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| 2. |
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| 3. |
- Korenblik, R., et al.
(författare)
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Dragon 1 Protocol Manuscript : Training, Accreditation, Implementation and Safety Evaluation of Portal and Hepatic Vein Embolization (PVE/HVE) to Accelerate Future Liver Remnant (FLR) Hypertrophy
- 2022
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Ingår i: Cardiovascular and Interventional Radiology. - : Springer. - 0174-1551 .- 1432-086X. ; 45, s. 1391-1398
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Tidskriftsartikel (refereegranskat)abstract
- Study Purpose The DRAGON 1 trial aims to assess training, implementation, safety and feasibility of combined portal- and hepatic-vein embolization (PVE/HVE) to accelerate future liver remnant (FLR) hypertrophy in patients with borderline resectable colorectal cancer liver metastases. Methods The DRAGON 1 trial is a worldwide multicenter prospective single arm trial. The primary endpoint is a composite of the safety of PVE/HVE, 90-day mortality, and one year accrual monitoring of each participating center. Secondary endpoints include: feasibility of resection, the used PVE and HVE techniques, FLR-hypertrophy, liver function (subset of centers), overall survival, and disease-free survival. All complications after the PVE/HVE procedure are documented. Liver volumes will be measured at week 1 and if applicable at week 3 and 6 after PVE/HVE and follow-up visits will be held at 1, 3, 6, and 12 months after the resection. Results Not applicable. Conclusion DRAGON 1 is a prospective trial to assess the safety and feasibility of PVE/HVE. Participating study centers will be trained, and procedures standardized using Work Instructions (WI) to prepare for the DRAGON 2 randomized controlled trial. Outcomes should reveal the accrual potential of centers, safety profile of combined PVE/HVE and the effect of FLR-hypertrophy induction by PVE/HVE in patients with CRLM and a small FLR.
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| 4. |
- Östling, Jörgen, et al.
(författare)
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IL-17-high asthma with features of a psoriasis immunophenotype
- 2019
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Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier. - 0091-6749 .- 1097-6825. ; 144:5, s. 1198-1213
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Tidskriftsartikel (refereegranskat)abstract
- Background: The role of IL-17 immunity is well established in patients with inflammatory diseases, such as psoriasis and inflammatory bowel disease, but not in asthmatic patients, in whom further study is required.Objective: We sought to undertake a deep phenotyping study of asthmatic patients with upregulated IL-17 immunity.Methods: Whole-genome transcriptomic analysis was performed by using epithelial brushings, bronchial biopsy specimens (91 asthmatic patients and 46 healthy control subjects), and whole blood samples (n = 498) from the Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED) cohort. Gene signatures induced in vitro by IL-17 and IL-13 in bronchial epithelial cells were used to identify patients with IL-17–high and IL-13–high asthma phenotypes.Results: Twenty-two of 91 patients were identified with IL-17, and 9 patients were identified with IL-13 gene signatures. The patients with IL-17–high asthma were characterized by risk of frequent exacerbations, airway (sputum and mucosal) neutrophilia, decreased lung microbiota diversity, and urinary biomarker evidence of activation of the thromboxane B2 pathway. In pathway analysis the differentially expressed genes in patients with IL-17-high asthma were shared with those reported as altered in psoriasis lesions and included genes regulating epithelial barrier function and defense mechanisms, such as IL1B, IL6, IL8, and β-defensin.Conclusion: The IL-17–high asthma phenotype, characterized by bronchial epithelial dysfunction and upregulated antimicrobial and inflammatory response, resembles the immunophenotype of psoriasis, including activation of the thromboxane B2 pathway, which should be considered a biomarker for this phenotype in further studies, including clinical trials targeting IL-17.
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| 5. |
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| 6. |
- Karlsson, J, 1966-, et al.
(författare)
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Sequencing of the Francisella tularensis strain Schu 4 genome reveals the shikimate and purine metabolic pathways, targets for the construction of a rationally attenuated auxotrophic vaccine.
- 2000
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Ingår i: Microbial & Comparative Genomics. - : Mary Ann Liebert Inc. - 1090-6592 .- 2168-6637. ; 5:1, s. 25-39
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Tidskriftsartikel (refereegranskat)abstract
- Francisella tularensis is the etiological agent of tularemia, a serious disease in several Northern hemisphere countries. The organism has fastidious growth requirements and is very poorly understood at the genetic and molecular levels. Given the lack of data on this organism, we undertook the sample sequencing of its genome. A random library of DNA fragments from a highly virulent strain (Schu 4) of F. tularensis was constructed and the nucleotide sequences of 13,904 cloned fragments were determined and assembled into 353 contigs. A total of 1.83 Mb of nucleotide sequence was obtained that had a G+C content of 33.2%. Genes located on plasmids pOM1 and pNFL10, which had been previously isolated from low virulence strains of F. tularensis, were absent but all of the other known F. tularensis genes were represented in the assembled data. F. tularensis Schu4 was able to grow in the absence of aromatic amino acids and orthologues of genes which could encode enzymes in the shikimate pathway in other bacteria were identified in the assembled data. Genes that could encode all of the enzymes in the purine biosynthetic and most of the en- zymes in the purine salvage pathways were also identified. This data will be used to develop defined rationally attenuated mutants of F. tularensis, which could be used as replacements for the existing genetically undefined live vaccine strain.
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| 7. |
- Landin-Olsson, Mona, et al.
(författare)
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Immunoreactive trypsin(Ogen) in the sera of children with recent-onset insulin-dependent diabetes and matched controls
- 1990
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Ingår i: Pancreas. - : Ovid Technologies (Wolters Kluwer Health). - 0885-3177. ; 5:3, s. 241-247
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Tidskriftsartikel (refereegranskat)abstract
- To evaluate the exocrine pancreatic function at the time of diagnosis of insulin-dependent diabetes mellitus, we determined immunoreactive an-odal and cathodal trypsin(ogen) levels in sera from almost all children (n = 375) 0-14 years of age in Sweden in whom diabetes developed during 1 year, and in sex-, age-, and geographically matched control subjects (n = 312). The median level of anodal trypsin(ogen) was 5 (quartile range, 3-7) µg/L in children with newly diagnosed diabetes, compared with a median level of 7 (quartile range, 4-8) µg/L in control subjects (p < 0.0001). Similarly, the median level of cathodal trypsin(ogen) was 8 (quartile range, 4-10) µg/L in children with diabetes, compared with a median level of 11 (quartile range, 7-15) µg/L in control subjects (p < 0.0001). The median of the individual ratios between cathodal and anodal trypsin(ogen) was 1.4 in the diabetic patients and 1.7 in the control children (p < 0.001). In a multivariate test, however, only the decrease in cathodal trypsin(ogen) concentration was associated with diabetes. The levels of trypsin(ogen)s did not correlate with levels of islet cell antibodies, present in 81% of the diabetic children. Several mechanisms may explain our findings, for example, similar pathogenetic factors may affect both the endocrine and exocrine pancreas simultaneously, a failing local trophic stimulation by insulin on the exocrine cells may decrease the trypsinogen production, and there may be an increased elimination of trypsin(ogen) because of higher filtration through the kidneys in the hyperglycemic state.
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| 8. |
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| 9. |
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| 10. |
- Callaghan, Terry, et al.
(författare)
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Multi-Decadal Changes in Tundra Environments and Ecosystems : Synthesis of the International Polar Year-Back to the Future Project (IPY-BTF)
- 2011
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Ingår i: Ambio. - : Springer Science and Business Media LLC. - 0044-7447 .- 1654-7209. ; 40:6, s. 705-716
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Tidskriftsartikel (refereegranskat)abstract
- Understanding the responses of tundra systemsto global change has global implications. Most tundraregions lack sustained environmental monitoring and oneof the only ways to document multi-decadal change is toresample historic research sites. The International PolarYear (IPY) provided a unique opportunity for such researchthrough the Back to the Future (BTF) project (IPY project#512). This article synthesizes the results from 13 paperswithin this Ambio Special Issue. Abiotic changes includeglacial recession in the Altai Mountains, Russia; increasedsnow depth and hardness, permafrost warming, andincreased growing season length in sub-arctic Sweden;drying of ponds in Greenland; increased nutrient availabilityin Alaskan tundra ponds, and warming at mostlocations studied. Biotic changes ranged from relativelyminor plant community change at two sites in Greenland tomoderate change in the Yukon, and to dramatic increasesin shrub and tree density on Herschel Island, and in subarcticSweden. The population of geese tripled at one sitein northeast Greenland where biomass in non-grazed plotsdoubled. A model parameterized using results from a BTFstudy forecasts substantial declines in all snowbeds andincreases in shrub tundra on Niwot Ridge, Colorado overthe next century. In general, results support and provideimproved capacities for validating experimental manipulation,remote sensing, and modeling studies.
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| 11. |
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| 12. |
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| 13. |
- Hill, Daniel, et al.
(författare)
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Microfluidic and Transducer Technologies for Lab on a Chip Applications
- 2010
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Ingår i: 2010 ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY (EMBC). - : IEEE conference proceedings. - 9781424441242 ; , s. 305-307
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Konferensbidrag (refereegranskat)abstract
- Point-of-care diagnostic devices typically require six distinct qualities: they must deliver at least the same sensitivity and selectivity, and for a cost per assay no greater than that of today's central lab technologies, deliver results in a short period of time (<15 min at GP; <2h in hospital), be portable or at least small in scale, and require no or extremely little sample preparation. State-of-the-art devices deliver information of several markers in the same measurement.
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| 14. |
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| 15. |
- Korrel, Maarten, et al.
(författare)
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Minimally invasive versus open distal pancreatectomy: an individual patient data meta-analysis of two randomized controlled trials
- 2021
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Ingår i: HPB. - : ELSEVIER SCI LTD. - 1365-182X .- 1477-2574. ; 23:3, s. 323-330
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Forskningsöversikt (refereegranskat)abstract
- Background: Minimally invasive distal pancreatectomy (MIDP) has been suggested to reduce postoperative outcomes as compared to open distal pancreatectomy (ODP). Recently, the first randomized controlled trials (RCTs) comparing MIDP to ODP were published. This individual patient data meta analysis compared outcomes after MIDP versus ODP combining data from both RCTs. Methods: A systematic literature search was performed to identify RCTs on MIDP vs. ODP, and individual patient data were harmonized. Primary endpoint was the rate of major (Clavien-Dindo > III) complications. Sensitivity analyses were performed in high-risk subgroups. Results: A total of 166 patients from the LEOPARD and LAPOP RCTs were included. The rate of major complications was 21% after MIDP vs. 35% after ODP (adjusted odds ratio 0.54; p = 0.148). MIDP significantly reduced length of hospital stay (6 vs. 8 days, p = 0.036), and delayed gastric emptying (4% vs. 16%, p = 0.049), as compared to ODP. A trend towards higher rates of postoperative pancreatic fistula was observed after MIDP (36% vs. 28%, p = 0.067). Outcomes were comparable in high-risk subgroups. Conclusion: This individual patient data meta-analysis showed that MIDP, when performed by trained surgeons, may be regarded as the preferred approach for distal pancreatectomy. Outcomes are improved after MIDP as compared to ODP, without obvious downsides in high-risk subgroups.
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| 16. |
- Korrel, Maarten, et al.
(författare)
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Minimally invasive versus open distal pancreatectomy for resectable pancreatic cancer (DIPLOMA): an international randomised non-inferiority trial
- 2023
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Ingår i: The Lancet Regional Health. - : ELSEVIER. - 2666-7762. ; 31
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Tidskriftsartikel (refereegranskat)abstract
- Background The oncological safety of minimally invasive surgery has been questioned for several abdominal cancers. Concerns also exist regarding the use of minimally invasive distal pancreatectomy (MIDP) in patients with resectable pancreatic cancer as randomised trials are lacking. Methods In this international randomised non-inferiority trial, we recruited adults with resectable pancreatic cancer from 35 centres in 12 countries. Patients were randomly assigned to either MIDP (laparoscopic or robotic) or open distal pancreatectomy (ODP). Both patients and pathologists were blinded to the assigned approach. Primary endpoint was radical resection (R0, & GE;1 mm free margin) in patients who had ultimately undergone resection. Analyses for the primary endpoint were by modified intention-to-treat, excluding patients with missing data on primary endpoint. The pre-defined non-inferiority margin of -7% was compared with the lower limit of the two-sided 90% confidence interval (CI) of absolute difference in the primary endpoint. This trial is registered with the ISRCTN registry (ISRCTN44897265). Findings Between May 8, 2018 and May 7, 2021, 258 patients were randomly assigned to MIDP (131 patients) or ODP (127 patients). Modified intention-to-treat analysis included 114 patients in the MIDP group and 110 patients in the ODP group. An R0 resection occurred in 83 (73%) patients in the MIDP group and in 76 (69%) patients in the ODP group (difference 3.7%, 90% CI -6.2 to 13.6%; pnon-inferiority = 0.039). Median lymph node yield was comparable (22.0 [16.0-30.0] vs 23.0 [14.0-32.0] nodes, p = 0.86), as was the rate of intraperitoneal recurrence (41% vs 38%, p = 0.45). Median follow-up was 23.5 (interquartile range 17.0-30.0) months. Other postoperative outcomes were comparable, including median time to functional recovery (5 [95% CI 4.5-5.5] vs 5 [95% CI 4.7-5.3] days; p = 0.22) and overall survival (HR 0.99, 95% CI 0.67-1.46, p = 0.94). Serious adverse events were reported in 23 (18%) of 131 patients in the MIDP group vs 28 (22%) of 127 patients in the ODP group. Interpretation This trial provides evidence on the non-inferiority of MIDP compared to ODP regarding radical resection rates in patients with resectable pancreatic cancer. The present findings support the applicability of minimally invasive surgery in patients with resectable left-sided pancreatic cancer. Funding Medtronic Covidien AG, Johnson & Johnson Medical Limited, Dutch Gastroenterology Society. Copyright & COPY; 2023 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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| 17. |
- Mosomtai, G., et al.
(författare)
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Characterizing movement patterns of nomadic pastoralists and their exposure to rift valley fever in Kenya
- 2023
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Ingår i: The international archives of the photogrammetry, remote sensing and spatial information sciences. - : Copernicus GmbH. - 1682-1750 .- 2194-9034. ; , s. 211-216
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Konferensbidrag (refereegranskat)abstract
- The role of animal movement in spreading infectious diseases is highly recognized by various legislations and institutions such as the World Organisation for Animal Health and the International Animal Health Code. The increased interactions at the nexus of human-animal-ecosystem interface have seen an unprecedented introduction and reintroduction of new zoonotic diseases with high socio-economic impacts such as the COVID-19 pandemic. Rift Valley fever (RVF) is a zoonotic disease that affects both humans and animals and is transmitted by Aedes mosquitoes or through contact with the body fluids of infected animals. This study seeks to characterize movement patterns of pastoralist and how this movement behaviour increases their susceptibility to RVF virus exposure. We levarage on a rapidly growing field of movement ecology to monitor five herds collared from 2013 - 2015 in an RVF endemic semi-arid region in Kenya. The herds were also sampled for RVF antibodies to assess their exposure to RVF virus during the rainy seasons. adehabitatLT package in R was used to analyze the trajectory data whereas the first passage time (FPT) analysis was used to measure the area utilized in grazing. Sedentary herds grazed within 15km radius while migrating herds presented restricted space use patterns during the dry seasons and transient movement during the start and end of the rainy season. Furthermore, RVF virus antibodies were generally low for sedentary herds whereas the migrating herds recorded high levels during their transition periods. This study can be used to identify RVF risk zones for timely and targeted management strategies.
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| 18. |
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| 19. |
- Samuelson, Gösta, 1930-, et al.
(författare)
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Food and nutrient intakes in Swedish diabetic children.
- 1989
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Ingår i: European Journal of Clinical Nutrition. - 0954-3007 .- 1476-5640. ; 43:11, s. 801-3
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Tidskriftsartikel (refereegranskat)abstract
- Food and energy intakes in diabetic children, 7-9 and 12-14 years of age, were studied by the 7-d record method. The mean duration of diabetes in the younger group was 3.0 years and in the older group 4.2. The children had 3 main meals and 3.4 light meals daily. The median daily number of sandwiches was 7, often offered as snacks. All children used a low-fat margarine, low-fat cheese and low-fat milk. Sweets and diabetic food were seldom used. Of the energy intake protein contributed 18 per cent, fat 32 per cent and carbohydrates 50 per cent, including sucrose 2 per cent. Mean daily intake of fibre was 20 g. Compared to healthy children of the same age and from the same areas of Sweden the diabetics had a more regular meal pattern, their energy intakes did not differ, but the diet of diabetics was lower in fat and sucrose and higher in protein. The mean height, weight and BMI did not differ from healthy children.
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| 20. |
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| 21. |
- Sandström, Ulf G, et al.
(författare)
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Är miljömålsåtgärder effektiva?En utvärdering i Dalarnas,Gävleborgs, Värmlands och Örebro län
- 2012
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Länsstyrelserna och Skogsstyrelsen ska, med utgångspunkt från de nationella miljökvalitetsmålen,samordna arbetet med regionala miljömål och stimulera åtgärder för att nådem. Syftet med denna studie är att utvärdera regionala miljömålsåtgärders effektivitetgenom att studera utfallet i relation till kostnaderna för att genomföra åtgärderna.Resultatet ger bland annat vägledning för utformning av framtida miljömålsåtgärder,men visar också exempel på vad som krävs för att åtgärders effektivitet ska kunnautvärderas.Här har miljönytta, miljömålsuppfyllelse och kostnadseffektivitet utvärderats för 19miljömålsåtgärder inom områdena energi/klimat, giftfri miljö, ytvatten samt biologiskmångfald. Dessutom har framgångsfaktorer och hinder för åtgärdernas genomförandeidentifierats. Utvärderingen grundar sig på dokumentgranskning, enkät, telefonintervjuersamt vår samlade kompetens.Kvantitativa utvärderingar och uppföljningar av miljömålsuppfyllelse, miljönyttaoch kostnadseffektivitet ställer stora krav på underlag som beskriver förbrukade resurserför genomförandet och åtgärdens miljönytta. Eftersom biologiska system i mångafall behöver flera år för att återhämta sig är det ofta svårt att utvärdera miljönyttan korttid efter avslutad åtgärd. Kostnadseffektiviteten kunde inte bedömas för en tredjedelav åtgärderna på grund av brister i underlagen.I denna utvärdering karakteriseras de effektivaste åtgärderna av att de var konkreta,att länsstyrelsen hade beslutat att de skulle genomföras och att det fanns kompetensoch engagemang för att genomföra dem. Generellt är effektiviteten högre för åtgärdersom genomförts med hjälp av styrmedel somsamhällsplanering, lagar och ekonomi, än desom använtinformation som styrmedel.För utformning och utvärdering av framtida regionala miljömålsåtgärder drar vi följandeslutsatser:•Det är viktigt att länsstyrelsen/Skogsstyrelsen initierar och samordnar regionalt åtgärdsarbete.•En viktig uppgift för länsstyrelsen är att tillhandahålla adekvata kunskapsunderlag.•Underlag som redovisar hur miljön såg ut innan specifika åtgärder genomförs krävs.•Att formulera en tydlig målbild för varje åtgärd är viktigt.•Redan när åtgärder planeras ska möjligheten att kontinuerligt följa upp dem beaktas.•Länsprojekt som involverar kommunerna (t.ex. tillsyn, inventering) ger synergieffekteroch högre kostnadseffektivitet.•När åtgärder planeras bör ekonomiska förutsättningar diskuteras med berörda kommuner.•Det är en fördel om åtgärder som involverar kommuner är politiskt förankrade.•Länsstyrelsen bör underlätta för resurssvaga kommuner att delta i länsgemensammaåtgärder.•Åtgärder måste kopplas ihop med övrigt miljö- och naturvårdsarbete vid länsstyrelse/kommun.Bland de viktigaste framgångsfaktorer vi har identifierat finns:•Konstruktiv medverkan från många olika aktörer (ger kunskaps-/erfarenhetsutbyte).•Så kallade ”eldsjälar”, dvs. personer med stort engagemang och tydlig målbild.•Bra dialog mellan länsstyrelse och kommuner.•Länsövergripande administrativa verktyg och underlag för länets kommuner.•Höjd kunskapsnivå hos verksamhetsutövare och andra.•Nya forum och nätverk för samverkan.•Politiska prioriteringar och beslut.•Tillräckliga resurser avsätts för arbetet.•Förekomsten av ekonomiska styrmedel eller incitament.Bland de vanligaste hindren för effektiva åtgärder finns begränsande ekonomiska resurser,oklar ansvarsfördelning, bristande politisk förankring, brister i underlag frånlänsstyrelsen och stor personalomsättning.Denna studie bör ses som ett bidrag till arbetet med att utveckla metoder för utvärderingav miljömålsåtgärders effektivitet på regional nivå. Urvalet av åtgärder i dennautvärdering har varit mycket begränsat och vi föreslår en bredare och mer förutsättningslösutvärdering av regionala miljömålsåtgärder. Det vore också intressant attgranska hur länsstyrelser och kommuner arbetar med uppföljning och utvärdering avåtgärder. Vi rekommenderar även ytterligare studier för att kunna fastställa eventuellasamband mellan styrmedel och åtgärders effektivitet.Nyckelord:miljömål, åtgärder, utvärdering, miljönytta, måluppfyllelse, kostnadseffektivitet,framgångsfaktor, hinder, energi, klimat, giftfri miljö, ytvatten, biologisk mångfald,länsstyrelse
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| 22. |
- Shaw, DE, et al.
(författare)
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Clinical and inflammatory characteristics of the European U-BIOPRED adult severe asthma cohort
- 2015
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Ingår i: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 46:5, s. 1308-1321
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Tidskriftsartikel (refereegranskat)abstract
- U-BIOPRED is a European Union consortium of 20 academic institutions, 11 pharmaceutical companies and six patient organisations with the objective of improving the understanding of asthma disease mechanisms using a systems biology approach.This cross-sectional assessment of adults with severe asthma, mild/moderate asthma and healthy controls from 11 European countries consisted of analyses of patient-reported outcomes, lung function, blood and airway inflammatory measurements.Patients with severe asthma (nonsmokers, n=311; smokers/ex-smokers, n=110) had more symptoms and exacerbations compared to patients with mild/moderate disease (n=88) (2.5 exacerbations versus 0.4 in the preceding 12 months; p<0.001), with worse quality of life, and higher levels of anxiety and depression. They also had a higher incidence of nasal polyps and gastro-oesophageal reflux with lower lung function. Sputum eosinophil count was higher in severe asthma compared to mild/moderate asthma (median count 2.99% versus 1.05%; p=0.004) despite treatment with higher doses of inhaled and/or oral corticosteroids.Consistent with other severe asthma cohorts, U-BIOPRED is characterised by poor symptom control, increased comorbidity and airway inflammation, despite high levels of treatment. It is well suited to identify asthma phenotypes using the array of “omic” datasets that are at the core of this systems medicine approach.
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| 23. |
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| 27. |
- Andersson, Ken G, et al.
(författare)
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Comparative evaluation of 111In-labeled NOTA‑conjugated affibody molecules for visualization of HER3 expression in malignant tumors
- 2015
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Ingår i: Oncology Reports. - : Spandidos Publications. - 1021-335X .- 1791-2431. ; 34:2, s. 1042-8
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Tidskriftsartikel (refereegranskat)abstract
- Expression of human epidermal growth factor receptor type 3 (HER3) in malignant tumors has been associated with resistance to a variety of anticancer therapies. Several anti-HER3 monoclonal antibodies are currently under pre-clinical and clinical development aiming to overcome HER3-mediated resistance. Radionuclide molecular imaging of HER3 expression may improve treatment by allowing the selection of suitable patients for HER3-targeted therapy. Affibody molecules are a class of small (7kDa) high-affinity targeting proteins with appreciable potential as molecular imaging probes. In a recent study, we selected affibody molecules with affinity to HER3 at a low picomolar range. The aim of the present study was to develop an anti-HER3 affibody molecule suitable for labeling with radiometals. The HEHEHE-Z08698-NOTA and HEHEHE-Z08699-NOTA HER3-specific affibody molecules were labeled with indium‑111 (111In) and assessed invitro and invivo for imaging properties using single photon emission computed tomography (SPECT). Labeling of HEHEHE-Z08698-NOTA and HEHEHE-Z08699-NOTA with 111In provided stable conjugates. Invitro cell tests demonstrated specific binding of the two conjugates to HER3-expressing BT‑474 breast carcinoma cells. In mice bearing BT‑474 xenografts, the tumor uptake of the two conjugates was receptor‑specific. Direct invivo comparison of 111In-HEHEHE-Z08698-NOTA and 111In-HEHEHE-Z08699‑NOTA demonstrated that the two conjugates provided equal radioactivity uptake in tumors, although the tumor-to-blood ratio was improved for 111In-HEHEHE-Z08698-NOTA [12±3 vs. 8±1, 4h post injection (p.i.)] due to more efficient blood clearance. 111In-HEHEHE-Z08698-NOTA is a promising candidate for imaging of HER3-expression in malignant tumors using SPECT. Results of the present study indicate that this conjugate could be used for patient stratification for anti-HER3 therapy.
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| 28. |
- Andersson, Pontus, 1971, et al.
(författare)
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Radiative lifetimes of metastable states of negative ions
- 2006
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Ingår i: Physical Review A. Atomic, Molecular, and Optical Physics. - 1050-2947 .- 1094-1622 .- 2469-9926 .- 2469-9934. ; 73, s. 032705-
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Tidskriftsartikel (refereegranskat)abstract
- We present a technique for measuring the radiative lifetimes of metastable states of negative ions that involves the use of a heavy-ion storage ring. The method has been applied to investigate the radiative decay of the np(3) P-2(1/2) levels of Te-(n=5) and Se-(n=4) and the 3p(3) D-2 state of Si- for which the J=3/2 and 5/2 levels were unresolved. All of these states are metastable and decay primarily by emission of E2 and M1 radiation. Multi Configuration Dirac-Hartree-Fock calculations of rates for the transitions in Te- and Se- yielded lifetimes of 0.45 s and 4.7 s, respectively. The measured values agree well with these predicted values. In the case of the D-2 state of Si-, however, our measurement was only able to set a lower limit on the lifetime. The upper limit of the lifetime that can be measured with our apparatus is set by how long the ions can be stored in the ring, a limit determined by the rate of collisional detachment. Our lower limit of 1 min for the lifetime of the D-2 state is consistent with both the calculated lifetimes of 162 s for the D-2(3/2) level and 27.3 h for the D-2(5/2) level reported by O'Malley and Beck and 14.5 h and 12.5 h, respectively, from our Breit-Pauli calculations.
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| 29. |
- Aycik, G.A., et al.
(författare)
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Leaching of radioactive isotopes from ash
- 2003
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The aim of the study is to reduce the environmental impact of ash deposits. Ash from coal and biomass combustion, containing uranium and thorium from Yatagan-Silopi and Tuncbilek coal; cesium-137 from forests in northeastern Turkey and central Sweden. Turkey is dependent on coal for power generation and huge volumes of ash (>15 Mton/yr) are produced every year. Because of that certain coals, in particular Yatagan, with known problems from Mo and U leaching to the ground water, and Silopi oil shales/asphaltites were studied. Biomass ash comes from branches, bark and other unused parts of the trees and plants. This ash has low concentration of environmentally hazardous metals, but {sup 137}Cs is a problem in certain regions and it is of interest to investigate the possibilities to leach this metal from the ash. Washing ash through rapid chemical leaching at low pH reduces the slow release of metals from ash due to precipitation and besides it may lead to metal recovery from the ash. Initial experiments were done in batch form, in which the neutralizing capacity at pH 1-1.5 was measured by adding sulfuric acid to maintain pH for mixtures of ash and water. Subsequent experiments were done in bench scale. The process also reduced the metal content of the ash, due to chemical leaching of metal oxides and ion exchange at the surfaces of stable oxides. This means that treated ash will not release further metals and, eventually, relaxes the requirements on depositories and allows the ash from coal to be used as an admixture in cement, and to be used as a fertilizer following after treatment of ash from biomass
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| 30. |
- Bergvall, Niklas, et al.
(författare)
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Corefining of Fast Pyrolysis Bio-Oil with Vacuum Residue and Vacuum Gas Oil in a Continuous Slurry Hydrocracking Process
- 2020
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Ingår i: Energy & Fuels. - : American Chemical Society. - 0887-0624 .- 1520-5029. ; 34:7, s. 8452-8465
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Tidskriftsartikel (refereegranskat)abstract
- Integration of renewable raw materials in existing refineries is most likely the shortest way for the successful, large-scale introduction of biofuels in the transport sector in the short term and medium term. One possible renewable raw material for this application is fast pyrolysis bio-oil (FPBO), which in this study has been coprocessed (at 0 and 20 wt %) with vacuum residue (VR, 50 wt %) and vacuum gas oil (VGO, balance) in a continuous, as well as a semibatch, slurry hydrocracking process. Experiments both with and without FPBO were performed at 450°C and 150 bar with a continuous hydrogen flow through the reactor. Oil-soluble molybdenum hexacarbonyl and molybdenum 2-ethylhexanoate were used as catalyst precursors, to be sulfided in situ. The continuous trials resulted in reactor walls completely free of coking, and they resulted in a low overall coke yield (about 1 wt %). The hydrodeoxygenation reached almost 92%, and the total acid number was reduced by nearly 99% in the FPBO experiment A mass balance of the renewable carbon from FPBO, based on the performed experiments, showed that the fossil CO2 emissions can be lowered by 1.35 kg per kg of processed FPBO if all renewable carbon in gaseous and liquid hydrocarbons is used to replace its fossil counterparts, and all methane formed from FPBO is used to produce hydrogen. Semibatch experiments gave less successful results when upgrading FPBO-containing feedstock, with a high coke yield (8 wt %) as well as a high gas yield (24 wt %). The results of this study demonstrate that FPBO can be successfully coprocessed with heavy fossil oils in a continuous slurry hydrocracking process without neg. affecting the processing of the fossil components of the feed and that a continuous process is preferred over batch or semibatch processes when studying coprocessing of bio-oils.
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| 31. |
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| 32. |
- Bohnenkamp, U., et al.
(författare)
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Electrical resistivity of steels and face-centered-cubic iron
- 2002
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Ingår i: Journal of Applied Physics. - : AIP Publishing. - 0021-8979 .- 1089-7550. ; 92:8, s. 4402-4407
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Tidskriftsartikel (refereegranskat)abstract
- Literature data for the electrical resistivity of austenitic and ferritic steels are analyzed in a model that takes into account their composition and microstructure. The resistivity in these systems is so high that one must allow for its saturation. That effect is described with the shunt-resistor model, and saturation at 1.68 muOmegam. Our analysis yields the contributions to the resistivity of austenite per weight percent from the solute elements N, C, Nb, Si, Ti, Cu, Ni, Cr, and Mo, with the contribution decreasing in this order. For ferrite, the contribution of the solute elements Si, Mn, Cu, Ni, Mo, and Cr was determined, with the contribution decreasing in this order. The data allow us to obtain the previously unknown resistivity of metastable pure gamma-iron (fcc Fe) near room temperature, and find an interpolation formula for the resistivity up to 1183 K where the gamma phase becomes stable. The resistivity in metastable gamma-iron is significantly larger than the resistivity in stable alpha-Fe (bcc Fe) below 1000 K. This difference is attributed to a strong electron scattering due to spin disorder in gamma-iron at intermediate temperatures.
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| 33. |
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| 34. |
- Cadete, Raquel M., et al.
(författare)
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Exploring xylose metabolism in Spathaspora species : XYL1.2 from Spathaspora passalidarum as the key for efficient anaerobic xylose fermentation in metabolic engineered Saccharomyces cerevisiae
- 2016
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Ingår i: Biotechnology for Biofuels. - : Springer Science and Business Media LLC. - 1754-6834. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The production of ethanol and other fuels and chemicals from lignocellulosic materials is dependent of efficient xylose conversion. Xylose fermentation capacity in yeasts is usually linked to xylose reductase (XR) accepting NADH as cofactor. The XR from Scheffersomyces stipitis, which is able to use NADH as cofactor but still prefers NADPH, has been used to generate recombinant xylose-fermenting Saccharomyces cerevisiae. Novel xylose-fermenting yeasts species, as those from the Spathaspora clade, have been described and are potential sources of novel genes to improve xylose fermentation in S. cerevisiae. Results: Xylose fermentation by six strains from different Spathaspora species isolated in Brazil, plus the Sp. passalidarum type strain (CBS 10155T), was characterized under two oxygen-limited conditions. The best xylose-fermenting strains belong to the Sp. passalidarum species, and their highest ethanol titers, yields, and productivities were correlated to higher XR activity with NADH than with NADPH. Among the different Spathaspora species, Sp. passalidarum appears to be the sole harboring two XYL1 genes: XYL1.1, similar to the XYL1 found in other Spathaspora and yeast species and XYL1.2, with relatively higher expression level. XYL1.1p and XYL1.2p from Sp. passalidarum were expressed in S. cerevisiae TMB 3044 and XYL1.1p was confirmed to be strictly NADPH-dependent, while XYL1.2p to use both NADPH and NADH, with higher activity with the later. Recombinant S. cerevisiae strains expressing XYL1.1p did not show anaerobic growth in xylose medium. Under anaerobic xylose fermentation, S. cerevisiae TMB 3504, which expresses XYL1.2p from Sp. passalidarum, revealed significant higher ethanol yield and productivity than S. cerevisiae TMB 3422, which harbors XYL1p N272D from Sc. stipitis in the same isogenic background (0.40 vs 0.34 g g CDW -1 and 0.33 vs 0.18 g g CDW -1 h-1, respectively). Conclusion: This work explored a new clade of xylose-fermenting yeasts (Spathaspora species) towards the engineering of S. cerevisiae for improved xylose fermentation. The new S. cerevisiae TMB 3504 displays higher XR activity with NADH than with NADPH, with consequent improved ethanol yield and productivity and low xylitol production. This meaningful advance in anaerobic xylose fermentation by recombinant S. cerevisiae (using the XR/XDH pathway) paves the way for the development of novel industrial pentose-fermenting strains.
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| 35. |
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| 36. |
- Damian, Emiliana, et al.
(författare)
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Theoretical and experimental sulfur K-edge X-ray absorption spectroscopic (XANES) study of cysteine, cystine, methionine and methionine sulfoxide
- 2009
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Ingår i: Dalton Transactions. - 1477-9226 .- 1477-9234. ; 18, s. 3542-3558
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Tidskriftsartikel (refereegranskat)abstract
- The experimental sulfur K-edge x-ray absorption near edge structure (XANES) spectra of the amino acids cysteine, homocysteine, penicillamine, methionine, the oxidation products methionine sulfoxide and the disulfide cystine, have been analyzed by transition potential DFT calculations. The absolute energies and intensities of the main pre-edge sulfur 1s electron transitions have been computed to determine the character of the receiving low energy unoccupied molecular orbitals (MO), and to investigate the influence of external interactions, especially by introducing water molecules hydrogen bonded to the ionic species present in different pH ranges. When the thiol group deprotonates for the three amino acids cysteine, homocysteine and penicillamine the energy of the main transition, to an MO with antibonding σ*(S-H) character, reduces by ~1.1 eV and the receiving MO obtains σ*(S-C) character. The energy shifts due to hydrogen bonding were in most cases found to be relatively small, although the transition intensities could vary significantly due to the changes induced in the molecular charge distribution, thereby affecting the shapes of the spectral features. For the cysteine and penicillamine zwitterions deconvolution of the experimental spectra allowed the microscopic acid dissociation constants to be extracted separately for the thiol and the protonated amine groups, pKaT = 8.5 ± 0.1 and 8.2 ± 0.1, and pKaN = 8.9 ± 0.1 and 8.8 ± 0.1, respectively, in both cases with the thiol group the more acidic. Coordination of cysteine to nickel(II) or mercury(II) introduced a new low energy transition involving metal ion orbitals in the receiving LUMO. The small experimentally observed energy differences between the similar main absorption features of the cysteine and methionine zwitterions, 0.2-0.3 eV in comparable surrounding, as well as a minor difference in their intensity ratio, are reflected in the calculated transitions. The S K-edge XANES spectrum of the disulfide cystine displays a characteristic double peak with the lower energy transition (2469.9 eV) into the antibonding σ*(S-S) MO. The second peak, at 2471.5 eV in aqueous solution, contains several transitions into MO:s with σ*(S-C) character involving also charge transfer to the water molecules hydrating the protonated amine groups (NH3+) of cystine. The experimental energy difference between the two peaks increases by 0.2 eV for solid cystine, while no such increase occurs for the –S-S- bond between the cysteine residues in the oxidized disulfide of glutathione, where the amine groups are engaged in peptide bonds. This study shows that externally induced changes in the intramolecular bonding, e.g. by coordination, conformation geometry or hydrogen bonding, can significantly influence the S K-edge spectra, and emphasizes the importance of a similar chemical surrounding of the model compounds for standard spectra of sulfur functional groups, used to deconvolute composite experimental spectra.
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| 37. |
- Davis, V. T., et al.
(författare)
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Photo-double detachment from the F- ion
- 2005
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Ingår i: Journal of Physics B-Atomic Molecular and Optical Physics. - : IOP Publishing. - 0953-4075 .- 1361-6455. ; 38:14, s. 2579-2589
-
Tidskriftsartikel (refereegranskat)
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| 38. |
- de las Heras, Alejandro Muñoz, et al.
(författare)
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Anaerobic poly-3-d-hydroxybutyrate production from xylose in recombinant Saccharomyces cerevisiae using a NADH-dependent acetoacetyl-CoA reductase
- 2016
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Ingår i: Microbial Cell Factories. - : Springer Science and Business Media LLC. - 1475-2859. ; 15:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Poly-3-d-hydroxybutyrate (PHB) that is a promising precursor for bioplastic with similar physical properties as polypropylene, is naturally produced by several bacterial species. The bacterial pathway is comprised of the three enzymes β-ketothiolase, acetoacetyl-CoA reductase (AAR) and PHB synthase, which all together convert acetyl-CoA into PHB. Heterologous expression of the pathway genes from Cupriavidus necator has enabled PHB production in the yeast Saccharomyces cerevisiae from glucose as well as from xylose, after introduction of the fungal xylose utilization pathway from Scheffersomyces stipitis including xylose reductase (XR) and xylitol dehydrogenase (XDH). However PHB titers are still low. Results: In this study the acetoacetyl-CoA reductase gene from C. necator (CnAAR), a NADPH-dependent enzyme, was replaced by the NADH-dependent AAR gene from Allochromatium vinosum (AvAAR) in recombinant xylose-utilizing S. cerevisiae and PHB production was compared. A. vinosum AAR was found to be active in S. cerevisiae and able to use both NADH and NADPH as cofactors. This resulted in improved PHB titers in S. cerevisiae when xylose was used as sole carbon source (5-fold in aerobic conditions and 8.4-fold under oxygen limited conditions) and PHB yields (4-fold in aerobic conditions and up to 5.6-fold under oxygen limited conditions). Moreover, the best strain was able to accumulate up to 14% of PHB per cell dry weight under fully anaerobic conditions. Conclusions: This study reports a novel approach for boosting PHB accumulation in S. cerevisiae by replacement of the commonly used AAR from C. necator with the NADH-dependent alternative from A. vinosum. Additionally, to the best of our knowledge, it is the first demonstration of anaerobic PHB synthesis from xylose.
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| 39. |
- Eklund, Linda M., et al.
(författare)
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Cold air exposure at -15 °C induces more airway symptoms and epithelial stress during heavy exercise than rest without aggravated airway constriction
- 2022
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Ingår i: European Journal of Applied Physiology. - : Springer. - 1439-6319 .- 1439-6327. ; 122:12, s. 2533-2544
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Exposure to cold air may harm the airways. It is unclear to what extent heavy exercise adds to the cold-induced effects on peripheral airways, airway epithelium, and systemic immunity among healthy individuals. We investigated acute effects of heavy exercise in sub-zero temperatures on the healthy airways.Methods: Twenty-nine healthy individuals underwent whole body exposures to cold air in an environmental chamber at − 15 °C for 50 min on two occasions; a 35-min exercise protocol consisting of a 5-min warm-up followed by 2 × 15 min of running at 85% of VO2max vs. 50 min at rest. Lung function was measured by impulse oscillometry (IOS) and spirometry before and immediately after exposures. CC16 in plasma and urine, and cytokines in plasma were measured before and 60 min after exposures. Symptoms were surveyed pre-, during and post-trials.Results: FEV1 decreased after rest (− 0.10 ± 0.03 L, p < 0.001) and after exercise (− 0.06 ± 0.02 L, p = 0.012), with no difference between trials. Exercise in − 15 °C induced greater increases in lung reactance (X5; p = 0.023), plasma CC16 (p < 0.001) as well as plasma IL-8 (p < 0.001), compared to rest. Exercise induced more intense symptoms from the lower airways, whereas rest gave rise to more general symptoms.Conclusion: Heavy exercise during cold air exposure at − 15 °C induced signs of an airway constriction to a similar extent as rest in the same environment. However, biochemical signs of airway epithelial stress, cytokine responses, and symptoms from the lower airways were more pronounced after the exercise trial.
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| 40. |
- Elander, Ingemar, et al.
(författare)
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Biodiversity in urban governance and planning : Examples from Swedish cities
- 2005
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Ingår i: Planning Theory & Practice. - : Routledge. - 1464-9357 .- 1470-000X. ; 6:3, s. 283-301
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Tidskriftsartikel (refereegranskat)abstract
- One of the key agreements adopted at the Rio Conference in 1992 was the Convention on Biological Diversity (CBD). Both in practice and research biodiversity has been mainly addressed in a non-urban context, often discussed in relation to issues such as the depletion of rainforests and desertification. However, as more than half of the world population are urban dwellers, it is increasingly urgent to discuss the application of the concept of biodiversity within an urban context. Issues approached in this article are: What does it mean to talk about biodiversity in an urban context? Is biodiversity a meaningful goal for urban politics and planning? Is there empirical evidence of implementing biodiversity in urban politics and planning. After an introduction, the article is organized into four sections. In the second section the concept of biological diversity is defined with special reference to its application in an urban context. Biodiversity and its relationship to urban governance is the topic of the third section, followed by a section analysing examples of how this relationship is practised in selected Swedish cities. The final section highlights five major conclusions with regard to the application of biodiversity in an urban context: (1) that all cities studied have adopted overall 'green' policies, including biodiversity as one component; (2) that local coalitions in favour of implementing biodiversity have been established between employees at different offices, between employees and politicians, and between employees and NGOs; (3) that there are in all cases tangible signs of spatial patterns and structures that are favourable to biodiversity; (4) that urban biodiversity, for its successful implementation, needs to be related, and accommodated to other values given priority in current policymaking, such as recreation; (5) that mainstream biodiversity analysis should be complemented by an urban landscape approach. Finally, the article returns to the more general question of what biodiversity could and should mean in urban planning.
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| 41. |
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| 42. |
- Engstrand, J., et al.
(författare)
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Liver resection and ablation for squamous cell carcinoma liver metastases
- 2021
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Ingår i: BJS Open. - Oxford, United Kingdom : Oxford University Press. - 2474-9842. ; 5:4
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Limited evidence exists to guide the management of patients with liver metastases from squamous cell carcinoma (SCC). The aim of this retrospective multicentre cohort study was to describe patterns of disease recurrence after liver resection/ablation for SCC liver metastases and factors associated with recurrence-free survival (RFS) and overall survival (OS).METHOD: Members of the European-African Hepato-Pancreato-Biliary Association were invited to include all consecutive patients undergoing liver resection/ablation for SCC liver metastases between 2002 and 2019. Patient, tumour and perioperative characteristics were analysed with regard to RFS and OS.RESULTS: Among the 102 patients included from 24 European centres, 56 patients had anal cancer, and 46 patients had SCC from other origin. RFS in patients with anal cancer and non-anal cancer was 16 and 9 months, respectively (P = 0.134). A positive resection margin significantly influenced RFS for both anal cancer and non-anal cancer liver metastases (hazard ratio 6.82, 95 per cent c.i. 2.40 to 19.35, for the entire cohort). Median survival duration and 5-year OS rate among patients with anal cancer and non-anal cancer were 50 months and 45 per cent and 21 months and 25 per cent, respectively. For the entire cohort, only non-radical resection was associated with worse overall survival (hazard ratio 3.21, 95 per cent c.i. 1.24 to 8.30).CONCLUSION: Liver resection/ablation of liver metastases from SCC can result in long-term survival. Survival was superior in treated patients with liver metastases from anal versus non-anal cancer. A negative resection margin is paramount for acceptable outcome.
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| 43. |
- Engström, Gunnar, et al.
(författare)
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The Swedish CArdioPulmonary BioImage Study : objectives and design
- 2015
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 278:6, s. 645-659
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Tidskriftsartikel (refereegranskat)abstract
- Cardiopulmonary diseases are major causes of death worldwide, but currently recommended strategies for diagnosis and prevention may be outdated because of recent changes in risk factor patterns. The Swedish CArdioPulmonarybioImage Study (SCAPIS) combines the use of new imaging technologies, advances in large-scale 'omics' and epidemiological analyses to extensively characterize a Swedish cohort of 30 000 men and women aged between 50 and 64 years. The information obtained will be used to improve risk prediction of cardiopulmonary diseases and optimize the ability to study disease mechanisms. A comprehensive pilot study in 1111 individuals, which was completed in 2012, demonstrated the feasibility and financial and ethical consequences of SCAPIS. Recruitment to the national, multicentre study has recently started.
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| 44. |
- Engström, Karin, et al.
(författare)
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Directed evolution of an enantioselective lipase with broad substrate scope for hydrolysis of α-substituted esters
- 2010
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 132:20, s. 7038-7042
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Tidskriftsartikel (refereegranskat)abstract
- A variant of Candida antarctica lipase A (CalA) was developed for the hydrolysis of α-substituted p-nitrophenyl esters by directed evolution. The E values of this variant for 7 different esters was 45−276, which is a large improvement compared to 2−20 for the wild type. The broad substrate scope of this enzyme variant is of synthetic use, and hydrolysis of the tested substrates proceeded with an enantiomeric excess between 95−99%. A 30-fold increase in activity was also observed for most substrates. The developed enzyme variant shows (R)-selectivity, which is reversed compared to the wild type that is (S)-selective for most substrates.
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| 45. |
- Engström, Karin, et al.
(författare)
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Enantioselective Kinetic Resolution of p-Nitrophenyl 2-Phenylpropanoate by a Variant of Candida antarctica Lipase A Developed by Directed Evolution
- 2010
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society. - 0002-7863 .- 1520-5126. ; 132:20, s. 7038-7042
-
Tidskriftsartikel (refereegranskat)abstract
- A variant of Candida antarctica lipase A (CalA) was developed for the hydrolysis of α-substituted p-nitrophenyl esters by directed evolution. The E values of this variant for 7 different esters was 45−276, which is a large improvement compared to 2−20 for the wild type. The broad substrate scope of this enzyme variant is of synthetic use, and hydrolysis of the tested substrates proceeded with an enantiomeric excess between 95−99%. A 30-fold increase in activity was also observed for most substrates. The developed enzyme variant shows (R)-selectivity, which is reversed compared to the wild type that is (S)-selective for most substrates.
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| 46. |
- Ericsson, Daniel J., et al.
(författare)
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X-Ray structure of Candida antarctica lipase A shows a novel lid structure and a likely mode of interfacial activation
- 2008
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Ingår i: Journal of Molecular Biology. - : Elsevier. - 0022-2836 .- 1089-8638. ; 376:1, s. 109-119
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Tidskriftsartikel (refereegranskat)abstract
- In nature, lipases (EC 3.1.1.3) catalyze the hydrolysis of triglycerides to form glycerol and fatty acids. Under the appropriate conditions, the reaction is reversible, and so biotechnological applications commonly make use of their capacity for esterification as well as for hydrolysis of a wide variety of compounds. In the present paper, we report the X-ray structure of lipase A from Candida antarctica, solved by single isomorphous replacement with anomalous scattering, and refined to 2.2-Å resolution. The structure is the first from a novel family of lipases. Contrary to previous predictions, the fold includes a well-defined lid as well as a classic α/β hydrolase domain. The catalytic triad is identified as Ser184, Asp334 and His366, which follow the sequential order considered to be characteristic of lipases; the serine lies within a typical nucleophilic elbow. Computer docking studies, as well as comparisons to related structures, place the carboxylate group of a fatty acid product near the serine nucleophile, with the long lipid tail closely following the path through the lid that is marked by a fortuitously bound molecule of polyethylene glycol. For an ester substrate to bind in an equivalent fashion, loop movements near Phe431 will be required, suggesting the primary focus of the conformational changes required for interfacial activation. Such movements will provide virtually unlimited access to solvent for the alcohol moiety of an ester substrate. The structure thus provides a basis for understanding the enzyme's preference for acyl moieties with long, straight tails, and for its highly promiscuous acceptance of widely different alcohol and amine moieties. An unconventional oxyanion hole is observed in the present structure, although the situation may change during interfacial activation
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| 47. |
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| 48. |
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| 49. |
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