4,324 research outputs found

    Introducing the Journal of Deliberative Democracy

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    This editorial introduction provides a statement of our vision for the Journal of Deliberative Democracy and an overview of the Special Issue on the Frontiers of Deliberative Democracy

    Measurements of proton induced reaction cross sections on 120Te for the astrophysical p-process

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    The total cross sections for the 120Te(p,gamma)121I and 120Te(p,n)120I reactions have been measured by the activation method in the effective center-of-mass energies between 2.47 MeV and 7.93 MeV. The targets were prepared by evaporation of 99.4 % isotopically enriched 120Te on Aluminum and Carbon backing foils, and bombarded with proton beams provided by the FN tandem accelerator at the University of Notre Dame. The cross sections and SS factors were deduced from the observed gamma ray activity, which was detected off-line by two Clover HPGe detectors mounted in close geometry. The results are presented and compared with the predictions of statistical model calculations using the codes NON-SMOKER and TALYS.Comment: 17 pages, 5 figures, 5 tables, regular articl

    Overlapping properties of the short membrane-active peptide BP100 with (i) Polycationic TAT and (ii) α-helical Magainin Family Peptides

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    Copyright © 2021 Mink, Strandberg, Wadhwani, Melo, Reichert, Wacker, Castanho and Ulrich. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.BP100 is a short, designer-made membrane-active peptide with multiple functionalities: antimicrobial, cell-penetrating, and fusogenic. Consisting of five lysines and 6 hydrophobic residues, BP100 was shown to bind to lipid bilayers as an amphipathic a-helix, but its mechanism of action remains unclear. With these features, BP100 embodies the characteristics of two distinctly different classes of membrane-active peptides, which have been studied in detail and where the mechanism of action is better understood. On the one hand, its amphiphilic helical structure is similar to the pore forming magainin family of antimicrobial peptides, though BP100 is much too short to span the membrane. On the other hand, its length and high charge density are reminiscent of the HIV-TAT family of cell penetrating peptides, for which inverted micelles have been postulated as translocation intermediates, amongst other mechanisms. Assays were performed to test the antimicrobial and hemolytic activity, the induced leakage and fusion of lipid vesicles, and cell uptake. From these results the functional profiles of BP100, HIV-TAT, and the magainin-like peptides magainin 2, PGLa, MSI-103, and MAP were determined and compared. It is observed that the activity of BP100 resembles most closely the much longer amphipathic a-helical magainin-like peptides, with high antimicrobial activity along with considerable fusogenic and hemolytic effects. In contrast, HIV-TAT shows almost no antimicrobial, fusogenic, or hemolytic effects. We conclude that the amphipathic helix of BP100 has a similar membranebased activity as magainin-like peptides and may have a similar mechanism of action.This work was supported financially by the BIF-TM program of the Helmholtz-Gemeinschaft; by the DFG grant INST 121384/58-1 FUGG; and by the DAAD “Portugal - Acções Integradas Luso-Alemãs/DAAD-GRIC” grant D/07/13644.info:eu-repo/semantics/publishedVersio

    Essential steps in primary care management of older people with Type 2 diabetes: an executive summary on behalf of the European geriatric medicine society (EuGMS) and the European diabetes working party for older people (EDWPOP) collaboration

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    We present an executive summary of a guideline for management of type 2 diabetes mellitus in primary care written by the European Geriatric Medicine Society, the European Diabetes Working Party for Older People with contributions from primary care practitioners and participation of a patient’s advocate. This consensus document relies where possible on evidence-based recommendations and expert opinions in the fields where evidences are lacking. The full text includes 4 parts: a general strategy based on comprehensive assessment to enhance quality and individualised care plan, treatments decision guidance, management of complications, and care in case of special conditions. Screening for frailty and cognitive impairment is recommended as well as a comprehensive assessment all health conditions are concerned, including end of life situations. The full text is available online at the following address: essential_steps_inprimary_care_in_older_people_with_diabetes_-_EuGMS-EDWPOP___3_.pdf

    Protecting Older Patients with Cardiovascular Diseases from COVID-19 Complications Using Current Medications

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    Purpose: In the pathogenesis of severe COVID-19 complications, derangements of renin-angiotensin-aldosterone system (RAAS), vascular endothelial dysfunction leading to inflammation and coagulopathy, and arrhythmias play an important role. Therefore, it is worth considering the use of currently available drugs to protect COVID-19 patients with cardiovascular diseases. Methods: We review the current experience of conventional cardiovascular drugs [angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers, anticoagulants, acetosalicylic acid, antiarrhythmic drugs, statins] as well as some other drug classes (antidiabetic drugs, vitamin D and NSAIDs) frequently used by older patients with cardiovascular diseases. Data were sought from clinical databases for COVID-19 and appropriate key words. Conclusions and recommendations are based on a consensus among all authors. Results: Several cardiovascular drugs have a potential to protect patients with COVID-19, although evidence is largely based on retrospective, observational studies. Despite propensity score adjustments used in many analyses observational studies are not equivalent to randomised controlled trials (RCTs). Ongoing RCTs include treatment with antithrombotics, pulmonary vasodilators, RAAS-related drugs, and colchicine. RCTs in the acute phase of COVID-19 may not, however, recognise the benefits of long term anti-atherogenic therapies, such as statins. Conclusions: Most current cardiovascular drugs can be safely continued during COVID-19. Some drug classes may even be protective. Age-specific data are scarce, though, and conditions which are common in older patients (frailty, comorbidities, polypharmacy) must be individually considered for each drug group.info:eu-repo/semantics/publishedVersio

    Temperature‐Dependent Re‐alignment of the Short Multifunctional Peptide BP100 in Membranes Revealed by Solid‐State NMR Spectroscopy and Molecular Dynamics Simulations

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    BP100 is a cationic undecamer peptide with antimicrobial and cell-penetrating activities. The orientation of this amphiphilic α-helix in lipid bilayers was examined under numerous conditions using solid-state 19F, 15N and 2H NMR. At high temperatures in saturated phosphatidylcholine lipids, BP100 lies flat on the membrane surface, as expected. Upon lowering the temperature towards the lipid phase transition, the helix is found to flip into an upright transmembrane orientation. In thin bilayers, this inserted state was stable at low peptide concentration, but thicker membranes required higher peptide concentrations. In the presence of lysolipids, the inserted state prevailed even at high temperature. Molecular dynamics simulations suggest that BP100 monomer insertion can be stabilized by snorkeling lysine side chains. These results demonstrate that even a very short helix like BP100 can span (and thereby penetrate through) a cellular membrane under suitable conditions

    Tau PET correlates with different Alzheimer's disease-related features compared to CSF and plasma p-tau biomarkers

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    PET, CSF and plasma biomarkers of tau pathology may be differentially associated with Alzheimer's disease (AD)-related demographic, cognitive, genetic and neuroimaging markers. We examined 771 participants with normal cognition, mild cognitive impairment or dementia from BioFINDER-2 (n = 400) and ADNI (n = 371). All had tau-PET ([18F]RO948 in BioFINDER-2, [18F]flortaucipir in ADNI) and CSF p-tau181 biomarkers available. Plasma p-tau181 and plasma/CSF p-tau217 were available in BioFINDER-2 only. Concordance between PET, CSF and plasma tau biomarkers ranged between 66 and 95%. Across the whole group, ridge regression models showed that increased CSF and plasma p-tau181 and p-tau217 levels were independently of tau PET associated with higher age, and APOEɛ4-carriership and Aβ-positivity, while increased tau-PET signal in the temporal cortex was associated with worse cognitive performance and reduced cortical thickness. We conclude that biofluid and neuroimaging markers of tau pathology convey partly independent information, with CSF and plasma p-tau181 and p-tau217 levels being more tightly linked with early markers of AD (especially Aβ-pathology), while tau-PET shows the strongest associations with cognitive and neurodegenerative markers of disease progression

    VALIDATION OF ENVISAT-1 LEVEL-2 PRODUCTS RELATED TO LOWER ATMOSPHERE O3 AND NOy CHEMISTRY BY A FTIR QUASI-GLOBAL NETWORK

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    A coordinated action involving eleven stations of the ground-based Network for Detection of Stratospheric Change (NDSC) equipped with Fourier transform infrared (FTIR) instruments was conducted to contribute to the validation of the three atmospheric chemistry instruments onboard ENVISAT, that are MIPAS, SCIAMACHY and GOMOS. The target products for validation are total columns of O3, CH4, CO and some important NOy species (NO2, HNO3, NO) and the source gas N2O. Together the eleven stations cover the latitudes between 79 °N and 78°S, including polar, mid -latitude and subtropical and tropical locations. The goal is to contribute to the assessment of the data quality of the aforementioned ENVISAT instruments, from a quasi-global perspective. The period of intensive ground-based data collection for the benefit of the ENVISAT Validation Commissioning Phase that is dealt with in the present paper is July 15 to December 1, 2002. The FTIR network involved collected a data set corresponding to an equivalent of approximately 400 days of measurements; about three quarter of the data have already been submitted to the ENVISAT Calval database and are included in the present work. Unfortunately, the distribution of ENVISAT data has been slow and limited. Only a limited number of coincidences has been found for making data inter-comparisons. Therefore, the conclusions drawn in this paper are very preliminary and cover only a limited set of data products from SCIAMACHY only. Our findings up to now concerning the above mentioned target products are the following: (1) SCIAMACHY near infrared operational products (CO, CH4, N2O) have no scientific meaning yet, (2), the operational SCIAMACHY total vertical O3 column product derived in the ultraviolet window has undergone some improvements with changing versions of the processor(s) but it still underestimates the column by about 5 – 10 %, (3), the operational SCIAMACHY total vertical O3 column product derived in the visible window is unrealistically large, and (3), the operational NO2 total column product from SCIAMACHY seems to largely overestimate the real column, but very few coincidences and large dispersions of the data do inhibit any further conclusion at present. In a next phase, the same ground-based correlative data set will be exploited to further validate the ENVISAT data as soon as more and reprocessed data will be distributed
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