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- Marganiec, J., et al.
(author)
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Coulomb breakup of 17Ne from the viewpoint of nuclear astrophysics
- 2012
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In: Proceedings of Science. - Proceedings of Science : Sissa. - 1824-8039.
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Conference paper (peer-reviewed)abstract
- By the Coulomb breakup of 17Ne, the time-reversed reaction 15O(2p,γ)17Ne has been studied. This reaction might play an important role in the rp process, as a break-out reaction of the hot CNO cycle. The secondary 17Ne ion beam with an energy of 500 MeV/nucleon has been dissociated in a Pb target. The reaction products have been detected with the LAND-R3B experimental setup at GSI. The preliminary differential and integral Coulomb dissociation cross section sCoul has been determined, which then will be converted into a photo-absorption cross section sphoto, and a two-proton radiative capture cross section σcap. Additionally, information about the structure of the 17Ne, a potential two-proton halo nucleus, will be received. The analysis is in progress. © Copyright owned by the author(s) under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike Licence.
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- Gustafsson, Mattias C U, et al.
(author)
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Factor H Binds to the Hypervariable Region of Many Streptococcus pyogenes M Proteins but Does Not Promote Phagocytosis Resistance or Acute Virulence.
- 2013
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In: PLoS Pathogens. - : Public Library of Science (PLoS). - 1553-7366 .- 1553-7374. ; 9:4
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Journal article (peer-reviewed)abstract
- Many pathogens express a surface protein that binds the human complement regulator factor H (FH), as first described for Streptococcus pyogenes and the antiphagocytic M6 protein. It is commonly assumed that FH recruited to an M protein enhances virulence by protecting the bacteria against complement deposition and phagocytosis, but the role of FH-binding in S. pyogenes pathogenesis has remained unclear and controversial. Here, we studied seven purified M proteins for ability to bind FH and found that FH binds to the M5, M6 and M18 proteins but not the M1, M3, M4 and M22 proteins. Extensive immunochemical analysis indicated that FH binds solely to the hypervariable region (HVR) of an M protein, suggesting that selection has favored the ability of certain HVRs to bind FH. These FH-binding HVRs could be studied as isolated polypeptides that retain ability to bind FH, implying that an FH-binding HVR represents a distinct ligand-binding domain. The isolated HVRs specifically interacted with FH among all human serum proteins, interacted with the same region in FH and showed species specificity, but exhibited little or no antigenic cross-reactivity. Although these findings suggested that FH recruited to an M protein promotes virulence, studies in transgenic mice did not demonstrate a role for bound FH during acute infection. Moreover, phagocytosis tests indicated that ability to bind FH is neither sufficient nor necessary for S. pyogenes to resist killing in whole human blood. While these data shed new light on the HVR of M proteins, they suggest that FH-binding may affect S. pyogenes virulence by mechanisms not assessed in currently used model systems.
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- Lennernäs, Hans, et al.
(author)
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Oral biopharmaceutics tools - Time for a new initiative - An introduction to the IMI project OrBiTo
- 2014
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In: European Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0928-0987 .- 1879-0720. ; 57:SI, s. 292-299
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Research review (peer-reviewed)abstract
- OrBiTo is a new European project within the IMI programme in the area of oral biopharmaceutics tools that includes world leading scientists from nine European universities, one regulatory agency, one non-profit research organization, four SMEs together with scientists from twelve pharmaceutical companies. The OrBiTo project will address key gaps in our knowledge of gastrointestinal (GI) drug absorption and deliver a framework for rational application of predictive biopharmaceutics tools for oral drug delivery. This will be achieved through novel prospective investigations to define new methodologies as well as refinement of existing tools. Extensive validation of novel and existing biopharmaceutics tools will be performed using active pharmaceutical ingredient (API), formulations and supporting datasets from industry partners. A combination of high quality in vitro or in silico characterizations of API and formulations will be integrated into physiologically based in silica biopharmaceutics models capturing the full complexity of GI drug absorption. This approach gives an unparalleled opportunity to initiate a transformational change in industrial research and development to achieve model-based pharmaceutical product development in accordance with the Quality by Design concept. Benefits include an accelerated and more efficient drug candidate selection, formulation development process, particularly for challenging projects such as low solubility molecules (BCS II and IV), enhanced and modified-release formulations, as well as allowing optimization of clinical product performance for patient benefit. In addition, the tools emerging from OrBiTo are expected to significantly reduce demand for animal experiments in the future as well as reducing the number of human bioequivalence studies required to bridge formulations after manufacturing or composition changes.
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- Ljunggren, Stefan, et al.
(author)
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Changes in Human Liportein Composition in Patients with Acute Coronary Syndrome
- 2011
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In: Atherosclerosis Supplements. - : Elsevier. - 1567-5688 .- 1878-5050. ; 12:1, s. 14-14
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Journal article (other academic/artistic)abstract
- The protein composition of lipoproteins may serve as biomarkers or reveal underlying mechanisms during different states of disease. Here we have analysed the protein composition of LDL and HDL from patients with acute coronary syndrome (ACS) and patients receiving statins after previous ACS. Plasma samples were obtained from males, namely 12 healthy donors, 9 patients with ACS and 7 stable patients receiving statin treatment after previous ACS. LDL and HDL were isolated by two-step density ultracentrifugation. LDL proteins were analysed with two-dimensional gel electrophoresis and mass spectrometry. Paraoxonase 1 (PON-1) in HDL was analyzed with SDSPAGE/Western Blot.Concentrations of apo A-IV, a1-antitrypsin and transthyretin were significantly increased (P < 0.05) in LDL from patients with ACS compared to healthy controls. In patients receiving statins, a1-antitrypsin remained increased while serum amyloid A4 was decreased. By western blot analysis, a non-significant increase in PON-1 was found in HDL from patients with ACS. Interestingly, a truncated form of PON-1 was detected in all patients with ACS but not in any of the controls.In conclusion, we confirm previous findings that LDL-associated transthyretin is a possible biomarker of myocardial infarction. Moreover, the increased concentration of the inflammatory marker a1-antitrypsin in LDL from both ACS patients and stable patients after ACS indicate that the enrichment does not only reflect an acute phase response. The presence of a truncated form of the antioxidant protein PON-1 in HDL may explain previous findings showing increased amounts but lower activity of PON-1 in patients with ACS.
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- Puymirat, E, et al.
(author)
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Euro Heart Survey 2009 Snapshot : regional variations in presentation and management of patients with AMI in 47 countries
- 2013
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In: European Heart Journal. - : Oxford University Press (OUP). - 2048-8726 .- 2048-8734. ; 2:4, s. 359-370
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Journal article (peer-reviewed)abstract
- AIMS:Detailed data on patients admitted for acute myocardial infarction (AMI) on a European-wide basis are lacking. The Euro Heart Survey 2009 Snapshot was designed to assess characteristics, management, and hospital outcomes of AMI patients throughout European Society of Cardiology (ESC) member countries in a contemporary 'real-world' setting, using a methodology designed to improve the representativeness of the survey.METHODS:Member countries of the ESC were invited to participate in a 1-week survey of all patients admitted for documented AMI in December 2009. Data on baseline characteristics, type of AMI, management, and complications were recorded using a dedicated electronic form. In addition, we used data collected during the same time period in national registries in Sweden, England, and Wales. Data were centralized at the European Heart House.RESULTS:Overall, 4236 patients (mean age 66±13 years; 31% women) were included in the study in 47 countries. Sixty per cent of patients had ST-segment elevation myocardial infarction, with 50% having primary percutaneous coronary intervention and 21% fibrinolysis. Aspirin and thienopyridines were used in >90%. Unfractionated and low-molecular-weight heparins were the most commonly used anticoagulants. Statins, beta-blockers, and angiotensin-converting enzyme inhibitors were used in >80% of the patients. In-hospital mortality was 6.2%. Regional differences were observed, both in terms of population characteristics, management, and outcomes.CONCLUSIONS:In-hospital mortality of patients admitted for AMI in Europe is low. Although regional variations exist in their presentation and management, differences are limited and have only moderate impact on early outcomes.
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