| 1. |
- Abdo, A. A., et al.
(author)
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FERMI/LARGE AREA TELESCOPE DISCOVERY OF GAMMA-RAY EMISSION FROM THE FLAT-SPECTRUM RADIO QUASAR PKS 1454-354
- 2009
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In: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 697:1, s. 934-941
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Journal article (peer-reviewed)abstract
- We report the discovery by the Large Area Telescope (LAT) onboard the Fermi Gamma-Ray Space Telescope of high-energy gamma-ray (GeV) emission from the flat-spectrum radio quasar PKS 1454-354 (z = 1.424). On 2008 September 4, the source rose to a peak flux of (3.5 +/- 0.7) x 10(-6) ph cm(-2) s(-1) (E > 100 MeV) on a timescale of hours and then slowly dropped over the following 2 days. No significant spectral changes occurred during the flare. Fermi/LAT observations also showed that PKS 1454-354 is the most probable counterpart of the unidentified EGRET source 3EG J1500-3509. Multiwavelength measurements performed during the following days (7 September with Swift; 6-7 September with the ground-based optical telescope Automated Telescope for Optical Monitoring; 13 September with the Australia Telescope Compact Array) resulted in radio, optical, UV, and X-ray fluxes greater than archival data, confirming the activity of PKS 1454-354.
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| 2. |
- Abdo, A. A., et al.
(author)
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SUZAKU OBSERVATIONS OF LUMINOUS QUASARS : REVEALING THE NATURE OF HIGH-ENERGY BLAZAR EMISSION IN LOW-LEVEL ACTIVITY STATES
- 2010
-
In: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 716:1, s. 835-849
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Journal article (peer-reviewed)abstract
- We present the results from the Suzaku X-ray observations of five flat-spectrum radio quasars (FSRQs), namely PKS 0208-512, Q 0827+243, PKS 1127-145, PKS 1510-089, and 3C 454.3. All these sources were additionally monitored simultaneously or quasi-simultaneously by the Fermi satellite in gamma rays and the Swift UVOT in the UV and optical bands, respectively. We constructed their broadband spectra covering the frequency range from 10(14) Hz up to 10(25) Hz, and those reveal the nature of high-energy emission of luminous blazars in their low-activity states. The analyzed X-ray spectra are well fitted by a power-law model with photoelectric absorption. In the case of PKS 0208-512, PKS 1127-145, and 3C 454.3, the X-ray continuum showed indication of hardening at low energies. Moreover, when compared with the previous X-ray observations, we see a significantly increasing contribution of low-energy photons to the total X-ray fluxes when the sources are getting fainter. The same behavior can be noted in the Suzaku data alone. A likely explanation involves a variable, flat-spectrum component produced via inverse-Compton emission, plus an additional, possibly steady soft X-ray component prominent when the source gets fainter. This soft X-ray excess is represented either by a steep power-law (photon indices Gamma similar to 3-5) or a blackbody-type emission with temperatures kT similar to 0.1-0.2 keV. We model the broadband spectra of the five observed FSRQs using synchrotron self-Compton and/or external-Compton radiation models. Our modeling suggests that the difference between the low-and high-activity states in luminous blazars is due to the different total kinetic power of the jet, most likely related to varying bulk Lorentz factor of the outflow within the blazar emission zone.
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| 3. |
- Bottai, Matteo, et al.
(author)
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EULAR/ACR classification criteria for adult and juvenile idiopathic inflammatory myopathies and their major subgroups : a methodology report
- 2017
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In: RMD Open. - : BMJ. - 2056-5933. ; 3:2
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Journal article (peer-reviewed)abstract
- Objective To describe the methodology used to develop new classification criteria for adult and juvenile idiopathic inflammatory myopathies (IIMs) and their major subgroups.Methods An international, multidisciplinary group of myositis experts produced a set of 93 potentially relevant variables to be tested for inclusion in the criteria. Rheumatology, dermatology, neurology and paediatric clinics worldwide collected data on 976 IIM cases (74% adults, 26% children) and 624 non-IIM comparator cases with mimicking conditions (82% adults, 18% children). The participating clinicians classified each case as IIM or non-IIM. Generally, the classification of any given patient was based on few variables, leaving remaining variables unmeasured. We investigated the strength of the association between all variables and between these and the disease status as determined by the physician. We considered three approaches: (1) a probability-score approach, (2) a sum-of-items approach criteria and (3) a classification-tree approach.Results The approaches yielded several candidate models that were scrutinised with respect to statistical performance and clinical relevance. The probability-score approach showed superior statistical performance and clinical practicability and was therefore preferred over the others. We developed a classification tree for subclassification of patients with IIM. A calculator for electronic devices, such as computers and smartphones, facilitates the use of the European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria.Conclusions The new EULAR/ACR classification criteria provide a patient's probability of having IIM for use in clinical and research settings. The probability is based on a score obtained by summing the weights associated with a set of criteria items.
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| 4. |
- Chester, Mikhail V., et al.
(author)
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Sensemaking for entangled urban social, ecological, and technological systems in the Anthropocene
- 2023
-
In: npj Urban Sustainability. - 2661-8001. ; 3:1
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Journal article (peer-reviewed)abstract
- Our urban systems and their underlying sub-systems are designed to deliver only a narrow set of human-centered services, with little or no accounting or understanding of how actions undercut the resilience of social-ecological-technological systems (SETS). Embracing a SETS resilience perspective creates opportunities for novel approaches to adaptation and transformation in complex environments. We: i) frame urban systems through a perspective shift from control to entanglement, ii) position SETS thinking as novel sensemaking to create repertoires of responses commensurate with environmental complexity (i.e., requisite complexity), and iii) describe modes of SETS sensemaking for urban system structures and functions as basic tenets to build requisite complexity. SETS sensemaking is an undertaking to reflexively bring sustained adaptation, anticipatory futures, loose-fit design, and co-governance into organizational decision-making and to help reimagine institutional structures and processes as entangled SETS.
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| 5. |
- Das, Indra J., et al.
(author)
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Report of AAPM Task Group 155 : Megavoltage photon beam dosimetry in small fields and non-equilibrium conditions
- 2021
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In: Medical physics (Lancaster). - : John Wiley & Sons. - 0094-2405 .- 2473-4209. ; 48:10, s. E886-E921
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Journal article (peer-reviewed)abstract
- Small-field dosimetry used in advance treatment technologies poses challenges due to loss of lateral charged particle equilibrium (LCPE), occlusion of the primary photon source, and the limited choice of suitable radiation detectors. These challenges greatly influence dosimetric accuracy. Many high-profile radiation incidents have demonstrated a poor understanding of appropriate methodology for small-field dosimetry. These incidents are a cause for concern because the use of small fields in various specialized radiation treatment techniques continues to grow rapidly. Reference and relative dosimetry in small and composite fields are the subject of the International Atomic Energy Agency (IAEA) dosimetry code of practice that has been published as TRS-483 and an AAPM summary publication (IAEA TRS 483; Dosimetry of small static fields used in external beam radiotherapy: An IAEA/AAPM International Code of Practice for reference and relative dose determination, Technical Report Series No. 483; Pal-mans et al., Med Phys 45(11):e1123, 2018). The charge of AAPM task group 155 (TG-155) is to summarize current knowledge on small-field dosimetry and to provide recommendations of best practices for relative dose determination in small megavoltage photon beams. An overview of the issue of LCPE and the changes in photon beam perturbations with decreasing field size is provided. Recommendations are included on appropriate detector systems and measurement methodologies. Existing published data on dosimetric parameters in small photon fields (e.g., percentage depth dose, tissue phantom ratio/tissue maximum ratio, off-axis ratios, and field output factors) together with the necessary perturbation corrections for various detectors are reviewed. A discussion on errors and an uncertainty analysis in measurements is provided. The design of beam models in treatment planning systems to simulate small fields necessitates special attention on the influence of the primary beam source and collimating devices in the computation of energy fluence and dose. The general requirements for fluence and dose calculation engines suitable for modeling dose in small fields are reviewed. Implementations in commercial treatment planning systems vary widely, and the aims of this report are to provide insight for the medical physicist and guidance to developers of beams models for radiotherapy treatment planning systems.
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| 6. |
- Adelani, David Ifeoluwa, et al.
(author)
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MasakhaNER 2.0: Africa-centric Transfer Learning for Named Entity Recognition
- 2022
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In: Proceedings of the 2022 Conference on Empirical Methods in Natural Language Processing. - : Association for Computational Linguistics (ACL). ; , s. 4488-4508
-
Conference paper (peer-reviewed)abstract
- African languages are spoken by over a billion people, but are underrepresented in NLP research and development. The challenges impeding progress include the limited availability of annotated datasets, as well as a lack of understanding of the settings where current methods are effective. In this paper, we make progress towards solutions for these challenges, focusing on the task of named entity recognition (NER). We create the largest human-annotated NER dataset for 20 African languages, and we study the behavior of state-of-the-art cross-lingual transfer methods in an Africa-centric setting, demonstrating that the choice of source language significantly affects performance. We show that choosing the best transfer language improves zero-shot F1 scores by an average of 14 points across 20 languages compared to using English. Our results highlight the need for benchmark datasets and models that cover typologically-diverse African languages.
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| 7. |
- Chester, Lucy A., et al.
(author)
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Effects of Cannabidiol and Delta-9-Tetrahydrocannabinol on Plasma Endocannabinoid Levels in Healthy Volunteers : A Randomized Double-Blind Four-Arm Crossover Study
- 2024
-
In: Cannabis and cannabinoid research. - : Mary Ann Liebert. - 2378-8763 .- 2378-8763 .- 2578-5125. ; 9:1, s. 188-198
-
Journal article (peer-reviewed)abstract
- Background: The effects of cannabis are thought to be mediated by interactions between its constituents and the endocannabinoid system. Delta-9-tetrahydrocannabinol (THC) binds to central cannabinoid receptors, while cannabidiol (CBD) may influence endocannabinoid function without directly acting on cannabinoid receptors. We examined the effects of THC coadministered with different doses of CBD on plasma levels of endocannabinoids in healthy volunteers.Methods: In a randomized, double-blind, four-arm crossover study, healthy volunteers (n=46) inhaled cannabis vapor containing 10 mg THC plus either 0, 10, 20, or 30 mg CBD, in four experimental sessions. The median time between sessions was 14 days (IQR=20). Blood samples were taken precannabis inhalation and at 0-, 5-, 15-, and 90-min postinhalation. Plasma concentrations of THC, CBD, anandamide, 2-arachidonoylglycerol (2-AG), and related noncannabinoid lipids were measured using liquid chromatography-mass spectrometry.Results: Administration of cannabis induced acute increases in plasma concentrations of anandamide (+18.0%, 0.042 ng/mL [95%CI: 0.023-0.062]), and the noncannabinoid ethanolamides, docosatetraenylethanolamide (DEA; +35.8%, 0.012 ng/mL [95%CI: 0.008-0.016]), oleoylethanolamide (+16.1%, 0.184 ng/mL [95%CI: 0.076-0.293]), and N-arachidonoyl-L-serine (+25.1%, 0.011 ng/mL [95%CI: 0.004-0.017]) (p<0.05). CBD had no significant effect on the plasma concentration of anandamide, 2-AG or related noncannabinoid lipids at any of three doses used. Over the four sessions, there were progressive decreases in the preinhalation concentrations of anandamide and DEA, from 0.254 ng/mL [95%CI: 0.223-0.286] to 0.194 ng/mL [95%CI: 0.163-0.226], and from 0.039 ng/mL [95%CI: 0.032-0.045] to 0.027 ng/mL [95%CI: 0.020-0.034] (p<0.05), respectively.Discussion: THC induced acute increases in plasma levels of anandamide and noncannabinoid ethanolamides, but there was no evidence that these effects were influenced by the coadministration of CBD. It is possible that such effects may be evident with higher doses of CBD or after chronic administration. The progressive reduction in pretreatment anandamide and DEA levels across sessions may be related to repeated exposure to THC or participants becoming less anxious about the testing procedure and requires further investigation. The study was registered on clinicaltrials.gov (NCT05170217).
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| 8. |
- Darwich, Adam S., et al.
(author)
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IMI - Oral biopharmaceutics tools project - Evaluation of bottom-up PBPK prediction success part 3 : Identifying gaps in system parameters by analysing In Silico performance across different compound classes
- 2017
-
In: European Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0928-0987 .- 1879-0720. ; 96, s. 626-642
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Journal article (peer-reviewed)abstract
- Three Physiologically Based Pharmacokinetic software packages (GI-Sim, Simcyp (R) Simulator, and GastroPlus (TM)) were evaluated as part of the Innovative Medicine Initiative Oral Biopharmaceutics Tools project (OrBiTo) during a blinded "bottom-up" anticipation of human pharmacokinetics. After data analysis of the predicted vs. measured pharmacokinetics parameters, it was found that oral bioavailability (F-oral) was underpredicted for compounds with low permeability, suggesting improper estimates of intestinal surface area, colonic absorption and/or lack of intestinal transporter information. Foralwas also underpredicted for acidic compounds, suggesting overestimation of impact of ionisation on permeation, lack of information on intestinal transporters, or underestimation of solubilisation of weak acids due to less than optimal intestinal model pH settings or underestimation of bile micelle contribution. F-oral was overpredicted for weak bases, suggesting inadequate models for precipitation or lack of in vitro precipitation information to build informed models. Relative bioavailability was underpredicted for both high logP compounds as well as poorly water-soluble compounds, suggesting inadequate models for solubility/dissolution, underperforming bile enhancement models and/or lack of biorelevant solubility measurements. These results indicate areas for improvement in model software, modelling approaches, and generation of applicable input data. However, caution is required when interpreting the impact of drug-specific properties in this exercise, as the availability of input parameters was heterogeneous and highly variable, and the modellers generally used the data "as is" in this blinded bottom-up prediction approach.
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| 9. |
- Mannheimer, C, et al.
(author)
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The problem of chronic refractory angina
- 2002
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In: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 23:5, s. 355-370
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Journal article (peer-reviewed)abstract
- It has been recognized that there is a group of patients with severe disabling angina and coronary artery disease who are refractory to conventional forms of treatment. Although this issue has already been debated at the level of the National Societies, we felt that it was appropriate to also tackle it at the European level. This is particularly important in view of the rapid pace of growth of this problem and the lack of a standardized approach. This has encouraged the development of a variety of treatments that vary considerably in terms of cost-effectiveness and safety and require proper validation procedures. The aim of this paper is to draw attention to the problem and start a process that will lead to improvement and harmonization of the care of patients with refractory angina.
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| 10. |
- Margolskee, Alison, et al.
(author)
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IMI - Oral biopharmaceutics tools project - Evaluation of bottom-up PBPK prediction success part 2 : An introduction to the simulation exercise and overview of results
- 2017
-
In: European Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0928-0987 .- 1879-0720. ; 96, s. 610-625
-
Journal article (peer-reviewed)abstract
- Orally administered drugs are subject to a number of barriers impacting bioavailability (F-oral), causing challenges during drug and formulation development. Physiologically-based pharmacokinetic (PBPK) modelling can help during drug and formulation development by providing quantitative predictions through a systems approach. The performance of three available PBPK software packages (GI-Sim, Simcyp (R), and GastroPlus (TM)) were evaluated by comparing simulated and observed pharmacokinetic (PK) parameters. Since the availability of input parameters was heterogeneous and highly variable, caution is required when interpreting the results of this exercise. Additionally, this prospective simulation exercise may not be representative of prospective modelling in industry, as API information was limited to sparse details. 43 active pharmaceutical ingredients (APIs) from the OrBiTo database were selected for the exercise. Over 4000 simulation output files were generated, representing over 2550 study arm-institution-software combinations and approximately 600 human clinical study arms simulated with overlap. 84% of the simulated study arms represented administration of immediate release formulations, 11% prolonged or delayed release, and 5% intravenous (i.v.). Higher percentages of i.v. predicted area under the curve (AUC) were within two-fold of observed (52.9%) compared to per oral (p.o.) (37.2%), however, F-oral and relative AUC (F-rel) between p.o. formulations and solutions were generally well predicted (64.7% and 75.0%). Predictive performance declined progressing from i.v. to solution and immediate release tablet, indicating the compounding error with each layer of complexity. Overall performance was comparable to previous large-scale evaluations. A general overprediction of AUC was observed with average fold error (AFE) of 1.56 over all simulations. AFE ranged from 0.0361 to 64.0 across the 43 APIs, with 25 showing overpredictions. Discrepancies between software packages were observed for a few APIs, the largest being 606, 171, and 81.7-fold differences in AFE between SimCYP and GI-Sim, however average performance was relatively consistent across the three software platforms.
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| 11. |
- McPhearson, Timon, et al.
(author)
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A social-ecological-technological systems framework for urban ecosystem services
- 2022
-
In: One Earth. - : Elsevier BV. - 2590-3330 .- 2590-3322. ; 5:5, s. 505-518
-
Journal article (peer-reviewed)abstract
- As rates of urbanization and climatic change soar, decision-makers are increasingly challenged to provide innovative solutions that simultaneously address climate change impacts and risks and inclusively ensure quality of life for urban residents. Cities have turned to nature-based solutions to help address these challenges. Nature-based solutions, through the provision of ecosystem services, can yield numerous benefits for people and address multiple challenges simultaneously. Yet, efforts to mainstream nature-based solutions are impaired by the complexity of the interacting social, ecological, and technological dimensions of urban systems. This complexity must be understood and managed to ensure ecosystem-service provisioning is effective, equitable, and resilient. Here, we provide a social-ecological-technological system (SETS) framework that builds on decades of urban ecosystem services research to better understand four core challenges associated with urban nature-based solutions: multi-functionality, systemic valuation, scale mismatch of ecosystem services, and inequity and injustice. The framework illustrates the importance of coordinating natural, technological, and socio-economic systems when designing, planning, and managing urban nature-based solutions to enable optimal social-ecological outcomes.
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| 12. |
- Olsson, Martin L, et al.
(author)
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Genomic analysis of clinical samples with serologic ABO blood grouping discrepancies: identification of 15 novel A and B subgroup alleles
- 2001
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In: Blood. - 1528-0020. ; 98:5, s. 1585-1593
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Journal article (peer-reviewed)abstract
- Since the cloning in 1990 of complementary DNA corresponding to messenger RNA transcribed at the blood group ABO locus, polymorphisms and phenotype-genotype correlations have been reported by several investigators. Exons 6 and 7, constituting 77% of the gene, have been analyzed previously in samples with variant phenotypes but for many subgroups the molecular basis remains unknown. This study analyzed 324 blood samples involved in ABO grouping discrepancies and determined their ABO genotype. Samples from individuals found to have known subgroup alleles (n = 53), acquired ABO phenotypes associated with different medical conditions (n = 65), probable chimerism (n = 3), and common red blood cell phenotypes (n = 109) were evaluated by ABO genotype screening only. Other samples (n = 94) from apparently healthy donors with weak expression of A or B antigens were considered potential subgroup samples without known molecular background. The full coding region (exons 1-7) and 2 proposed regulatory regions of the ABO gene were sequenced in selected A (n = 22) or B (n = 12) subgroup samples. Fifteen novel ABO subgroup alleles were identified, 2 of which are the first examples of mutations outside exon 7 associated with weak subgroups. Each allele was characterized by a missense or nonsense mutation for which screening by allele-specific primer polymerase chain reaction was performed. The novel mutations were encountered in 28 of the remaining 60 A and B subgroup samples but not among normal donors. As a result of this study, the number of definable alleles associated with weak ABO subgroups has increased from the 14 previously published to 29.
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| 13. |
- Screaton, E., et al.
(author)
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Interactions between deformation and fluids in the frontal thrust region of the NanTroSEIZE transect offshore the Kii Peninsula, Japan : Results from IODP Expedition 316 Sites C0006 and C0007
- 2009
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In: Geochemistry Geophysics Geosystems. - 1525-2027. ; 10, s. Q0AD01-
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Journal article (peer-reviewed)abstract
- Integrated Ocean Drilling Program (IODP) Expedition 316 Sites C0006 and C0007 examined the deformation front of the Nankai accretionary prism offshore the Kii Peninsula, Japan. In the drilling area, the frontal thrust shows unusual behavior as compared to other regions of the Nankai Trough. Drilling results, integrated with observations from seismic reflection profiles, suggest that the frontal thrust has been active since similar to 0.78-0.436 Ma and accommodated similar to 13 to 34% of the estimated plate convergence during that time. The remainder has likely been distributed among out-of-sequence thrusts further landward and/or accommodated through diffuse shortening. Unlike results of previous drilling on the Nankai margin, porosity data provide no indication of undercompaction beneath thrust faults. Furthermore, pore water geochemistry data lack clear indicators of fluid flow from depth. These differences may be related to coarser material with higher permeability or more complex patterns of faulting that could potentially provide more avenues for fluid escape. In turn, fluid pressures may affect deformation. Well-drained, sand-rich material under the frontal thrust could have increased fault strength and helped to maintain a large taper angle near the toe. Recent resumption of normal frontal imbrication is inferred from seismic reflection data. Associated decollement propagation into weaker sediments at depth may help explain evidence for recent slope failures within the frontal thrust region. This evidence consists of seafloor bathymetry, normal faults documented in cores, and low porosities in near surface sediments that suggest removal of overlying material. Overall, results provide insight into the complex interactions between incoming materials, deformation, and fluids in the frontal thrust region.
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| 14. |
- Bodelsson, Mikael, et al.
(author)
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Differential effect of hypothermia on the vascular tone and reactivity of the human coronary artery and graft vessels
- 1991
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In: Journal of Cardiovascular Surgery. - 0021-9509. ; 32:3, s. 288-294
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Journal article (peer-reviewed)abstract
- Hypothermia may contribute to vascular spasm during bypass surgery. The effect of cooling on the reactivity of the human coronary artery (CA), saphenous vein (SV) and internal mammary artery (IMA) was studied in vitro. In CA and IMA cooling diminished the resting tension and the contraction to potassium, noradrenaline and 5-hydroxytryptamine. In contrast, in SV the contraction to noradrenaline and 5-hydroxytryptamine was augmented by cooling. The effect of cold was reversible. These results demonstrate different effects of hypothermia in CA and the graft vessels. Thus, hypothermia augments the receptor-mediated contraction in SV but depresses it in IMA which thereby resembles CA. The difference is most marked in the contractile response to 5-hydroxytryptamine, which may accumulate during surgery. This may contribute to spasm in the saphenous vein grafts and may be involved in the mechanisms responsible for the inferior patency of SV compared to IMA as a graft vessel.
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| 15. |
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| 16. |
- Chester, Alan, et al.
(author)
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Alpha-L-fucosyltransferases in human submaxillary gland and stomach tissues associated with the H, Lea and Leb blood-group characters and ABH secretor status
- 1969
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In: Biochemical and Biophysical Research Communications. - 1090-2104. ; 34:6, s. 835-842
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Journal article (peer-reviewed)abstract
- Schemes for the biosynthetic steps in the formation of the blood group active glycoproteins in secretions postulate that α-Image -fucosyltransferases specified by the Image and Image genes control the addition of Image -fucose to different acceptor sites in a precursor substance to give H, Lea and Leb serologically active structures. 1,2. The presence of 2-, 3- and 4-α-Image -fucosyl-transferases in submaxillary glands and stomach mucosal linings from persons who are secretors of ABH, and of 3- and 4-α-Image -fucosyltransferases in tissues from non-secretor persons, is described in this paper.
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| 17. |
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| 18. |
- Chester, Alan, et al.
(author)
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Phenyl beta-D-Galactopyranoside as an Acceptor Substrate for the Blood-Group H Gene-Associated Guanosine Diphosphate L-Fucose:beta-D-Galactosyl alpha-2-L-Fucosyltransferase
- 1976
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In: European Journal of Biochemistry. - 0014-2956. ; 69:2, s. 583-592
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Journal article (peer-reviewed)abstract
- Phenyl β-d-galactopyranoside was found to be an efficient acceptor of l-[14C]fucose when guanosine diphosphate l-[14C]fucose was used as the donor substrate and human serum, submaxillary glands or stomach mucosa were the sources of l-fucosyltransferase. The enzyme utilising phenyl β-D-galactoside was present in the serum of donors of all ABO blood-groups examined, except those of the rare Oh (Bombay) and Bh phenotypes, but was clearly demonstrable in submaxillary gland preparations only when the glands came from individuals who were secretors of ABH blood-group substances. This distribution coincides with that previously established for the blood-group H gene-specified α-2-l-fucosyltransferase. The product of l-[14C]fucosyl transfer to phenyl β-d-galactoside is separable from the other radioactive components in the enzyme digest by chromatography for 4 h in ethyl acetate/pyridine/water (10/4/3, by vol.); it was characterised as phenyl 2-O-(α-l-[14C]fucopyranosyl)β-d-galactopyranoside by (a) the liberation of l-[14C]fucose by a specific α-2-l-fucosidase, (b) its resistance to degradation by alkali and (c) the identification of tritiated glycerol as a product of periodate oxidation after a 3H label had been introduced into the galactosyl moiety. The use of phenyl β-d-galactopyranoside as acceptor substrate thus provides a simple and relatively rapid method for the assay of the blood-group H gene-specified α-2-l-fucosyltransferase.
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| 19. |
- Estalote, AC, et al.
(author)
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A novel blood group B subgroup: serological and genetic studies
- 2004
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In: Transfusion Medicine. - : Wiley. - 0958-7578 .- 1365-3148. ; 14:2, s. 173-180
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Journal article (peer-reviewed)abstract
- A discrepancy in the ABO blood groups between a newborn child and her parents was identified. Serological and DNA investigative techniques were performed. A weak variant of B (B-w) was detected on the erythrocytes of the child, her grandmother and great-uncle. Adsorption-elution studies showed that their erythrocytes adsorb and yield anti-B on elution. The B-w antigenic strength of the A(1)B(w) cells of her mother and maternal aunt was reduced when compared to that of the A(2)B(w) from another family member. Only one of 15 different anti-B sera agglutinated the A(1)B(w) erythrocytes. Agglutinin anti-B that reacted strongly with normal B erythrocytes and did not agglutinate the B-w cells, was found in the sera of the A(1)B(w) individuals. The B-w serum glycosyltransferase could not convert O cells into B cells and no B substance was found in saliva. All family members with the B-w/AB(w) phenotypes were heterozygous for a B allele and DNA sequencing revealed a novel missense mutation in exon 7 of the B allele (556A > G), resulting in M186V. This substitution changes a highly conserved region of the enzyme, proposed to be a disordered loop near the enzyme cleft, and is expected to diminish the enzyme's activity, leading to this B-w phenotype.
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| 20. |
- Guilcher, Sara J.T., et al.
(author)
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Medication self-management toolkits for adults with multiple sclerosis : A scoping review
- 2023
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In: Exploratory Research in Clinical and Social Pharmacy. - : Elsevier. - 2667-2766. ; 10
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Research review (peer-reviewed)abstract
- Background: Multiple sclerosis (MS) is an autoimmune disease that is often treated with multiple medications. Managing multiple medications, also known as polypharmacy, can be challenging for persons with MS. Toolkits are instructional resources designed to promote behaviour change. Toolkits may support medication self-management for adults with MS, as they have been useful in other populations with chronic conditions.Objective: The main purpose of this review was to identify and summarize medication self-management toolkits for MS, as related to the design, delivery, components, and measures used to evaluate implementation and/or outcomes.Methods: A scoping review was conducted following guidelines by JBI. Articles were included if they focused on adults (18 years or older) with MS.Results: Six articles reporting on four unique toolkits were included. Most toolkits were technology-based, including mobile or online applications, with only one toolkit being paper-based. The toolkits varied in type, frequency, and duration of medication management support. Varying outcomes were also identified, but there were improvements reported in symptom management, medication adherence, decision-making, and quality of life. The six studies were quantitative in design, with no studies exploring the user experience from a qualitative or mixed-methods design.Conclusions: There is limited research on medication self-management toolkits among adults with MS. Future development, implementation, and evaluation mixed-methods research are needed to explore user experiences and overall design of toolkits.
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| 21. |
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| 22. |
- Hosseini Maaf, Bahram, et al.
(author)
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Structural basis for red cell phenotypic changes in newly identified, naturally occurring subgroup mutants of the human blood group B glycosyltransferase.
- 2007
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In: Transfusion. - : Wiley. - 1537-2995 .- 0041-1132. ; 47:5, s. 864-875
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Journal article (peer-reviewed)abstract
- BACKGROUND: Four amino-acid-changing polymorphisms differentiate the blood group A and B alleles. Multiple missense mutations are associated with weak expression of A and B antigens but the structural changes causing subgroups have not been studied. STUDY DESIGN AND METHODS: Individuals or families having serologically weak B antigen on their red cells were studied. Alleles were characterized by sequencing of exons 1 through 7 in the ABO gene. Single crystal X-ray diffraction, three-dimensional-structure molecular modeling, and enzyme kinetics showed the effects of the B allele mutations on the glycosyltransferases. RESULTS: Seven unrelated individuals with weak B phenotypes possessed seven different B alleles, five of which are new and result in substitution of highly conserved amino acids: M189V, I192T, F216I, D262N, and A268T. One of these (F216I) was due to a hybrid allele resulting from recombination between B and O-1v alleles. The two other alleles were recently described in other ethnic groups and result in V175M and L232P. The first crystal-structure determination (A268T) of a subgroup glycosyltransferase and molecular modeling (F216I, D262N, L232P) indicated conformational changes in the enzyme that could explain the diminished enzyme activity. The effect of three mutations could not be visualized since they occur in a disordered loop. CONCLUSION: The genetic background for B-w phenotypes is very heterogeneous but usually arises through seemingly random missense mutations throughout the last ABO exon. The targeted amino acid residues, however, are well conserved during evolution. Based on analysis of the resulting structural changes in the glycosyltransferase, the mutations are likely to disrupt molecular bonds of importance for enzymatic function.
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| 23. |
- Irshaid, N M, et al.
(author)
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Allele-related variation in minisatellite repeats involved in the transcription of the blood group ABO gene
- 1999
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In: Transfusion Medicine. - : Wiley. - 0958-7578 .- 1365-3148. ; 9:3, s. 219-226
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Journal article (peer-reviewed)abstract
- Since the cloning in 1990 of cDNA corresponding to mRNA transcribed at the blood group ABO locus, polymorphisms at the ABO locus and phenotype-genotype correlation have been analysed by several investigators. An enhancer-active minisatellite motif reported to contain four 43-bp repeats has been analysed by PCR in blood samples from 160 random Swedish blood donors. Different sizes of the DNA fragments obtained led to further analysis by direct sequencing. Fragments with either one or four 43-bp repeats were identified. A nucleotide substitution (G-->A) at nt. 41 of 43 was found in all alleles with only one repeat. Correlation with the ABO genotypes of the samples, as determined by a panel of ABO genotyping techniques, revealed an allele-related variable number of tandem repeats (VNTR). The A1 and the infrequent O2 allele had only one repeat whilst A2, B, O1 and O1v had four repeats and thus generated longer (by 129 bp) fragments. A further 74 samples obtained from various geographical areas/ethnic groups indicated a widespread correlation with few exceptions. In conclusion, a novel ABO polymorphism located in the 5'-nontranslated region involved in transcriptional regulation of the ABO gene is reported and its relationship to common alleles at this locus defined.
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| 24. |
- Landreh, Michael, et al.
(author)
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Predicting the Shapes of Protein Complexes through Collision Cross Section Measurements and Database Searches
- 2020
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In: Analytical Chemistry. - : American Chemical Society (ACS). - 0003-2700 .- 1520-6882. ; 92:18, s. 12297-12303
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Journal article (peer-reviewed)abstract
- In structural biology, collision cross sections (CCSs) from ion mobility mass spectrometry (IM-MS) measurements are routinely compared to computationally or experimentally derived protein structures. Here, we investigate whether CCS data can inform about the shape of a protein in the absence of specific reference structures. Analysis of the proteins in the CCS database shows that protein complexes with low apparent densities are structurally more diverse than those with a high apparent density. Although assigning protein shapes purely on CCS data is not possible, we find that we can distinguish oblate- and prolate-shaped protein complexes by using the CCS, molecular weight, and oligomeric states to mine the Protein Data Bank (PDB) for potentially similar protein structures. Furthermore, comparing the CCS of a ferritin cage to the solution structures in the PDB reveals significant deviations caused by structural collapse in the gas phase. We then apply the strategy to an integral membrane protein by comparing the shapes of a prokaryotic and a eukaryotic sodium/proton antiporter homologue. We conclude that mining the PDB with IM-MS data is a time- effective way to derive low-resolution structural models.
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| 25. |
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