| 1. |
- Ahlgren, Sara, et al.
(author)
-
Evaluation of maleimide derivative of DOTA for site-specific labeling of recombinant affibody molecules
- 2008
-
In: Bioconjugate chemistry. - : American Chemical Society (ACS). - 1043-1802 .- 1520-4812. ; 19:1, s. 235-243
-
Journal article (peer-reviewed)abstract
- Affibody molecules are a new class of small (7 kDa) scaffold affinity proteins, which demonstrate promising properties as agents for in vivo radionuclide targeting. The Affibody scaffold is cysteine-free and therefore independent of disulfide bonds. Thus, a single thiol group can be engineered into the protein by introduction of one cysteine. Coupling of thiol-reactive bifunctional chelators can enable site-specific labeling of recombinantly produced Affibody molecules. In this study, the use of 1,4,7,10-tetraazacyclododecane-1,4,7-tris-acetic acid-10-maleimidoethylacetamide (MMA-DOTA) for 111 In-labeling of anti-HER2 Affibody molecules His 6-Z HER2:342-Cys and Z HER2:2395-Cys has been evaluated. The introduction of a cysteine residue did not affect the affinity of the proteins, which was 29 pM for His 6-Z HER2:342-Cys and 27 pM for Z HER2:2395-Cys, comparable with 22 pM for the parental Z HER2:342. MMA-DOTA was conjugated to DTT-reduced Affibody molecules with a coupling efficiency of 93% using a 1:1 molar ratio of chelator to protein. The conjugates were labeled with 111 In to a specific radioactivity of up to 7 GBq/mmol, with preserved binding for the target HER2. In vivo, the non-His-tagged variant 111 In-[MMA-DOTA-Cys61]-Z HER2:2395-Cys demonstrated appreciably lower liver uptake than its His-tag-containing counterpart. In mice bearing HER2-expressing LS174T xenografts, 111 In-[MMA-DOTA-Cys61]-Z HER2:2395-Cys showed specific and rapid tumor localization, and rapid clearance from blood and nonspecific compartments, leading to a tumor-to-blood-ratio of 18 +/- 8 already 1 h p.i. Four hours p.i., the tumor-to-blood ratio was 138 +/- 8. Xenografts were clearly visualized already 1 h p.i.
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| 2. |
- Claeson, Anna-Sara, 1974-, et al.
(author)
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Volatile organic compounds (VOCs) emitted from materials collected from buildings affected by microorganisms
- 2007
-
In: Journal of Environmental Monitoring. - : Royal Society of Chemistry. - 1464-0325 .- 1464-0333. ; 9:3, s. 240-245
-
Journal article (peer-reviewed)abstract
- In this study mould damaged materials, including carpet, concrete, gypsum board, insulation, plastic, sand and wood, from 20 different buildings with moisture problems were collected. To study emissions from these materials both conventional methods for sampling, such as collection on Tenax TA, were used as well as complementary methods for sampling a wider spectrum of compounds, such as more volatile VOCs, amines and aldehydes. Analysis was carried out using gas chromatography and high-performance liquid chromatography. Mass spectrometry was used for identification of compounds. Alcohols and ketones were almost exclusively emitted from the materials after they had been wet for a week. Acids were also emitted in large quantities from wet gypsum board and plastic. No primary or secondary amines could be identified, but two tertiary amines, trimethylamine and triethylamine, were emitted from sand contaminated by Bacillus. The most common moulds found were Penicillium and Aspergillus. A multivariate method (partial least squares, PLS) was used to investigate the emission patterns from the materials. Materials with bacterial growth had a different VOC profile to those with only mould growth.
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| 3. |
- Myléus, Anna, 1978-, et al.
(author)
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Celiac disease revealed in 3% of Swedish 12-year-olds born during an epidemic
- 2009
-
In: Journal of Pediatric Gastroenterology and Nutrition - JPGN. - New York : Raven P. - 0277-2116 .- 1536-4801. ; 49:2, s. 170-176
-
Journal article (peer-reviewed)abstract
- Objetive: Sweden experienced a marked epidemic of celiac disease between 1984 and 1996 in children younger than 2 years of age, partly explained by changes in infant feeding. The objective of this study was to determine the prevalence of celiac disease in 12-year-olds born during the epidemic (1993), including both symptomatic and screening detected cases.Patients and methods: All sixth-grade children in participating schools were invited (n = 10,041). Symptomatic and, therefore, previously diagnosed celiac disease cases were ascertained through the National Swedish Childhood Celiac Disease Register and/or medical records. All serum samples were analyzed for antihuman tissue transglutaminase (tTG)-IgA (Celikey), and serum-IgA, and some for tTG-IgG and endomysial antibodies. A small intestinal biopsy was recommended for all children with suspected undiagnosed celiac disease.Results: Participation was accepted by 7567 families (75%). Previously diagnosed celiac disease was found in 67 children; 8.9/1000 (95% confidence interval [CI] 6.7-11). In another 192 children, a small intestinal biopsy was recommended and was performed in 180. Celiac disease was verified in 145 children, 20/1000 (95% CI 17-23). The total prevalence was 29/1000 (95% CI 25-33).Conclusions: The celiac disease prevalence of 29/1000 (3%)-with two thirds of cases undiagnosed before screening-is 3-fold higher than the usually suggested prevalence of 1%. When these 12-year-olds were infants, the prevailing feeding practice was to introduce gluten abruptly, often without ongoing breast-feeding, which might have contributed to this unexpectedly high prevalence.
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| 4. |
- Tolmachev, Vladimir, et al.
(author)
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Evaluation of a maleimido derivative of CHX-A'' DTPA for site-specific labeling of affibody molecules
- 2008
-
In: Bioconjugate chemistry. - : American Chemical Society (ACS). - 1043-1802 .- 1520-4812. ; 19:8, s. 1579-1587
-
Journal article (peer-reviewed)abstract
- Affibody molecules are a new class of small targeting proteins based on a common three-helix bundle structure. Affibody molecules binding a desired target may be selected using phage-display technology. An Affibody molecule Z HER2:342 binding with subnanomolar affinity to the tumor antigen HER2 has recently been developed for radionuclide imaging in vivo. Introduction of a single cysteine into the cysteine-free Affibody scaffold provides a unique thiol group for site-specific labeling of recombinant Affibody molecules. The recently developed maleimido-CHX-A'' DTPA was site-specifically conjugated at the C-terminal cysteine of Z HER2:2395-C, a variant of Z HER2:342, providing a homogeneous conjugate with a dissociation constant of 56 pM. The yield of labeling with (111)In was >99% after 10 min at room temperature. In vitro cell tests demonstrated specific binding of (111)In-CHX-A'' DTPA-Z 2395-C to HER2-expressing cell-line SKOV-3 and good cellular retention of radioactivity. In normal mice, the conjugate demonstrated rapid clearance from all nonspecific organs except kidney. In mice bearing SKOV-3 xenografts, the tumor uptake of (111)In-CHX-A'' DTPA-Z 2395-C was 17.3 +/- 4.8% IA/g and the tumor-to-blood ratio 86 +/- 46 (4 h postinjection). HER2-expressing xenografts were clearly visualized 1 h postinjection. In conclusion, coupling of maleimido-CHX-A'' DTPA to cysteine-containing Affibody molecules provides a well-defined uniform conjugate, which can be rapidly labeled at room temperature and provides high-contrast imaging of molecular targets in vivo.
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| 5. |
- Tran, Thuy A., 1980-, et al.
(author)
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Design, synthesis and biological evaluation of a multifunctional HER2-specific Affibody molecule for molecular imaging
- 2009
-
In: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 36:11, s. 1864-1873
-
Journal article (peer-reviewed)abstract
- Purpose: The purpose of this study was to design and evaluate a novel platform for labelling of Affibody molecules, enabling for both recombinant and synthetic production and for site-specific labelling with 99mTc or trivalent radiometals. Methods: The HER2-specific Affibody molecule PEP05352 was made by peptide synthesis. The chelator sequence SECG (serine-glutamic acid-cysteine-glycine) was anchored on the C-terminal to allow 99mTc-labelling. The cysteine can alternatively serve as a conjugation site of the chelator DOTA for indium-labelling. The resulting 99mTc- and 111In-labelled Affibody molecules were evaluated both in vitro and in vivo. Results: Both conjugates retained their capacity to bind to HER2 receptors in vitro and in vivo. The tumour-to-blood ratio in LS174T xenografts was 30 at 4 h p.i. for both conjugates. Biodistribution data showed that 99mTc-labelled Affibody molecule had 4-fold lower kidney accumulation compared with 111In-labelled Affibody molecule while the accumulation in other organs was similar. Gamma-camera imaging of the conjugates could clearly visualise the tumours 4 h after injection. Conclusions: Incorporation of C-terminal SECG sequence in Affibody molecules provides a general multifunctional platform for site-specific labelling with different nuclides (technetium, indium, gallium, cobalt, or yttrium) and for a flexible production (chemical synthesis or recombinant).
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| 6. |
- Anderson, Helén, et al.
(author)
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Skapa kundnärvaro i innovationsprocessen
- 2008
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In: Innovationsförmåga. - Malmö : Holmbergs i Malmö AB. - 9789197785204 ; , s. 40-59
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Book chapter (pop. science, debate, etc.)
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| 7. |
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| 8. |
- Gisslén, Magnus, 1962, et al.
(author)
-
Antiretroviral treatment of HIV infection: Swedish recommendations 2005.
- 2006
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In: Scandinavian journal of infectious diseases. - : Informa UK Limited. - 0036-5548 .- 1651-1980. ; 38:2, s. 86-103
-
Journal article (peer-reviewed)abstract
- On 2 earlier occasions, in 2002 and 2003, the Swedish Medical Products Agency (MPA) and the Swedish Reference Group for Antiviral Therapy (RAV) have jointly publicized recommendations for the treatment of HIV infection. A working group from the same expert team that produced the 2002 report has now revised the text again. Since the publication of the last treatment recommendations, 4 new medicines have become available: emtricitabine, atazanavir, fosamprenavir, and enfuvirtid. The last-mentioned belongs to a new class of HIV medications called fusion inhibitors (Box 1). It is likely that tipranavir will also be on the market soon. Simultaneously, the drug zalcitabin has been deregistered. The following updated recommendations parallel the earlier ones, but increased knowledge allows us to be more specific in our recommendations. Thus, it is now suggested that the initial treatment for HIV infection consist of 2 nucleoside reverse transcriptase inhibitors (NRTIs) and 1 non-nucleoside reverse transcriptase inhibitor (NNRTI); or 2 NRTIs and 1 protease inhibitor (PI). In the group of the NRTIs, stavudine is no longer recommended for this purpose. In the NNRTI group, efavirenz should be preferred to nevirapine, except under special circumstances. Finally, PIs ought to be boosted with ritonavir (PI/r). Also new are recommendations regarding treatment choices for patients co-infected with hepatitis B virus (HBV) or tuberculosis (TB). As in the case of the previous publication, recommendations are evidence-graded in accordance with the Oxford Centre for Evidence Based Medicine, 2001 (see http://www.cebm.net/levels_of_evidence.asp#levels), and have been supplemented with references to newly-added sections and data not referred to in earlier background documentation.
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| 9. |
- Kaszowska, Marta, et al.
(author)
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Studies on the interactions between glycosylated beta(3)-peptides and the lectin Vicia villosa by saturation transfer difference NMR spectroscopy
- 2009
-
In: Carbohydrate Research. - : Elsevier BV. - 0008-6215 .- 1873-426X. ; 344:18, s. 2577-2580
-
Journal article (peer-reviewed)abstract
- Saturation transfer difference (STD) NMR spectroscopy was used to study the interaction of the lectin Vicia villosa (VVLB4) with alpha-D-GalNAc glycosylated beta(3)-peptides. The data were compared to those obtained with the monosaccharides D-Gal, D-GalNAc, and D-Glc as well as with those obtained with the Tn antigen alpha-glycopeptide (D-GalNAc-alpha-O-Ser/Thr), molecule naturally recognized by V. villosa. Evidence that the lectin also recognizes glycosylated beta(3)-peptides and has close contact with both the sugar and amino acid moieties was obtained.
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| 10. |
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| 11. |
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| 12. |
- Lindahl, Mattias, 1971-, et al.
(author)
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Learning networks : a method for Integrated Product and Service Engineering - experience from the IPSE project
- 2008
-
In: Manufacturing Systems and Technologies for the New Frontier. - London : Springer. - 9781848002661 - 9781848002678 ; , s. 495-500
-
Book chapter (other academic/artistic)abstract
- The aim with the Integrated Product and Service Engineering (IPSE) project is to develop a methodology for companies that want to make the journey of moving from selling products to also sell Integrated Product and Service Offerings. In order to achieve that major changes are needed in the companies. In this paper the learning network approach is described as well as the content of the workshop series that the companies participated in. The findings show that a learning network approach is beneficial methodology for achieving changes in the companies, since the participants learn from each other and from the researchers.
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| 13. |
- Lindkvist, Anna, et al.
(author)
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Konflikt och konsensus i skogen : intensivodling av skog ur ett humanistiskt och samhällsvetenskapligt perspektiv. Faktaunderlag till utredning om Möjligheter till intensivodling av skog
- 2009
-
Reports (other academic/artistic)abstract
- Den första delstudien, ”Skogslandskapet som arena”, syftar till att ge en bakgrund till dagens skogsbruk i Sverige och att sätta in skogspolitiken i ett idé- och miljöhistoriskt sammanhang. Sammantaget handlar undersökningen om hur skogen har brukats och hur detta brukande har motiverats, institutionaliserats, reglerats och ifrågasatts under de senaste århundradena. Den består av två delar. Den första delen inleds med en historik som tar upp maktförhållandena i skogen och hur skogen har nyttjats genom tiderna. Därefter följer en redogörelse över skogsbrukets och skogsvårdslagens förändring över tid fram till att miljörörelsen, rennäringen, kulturminnesvården och andra ”allmänna intressen” som värnar om skogen tar plats i skogsvårdslagen. I den andra delen diskuteras ett urval konflikter som uppkommit i anslutning till skogen och skogsbruket, främst med tyngdpunkt på 1970- och 1980-talen: debatten om plantering av skog i öppna landskap, kalhyggesdebatten, reaktionerna vid inplantering av främmande trädslag, debatten om bruket av bekämpningsmedel samt visionen om att utveckla och nyttja genmodifierade träd. Flera av dessa konflikter kan rimligen åter aktualiseras vid ett intensifierat skogsbruk av det slag som utredningen behandlar.Den andra delstudien, ”Attityder och värderingar”, undersöker privatpersoners och skogsägares inställningar till den svenska skogen i allmänhet och till intensivodling av skog i synnerhet. Privatpersoner betraktar vanligen skogen som en rekreationsresurs, medan skogsägare håller skogens traditionella, ekonomiska värden närmare hjärtat. När attityder mot skogen väl förändras beror det ofta på generationsväxlingar, ökat miljömedvetande och urbaniseringstrender. Sveriges stora demografiska och kulturella skillnader har även bidragit till att skogen idag uppfattas olika i olika delar av landet. Samtidigt som vi bor längre bort från skogen än tidigare ökar vår efterfrågan på dess sociala värden, vilket innebär att ungefär hälften av våra skogsbesök numera sker i tätortsnära skog, som främst är förknippad med rekreation och vila. Skogens ekonomiska värden är emellertid fortfarande viktiga, inte minst när det gäller skogens roll som framtida energikälla. Intervjuade skogsägare har visat sig vara förhållandevis positiva till intensivodling av skog, samtidigt som det av miljömässiga och ekonomiska skäl finns ett starkt motstånd mot att öka användningen av gödsel. Privatpersoner som intervjuats anser i regel att intensivodlade områden begränsar naturupplevelsen, skadar miljön och missgynnar mångfalden. Fördelar som ökad möjlighet att utvinna alternativa energibränslen och ökade exportmöjligheter för svensk industri har emellertid också nämnts.Den tredje delstudien, ”Potentiella synergier och målkonflikter”, relaterar intensivodling av skog dels till de av riksdagen fastställda miljömålen dels till eventuella intressemotsättningar som kan uppstå till följd av ett förändrat nyttjande av jordbruksmark. De målkonflikter som identifieras, främst mellan miljömålen ’Begränsad klimatpåverkan’ och ’Ett rikt växt- och djurliv’, kan inte enbart lösas på teknisk väg utan kräver någon form av politisk avvägning. För att ansvariga myndigheter ska kunna göra en sådan avvägning krävs dock att det utarbetas någon form av politisk prioriteringsordning som kan vägleda myndigheterna i det arbetet. När det gäller eventuella intressemotsättningar som kan uppstå till följd av intensivodling framgår det av intervjuer med olika intresseorganisationer att många konflikter sannolikt kan undvikas om synpunkter från olika intressen beaktas i samband med planering av förändrat marknyttjande.
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| 14. |
- Orlova, Anna, et al.
(author)
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Evaluation of [(111/114m)In]CHX-A''-DTPA-ZHER2:342, an affibody ligand coniugate for targeting of HER2-expressing malignant tumors
- 2007
-
In: The Quarterly Journal of Nuclear Medicine and Molecular Imaging. - 1824-4785. ; 51:4, s. 314-323
-
Journal article (peer-reviewed)abstract
- AIM: Radionuclide imaging of the HER2 receptor, which is a target for trastuzumab therapy, can provide important diagnostic information. Further, targeting radionuclide therapy might be an option for treatment of HER2 expressing tumors. The phage-display selected Affibody ligand Z(HER2:342), which binds to HER2 with an affinity of 22 pM, may here play an important role. The small size of the Z(HER2:342), 7.5 kDa, enables quick tumor localization and fast blood clearance. Earlier, successful targeting of HER2-expressing xenografts using Z(HER2:342) labeled using [(111)In]benzyl-DTPA was reported. By changing to the CHX-A''-DTPA chelator, the stability and labeling kinetics of the radiometal-Z(HER2:342) conjugate can be improved. The aim of this study was to evaluate the labeling of the CHX-A''-DTPA-Z(HER2:342) conjugate with (111)In for diagnostic imaging and with (114m)In for locoregional radionuclide therapy. METHODS: The isothiocyanate derivative of CHX-A''-DTPA was coupled to Z(HER2:342) in alkaline conditions at 37 degrees C. The conjugate was labeled with both (111)In and (114m)In and evaluated in vitro and in vivo. RESULTS: Labeling with (111)In and (114m)In provided >95% yield after 30 min at RT. Specific radioactivity was 0.5 and 12 MBq/nmol, for (114m)In and (111)In, respectively. The radiolabeled conjugates demonstrated specific binding to HER2 expressing SKOV-3 cells. In mice bearing SKOV-3 xenografts, the tumor uptake of [(111)In]CHX-A''-DTPA-Z(HER2:342) 4 h postinjection was 10.3+/-3.6% IA/g and tumor-to-blood ratio about 190. CONCLUSION: [(111)In]CHX-A''-DTPA-Z(HER2:342) is a promising candidate for the visualization of HER2 expression in malignant tumors. Labeled with (114m)In it could also be used for locoregional treatment of HER2 expressing tumors.
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| 15. |
- Orlova, Anna, et al.
(author)
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Synthetic affibody molecules : a novel class of affinity ligands for molecular imaging of HER2-expressing malignant tumors
- 2007
-
In: Cancer Research. - 0008-5472 .- 1538-7445. ; 67:5, s. 2178-2186
-
Journal article (peer-reviewed)abstract
- The Affibody molecule Z(HER2:342-pep2), site-specifically and homogeneously conjugated with a 1,4,7,10-tetra-azacylododecane-N,N',N'',N'''-tetraacetic acid (DOTA) chelator, was produced in a single chemical process by peptide synthesis. DOTA-Z(HER2:342-pep2) folds spontaneously and binds HER2 with 65 pmol/L affinity. Efficient radiolabeling with >95% incorporation of (111)In was achieved within 30 min at low (room temperature) and high temperatures (up to 90 degrees C). Tumor uptake of (111)In-DOTA-Z(HER2:342-pep2) was specific for HER2-positive xenografts. A high tumor uptake of 23% injected activity per gram tissue, a tumor-to-blood ratio of >7.5, and high-contrast gamma camera images were obtained already 1 h after injection. Pretreatment with Herceptin did not interfere with tumor targeting, whereas degradation of HER2 using the heat shock protein 90 inhibitor 17-allylamino-geldanamycin before administration of (111)In-DOTA-Z(HER2:342-pep2) obliterated the tumor image. The present results show that radiolabeled synthetic DOTA-Z(HER2:342-pep2) has the potential to become a clinically useful radiopharmaceutical for in vivo molecular imaging of HER2-expressing carcinomas.
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| 16. |
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| 17. |
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| 18. |
- Rönn, Robert, et al.
(author)
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Hepatitis C Virus NS3 Protease Inhibitors Comprising a Novel Aromatic P1 Moiety
- 2008
-
In: Bioorganic & Medicinal Chemistry. - : Elsevier BV. - 0968-0896 .- 1464-3391. ; 16:6, s. 2955-2967
-
Journal article (peer-reviewed)abstract
- Inhibition of the hepatitis C virus (HCV) NS3 protease has emerged as an attractive approach to defeat the global hepatitis C epidemic. In this work, we present the synthesis and biochemical evaluation of HCV NS3 protease inhibitors comprising a non-natural aromatic P-1 moiety. A series of inhibitors with aminobenzoyl sulfonamides displaying submicromolar potencies in the full-length NS3 protease assay was prepared through a microwave-irradiated, palladium-catalyzed, amidocarbonylation protocol.
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| 19. |
- Sandström, Anna
(author)
-
Inventering av makrofyter i Stockholms län 2007 - Bedömning av ekologisk status enligt de nya bedömningsgrunderna i 12 sjöar - Inventering av makrofyter i 15 sjöar inför skydd och utformande av skötselplaner
- 2007
-
Reports (other academic/artistic)abstract
- Under sommaren 2007 inventerade Calluna makrofyter i 27 sjöar i Stockholms län på uppdrag av länsstyrelsen i Stockholms län. Uppdraget bestod av två delar:1. Bedömning av ekologisk status enligt de nya bedömningsgrunderna för makrofyter (Ecke 2007) i tolv sjöar. Sammanlagt 41 arter av flytblads- och undervattensväxter hittades i de tolv inventerade sjöarna varav en var den sällsynta och rödlistade kransalgen mellansträfse (NT). Kyrksjön vid Norrtälje stad hade flest arter, klarast vatten med högst siktdjup och undervattensväxter ända ner till drygt 5 meter. Även om den enligt de nya bedömningsgrunderna klassas till måttlig ekologisk status argumenterar vi i denna rapport för att den ska ha hög status. Lommaren och Limmaren bör också klassas till högre status än vad de nya bedömningsgrunderna säger. När det gäller Vallentunasjön och Ösmaren var vattnet så grumligt och vattenväxterna växte så grunt att de bör nedklassas till otillfredsställande status. Övriga sjöar hade en måttlig status.2. Inventering av makrofyter i femton sjöar inför beslut om skydd och/eller utformande av skötselplaner. Sammanlagt hittades 20 arter av flytblads- och undervattensväxter i dessa sjöar. Den starkt hotade spretsträfse (EN) som är en rödlistad kransalg hittades i Bergbofjärden och Mörtsjön. Beläggexemplar saknas varför fynden är osäkra. Fyndlokalerna kommer att återbesökas under 2008 för verifiering av fynden och insamling av beläggexemplar. Fyrsjön hade endast nio arter men ändå högst antal av de femton sjöar som inventerades. Här påträffades också den sårbara arten bandnate (VU). Enligt åtgärdsprogrammet för hotade natearter är målet att bandnate 2011 ska finnas i livskraftiga bestånd på alla lokaler där den påträffades 2005. Fyrsjön har redan en livskraftig population så det är viktigt att behålla de goda förutsättningarna som finns här för arten. Bergbofjärdens heltäckande mattor av kransalger har en avgörande betydelse för vattenkvalitet, sjöns funktion och biologiska mångfald. Det klara vattnet och den rikliga förekomsten av kransalger i Mårdsjön är ovanligt i den här typen av sjöar med omgivningar av myr och barrskog, vilket ger sjön en ovanlig karaktär och ett högt naturvärde. Makrofyterna i Stormaren och Lillträsket på Gisslingsö motiverar inget naturskydd, men öns andra naturvärden bör utredas. Gisslingsös havsvik hyser dessutom rikligt med makrofyter och bör inventeras. I de natursköna myrmarkena runt Långviksträsk finns rikligt med död ved i form av gamla tallrakor vilket höjer sjöns natur- och rekreationsvärde. Övriga sjöar hade låga naturvärden baserat på makrofyterna.Den sällsynta kransalgen mellansträfse (NT) växte i sjön Gisen i Norrtälje kommun.
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| 20. |
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| 21. |
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| 22. |
- Sandström, Marianne, et al.
(author)
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A pilot study of eye movement desensitisation and reprocessing treatment (EMDR) for post-traumatic stress after childbirth
- 2008
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In: Midwifery. - : Elsevier. - 0266-6138 .- 1532-3099. ; 24:1, s. 62-73
-
Journal article (peer-reviewed)abstract
- Objective: to explore the possibility of using eye movement desensitisation and reprocessing (EMDR) to treat women who have experienced post-traumatic stress after childbirth.Design: the pilot study consisted of a ‘before and after’ treatment design combined with follow-up measurements 1–3 years after EMDR treatment. Quantitative data from questionnaires (Traumatic Event Scale [TES]) were collected. In addition, qualitative data from individual interviews with the participants were collected as well as data from the psychotherapist's treatment notes of the EMDR treatment sessions.Setting: the north of Sweden.Participants: four women with post-traumatic stress disorder (PTSD) after childbirth (one pregnant and three non-pregnant).Findings: all participants reported reduction of post-traumatic stress after treatment. After 1–3 years, the beneficial effects of EMDR treatment remained for three of the four women. Symptoms of intrusive thoughts and avoidance seemed most sensitive for treatment.Implications for practice: EMDR might be a useful tool in the treatment of non-pregnant women severely traumatised by childbirth; however, further research is required.
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| 23. |
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| 24. |
- Sundin, Erik, 1974-, et al.
(author)
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Challenges for Industrial Product/Service Systems : Experiences from a learning network of large companies
- 2009
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In: Industrial product-service systems (IPS2) : proceedings of the 1st CIRP IPS² Conference. - Cranfield, UK : Cranfield University Press. - 9780955743658 ; , s. 298-304
-
Conference paper (other academic/artistic)abstract
- In Sweden, there are a growing number of manufacturers that are using the approach of industrial product/service systems. This paper explores how manufacturers and university researchers have started a workshop series where important and topical product/service system issues are elucidated. The companies face many challenges in order to achieve a good product/service system business. Many challenges are related to changing different peoples’ mindset within the company and/or with external companies and customers. Having a learning network approach of dealing with these challenges has been perceived as a good manner of tackling the questions raised within the product/service system providing companies.
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| 25. |
- Sundin, Erik, et al.
(author)
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Challenges for industrial product/service systems - Experiences from a learning network of large companies
- 2009
-
In: Industrial product-service systems (IPS2). - Cranfield : Cranfield University Press. - 9780955743658
-
Conference paper (peer-reviewed)abstract
- In Sweden, manufacturers have a growing need to extend the control of their products in the supply chain. This need is fulfilled by some manufacturers through the use of a product/service system business approach. This paper explores how a group of Swedish manufacturers, working together with academia, have started a workshop series where the most important and topical issues for their integrated product/service offering approaches are dealt with. The large company network studied in this paper faces many challenges in order to achieve a good product/service system business. Much of these challenges are related to changing different peoples' mindset whether it is within the company and/or with external companies and customers. Having a learning network approach of dealing with these challenges has so far been perceived as a good manner of tackling the questions raised within the product/service system providing companies.
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| 26. |
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| 27. |
- Sundin, Erik, 1974-, et al.
(author)
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Remanufacturing of Products used in Product Service System Offerings
- 2008. - 1
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In: Manufacturing Systems and Technologies for the New Frontier. - London, UK : Springer London. - 9781848002661 - 9781848002678 ; , s. 537-542
-
Conference paper (other academic/artistic)abstract
- As a product service system provider it is important to consider its benefits and drawbacks. Connecting the product service system with a remanufacturing system has a good potential of being economically and environmentally beneficial. This paper elucidates the case of three different remanufacturers and how their relation with their core provider affects their business. Products sold as a part of a product service system have great potential of being remanufactured in an efficient manner. This is for example due to large possibilities to plan the remanufacturing operations and to achieve pre-information about the cores coming in to the remanufacturing facilities.
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| 28. |
- Sundin, Erik, 1974-, et al.
(author)
-
Using company-academia networks for improving Product/Service Systems at large companies
- 2009. - 1
-
In: Introduction to Product/Service-System Design. - London : Springer. - 9781848829084 - 9781848829091 ; , s. 185-196
-
Book chapter (peer-reviewed)abstract
- Many manufacturers are shifting focus for different reasons from being providers of mainly physical products, to providing increased services in their customer offerings. Traditionally, the focus at manufacturing companies has been more on product development than service development; this is one reason why it is important for PSS developers to meet others who understand this situation. This chapter describes challenges large PSS providers in Sweden are facing, and how these can be explored and discussed within a Product/Service System company-academia network setting. It is concluded that during the three first years of network meetings, this approach has been a success. In addition, the experiences gained from participation in this network have resulted in recommendations for PSS providers and researchers thinking of starting up similar networks and/or building ones already begun.
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| 29. |
- Tolmachev, Vladimir, et al.
(author)
-
Affibody molecules for epidermal growth factor receptor targeting in vivo : aspects of dimerization and labeling chemistry
- 2009
-
In: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 1535-5667 .- 2159-662X. ; 50:2, s. 274-283
-
Journal article (peer-reviewed)abstract
- Noninvasive detection of epidermal growth factor receptor (EGFR) expression in malignant tumors by radionuclide molecular imaging may provide diagnostic information influencing patient management. The aim of this study was to evaluate a novel EGFR-targeting protein, the ZEGFR:1907 Affibody molecule, for radionuclide imaging of EGFR expression, to determine a suitable tracer format (dimer or monomer) and optimal label. METHODS: An EGFR-specific Affibody molecule, ZEGFR:1907, and its dimeric form, (ZEGFR:1907)2, were labeled with 111In using benzyl-diethylenetriaminepentaacetic acid and with 125I using p-iodobenzoate. Affinity and cellular retention of conjugates were evaluated in vitro. Biodistribution of radiolabeled Affibody molecules was compared in mice bearing EGFR-expressing A431 xenografts. Specificity of EGFR targeting was confirmed by comparison with biodistribution of non-EGFR-specific counterparts. RESULTS: Head-to-tail dimerization of the Affibody molecule improved the dissociation rate. In vitro, dimeric forms demonstrated superior cellular retention of radioactivity. For both molecular set-ups, retention was better for the 111In-labeled tracer than for the radioiodinated counterpart. In vivo, all conjugates accumulated specifically in xenografts and in EGFR-expressing tissues. The retention of radioactivity in tumors was better in vivo for dimeric forms; however, the absolute uptake values were higher for monomeric tracers. The best tracer, 111In-labeled ZEGFR:1907, provided a tumor-to-blood ratio of 100 (24 h after injection). CONCLUSION: The radiometal-labeled monomeric Affibody molecule ZEGFR:1907 has a potential for radionuclide molecular imaging of EGFR expression in malignant tumors.
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| 30. |
- Tolmachev, Vladimir, et al.
(author)
-
Radionuclide therapy of HER2-positive microxenografts using a 177Lu-labeled HER2-specific Affibody molecule
- 2007
-
In: Cancer Research. - 0008-5472 .- 1538-7445. ; 67:6, s. 2773-2782
-
Journal article (peer-reviewed)abstract
- A radiolabeled anti-HER2 Affibody molecule (Z(HER2:342)) targets HER2-expressing xenografts with high selectivity and gives good imaging contrast. However, the small size (approximately 7 kDa) results in rapid glomerular filtration and high renal accumulation of radiometals, thus excluding targeted therapy. Here, we report that reversible binding to albumin efficiently reduces the renal excretion and uptake, enabling radiometal-based nuclide therapy. The dimeric Affibody molecule (Z(HER2:342))(2) was fused with an albumin-binding domain (ABD) conjugated with the isothiocyanate derivative of CHX-A''-DTPA and labeled with the low-energy beta-emitter (177)Lu. The obtained conjugate [CHX-A''-DTPA-ABD-(Z(HER2:342))(2)] had a dissociation constant of 18 pmol/L to HER2 and 8.2 and 31 nmol/L for human and murine albumin, respectively. The radiolabeled conjugate displayed specific binding to HER2-expressing cells and good cellular retention in vitro. In vivo, fusion with ABD enabled a 25-fold reduction of renal uptake in comparison with the nonfused dimer molecule (Z(HER2:342))(2). Furthermore, the biodistribution showed high and specific uptake of the conjugate in HER2-expressing tumors. Treatment of SKOV-3 microxenografts (high HER2 expression) with 17 or 22 MBq (177)Lu-CHX-A''-DTPA-ABD-(Z(HER2:342))(2) completely prevented formation of tumors, in contrast to mice given PBS or 22 MBq of a radiolabeled non-HER2-binding Affibody molecule. In LS174T xenografts (low HER2 expression), this treatment resulted in a small but significant increase of the survival time. Thus, fusion with ABD improved the in vivo biodistribution, and the results highlight (177)Lu-CHX-A''-DTPA-ABD-(Z(HER2:342))(2) as a candidate for treatment of disseminated tumors with a high level of HER2 expression.
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| 31. |
- Tran, Thuy, et al.
(author)
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99mTc-maEEE-ZHER2:342, an Affibody Molecule-Based Tracer for the Detection of HER2 Expression in Malignant Tumors
- 2007
-
In: Bioconjugate chemistry. - : American Chemical Society (ACS). - 1043-1802 .- 1520-4812. ; 18:6, s. 1956-1964
-
Journal article (peer-reviewed)abstract
- Detection of HER2-overexpression in tumors and metastases is important for the selection of patients who will benefit from trastuzumab treatment. Earlier investigations showed successful imaging of HER2-positive tumors in patients using indium- or gallium-labeled Affibody molecules. The goal of this study was to evaluate the use of 99mTc-labeled Affibody molecules for the detection of HER2 expression. The Affibody molecule ZHER2:342 with the chelator sequences mercaptoacetyl-Gly-Glu-Gly (maGEG) and mercaptoacetyl-Glu-Glu-Glu (maEEE) was synthesized by peptide synthesis and labeled with technetium-99m. Binding specificity, cellular retention, and in vitro stability were investigated. The biodistribution of 99mTc-maGEG-ZHER2:342 and 99mTc-maEEE-ZHER2:342 was compared with 99mTc-maGGG-ZHER2:342 in normal mice, and the tumor targeting properties of 99mTc-maEEE-ZHER2:342 were determined in SKOV-3 xenografted nude mice. The results showed that the Affibody molecules were efficiently labeled with technetium-99m. The labeled conjugates were highly stable in vitro with preserved HER2-binding capacity. The use of glutamic acid in the chelator sequences for 99mTc-labeling of ZHER2:342 reduced the hepatobiliary excretion 3-fold with a single Gly-to-Glu substitution and 10-fold with three Gly-to-Glu substitutions. 99mTc-maEEE-ZHER2:342 showed a receptor-specific tumor uptake of 7.9 ± 1.0 %IA/g and a tumor-to-blood ratio of 38 at 4 h pi. Gamma-camera imaging with 99mTc-maEEE-ZHER2:342 could detect HER2-expressing tumors in xenografts already at 1 h pi. It was concluded that peptide synthesis for the coupling of chelator sequences to Affibody molecules for 99mTc labeling is an efficient way to modify the in vivo kinetics. Increased hydrophilicity, combined with improved stability of the mercaptoacetyl-triglutamyl chelator, resulted in favorable biodistribution, making 99mTc-maEEE-ZHER2:342 a promising tracer for clinical imaging of HER2 overexpression in tumors.
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| 32. |
- Tran, Thuy, et al.
(author)
-
Comparison of benzoate- and dodecaborate-based linkers for attachment of radioiodine to HER2-targeting Affibody ligand
- 2007
-
In: International Journal of Molecular Medicine. - 1107-3756 .- 1791-244X. ; 19:3, s. 485-493
-
Journal article (peer-reviewed)abstract
- The use of radionuclide molecular imaging enables the selection of patients for treatment using molecular medicine. Preclinical studies have demonstrated that a novel low-molecular-weight affinity ligand, Affibody molecule Z(HER2:342) can image the expression of HER2 with high sensitivity and specificity in tumour xenografts and has a potential for the selection of patients for treatment using Herceptin or other anti-HER2 medicine. In this study, we performed a comparative evaluation of two possible linkers for radioiodination of the Affibody molecule Z(HER2:342), 4-iodobenzoate (PIB) and [4-isothiocyanatobenzyl)-amino]-undecahydro-closo-dodecaborate (DABI). It was shown that the use of DABI makes it possible to obtain radioiodinated Z(HER2:342) with preserved capacity for selective binding to HER2-expressing cells. There was no difference between 125I-PIB-Z(HER2:342) and 125I-DABI-Z(HER2:342) in cellular retention of radioactivity after interrupted incubation with radiolabelled Affibody ligands. In vivo, the biodistribution of 125I-PIB-Z(HER2:342) was characterized by a high tumour uptake at 4 h pi (12.7+/-4.6% IA/g) and a quick clearance from blood and normal organs. The tumour uptake of 125I-DABI-Z(HER2:342) was appreciably lower (2.7+/-1.2% IA/g), and a high uptake of this conjugate in the liver was observed. A gamma-camera experiment (at 6 h pi) demonstrated that the use of 125I-PIB-Z(HER2:342) provided a much better contrast of imaging HER2-expressing xenografts than the use of 125I-DABI-Z(HER2:342). In conclusion, 125I-PIB-Z(HER2:342) is superior to 125I-DABI-Z(HER2:342) as an agent for imaging HER2 expression in vivo.
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| 33. |
- Wiklund, Anna-Lena, 1970-
(author)
-
The Syntax of Tenselessness : On Copying Constructions in Swedish
- 2005
-
Doctoral thesis (other academic/artistic)abstract
- This thesis investigates three construction types in Swedish where two (or more) verbs display identical inflectional morphology (COPYING) and share one overt subject. The constructions are referred to as (i) T(ENSE)M(OOD)A(SPECT)-COPYING complements, of the form John started and wrote (John started writing), (ii) PARTICIPLE COPYING complements, of the form John had been-able written (John had been able to write), and (iii) PSEUDOCOORDINATIONS, of the form John sat and wrote (John was writing). (i) and (ii) differ from (iii) in alternating with infinitives. (ii) differs from (i) and (iii) in restricting copying to participial form and in being incompatible with a linking element (corresponding to 'and'). The main claim is that the construction types are three surface variants of one and the same phenomenon, involving complementation and semantically vacuous inflection on the embedded verb(s). The differences between them are argued to be derivable from independent factors. (i) and (iii) are shown to differ from (ii) w.r.t. amount of functional structure present in the embedded clause. Matrix verbs in (iii) are shown to instantiate light verb uses of otherwise lexical verbs. Copying complements are argued to instantiate subtypes of "tenseless" infinitivals (infinitivals whose tense orientation fully overlaps with that of the matrix clause), characterized by an underspecified functional domain. Copying is assumed to be a surface reflection of (Agree-type) dependencies between functional heads of the same label; features of the embedded functional heads copy values from the corresponding functional heads in the matrix clause. Arguments for treating copying complements as instantiating restructuring are presented. It is proposed that copying complements differ from non-copying infinitival complements in being subject to valuation from the matrix functional domain. This suggests that an imporant aspect of (possibility of) restructuring is alternation between unmarked (negatively specified) and unvalued varieties of the same features.
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| 34. |
- Wing, Kajsa, 1977, et al.
(author)
-
CD4+ CD25+ FOXP3+ regulatory T cells from human thymus and cord blood suppress antigen-specific T cell responses
- 2005
-
In: Immunology. ; 115:4, s. 516-25
-
Journal article (peer-reviewed)abstract
- Activation of self-reactive T cells in healthy adults is prevented by the presence of autoantigen-specific CD4+CD25+ regulatory T cells (CD25+ Treg). To explore the functional development of autoantigen-reactive CD25+ Treg in humans we investigated if thymic CD25+ Treg from children aged 2 months to 11 years and cord blood CD25+ Treg are able to suppress proliferation and cytokine production induced by specific antigens. While CD4+CD25- thymocytes proliferated in response to myelin oligodendrocyte glycoprotein (MOG), tetanus toxoid and beta-lactoglobulin, suppression of proliferation was not detected after the addition of thymic CD25+ Treg. However, CD25+ Treg inhibited interferon (IFN)-gamma production induced by MOG, which indicates that MOG-reactive CD25+ Treg are present in the thymus. In contrast, cord blood CD25+ Treg suppressed both proliferation and cytokine production induced by MOG. Both cord blood and thymic CD25+ Treg expressed FOXP3 mRNA. However, FOXP3 expression was lower in cord blood than in thymic CD25+ T cells. Further characterization of cord blood CD25+ T cells revealed that FOXP3 was highly expressed by CD25+CD45RA+ cells while CD25+CD45RA- cells contained twofold less FOXP3, which may explain the lower expression level of FOXP3 in cord blood CD25+ T cells compared to thymic CD25+ T cells. In conclusion, our data demonstrate that low numbers of MOG-reactive functional CD25+ Treg are present in normal thymus, but that the suppressive ability of the cells is broader in cord blood. This suggests that the CD25+ Treg may be further matured in the periphery after being exported from the thymus.
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| 35. |
- Zhou, Qin, et al.
(author)
-
The C-terminal amidated analogue of the Substance P (SP) fragment SP (1-7) attenuates the expression of naloxone- precipitated withdrawal in morphine dependent rats
- 2009
-
In: Peptides. - : Elsevier BV. - 0196-9781 .- 1873-5169. ; 30:12, s. 2418-2422
-
Journal article (peer-reviewed)abstract
- We previously demonstrated that intracerebroventricular (i.c.v.) administration of the substance P (SP) aminoterminal fragment SP(1-7) attenuates the expression of morphine withdrawal in the male rat. In this study we have used a synthetic analogue of this peptide, i.e. the SP(1-7) amide showing higher binding potency than the native heptapeptide, in a similar experimental set-up. Thus, Wistar male rats were made tolerant to morphine by daily injections of the opiate during 8 days. Following peptide administration (i.c.v.) and a subsequent naloxone challenge a variety of physical syndromes of withdrawal were recorded. We observed that the SP(1-7) amide potently and dose-dependently reduced several signs of reaction to morphine withdrawal. Interestingly, the effect of the peptide amide was significantly attenuated by the addition of the sigma agonist (+)-SKF-10047. We conclude that the SP(1-7) amide mimics the effect of the native SP fragment and that the mechanisms for its action involve a sigma receptor site.
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| 36. |
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| 37. |
- Ölundh Sandström, Gunilla, et al.
(author)
-
Managing Innovation Processes for a Business-Driven Collaborative Network to Export Total Technical Solutions
- 2008
-
In: Proceedings of the 1st ISPIM Innovation Symposium. - Singapore : ISPIM. - 9789522146656
-
Conference paper (peer-reviewed)abstract
- There is a large need of environmental solutions at developing countries, where a network of small firms, e.g. in Sweden, have much opportunity for their business. This paper discusses, from both theoretical and from practical aspects, the high degree of complexity that needs to be managed when small firms export environmental-technology innovation to emerging markets. Especially, it deals with how a network of firms should manage its innovation processes. Based on the review of some 50 literature, the paper explains the methodologies adopted in an on-going project to study these issues. Discussions include differences with development of an integration of products/services within a single firm.
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