| 1. |
- Niemi, MEK, et al.
(author)
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- 2021
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swepub:Mat__t
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| 2. |
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| 3. |
- Klionsky, Daniel J., et al.
(author)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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In: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Research review (peer-reviewed)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 4. |
- Ackermann, M., et al.
(author)
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Fermi-LAT Observations of the Gamma-Ray Burst GRB 130427A
- 2014
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 343:6166, s. 42-47
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Journal article (peer-reviewed)abstract
- The observations of the exceptionally bright gamma-ray burst (GRB) 130427A by the Large Area Telescope aboard the Fermi Gamma-ray Space Telescope provide constraints on the nature of these unique astrophysical sources. GRB 130427A had the largest fluence, highest-energy photon (95 GeV), longest gamma-ray duration (20 hours), and one of the largest isotropic energy releases ever observed from a GRB. Temporal and spectral analyses of GRB 130427A challenge the widely accepted model that the nonthermal high-energy emission in the afterglow phase of GRBs is synchrotron emission radiated by electrons accelerated at an external shock.
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| 5. |
- Preece, R., et al.
(author)
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The First Pulse of the Extremely Bright GRB 130427A : A Test Lab for Synchrotron Shocks
- 2014
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 343:6166, s. 51-54
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Journal article (peer-reviewed)abstract
- Gamma-ray burst (GRB) 130427A is one of the most energetic GRBs ever observed. The initial pulse up to 2.5 seconds is possibly the brightest well-isolated pulse observed to date. A fine time resolution spectral analysis shows power-law decays of the peak energy from the onset of the pulse, consistent with models of internal synchrotron shock pulses. However, a strongly correlated power-law behavior is observed between the luminosity and the spectral peak energy that is inconsistent with curvature effects arising in the relativistic outflow. It is difficult for any of the existing models to account for all of the observed spectral and temporal behaviors simultaneously.
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| 6. |
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| 7. |
- Baldsiefen, G, et al.
(author)
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Shears bands in Pb-193
- 1996
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In: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 54:3, s. 1106-1116
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Journal article (peer-reviewed)abstract
- Four bands of enhanced dipole transitions, with weak crossovers, have been observed in Pb-195. Three of these bands are connected to the spherical levels. in addition, the spherical level scheme has been extended. The nuclear spectroscopy was done with the early implementation of GAMMASPHERE and HERA arrays of Get detectors. The nucleus Pb-193 was populated in the Yb-174(Mg-24,5n) reaction at beam energies of 129, 131, and 134 MeV. The experimental results are compared to tilted-axis cranking calculations. The systematical behavior of the dipole bands in the heavier odd-A Pb isotopes, Pb-195,Pb-197,Pb-199,Pb-201, is also discussed.
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| 8. |
- Brinkman, M J, et al.
(author)
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Decay from a superdeformed band in Pb-194
- 1996
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In: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 53:4, s. R1461-R1464
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Journal article (peer-reviewed)abstract
- Three experiments using the (174) Yb(Mg-25,5n)Pb-194 reaction have been undertaken at the Early Implementation of Gammasphere to study the decay of known superdeformed states in Pb-194. A single discrete transition with an energy of 2.746(2) MeV carrying 6(2)% of the full superdeformed band intensity has been identified. A discussion of our results and the assignment of the 2.746-MeV transition as a discrete gamma ray directly connecting the superdeformed 8(+) and low-lying 6(+) levels will be presented.
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| 9. |
- McNabb, D P, et al.
(author)
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Superdeformation in Po-198
- 1996
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In: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 53:2, s. R541-R543
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Journal article (peer-reviewed)abstract
- The Yb-174(Si-29,5n) reaction at 148 MeV with thin targets was used to populate high-angular momentum states in Po-198. Resulting gamma rays were observed with Gammasphere. A weakly populated superdeformed band of 10 gamma-ray transitions was found and has been assigned to Po-198. This is the first observation of an SD band in the A approximate to 190 region in a nucleus with Z > 83. The J((2))) of the new band is very similar to those of the yrast SD bands in Hg-194 and Pb-196. The intensity profile suggests that this band is populated through states close to where the SD band crosses the yrast line and the angular momentum at which the fission process dominates.
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| 10. |
- Bhat, P. Narayana, et al.
(author)
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THE THIRD FERMI GBM GAMMA-RAY BURST CATALOG : THE FIRST SIX YEARS
- 2016
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In: Astrophysical Journal Supplement Series. - : Institute of Physics Publishing (IOPP). - 0067-0049 .- 1538-4365. ; 223:2
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Journal article (peer-reviewed)abstract
- Since its launch in 2008, the Fermi Gamma-ray Burst Monitor (GBM) has triggered and located on average approximately two.-ray bursts (GRBs) every three days. Here, we present the third of a series of catalogs of GRBs detected by GBM, extending the second catalog by two more years through the middle of 2014 July. The resulting list includes 1405 triggers identified as GRBs. The intention of the GBM GRB catalog is to provide information to the community on the most important observables of the GBM-detected GRBs. For each GRB, the location and main characteristics of the prompt emission, the duration, peak flux, and fluence are derived. The latter two quantities are calculated for the 50-300 keV energy band where the maximum energy release of GRBs in the instrument reference system is observed, and also for a broader energy band from 10 to 1000 keV, exploiting the full energy range of GBM's low-energy [NaI[Tl)] detectors. Using statistical methods to assess clustering, we find that the hardness and duration of GRBs are better fit by a two-component model with short-hard and long-soft bursts than by a model with three components. Furthermore, information is provided on the settings and modifications of the triggering criteria and exceptional operational conditions during years five and six in the mission. This third catalog is an official product of the Fermi GBM science team, and the data files containing the complete results are available from the High-Energy Astrophysics Science Archive Research Center.
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| 11. |
- BERNSTEIN, LA, et al.
(author)
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ONSET OF COLLECTIVITY IN NEUTRON-DEFICIENT PO-196,PO-198
- 1995
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In: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 52:2, s. 621-627
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Journal article (peer-reviewed)abstract
- We have studied via in-beam gamma-ray spectroscopy Po-196 and Po-198, which are the first neutron-deficient Po isotopes to exhibit a collective low-lying structure. The ratios of yrast state energies and the E2 branching ratios of transitions from non-yrast to yrast states are indicative of a low-lying vibrational structure. The onset of collective motion in these isotopes can be attributed to the opening of the neutron i(13/2) orbital at N approximate to 112 and the resulting large overlap between the two valence protons in the h(9/2) orbital and the valence neutrons in the i(13/2) orbital.
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| 12. |
- Elkadeem, M. R., et al.
(author)
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Agrivoltaic systems potentials in Sweden : A geospatial-assisted multi-criteria analysis
- 2024
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In: Applied Energy. - : Elsevier Ltd. - 0306-2619 .- 1872-9118. ; 356
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Journal article (peer-reviewed)abstract
- Agrivoltaic systems represent an intelligent solution combining electricity production from solar photovoltaic technology with agricultural production to avoid land use conflicts. Geographic Information System technologies can support the implementation and spread of agrivoltaic systems by identifying the most suitable areas using useful spatially explicit information concerning techno-agro-socio-economic criteria. In this study, we have developed a procedure to identify and classify suitable areas for agrivoltaic systems in Sweden. An Ordinal Priority Approach based multi-criteria decision-making algorithm is established to calculate the weights of the selected evaluation criteria through expert interviews. The land use data refers to the Corine Land Cover 2018 product. The results show that about 8.6% of the Swedish territory, approximately 38,485 km2, is suitable for installing agrivoltaic systems. Among this area, about 0.2% is classified as “excellent”, about 15% as “very good”, about 72% as “good”, about 13% as “moderate”, and about 0.1% as “poor”. Most “excellent”-classified areas are in Kalmar, Skåne, and Gotland. In contrast, most “very good” sites are in Skåne, Kalmar, and Östergötland. By deploying vertically mounted agrivoltaic systems with bifacial photovoltaic modules, the total potential installed capacity for “excellent” areas is about 2.5 GWp, while for areas classified “excellent” and “very good” is about 221 GWp. The total “excellent” areas can potentially supply about 2.4 TWh of electricity against the electricity consumption in 2021 of about 143 TWh. On the other hand, the land classified as “excellent” and “very good” could potentially provide about 207 TWh. The County of Västra Götaland shows the greatest potentials in terms of total potential electricity supply from agrivoltaic systems with about 227 TWh, followed by Skåne with a total potential of 206 TWh.
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| 13. |
- Elkadeem, M. R., et al.
(author)
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Geospatial-assisted multi-criterion analysis of solar and wind power geographical-technical-economic potential assessment
- 2022
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In: Applied Energy. - : Elsevier Ltd. - 0306-2619 .- 1872-9118. ; 322
-
Journal article (peer-reviewed)abstract
- Amid the increasing electricity demand, energy crisis and pollution, the transition to renewable energy (RE) is becoming a preoccupation and major global challenge due to the multidimensional and intricate problem of RE planning. In Egypt, about 90% of gross power generation comes from carbon-intensive power plants (natural gas and coal). Here, we propose a novel geospatial-decision-making model aimed at geographical-technical–economic potential mapping and assessment of solar photovoltaic (PV) and onshore wind turbine (WT) power plants at a high level of resolution (1 km2) in Egypt. We identify the locations suitable for PV and WT development considering sixteen restrictive and contradictory evaluation criteria. These locations have been further analyzed to estimate how much energy generation is available and at what energy cost. The analysis identifies Middle-Upper Egypt and Suez Canal as hosting the majority of highly suitable locations for PV and WT power plants, respectively. Our finding reveals that the proper planning on RE projects at the proposed optimum locations could support the country's energy mix with a sizable 32% share of the projected country's electricity consumption from PV and 50% share from WT, by 2030. Furthermore, we show that the investment opportunities of PV and WT generation are potentially attractive with affordable competitive prices estimated at 57.84 $/MWh and 32.36 $/MWh, respectively, against conventional generation for today and the future. We anticipate that our results will provide valuable support in realizing Egypt's vision for sustainable electricity generation and in keeping abreast of the global transformation in power systems being witnessed. Ultimately, the method's relevance extends beyond the geographical boundaries of the present territory; it features a strategic, clear and reproducible approach that may be applied to a larger area or continent, provided the necessary input data and criteria are introduced.
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| 14. |
- Govaere, O., et al.
(author)
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Macrophage scavenger receptor 1 mediates lipid-induced inflammation in non-alcoholic fatty liver disease
- 2022
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In: Journal of Hepatology. - : Elsevier BV. - 0168-8278 .- 1600-0641. ; 76:5, s. 1001-1012
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Journal article (peer-reviewed)abstract
- Background & Aims: Obesity-associated inflammation is a key player in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). However, the role of macrophage scavenger receptor 1 (MSR1, CD204) remains incompletely understood. Methods: A total of 170 NAFLD liver biopsies were processed for transcriptomic analysis and correlated with clinicopathological features. Msr1-/- and wild-type mice were subjected to a 16-week high-fat and high-cholesterol diet. Mice and ex vivo human liver slices were treated with a monoclonal antibody against MSR1. Genetic susceptibility was assessed using genome-wide association study data from 1,483 patients with NAFLD and 430,101 participants of the UK Biobank. Results: MSR1 expression was associated with the occurrence of hepatic lipid-laden foamy macrophages and correlated with the degree of steatosis and steatohepatitis in patients with NAFLD. Mice lacking Msr1 were protected against diet-induced metabolic disorder, showing fewer hepatic foamy macrophages, less hepatic inflammation, improved dyslipidaemia and glucose tolerance, and altered hepatic lipid metabolism. Upon induction by saturated fatty acids, MSR1 induced a pro-inflammatory response via the JNK signalling pathway. In vitro blockade of the receptor prevented the accumulation of lipids in primary macrophages which inhibited the switch towards a pro-inflammatory phenotype and the release of cytokines such as TNF-ɑ. Targeting MSR1 using monoclonal antibody therapy in an obesity-associated NAFLD mouse model and human liver slices resulted in the prevention of foamy macrophage formation and inflammation. Moreover, we identified that rs41505344, a polymorphism in the upstream transcriptional region of MSR1, was associated with altered serum triglycerides and aspartate aminotransferase levels in a cohort of over 400,000 patients. Conclusions: Taken together, our data suggest that MSR1 plays a critical role in lipid-induced inflammation and could thus be a potential therapeutic target for the treatment of NAFLD. Lay summary: Non-alcoholic fatty liver disease (NAFLD) is a chronic disease primarily caused by excessive consumption of fat and sugar combined with a lack of exercise or a sedentary lifestyle. Herein, we show that the macrophage scavenger receptor MSR1, an innate immune receptor, mediates lipid uptake and accumulation in Kupffer cells, resulting in liver inflammation and thereby promoting the progression of NAFLD in humans and mice. © 2021 The Authors
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| 15. |
- Gül, Ersin, et al.
(author)
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The microbiota conditions a gut milieu that selects for wild-type Salmonella Typhimurium virulence
- 2023
-
In: PLoS biology. - : Public Library of Science (PLoS). - 1544-9173 .- 1545-7885. ; 21:8
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Journal article (peer-reviewed)abstract
- Salmonella Typhimurium elicits gut inflammation by the costly expression of HilD-controlled virulence factors. This inflammation alleviates colonization resistance (CR) mediated by the microbiota and thereby promotes pathogen blooms. However, the inflamed gut-milieu can also select for hilD mutants, which cannot elicit or maintain inflammation, therefore causing a loss of the pathogen's virulence. This raises the question of which conditions support the maintenance of virulence in S. Typhimurium. Indeed, it remains unclear why the wild-type hilD allele is dominant among natural isolates. Here, we show that microbiota transfer from uninfected or recovered hosts leads to rapid clearance of hilD mutants that feature attenuated virulence, and thereby contributes to the preservation of the virulent S. Typhimurium genotype. Using mouse models featuring a range of microbiota compositions and antibiotic- or inflammation-inflicted microbiota disruptions, we found that irreversible disruption of the microbiota leads to the accumulation of hilD mutants. In contrast, in models with a transient microbiota disruption, selection for hilD mutants was prevented by the regrowing microbiota community dominated by Lachnospirales and Oscillospirales. Strikingly, even after an irreversible microbiota disruption, microbiota transfer from uninfected donors prevented the rise of hilD mutants. Our results establish that robust S. Typhimurium gut colonization hinges on optimizing its manipulation of the host: A transient and tempered microbiota perturbation is favorable for the pathogen to both flourish in the inflamed gut and also minimize loss of virulence. Moreover, besides conferring CR, the microbiota may have the additional consequence of maintaining costly enteropathogen virulence mechanisms.
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| 16. |
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| 17. |
- von Kienlin, Andreas, et al.
(author)
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The Second Fermi GBM Gamma-Ray Burst Catalog : The First Four Years
- 2014
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In: Astrophysical Journal Supplement Series. - : Institute of Physics Publishing (IOPP). - 0067-0049 .- 1538-4365. ; 211:1
-
Journal article (peer-reviewed)abstract
- This is the second of a series of catalogs of gamma-ray bursts (GRBs) observed with the Fermi Gamma-ray Burst Monitor (GBM). It extends the first two-year catalog by two more years, resulting in an overall list of 953 GBM triggered GRBs. The intention of the GBM GRB catalog is to provide information to the community on the most important observables of the GBM detected GRBs. For each GRB the location and main characteristics of the prompt emission, the duration, peak flux and fluence are derived. The latter two quantities are calculated for the 50-300 keV energy band, where the maximum energy release of GRBs in the instrument reference system is observed and also for a broader energy band from 10-1000 keV, exploiting the full energy range of GBMs low-energy detectors. Furthermore, information is given on the settings and modifications of the triggering criteria and exceptional operational conditions during years three and four in the mission. This second catalog is an official product of the Fermi GBM science team, and the data files containing the complete results are available from the High-Energy Astrophysics Science Archive Research Center.
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| 18. |
- Berggren, Martin, et al.
(author)
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Unified understanding of intrinsic and extrinsic controls of dissolved organic carbon reactivity in aquatic ecosystems
- 2022
-
In: Ecology. - : Wiley. - 0012-9658 .- 1939-9170. ; 103:9
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Journal article (peer-reviewed)abstract
- Despite our growing understanding of the global carbon cycle, scientific consensus on the drivers and mechanisms that control dissolved organic carbon (DOC) turnover in aquatic systems is lacking, hampered by the mismatch between research that approaches DOC reactivity from either intrinsic (inherent chemical properties) or extrinsic (environmental context) perspectives. Here we propose a conceptual view of DOC reactivity in which the combination of intrinsic and extrinsic factors controls turnover rates and determines which reactions will occur. We review three major types of reactions (biological, photochemical, and flocculation) from an intrinsic chemical perspective and further define the environmental features that modulate the expression of chemically inherent reactivity potential. Finally, we propose hypotheses of how extrinsic and intrinsic factors together shape patterns in DOC turnover across the land-to-ocean continuum, underscoring that there is no intrinsic DOC reactivity without environmental context. By acknowledging the intrinsic–extrinsic control duality, our framework intends to foster improved modeling of DOC reactivity and its impact on ecosystem services.
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| 19. |
- Elkadeem, M. R., et al.
(author)
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Sustainable siting and design optimization of hybrid renewable energy system : A geospatial multi-criteria analysis
- 2021
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In: Applied Energy. - : Elsevier Ltd. - 0306-2619 .- 1872-9118. ; 295
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Journal article (peer-reviewed)abstract
- The use of hybrid renewable energy system (HRES) holds great promise for sustainable electrification and support countries reaching their energy access goals. The site selection and design of HRES are strategic stages towards ensuring an affordable, sustainable, and well-performing project. However, both are multidimensional and intricate issues that involve multiple conflicting assessment criteria and alternatives, which are not yet investigated comprehensively and simultaneously in many of the existing literature. In this context, the paper aims to develop a systematic and conceptual decision-making framework for site suitability and optimal design of HRESs, with an application on a regional scale in Kenya, Sub-Saharan Africa. The suggested framework is applied through three consecutive phases. First, a geographical information system (GIS) is combined with Best Worst Method (BWM) decision-making approach to spatially investigate and analyze the potential sites of solar, wind, and hybrid solar/wind systems. Within the spatial investigation, 9 different climatology, environment, location, and orography criteria are considered. Second, energy-economy-ecology (E3) design optimization is conducted to determine the list of feasible alternatives among grid-extension, autonomous HRES, and stand-alone diesel genset electrification schemes for powering a representative remote rural village in Kenya. Third, a post-optimality multi-criteria decision-making (MCDM) analysis is applied to decide and assess the optimal energy access design against 12 key sustainability indicators. In the third phase, the BWM is employed to define the weights of each indicator. Then, the Technique for Order Preference by Similarity to an Ideal Solution (TOPSIS) and the VIšekriterijumsko KOmpromisno Rangiranje (VIKOR) decision making approaches are used for the final ranking of feasible alternatives. The obtained site suitability maps of Kenya show that 0.91% (5322 km2) and 1.5% (8828.4 km2) of the land is highly suitable, 10.25% (59687 km2) and 33.04% (192360 km2) is suitable, and 80.5% (470313 km2) and 65% (378407 km2) is permanently unsuitable for establishing solar and wind systems, respectively. Also, E3-MCDM results indicate that the development of solar/wind/diesel/battery HRES is the best sustainable solution to supply the studied region as compared to other feasible alternatives. The system does not only guarantee a reliable operation with an unmet load of 552 kWh/yr, but it also has the lowest net present and energy costs at 2.6 M$ and 0.28 $/kWh, respectively, meanwhile avoiding annual CO2 of 804 tons compared with diesel system.
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| 20. |
- Fottrell, Edward, et al.
(author)
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The effect of increased coverage of participatory women's groups on neonatal mortality in Bangladesh : A cluster randomized trial
- 2013
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In: JAMA pediatrics. - : American Medical Association. - 2168-6211 .- 2168-6203. ; 167:9, s. 816-25
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Journal article (peer-reviewed)abstract
- IMPORTANCE: Community-based interventions can reduce neonatal mortality when health systems are weak. Population coverage of target groups may be an important determinant of their effect on behavior and mortality. A women's group trial at coverage of 1 group per 1414 population in rural Bangladesh showed no effect on neonatal mortality, despite a similar intervention having a significant effect on neonatal and maternal death in comparable settings.OBJECTIVE: To assess the effect of a participatory women's group intervention with higher population coverage on neonatal mortality in Bangladesh.DESIGN: A cluster randomized controlled trial in 9 intervention and 9 control clusters.SETTING: Rural Bangladesh.PARTICIPANTS: Women permanently residing in 18 unions in 3 districts and accounting for 19 301 births during the final 24 months of the intervention.INTERVENTIONS: Women's groups at a coverage of 1 per 309 population that proceed through a participatory learning and action cycle in which they prioritize issues that affected maternal and neonatal health and design and implement strategies to address these issues.MAIN OUTCOMES AND MEASURES: Neonatal mortality rate.RESULTS: Analysis included 19 301 births during the final 24 months of the intervention. More than one-third of newly pregnant women joined the groups. The neonatal mortality rate was significantly lower in the intervention arm (21.3 neonatal deaths per 1000 live births vs 30.1 per 1000 in control areas), a reduction in neonatal mortality of 38% (risk ratio, 0.62 [95% CI, 0.43-0.89]) when adjusted for socioeconomic factors. The cost-effectiveness was US $220 to $393 per year of life lost averted. Cause-specific mortality rates suggest reduced deaths due to infections and those associated with prematurity/low birth weight. Improvements were seen in hygienic home delivery practices, newborn thermal care, and breastfeeding practices.CONCLUSIONS AND RELEVANCE: Women's group community mobilization, delivered at adequate population coverage, is a highly cost-effective approach to improve newborn survival and health behavior indicators in rural Bangladesh.TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN01805825.
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| 21. |
- Gül, Ersin, et al.
(author)
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Intraluminal neutrophils limit epithelium damage by reducing pathogen assault on intestinal epithelial cells during Salmonella gut infection
- 2023
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In: PLoS Pathogens. - : Public Library of Science (PLoS). - 1553-7366 .- 1553-7374. ; 19:6
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Journal article (peer-reviewed)abstract
- Recruitment of neutrophils into and across the gut mucosa is a cardinal feature of intestinal inflammation in response to enteric infections. Previous work using the model pathogen Salmonella enterica serovar Typhimurium (S.Tm) established that invasion of intestinal epithelial cells by S.Tm leads to recruitment of neutrophils into the gut lumen, where they can reduce pathogen loads transiently. Notably, a fraction of the pathogen population can survive this defense, re-grow to high density, and continue triggering enteropathy. However, the functions of intraluminal neutrophils in the defense against enteric pathogens and their effects on preventing or aggravating epithelial damage are still not fully understood. Here, we address this question via neutrophil depletion in different mouse models of Salmonella colitis, which differ in their degree of enteropathy. In an antibiotic pretreated mouse model, neutrophil depletion by an anti-Ly6G antibody exacerbated epithelial damage. This could be linked to compromised neutrophil-mediated elimination and reduced physical blocking of the gut-luminal S.Tm population, such that the pathogen density remained high near the epithelial surface throughout the infection. Control infections with a ssaV mutant and gentamycin-mediated elimination of gut-luminal pathogens further supported that neutrophils are protecting the luminal surface of the gut epithelium. Neutrophil depletion in germ-free and gnotobiotic mice hinted that the microbiota can modulate the infection kinetics and ameliorate epithelium-disruptive enteropathy even in the absence of neutrophil-protection. Together, our data indicate that the well-known protective effect of the microbiota is augmented by intraluminal neutrophils. After antibiotic-mediated microbiota disruption, neutrophils are central for maintaining epithelial barrier integrity during acute Salmonella-induced gut inflammation, by limiting the sustained pathogen assault on the epithelium in a critical window of the infection.
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| 22. |
- Kazankov, K, et al.
(author)
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Macrophage Markers Do Not Add to the Prediction of Liver Fibrosis by Transient Elastography in Patients With Metabolic Associated Fatty Liver Disease
- 2020
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In: Frontiers in medicine. - : Frontiers Media SA. - 2296-858X. ; 7, s. 616212-
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Journal article (peer-reviewed)abstract
- Background and Aims: Non-invasive fibrosis staging is essential in metabolic associated fatty liver disease (MAFLD). Transient elastography (TE) is a well-established method for liver fibrosis assessment. We have previously shown that the macrophage marker sCD163 is an independent predictor for fibrosis in MAFLD. In the present study we tested whether the combination of macrophage markers and TE improves fibrosis prediction.Methods: We measured macrophage markers soluble (s)CD163 and mannose receptor (sMR) in two independent cohorts from Italy (n = 141) and Sweden (n = 70) with biopsy-proven MAFLD and available TE.Results: In the Italian cohort, TE and sCD163 showed similar moderate associations with liver fibrosis (rho = 0.56, p < 0.001 and rho = 0.42, p < 0.001, respectively). TE had an area under the Receiver Operating Characteristics curve (AUROC, with 95% CI) for fibrosis; F ≥ 2 = 0.79 (0.72–0.86), F ≥ 3 = 0.81 (0.73–0.89), F4 = 0.95 (0.90–1.0). sCD163 also predicted fibrosis well [F ≥ 2 = 0.71 (0.63–0.80), F ≥ 3 = 0.82 (0.74–0.90), F4 = 0.89 (0.76–1.0)]. However, combining sCD163 and TE did not improve the AUROCs significantly [F ≥ 2 = 0.79 (0.72–0.86), F ≥ 3 = 0.85 (0.78–0.92), F4 = 0.97 (0.93–1.0)]. In the Swedish cohort, TE showed a closer association with fibrosis (rho = 0.73, p < 0.001) than sCD163 (rho = 0.43, p < 0.001) and sMR (rho = 0.46, p < 0.001). TE predicted fibrosis well [F ≥ 2 = 0.88 (0.80–0.97), F ≥ 3 = 0.90 (0.83–0.97), F4 = 0.87 (0.78–0.96)], whereas sCD163 did not (best AUROC 0.75). sMR showed a better prediction [F ≥ 2 = 0.68 (0.56–0.81), F ≥ 3 = 0.82 (0.71–0.92), F4 = 0.79 (0.66–0.93)], but the addition of sMR did not further improve the prediction of fibrosis by TE.Conclusion: In these cohorts of MAFLD patients, TE was superior to macrophage markers for fibrosis prediction and in contrast to our hypothesis the addition of these markers to TE did not improve its predictive capability.
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| 23. |
- Malaeb, Diana, et al.
(author)
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Knowledge, Attitude and Conspiracy Beliefs of Healthcare Workers in Lebanon towards Monkeypox
- 2023
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In: Tropical Medicine and Infectious Disease. - : MDPI AG. - 2414-6366. ; 8:2
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Journal article (peer-reviewed)abstract
- The emergence of a monkeypox (MPOX) outbreak in 2022 represented the most recent recognizable public health emergency at a global level. Improving knowledge and attitude towards MPOX, particularly among healthcare workers (HCWs), can be a valuable approach in public health preventive efforts aiming to halt MPOX virus spread. The aim of the current study was to evaluate the knowledge and attitude of HCWs in Lebanon towards MPOX and to assess their conspiratorial attitude towards emerging virus infections (EVIs). The current study was based on a cross-sectional online survey distributed via Google Forms during September–December 2022 implementing a convenience sampling approach. The final study sample comprised a total of 646 HCWs: physicians (n = 171, 26.5%), pharmacists (n = 283, 43.8%), and nurses (n = 168, 26.0%), among others (n = 24, 3.7%). Variable defects in MPOX knowledge were detected, with a third of the participants having MPOX knowledge above the 75th percentile (n = 218, 33.7%). Satisfactory attitude towards MPOX (>75th percentile) was observed in less than a third of the participants (n = 198, 30.7%), while a quarter of the study sample endorsed conspiracy beliefs towards EVIs at a high level (>75th percentile, n = 164, 25.4%). Slightly more than two thirds of the participants agreed that MPOX vaccination should be used in disease prevention (n = 440, 68.1%). Better levels of MPOX knowledge and attitude were significantly associated with postgraduate education and older age. Physicians had significantly higher MPOX knowledge compared to other occupational categories. Less endorsement of conspiracies towards EVIs was significantly associated with male sex, occupation as a physician, and postgraduate education. Higher MPOX knowledge was associated with better attitude towards the disease. The current study showed unsatisfactory MPOX knowledge among Lebanese HCWs. Educational efforts can be valuable to improve the attitude towards the disease. Despite the relatively low level of embracing conspiracy beliefs regarding EVIs among HCWs in this study compared to previous studies, this area should be considered based on its potential impact on health-seeking behavior.
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| 26. |
- Shoravi, Siamak, et al.
(author)
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In silico screening of molecular imprinting prepolymerization systems : oseltamivir selective polymers through full-system molecular dynamics-based studies
- 2016
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In: Organic and biomolecular chemistry. - : Royal Society of Chemistry (RSC). - 1477-0520 .- 1477-0539. ; 14:18, s. 4210-4219
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Journal article (peer-reviewed)abstract
- All-component molecular dynamics studies were used to probe a library of oseltamivir molecularly imprinted polymer prepolymerization mixtures. Polymers included one of five functional monomers (acrylamide, hydroxyethylmethacrylate, methacrylic acid, 2-(triflouromethyl)acrylic acid, 4-vinylpyridine) and one of three porogens (acetonitrile, chloroform, methanol) combined with the crosslinking agent ethylene glycol dimethacrylate and initiator 2,2'-azobis(2-methylpropionitrile). Polymers were characterized by nitrogen gas sorption measurements and SEM, and affinity studies performed using radioligand binding in various media. In agreement with the predictions made from the simulations, polymers prepared in acetonitrile using either methacrylic or trifluoromethacrylic acid demonstrated the highest affinities for oseltamivir. Further, the ensemble of interactions observed in the methanol system provided an explanation for the morphology of polymers prepared in this solvent. The materials developed here offer potential for use in solid-phase extraction or for catalysis. The results illustrate the strength of this in silico strategy as a potential prognostic tool in molecularly imprinted polymer design.
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| 27. |
- Thorarinsdottir, Elin H., et al.
(author)
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Polysomnographic characteristics of excessive daytime sleepiness phenotypes in obstructive sleep apnea : results from the international sleep apnea global interdisciplinary consortium
- 2024
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In: Sleep. - : Oxford University Press. - 0161-8105 .- 1550-9109. ; 47:4
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Journal article (peer-reviewed)abstract
- Study Objectives: Excessive daytime sleepiness (EDS) is a major symptom of obstructive sleep apnea (OSA). Traditional polysomnographic (PSG) measures only partially explain EDS in OSA. This study analyzed traditional and novel PSG characteristics of two different measures of EDS among patients with OSA. Methods: Sleepiness was assessed using the Epworth Sleepiness Scale (>10 points defined as "risk of dozing") and a measure of general sleepiness (feeling sleepy >= 3 times/week defined as "feeling sleepy"). Four sleepiness phenotypes were identified: "non-sleepy," "risk of dozing only," "feeling sleepy only," and "both at risk of dozing and feeling sleepy." Results: Altogether, 2083 patients with OSA (69% male) with an apnea-hypopnea index (AHI) >= 5 events/hour were studied; 46% were "non-sleepy," 26% at "risk of dozing only," 7% were "feeling sleepy only," and 21% reported both. The two phenotypes at "risk of dozing" had higher AHI, more severe hypoxemia (as measured by oxygen desaturation index, minimum and average oxygen saturation [SpO(2)], time spent < 90% SpO(2), and hypoxic impacts) and they spent less time awake, had shorter sleep latency, and higher heart rate response to arousals than "non-sleepy" and "feeling sleepy only" phenotypes. While statistically significant, effect sizes were small. Sleep stages, frequency of arousals, wake after sleep onset and limb movement did not differ between sleepiness phenotypes after adjusting for confounders. Conclusions: In a large international group of patients with OSA, PSG characteristics were weakly associated with EDS. The physiological measures differed among individuals characterized as "risk of dozing" or "non-sleepy," while "feeling sleepy only" did not differ from "non-sleepy" individuals.
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| 28. |
- Van, den Berg M, et al.
(author)
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Toxic equivalency factors (TEFs) for PCBs, PCDDs, PCDFs for humans and wildlife
- 1998
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In: ENVIRONMENTAL HEALTH PERSPECTIVES. - : US DEPT HEALTH HUMAN SERVICES PUBLIC HEALTH SERVICE. ; 106:12, s. 775-792
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Review (other academic/artistic)abstract
- An expert meeting was organized by the World Health Organization (WHO) and held in Stockholm on 15-18 June 1997. The objective of this meeting was to derive consensus toxic equivalency factors (TEFs) for polychlorinated dibenzo-p-dioxins (PCDDs) and diben
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| 30. |
- Younes, George, et al.
(author)
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X-Ray Burst and Persistent Emission Properties of the Magnetar SGR 1830-0645 in Outburst
- 2022
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In: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 924:2
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Journal article (peer-reviewed)abstract
- We report on NICER X-ray monitoring of the magnetar SGR 1830-0645 covering 223 days following its 2020 October outburst, as well as Chandra and radio observations. We present the most accurate spin ephemerides of the source so far: nu = 0.096008680(2) Hz, = -6.2(1) x 10(-14) Hz s(-1), and significant second and third frequency derivative terms indicative of nonnegligible timing noise. The phase-averaged 0.8-7 keV spectrum is well fit with a double-blackbody (BB) model throughout the campaign. The BB temperatures remain constant at 0.46 and 1.2 keV. The areas and flux of each component decreased by a factor of 6, initially through a steep decay trend lasting about 46 days, followed by a shallow long-term one. The pulse shape in the same energy range is initially complex, exhibiting three distinct peaks, yet with clear continuous evolution throughout the outburst toward a simpler, single-pulse shape. The rms pulsed fraction is high and increases from about 40% to 50%. We find no dependence of pulse shape or fraction on energy. These results suggest that multiple hot spots, possibly possessing temperature gradients, emerged at outburst onset and shrank as the outburst decayed. We detect 84 faint bursts with NICER, having a strong preference for occurring close to the surface emission pulse maximum-the first time this phenomenon is detected in such a large burst sample. This likely implies a very low altitude for the burst emission region and a triggering mechanism connected to the surface active zone. Finally, our radio observations at several epochs and multiple frequencies reveal no evidence of pulsed or burst-like radio emission.
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| 31. |
- Zeilstra, Dennis, et al.
(author)
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Perspective : Fundamental Limitations of the Randomized Controlled Trial Method in Nutritional Research: The Example of Probiotics
- 2018
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In: Advances in Nutrition. - : Oxford University Press. - 2161-8313 .- 2156-5376. ; 9:5, s. 561-571
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Journal article (peer-reviewed)abstract
- Studies on the relation between health and nutrition are often inconclusive. There are concerns about the validity of many research findings, and methods that can deliver high-quality evidence-such as the randomized controlled trial (RCT) method-have been embraced by nutritional researchers. Unfortunately, many nutritional RCTs also yield ambiguous results. It has been argued that RCTs are ill-suited for certain settings, including nutritional research. In this perspective, we investigate whether there are fundamental limitations of the RCT method in nutritional research. To this end, and to limit the scope, we use probiotic studies as an example. We use an epistemological approach and evaluate the presuppositions that underlie the RCT method. Three general presuppositions are identified and discussed. We evaluate whether these presuppositions can be considered true in probiotic RCTs, which appears not always to be the case. This perspective concludes by exploring several alternative study methods that may be considered for future probiotic or nutritional intervention trials.
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