Aktivierung und Inhibierung von intrazellulären Signalkaskaden in Makrophagen durch Lipopolysaccharid und N-Acetylcystein

Eine Überreaktion des Immunsystems kann den Körper, sowohl akut durch Störung der Kreislaufregulation und Verlust von Organfunktionen als auch durch chronische entzündliche Prozesse an Gelenken und verschiedenen Organen, schädigen. Makrophagen als Bestandteil der angeborenen Immunantwort erkennen eingedrungene Erreger durch spezifische Oberflächenmoleküle wie zum Beispiel Lipopolysaccharid, ein Zuckermolekül der Bakterienzellwand und leiten die Beseitigung des Pathogens unter anderem durch Ausschüttung entzündungsfördernder Zytokine sowie die Produktion von Sauer- und Stickstoffradikalen ein. N-Acetylcystein, Vorstufe des stärksten Antioxidanz des Körpers Glutathion, ist in der Lage durch Neutralisierung freier Radikale und Senkung der Zytokinausschüttung hemmend in den Entzündungsprozess einzugreifen. Ziel dieser Arbeit ist die Untersuchung der Wirkung von N-Acetylcystein auf entzündungsassoziierte Signalwege und den Transkriptionsfakor NFκB in Lipopolysaccharid-aktivierten Makrophagen. Material und Methoden: Dazu wurden mittels Westen Blot Signalmoleküle dieser Signalwege in Makrophagen, der Zellline THP-1 untersucht, die mit jeweils Lipopolysaccharid, N-Acetylcystein und beiden Detergenzien stimuliert wurden. Bei dieser Untersuchung wurden die Signalmoleküle IRAK-1 als Bestandteil des Aktivierungsweges des Toll-like-Rezeptors 4, ERK1/2 im RAS/MEK/ERK-Weg, STAT3 im JAK/STAT-Weg und der Transkriptionsfakor NFκB genauer betrachtet. Die Auswertung des Western Blots erfolgte über Chemilumineszenz-Methode und Detektion mit den Gel-Dokumentationssystem MF-ChemiBIS. Lipopolysaccharid aktiviert alle untersuchten entzündungsfördernden Signalkaskaden. N-Acetylcyctein führt ebenfalls zur einer schwächeren Aktivierung einige der untersuchten Signalwege. Eine Aktivierung von ERK1/2 unter N-Acetylcystein war nicht sichtbar. Die Behandlung der Lipopolysaccharid-aktivierten Makrophagen mit N-Acetylcystein zeigt neben einem hemmenden Effekt in Form einer Verzögerung der Aktivierungszeit einiger Signalwege wie den RAS/MEK/ERK-Weg sowie einer Hemmung der Aktivierung des Transkriptionsfaktors NFκB auch eine gesteigerte Phosphorylierung von Signalmolekülen, in diesem Fall von IRAK-1 des Rezeptor TLR-4 und STAT-3 des JAK-STAT-Weges der entzündungsfördernden Signalkaskaden. Die Ergebnisse weisen daraufhin, dass N-Acetylcystein durch Regulation verschiedener entzündungsassoziierter Signalwege Potenzial besitzen könnte, als entzündungshemmendes Medikament bei Erkrankungen wie septischem Schock oder chronisch-entzündlichen Darmerkrankungen eingesetzt zu werden

An empirical study of mobile-device use at Norwegian oil and gas processing plants

publishedVersio

Skill of large-scale seasonal drought impact forecasts

Forecasting of drought impacts is still lacking in drought early-warning systems (DEWSs), which presently do not go beyond hazard forecasting. Therefore, we developed drought impact functions using machine learning approaches (logistic regression and random forest) to predict drought impacts with lead times up to 7 months ahead. The observed and forecasted hydrometeorological drought hazards – such as the standardized precipitation index (SPI), standardized precipitation evaporation index (SPEI), and standardized runoff index (SRI) – were obtained from the The EU-funded Enhancing Emergency Management and Response to Extreme Weather and Climate Events (ANYWHERE) DEWS. Reported drought impact data, taken from the European Drought Impact Report Inventory (EDII), were used to develop and validate drought impact functions. The skill of the drought impact functions in forecasting drought impacts was evaluated using the Brier skill score and relative operating characteristic metrics for five cases representing different spatial aggregation and lumping of impacted sectors. Results show that hydrological drought hazard represented by SRI has higher skill than meteorological drought represented by SPI and SPEI. For German regions, impact functions developed using random forests indicate a higher discriminative ability to forecast drought impacts than logistic regression. Moreover, skill is higher for cases with higher spatial resolution and less lumped impacted sectors (cases 4 and 5), with considerable skill up to 3–4 months ahead. The forecasting skill of drought impacts using machine learning greatly depends on the availability of impact data. This study demonstrates that the drought impact functions could not be developed for certain regions and impacted sectors, owing to the lack of reported impacts

Approaches to analyse and model changes in impacts:reply to discussions of “How to improve attribution of changes in drought and flood impacts”^*

We thank the authors, Brunella Bonaccorso and Karsten Arnbjerg-Nielsen for their constructive contributions to the discussion about the attribution of changes in drought and flood impacts. We appreciate that they support our opinion, but in particular their additional new ideas on how to better understand changes in impacts. It is great that they challenge us to think a step further on how to foster the collection of long time series of data and how to use these to model and project changes. Here, we elaborate on the possibility to collect time series of data on hazard, exposure, vulnerability and impacts and how these could be used to improve e.g. socio-hydrological models for the development of future risk scenarios.</p

Aprotinin Attenuates the Elevation of Pulmonary Vascular Resistance After Cardiopulmonary Bypass

Pulmonary vascular resistance (PVR) is generally believed to be elevated after cardiopulmonary bypass (CPB) due to whole body inflammation. Aprotinin has an anti-inflammatory action, and it was hypothesized that aprotinin would attenuate the PVR increase induced by CPB. Ten mongrel dogs were placed under moderately hypothermic CPB for 2 hr. The experimental animals were divided into a control group (n=5, group I) and an aprotinin group (n=5, group II). In group II, aprotinin was administered during pre-bypass (50,000 KIU/kg) and post-bypass (10,000 KIU/kg) periods. Additional aprotinin (50,000 KIU/kg) was mixed in CPB priming solution. PVRs at pre-bypass and post-bypass 0, 1, 2, 3 hr were calculated, and lung tissue was obtained after the experiment. Post-bypass PVRs were significantly higher than prebypass levels in all animals (n=10, p<0.001). PVR elevation in group II was less than in group I at 3 hr post-bypass (p=0.0047). Water content of the lung was lower in group II (74±9.4%) compared to that of group I (83±9.5%), but the difference did not reach significance (p=0.076). Pathological examination showed a near normal lung structure in group II, whereas various inflammatory reactions were observed in group I. We concluded that aprotinin may attenuate CPB-induced PVR elevation through its anti-inflammatory effect

Natural hazard risk assessments at the global scale

Since 1990, natural hazards have led to over 1.6 million fatalities globally, and economic losses are estimated at an average of around USD 260–310 billion per year. The scientific and policy communities recognise the need to reduce these risks. As a result, the last decade has seen a rapid development of global models for assessing risk from natural hazards at the global scale. In this paper, we review the scientific literature on natural hazard risk assessments at the global scale, and we specifically examine whether and how they have examined future projections of hazard, exposure, and/or vulnerability. In doing so, we examine similarities and differences between the approaches taken across the different hazards, and we identify potential ways in which different hazard communities can learn from each other. For example, there are a number of global risk studies focusing on hydrological, climatological, and meteorological hazards that have included future projections and disaster risk reduction measures (in the case of floods), whereas fewer exist in the peer-reviewed literature for global studies related to geological hazards. On the other hand, studies of earthquake and tsunami risk are now using stochastic modelling approaches to allow for a fully probabilistic assessment of risk, which could benefit the modelling of risk from other hazards. Finally, we discuss opportunities for learning from methods and approaches being developed and applied to assess natural hazard risks at more continental or regional scales. Through this paper, we hope to encourage further dialogue on knowledge sharing between disciplines and communities working on different hazards and risk and at different spatial scales

Review article: Natural hazard risk assessments at the global scale

Since 1990, natural hazards have led to over 1.6 million fatalities globally, and economic losses are estimated at an average of around $260–310 billion per year. The scientific and policy community recognise the need to reduce these risks. As a result, the last decade has seen a rapid development of global models for assessing risk from natural hazards at the global scale. In this paper, we review the scientific literature on natural hazard risk assessments at the global scale, and specifically examine whether and how they have examined future projections of hazard, exposure, and/or vulnerability. In doing so, we examine similarities and differences between the approaches taken across the different hazards, and identify potential ways in which different hazard communities can learn from each other. For example, we show that global risk studies focusing on hydrological, climatological, and meteorological hazards, have included future projections and disaster risk reduction measures (in the case of floods), whilst these are missing in global studies related to geological hazards. The methods used for projecting future exposure in the former could be applied to the geological studies. On the other hand, studies of earthquake and tsunami risk are now using stochastic modelling approaches to allow for a fully probabilistic assessment of risk, which could benefit the modelling of risk from other hazards. Finally, we discuss opportunities for learning from methods and approaches being developed and applied to assess natural hazard risks at more continental or regional scales. Through this paper, we hope to encourage dialogue on knowledge sharing between scientists and communities working on different hazards and at different spatial scales

Impacts of European drought events: insights from an international database of text-based reports

Drought is a natural hazard that can cause a wide range of impacts affecting the environment, society, and the economy. Providing an impact assessment and reducing vulnerability to these impacts for regions beyond the local scale, spanning political and sectoral boundaries, requires systematic and detailed data regarding impacts. This study presents an assessment of the diversity of drought impacts across Europe based on the European Drought Impact report Inventory (EDII), a unique research database that has collected close to 5000 impact reports from 33 European countries. The reported drought impacts were classified into major impact categories, each of which had a number of subtypes. The distribution of these categories and types was then analyzed over time, by country, across Europe and for particular drought events. The results show that impacts on agriculture and public water supply dominate the collection of drought impact reports for most countries and for all major drought events since the 1970s, while the number and relative fractions of reported impacts in other sectors can vary regionally and from event to event. The analysis also shows that reported impacts have increased over time as more media and website information has become available and environmental awareness has increased. Even though the distribution of impact categories is relatively consistent across Europe, the details of the reports show some differences. They confirm severe impacts in southern regions (particularly on agriculture and public water supply) and sector-specific impacts in central and northern regions (e.g., on forestry or energy production). The protocol developed thus enabled a new and more comprehensive view on drought impacts across Europe. Related studies have already developed statistical techniques to evaluate the link between drought indices and the categorized impacts using EDII data. The EDII is a living database and is a promising source for further research on drought impacts, vulnerabilities, and risks across Europe. A key result is the extensive variety of impacts found across Europe and its documentation. This insight can therefore inform drought policy planning at national to international levels

Environment and ecosystem services

In this subchapter, we discuss the need for investing in long-term assessment of impact on ecosystem services. We also think that governments should keep supporting national accounting of ecosystem services and that they should use the Common International Classification of Ecosystem Services (CICES) for that purpose. Mapping and assessment of the assets can also be employed for ecosystem accounting. Ecosystem services impact as- sessment, even though it is very important and necessary, cannot hide the facts that disaster risk management should move towards an ecosystem-based approach and that ecosystem degradation must be reversed. It is also important to highlight that impact on ecosystem services triggers a cascading effect that could be reflected in direct and indirect losses. These elements are discussed in detail, and we provide examples of and bibliographical references on how the ecosystem-based approach stands as a promising approach that can impact all elements of the disaster risk equation: mitigating hazards, reducing exposure, reducing vulnerabilities and increasing the resilience of exposed communities