and cap-interacting 3'-5' exoribonuclease that efficiently degrades eukaryotic mRNA poly(A) tails. PARN harbors, in addition to a well characterized RNA-recognition motif (RRM), another putative RNA-binding motif: the R3H-domain. R3H-domains have previously been found in a diverse range of proteins involved in single stranded nucleic acid binding suggesting that the domain is a nucleic acid interacting motif. However, its RNA binding properties has not been experimentally verified. Here, we show that the R3H domain of PARN binds poly(A) and poly(U). Therefore, our study verifies that the R3H domain binds RNA and suggests that the R3H-domain of PARN could play a role in recognizing poly(A).
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| 15. |
- Johannesson, Magnus, et al.
(författare)
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The impact of hormone replacement therapy on quality of life and willingness to pay
- 1997
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Ingår i: BJOG : an international journal of obstetrics and gynaecology. - : Blackwell Publishing Ltd. - 1471-0528 .- 1470-0328 .- 0306-5456. ; 104:10, s. 1191-1195
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Tidskriftsartikel (refereegranskat)abstract
- Objective To measure the gain in quality of life due to hormone replacement therapy for women with mild and severe menopausal symptoms. Design Prospective study where data on quality of life and willingness to pay were collected by interview. Setting Department of Gynaecology at Sodertalje Hospital near Stockholm. Participants One hundred and four women aged 45 to 65 years treated for menopausal symptoms for at least one month. Methods Quality oflife was measured by the time tradeoff and rating scale methods. The willingness to pay for hormone replacement therapy was investigated using the contingent valuation method. Main outcome measures The quality adjusted life year weight measured with the rating scale and time tradeoff methods, and willingness to pay. Results The increase in the quality adjusted life year weight due to hormone replacement therapy for women with mild symptoms was 0.26 according to the rating scale method and 0.18 according to the time tradeoff method. For women with severe symptoms the quality adjusted life year weight increased by 0.50 according to the rating scale method and by 0.42 according to the time tradeoff method. The mean willingness to pay for hormone replacement therapy per month was 2300 Swedish krone for women with mild symptoms and 4800 Swedish krone for women with severe symptoms (£1 = 10.3 Swedish krone). Conclusions Hormone replacement therapy leads to a major improvement in quality of life for women with menopausal symptoms. Both for women with mild and severe menopausal symptoms the willingness to pay for the treatment also greatly exceeds the costs, indicating that hormone replacement therapy is economically beneficial for women with menopausal symptoms.
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| 16. |
- Juth, Niklas, et al.
(författare)
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Should we accept a higher cost per health improvement for orphan drugs? A review and analysis of egalitarian arguments
- 2021
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Ingår i: Bioethics. - : WILEY. - 0269-9702 .- 1467-8519. ; 35:4, s. 307-314
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Forskningsöversikt (refereegranskat)abstract
- In recent years, the issue of accepting a higher cost per health improvement for orphan drugs has been the subject of discussion in health care policy agencies and the academic literature. This article aims to provide an analysis of broadly egalitarian arguments for and against accepting higher costs per health improvement. More specifically, we aim to investigate which arguments one should agree upon putting aside and where further explorations are needed. We identify three kinds of arguments in the literature: considerations of substantial equality, formal equality, and opportunity cost. We argue that considerations of substantial equality do not support higher costs per health improvement orphan drugs, even if such considerations are considered valid. On the contrary, arguments of formal equality may support accepting a higher cost per health improvement for orphan drugs. However, in order to do so, a number of both normative and empirical issues must be resolved; these issues are identified in the article. For instance, it must be settled to what extent the opportunity cost in terms of foregone health for other patients is acceptable in order to uphold formal equality. We conclude that certain arguments can be set aside, and future focus should be put on the unresolved normative and empirical issues related to formal equality and opportunity cost.
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| 17. |
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| 18. |
- Lindqvist, C Mårten, et al.
(författare)
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The Mutational Landscape in Pediatric Acute Lymphoblastic Leukemia Deciphered by Whole Genome Sequencing
- 2015
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Ingår i: Human Mutation. - : Hindawi Limited. - 1059-7794 .- 1098-1004. ; 36:1, s. 118-128
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Tidskriftsartikel (refereegranskat)abstract
- Genomic characterization of pediatric acute lymphoblastic leukemia (ALL) has identified distinct patterns of genes and pathways altered in patients with well-defined genetic aberrations. To extend the spectrum of known somatic variants in ALL, we performed whole genome and transcriptome sequencing of three B-cell precursor patients, of which one carried the t(12;21)ETV6-RUNX1 translocation and two lacked a known primary genetic aberration, and one T-ALL patient. We found that each patient had a unique genome, with a combination of well-known and previously undetected genomic aberrations. By targeted sequencing in 168 patients, we identified KMT2D and KIF1B as novel putative driver genes. We also identified a putative regulatory non-coding variant that coincided with overexpression of the growth factor MDK. Our results contribute to an increased understanding of the biological mechanisms that lead to ALL and suggest that regulatory variants may be more important for cancer development than recognized to date. The heterogeneity of the genetic aberrations in ALL renders whole genome sequencing particularly well suited for analysis of somatic variants in both research and diagnostic applications.
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| 19. |
- Magnusson, Hans, 1943-, et al.
(författare)
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Integrating prehydrolysis kraft pulping of softwood and viscose fibre manufacturing
- 2016
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Ingår i: Appita journal. - Macleod Vic, Australia : Appita, Inc.. - 1038-6807. ; 69:3, s. 264-272
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Tidskriftsartikel (refereegranskat)abstract
- This work investigates the potential to integrate modern viscose manufacturing with prehydrolysis kraft pulping in order to improve the economic and environmental feasibility for production of regenerate cellulose fibers from wood. The study is largely based on calculations from literature data, but key stages are also tested experimentally. It is concluded that a kraft pulp mill can supply the acid demands of the viscose plant via acetic acid formed in the prehydrolysis and sulphuric acid for coagulation, with alkali for mercerization and dissolution, and it can also take care of spent liquors from the viscose plant. The pulp used for regenerated cellulose manufacture is delivered as wet pulp from the pulp mill, no drying is needed and a considerable amount of energy is saved. However, in an integrated production the viscose mill cannot use the whole production of cellulose from the kraft mill. One method of removing zinc ions from the coagulation bath effluents, based on precipitation of zinc sulphide via a well-controlled addition of green liquor from the pulp mill, has been studied.
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| 20. |
- Mattsson, Tuve, et al.
(författare)
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The Development of a Wood-based Materials-biorefinery
- 2017
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Ingår i: BioResources. - : North Carolina State University. - 1930-2126. ; 12:4, s. 9152-9182
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Tidskriftsartikel (refereegranskat)abstract
- Several different methods for the extraction, separation, and purification of wood constituents were combined in this work as a unified process with the purpose of achieving a high overall efficiency of material extraction and utilization. This study aimed to present a laboratory-scale demonstrator biorefinery that illustrated how the different wood constituents could be separated from the wood matrix for later use in the production of new bio-based materials and chemicals by combining several approaches. This study builds on several publications and ongoing activities within the Wallenberg Wood Science Center (WWSC) in Sweden on the theme "From wood to material components." Combining the approaches developed in these WWSC projects - including mild steam explosion, membrane and chromatographic separation, enzymatic treatment and leaching, ionic liquid extraction, and fractionation together with Kraft pulping - formed an outline for a complete materials-biorefinery. The process steps involved were tested as integral steps in a linked process. The scale of operations ranged from the kilogram-scale to the gram-scale. The feasibility and efficiency of these process steps in a biorefinery system were assessed, based on the data, beginning with whole wood.
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| 21. |
- Mattsson, Tuve, 1979, et al.
(författare)
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The Development of a Wood-based Materials-biorefinery
- 2017
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Ingår i: BioResources. - : BioResources. - 1930-2126 .- 1930-2126. ; 12:4, s. 9152-9182
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Tidskriftsartikel (refereegranskat)abstract
- Several different methods for the extraction, separation, and purification of wood constituents were combined in this work as a unified process with the purpose of achieving a high overall efficiency of material extraction and utilization. This study aimed to present a laboratory-scale demonstrator biorefinery that illustrated how the different wood constituents could be separated from the wood matrix for later use in the production of new bio-based materials and chemicals by combining several approaches. This study builds on several publications and ongoing activities within the Wallenberg Wood Science Center (WWSC) in Sweden on the theme "From wood to material components." Combining the approaches developed in these WWSC projects - including mild steam explosion, membrane and chromatographic separation, enzymatic treatment and leaching, ionic liquid extraction, and fractionation together with Kraft pulping - formed an outline for a complete materials-biorefinery. The process steps involved were tested as integral steps in a linked process. The scale of operations ranged from the kilogram-scale to the gram-scale. The feasibility and efficiency of these process steps in a biorefinery system were assessed, based on the data, beginning with whole wood.
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| 22. |
- Mattsson, Tuve, et al.
(författare)
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Towards a wood based material biorefinery - A demonstrator
- 2015
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Ingår i: 6th Nordic Wood Biorefinery Conference, NWBC 2015. - : VTT Technical Research Centre of Finland. - 9789513883539 ; , s. 92-101
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Konferensbidrag (refereegranskat)abstract
- Wood, the most abundant ligno-cellulosic raw material available, is a key potential feedstock for production of more sustainable alternatives to fossil-based materials. However advances within the fields of extraction and treatment processes within what is often referred to as the biorefinery concept is essential to allow for such transition. In this study, several different methods for the extraction and separation of wood constituents have been combined in a single process with the purpose of achieving a high overall efficiency of material extraction and utilisation. The work builds on several activities within the Wallenberg Wood Science Center (WWSC). The aim is to present a laboratory-scale demonstrator that illustrates how the different constituents can be separated from the wood matrix for later use in the production of bio-based materials and chemicals. The process steps involved have been tested as integral steps in a linked process for a scale of operations that range from the kilogram-scale down to the gram-scale. Industrially chipped softwood, containing mainly spruce with some pine, was used as raw material.
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| 23. |
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| 24. |
- Nilsson, Martin, et al.
(författare)
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High risk of in-breast tumor recurrence after BRCA1/2-associated breast cancer.
- 2014
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Ingår i: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 1573-7217 .- 0167-6806. ; 147:3, s. 571-578
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of the study was to compare breast-conserving therapy (BCT) and mastectomy (M) in BRCA1/2 mutation carriers. Women with invasive breast cancer and a pathogenic mutation in BRCA1 or BRCA2 were included in the study (n = 162). Patients treated with BCT (n = 45) were compared with patients treated with M (n = 118). Endpoints were local recurrence as first recurrence (LR), overall survival (OS), breast cancer death, and distant recurrence. Cumulative incidence was calculated in the presence of competing risks. For calculation of hazard ratios and for multivariable analysis, cause-specific Cox proportional hazards regression was used. Compared to M, BCT was associated with an increased risk of LR in univariable analysis (HR 4.0; 95 % CI 1.6-9.8) and in multivariable analysis adjusting for tumor stage, age, and use of adjuvant chemotherapy (HR 2.9; CI 1.1-7.8). Following M, all local recurrences were seen in the first 5 years after breast cancer diagnosis. Following BCT, the rate of LR continued to be high also after the first 5 years. The cumulative incidence of LR in the BCT group was 15, 25, and 32 % after 5, 10, and 15 years, respectively. There were no significant differences between BCT and M for OS, breast cancer death, or distant recurrence. BRCA1/2 mutation carriers treated with BCT have a high risk of LR, many of which are new primary breast cancers. This must be thoroughly discussed with the patient and is an example of how rapid treatment-focused genetic testing could influence choice of treatment.
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| 25. |
- Nilsson, Martin P., et al.
(författare)
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BRCAsearch : written pre-test information and BRCA1/2 germline mutation testing in unselected patients with newly diagnosed breast cancer
- 2018
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Ingår i: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 0167-6806 .- 1573-7217. ; 168:1, s. 117-126
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To evaluate a simplified method of pre-test information and germline BRCA1/2 mutation testing. Methods: In a prospective, single-arm study, comprehensive BRCA1/2 testing was offered to unselected patients with newly diagnosed breast cancer at three hospitals in south Sweden (BRCAsearch, ClinicalTrials.gov Identifier: NCT02557776). Pre-test information was provided by a standardized invitation letter, but the patients could contact a genetic counselor for telephone genetic counseling if they felt a need for that. Noncarriers were informed about the test result through a letter. Mutation carriers were contacted and offered an appointment for in-person post-test genetic counseling. Results: During the period Feb 2, 2015–Aug 26, 2016, eight hundred and eighteen patients were invited to participate in the study. Through Jan 31, 2017, five hundred and forty-two (66.2%) of them consented to analysis of BRCA1 and BRCA2. Eleven pathogenic mutations were found (BRCA1, n = 2; BRCA2, n = 9), corresponding to a mutation prevalence of 2.0%. Six out of 11 fulfilled the Swedish BRCA testing criteria, and 9 out of 11 fulfilled the NCCN testing criteria. None of the BRCA-associated tumors were of the luminal A-like subtype. Very few patients contacted us for telephone genetic counseling or practical questions, suggesting that a majority felt that the written pre-test information was sufficient for them to make a decision on testing. Conclusions: Streamlining the process of pre-test information, genetic testing, and delivery of test results was feasible and was associated with an uptake of genetic testing in 2/3 of the breast cancer patients.
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| 26. |
- Nilsson, Per, et al.
(författare)
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A multifunctional RNA recognition motif in poly(A)-specific ribonuclease with cap and poly(A) binding properties
- 2007
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 282:45, s. 32902-32911
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Tidskriftsartikel (refereegranskat)abstract
- Poly(A)-specific ribonuclease (PARN) is an oligomeric, processive and cap-interacting 3' exoribonuclease that efficiently degrades mRNA poly(A) tails. Here we show that the RNA recognition motif (RRM) of PARN harbors both poly(A) and cap binding properties, suggesting that the RRM plays an important role for the two critical and unique properties that are tightly associated with PARN activity, i.e. recognition and dependence on both the cap structure and poly(A) tail during poly(A) hydrolysis. We show that PARN and its RRM have micromolar affinity to the cap structure by using fluorescence spectroscopy and nanomolar affinity for poly(A) by using filter binding assay. We have identified one tryptophan residue within the RRM that is essential for cap binding but not required for poly(A) binding, suggesting that the cap- and poly(A)-binding sites associated with the RRM are both structurally and functionally separate from each other. RRM is one of the most commonly occurring RNA-binding domains identified so far, suggesting that other RRMs may have both cap and RNA binding properties just as the RRM of PARN.
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| 30. |
- Röijezon, Ulrik, et al.
(författare)
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An Initial Study on the Coordination of Rod and Line Hauling Movements in Distance Fly Casting
- 2017
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Ingår i: Annals of Applied Sport Science. - : Asian Exercise and Sport Science Association. - 2476-4981 .- 2322-4479. ; 5:2, s. 61-72
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Tidskriftsartikel (refereegranskat)abstract
- Background. The double haul is a unique feature of single-handed fly casting and is used in both fly fishing and fly casting competition. The movement behaviour during the double haul has not been investigated in previous research.Objectives. Describe the coordination of the rod and line hauling movements during distance fly casting.Methods. Elite fly casters performed distance casting with four different fly rod and fly line set-ups used in fly fishing and fly casting competition. Rod and hauling movements were measured with a 3D motion analysis system.Results. The rod and line hauling movements were coordinated in an order whereby peak translational speed of the rod occurs prior to the peak speed of the angular rotation of the rod, and the peak speed of the angular rotation of the rod occurs prior to the peak speed of the line haul. This was consistent for all cast sequences, i.e., the back and forward false casts and the delivery cast, and for all four equipment set-ups, i.e., a shooting-head line cast with a relatively stiff fly rod and a long-belly line cast with three different fly rods with different stiffness and action curves. Results also showed differences in movement coordination between cast sequences and rod and line set-ups.Conclusion. Among elite casters, single-handed fly casting with double haul is coordinated in an order of events whereby the peak speed occurs first for the translation of the rod, then for the rotation of the rod and finally for the line haul.
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| 31. |
- Souter, Petra, et al.
(författare)
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Patterns of genetic structuring in the coral Pocillopora damicornis on reefs in East Africa.
- 2009
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Ingår i: BMC Ecology. - : Springer Science and Business Media LLC. - 1472-6785. ; 9, s. 19-
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Tidskriftsartikel (refereegranskat)abstract
- This study showed that population differentiation in P. damicornis varied over spatial scales and that this variability occurred at both evolutionary and ecological time scales. This paradox is discussed in light of stochastic recruitment and small scale population structures found in other species of coral. The study also identifies potential source reefs, such as those within Mnemba Conservation area near Zanzibar and genetically isolated reefs such as those within Malindi Marine National Park and Reserve in northern Kenya.
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| 33. |
- Virtanen, Anders, et al.
(författare)
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Poly(A)-specific ribonuclease (PARN) : An allosterically regulated, processive and mRNA cap-interacting deadenylase
- 2013
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Ingår i: Critical reviews in biochemistry and molecular biology. - : Informa UK Limited. - 1040-9238 .- 1549-7798. ; 48:2, s. 192-209
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Forskningsöversikt (refereegranskat)abstract
- Deadenylation of eukaryotic mRNA is a mechanism critical for mRNA function by influencing mRNA turnover and efficiency of protein synthesis. Here, we review poly(A)-specific ribonuclease (PARN), which is one of the biochemically best characterized deadenylases. PARN is unique among the currently known eukaryotic poly(A) degrading nucleases, being the only deadenylase that has the capacity to directly interact during poly(A) hydrolysis with both the m 7 G-cap structure and the poly(A) tail of the mRNA. In short, PARN is a divalent metal-ion dependent poly(A)-specific, processive and cap-interacting 3'-5' exoribonuclease that efficiently degrades poly(A) tails of eukaryotic mRNAs. We discuss in detail the mechanisms of its substrate recognition, catalysis, allostery and processive mode of action. On the basis of biochemical and structural evidence, we present and discuss a working model for PARN action. Models of regulation of PARN activity by trans-acting factors are discussed as well as the physiological relevance of PARN.
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| 34. |
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| 35. |
- Westerberg, Niklas, 1981, et al.
(författare)
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Separation Of Galactoglucomannans, Lignin, And Lignin-Carbohydrate Complexes From Hot-Water-Extracted Norway Spruce By Cross-Flow Filtration And Adsorption Chromatography
- 2012
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Ingår i: BioResources. - : BioResources. - 1930-2126. ; 7:4, s. 4501-4516
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Tidskriftsartikel (refereegranskat)abstract
- A simple method to simultaneously recover polymeric carbohydrates, mainly galactoglucomannans (GGM), lignin, and lignin-carbohydrate complex (LCC) from hot-water-extracted Norway spruce wood is presented. The isolation method consists of cross-flow filtration, where high and low molecular mass species are removed, followed by fixed-bed adsorption on a hydrophobic polymeric resin (XAD-16) to remove lignins and lignans. In the second step of fixed-bed adsorption, a phenylic reversed-phase analytical chromatography column, where mass transport resistance is minimized and a very high selectivity towards aromatic compounds have been observed, was used to separate LCC from GGM. The isolated LCC fraction contained about 10% aromatics, whereas the upgraded GGM fraction contained about 1.5% aromatics and the lignin fraction contained about 56% aromatics. Polymeric xylan was accumulated in the GGM fraction, while mannose was the dominant sugar found in the LCC fraction. As products, approximately 7% was recovered in the lignin fraction in the first adsorptive step, 5% was recovered as LCC, and 88% as upgraded hemicelluloses.
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| 36. |
- Wu, Mousheng, et al.
(författare)
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Structural basis of m(7)GpppG binding to poly(A)-specific ribonuclease
- 2009
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Ingår i: Structure. - : Elsevier BV. - 0969-2126 .- 1878-4186. ; 17:2, s. 276-286
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Tidskriftsartikel (refereegranskat)abstract
- Poly(A)-specific ribonuclease (PARN) is a homodimeric, processive, and cap-interacting 3' exoribonuclease that efficiently degrades eukaryotic mRNA poly(A) tails. The crystal structure of a C-terminally truncated PARN in complex with m(7)GpppG reveals that, in one subunit, m(7)GpppG binds to a cavity formed by the RRM domain and the nuclease domain, whereas in the other subunit, it binds almost exclusively to the RRM domain. Importantly, our structural and competition data show that the cap-binding site overlaps with the active site in the nuclease domain. Mutational analysis demonstrates that residues involved in m(7)G recognition are crucial for cap-stimulated deadenylation activity, and those involved in both cap and poly(A) binding are important for catalysis. A modeled PARN, which shows that the RRM domain from one subunit and the R3H domain from the other subunit enclose the active site, provides a structural foundation for further studies to elucidate the mechanism of PARN-mediated deadenylation.
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