Skin sensitization in silico protocol

The assessment of skin sensitization has evolved over the past few years to include in vitro assessments of key events along the adverse outcome pathway and opportunistically capitalize on the strengths of in silico methods to support a weight of evidence assessment without conducting a test in animals. While in silico methods vary greatly in their purpose and format; there is a need to standardize the underlying principles on which such models are developed and to make transparent the implications for the uncertainty in the overall assessment. In this contribution, the relationship of skin sensitization relevant effects, mechanisms, and endpoints are built into a hazard assessment framework. Based on the relevance of the mechanisms and effects as well as the strengths and limitations of the experimental systems used to identify them, rules and principles are defined for deriving skin sensitization in silico assessments. Further, the assignments of reliability and confidence scores that reflect the overall strength of the assessment are discussed. This skin sensitization protocol supports the implementation and acceptance of in silico approaches for the prediction of skin sensitization

Inhibition of Fried Meat-Induced Colorectal DNA Damage and Altered Systemic Genotoxicity in Humans by Crucifera, Chlorophyllin, and Yogurt

Dietary exposures implicated as reducing or causing risk for colorectal cancer may reduce or cause DNA damage in colon tissue; however, no one has assessed this hypothesis directly in humans. Thus, we enrolled 16 healthy volunteers in a 4-week controlled feeding study where 8 subjects were randomly assigned to dietary regimens containing meat cooked at either low (100°C) or high temperature (250°C), each for 2 weeks in a crossover design. The other 8 subjects were randomly assigned to dietary regimens containing the high-temperature meat diet alone or in combination with 3 putative mutagen inhibitors: cruciferous vegetables, yogurt, and chlorophyllin tablets, also in a crossover design. Subjects were nonsmokers, at least 18 years old, and not currently taking prescription drugs or antibiotics. We used the Salmonella assay to analyze the meat, urine, and feces for mutagenicity, and the comet assay to analyze rectal biopsies and peripheral blood lymphocytes for DNA damage. Low-temperature meat had undetectable levels of heterocyclic amines (HCAs) and was not mutagenic, whereas high-temperature meat had high HCA levels and was highly mutagenic. The high-temperature meat diet increased the mutagenicity of hydrolyzed urine and feces compared to the low-temperature meat diet. The mutagenicity of hydrolyzed urine was increased nearly twofold by the inhibitor diet, indicating that the inhibitors enhanced conjugation. Inhibitors decreased significantly the mutagenicity of un-hydrolyzed and hydrolyzed feces. The diets did not alter the levels of DNA damage in non-target white blood cells, but the inhibitor diet decreased nearly twofold the DNA damage in target colorectal cells. To our knowledge, this is the first demonstration that dietary factors can reduce DNA damage in the target tissue of fried-meat associated carcinogenesis.ClinicalTrials.gov NCT00340743

Genetic toxicology in silico protocol.

In silico toxicology (IST) approaches to rapidly assess chemical hazard, and usage of such methods is increasing in all applications but especially for regulatory submissions, such as for assessing chemicals under REACH as well as the ICH M7 guideline for drug impurities. There are a number of obstacles to performing an IST assessment, including uncertainty in how such an assessment and associated expert review should be performed or what is fit for purpose, as well as a lack of confidence that the results will be accepted by colleagues, collaborators and regulatory authorities. To address this, a project to develop a series of IST protocols for different hazard endpoints has been initiated and this paper describes the genetic toxicity in silico (GIST) protocol. The protocol outlines a hazard assessment framework including key effects/mechanisms and their relationships to endpoints such as gene mutation and clastogenicity. IST models and data are reviewed that support the assessment of these effects/mechanisms along with defined approaches for combining the information and evaluating the confidence in the assessment. This protocol has been developed through a consortium of toxicologists, computational scientists, and regulatory scientists across several industries to support the implementation and acceptance of in silico approaches

In silico toxicology protocols

The present publication surveys several applications of in silico (i.e., computational) toxicology approaches across different industries and institutions. It highlights the need to develop standardized protocols when conducting toxicity-related predictions. This contribution articulates the information needed for protocols to support in silico predictions for major toxicological endpoints of concern (e.g., genetic toxicity, carcinogenicity, acute toxicity, reproductive toxicity, developmental toxicity) across several industries and regulatory bodies. Such novel in silico toxicology (IST) protocols, when fully developed and implemented, will ensure in silico toxicological assessments are performed and evaluated in a consistent, reproducible, and well-documented manner across industries and regulatory bodies to support wider uptake and acceptance of the approaches. The development of IST protocols is an initiative developed through a collaboration among an international consortium to reflect the state-of-the-art in in silico toxicology for hazard identification and characterization. A general outline for describing the development of such protocols is included and it is based on in silico predictions and/or available experimental data for a defined series of relevant toxicological effects or mechanisms. The publication presents a novel approach for determining the reliability of in silico predictions alongside experimental data. In addition, we discuss how to determine the level of confidence in the assessment based on the relevance and reliability of the information

Process simulation from spezific applications of the dual fluidized bed steam gasification technology for paper and pulp industry

Der jährlich steigende Energiebedarf bewirkt einen zunehmenden Verbrauch der begrenzt vorhandenen und nicht regenerierbaren fossilen Rohstoffe, weswegen früher oder später ein Umstieg auf alternative Energieträger unausweichlich ist. Die erstellte Vision über die Deckung des zukünftigen Energiebedarfs zeigt, dass für die Endenergieverbrauchssektoren Industrieöfen und Dampferzeugung am besten chemische Energieträger wie Biomasse und Reststoffe geeignet sind.Daraus leitet sich das Ziel dieser Arbeit ab, Anwendungsfälle für die Papier- und Zellstoffindustrie zu untersuchen (Machbarkeitsstudien), bei denen ein aus festen Brennstoffen (Holzhackschnitzel, Reststoffe) mit dem Verfahren der Zweibett-Wirbelschicht-Dampfvergasung hergestelltes, sogenanntes Produktgas anstatt fossiler Brennstoffe eingesetzt werden kann.Für die Durchführung der Machbarkeitsstudien ist die Prozesssimulationssoftware IPSEpro mit einer speziell für die Biomassevergasung entwickelten Modellbibliothek verwendet worden. Dazu werden die thermodynamischen Grundlagen und Stoffdaten vorgestellt. Es werden die im Rahmen der vorliegenden Arbeit entwickelten Grundsätze für die Modellierung von industriellen Prozessen in IPSEpro und Maßnahmen zur Sicherung qualitativ hochwertiger Berechnungsergebnisse dargelegt.Um für die Machbarkeitsstudien reale Richtwerte zu erhalten, wird die Zweibett-Wirbelschicht-Dampfvergasungsanlage von Oberwart in IPSEpro nachgerechnet. Im betrachteten Betriebszeitraum hat die Anlage 8 380 kW Biomasse und 610 kW sonstige Brennstoffe (Rapsmethylester und Erdgas) in 1 940 kW elektrische Energie (netto) und 860 kW Fernwärme umgewandelt.Im Rahmen der Simulationsdurchführung sind einige Anlagenmängel aufgedeckt worden, welche sich negativ auf den Umwandlungswirkungsgrad auswirken.Die erste Machbarkeitsstudie behandelt die Produktgaserzeugung für die Befeuerung eines Kalkofens bei der Zellstoffproduktion. Dabei werden geringe Anforderungen an den Teergehalt des Produktgases gestellt, wodurch der Produktgaswäscher mit der Lösungsmittelaufbereitung entfallen kann. Dies erlaubt neben dem Vorteil geringerer Investitionskosten auch eine höhere Produktgastemperatur von 450 °C nach der Reinigung, wodurch die in den Kalkofen eingebrachte fühlbare Wärmemenge größer ausfällt. Die Berechnung des Auslegungspunktes in IPSEpro ergibt, dass aus 12 430 kW Biomasse und 250 kW elektrischer Energie ein Produktgas mit 10 000 kW chemischer Leistung und 830 kW Wärmeinhalt sowie zusätzlich 400 kW auskoppelbare Wärme erzeugt werden kann. Mithilfe einer stärkeren Biomassetrocknung kann der Verbrauch an Biomasse und die auskoppelbare Wärme reduziert werden. Dadurch steigen allerdings die Trocknungsverluste, wodurch der Gesamtwirkungsgrad der Anlage geringfügig abnimmt. Um unerwünschte Anreicherungen im Zellstoffprozess auszuschließen, werden die im nutzbaren Produktgas enthaltenen Elemente, welche aus der Biomasse stammen, aufgeschlüsselt und in einem Worst-Case-Szenario quantifiziert. Aus wirtschaftlicher Sicht sind für die Umsetzung dieses Konzepts eine staatliche Förderung und/oder eine größere Anlagenleistung erforderlich.In der zweiten Machbarkeitsstudie wird die Produktgaserzeugung aus Papierfaserreststoffen und Rejekten für die Zuspeisung in erdgasbefeuerten Gasturbinen untersucht. Die Simulationsrechnung ergibt für den Auslegungspunkt eine Umwandlung von 10 530 kW Papierfaserreststoffen, 5 130 kW Rejekten, 970 kW elektrischer Energie und 200 kW Lösungsmittel in ein Produktgas mit einer chemischen Leistung von 10 000 kW und einer fühlbaren Wärme von 230 kW. Zusätzlich steht eine auskoppelbare Wärmemenge von 3 290 kW zur Verfügung. Das Auslegungskennfeld zeigt bei gleicher Produktgasleistung eine starke Zunahme der Brennstoffmenge mit steigendem Brennstoffwassergehalt nach Trockner. Um einen stabilen Anlagenbetrieb ohne Stützfeuerung zu erreichen, sollten die Brennstoffe zumindest auf zirka 30 Gew-% Wassergehalt getrocknet werden. In Bezug auf die Rauchgasemissionen werden für alle Schadstoffe außer Quecksilber praktische Untersuchungen angeraten, um möglicherweise zusätzlich erforderliche Rauchgasreinigungsmaßnahmen festzulegen. Die Schwermetallbelastung der Asche ist im Vergleich mit der Bodenrichtlinie nach ÖNORM L 1075 gering, außer bei Kupfer und Nickel werden die Richtwerte überschritten. Die wirtschaftliche Abschätzung weist einen sehr hohen Gewinn auf. Da für die Zweibett-Wirbelschicht-Dampfvergasung von Papierfaserreststoffen und Rejekten keine praktischen Erfahrungswerte existieren, wird die Durchführung von Vergasungsversuchen in einer Laboranlage empfohlen.Die durchgeführten Machbarkeitsstudien zeigen neue Einsatzgebiete der Zweibett-Wirbelschicht-Dampfvergasung und bieten die Möglichkeit zur Bewertung der vorgeschlagenen Konzepte aus energetischer, technischer und wirtschaftlicher Sicht.The yearly growing energy demand causes an increasing consumption of restricted available and not regenerative fossil raw materials. Sooner or later a change to renewable energy sources will be necessary. The vision about the supply of future power demand presents chemical energy sources, e.g. biomass and waste materials, as the best energy form for the consumption sectors industrial furnaces and steam production. So the aim of this work follows, to analyse applications for the paper und pulp industry (feasibility studies), in which solid fuels (wood chips, waste materials) are converted by dual fluidized bed steam gasification into a gaseous fuel (product gas). The product gas can be used instead of fossil fuels.The feasibility studies are carried out using the process simulation software IPSEpro with a model library, which has been developed especially for biomass gasification processes. Necessary thermo-dynamic basics and chemical property data are introduced in the present work.Furthermore, some methods for modelling industrial processes in IPSEpro are illustrated, which enable high-quality simulation results.To get a bench mark for the feasibility studies, the dual fluidized bed steam gasification plant Oberwart has been validated with IPSEpro. In the investigation period the plant has converted 10 840 kW of biomass together with 440 kW of other fuels (rape methyl ester and natural gas) into 1 940 kW of net electric energy and 860 kW of district heating.During the simulation work some plant malfunctions have been detected, which have a negative affect on conversion efficiency.The first feasibility study shows the product gas production for firing a lime kiln as a part of cellulose production. Thereby, low requirements exist for the tar content of the product gas. So a product gas scrubber with the solvent treatment is not required, which lowers the investment costs. Furthermore a higher product gas temperature of 450 °C after gas cleaning can be operated. Therefore the heat flow to the lime kiln is higher. The calculation of a defined design point in IPSEpro shows that 12 430 kW of biomass and 250 kW of electricity are converted into product gas with 10 000 kW chemical power and 830 kW sensible heat. In addition, it is possible to export 400 kW of heat. With the help of a more powerful biomass drying system the biomass consumption and the exportable heat can be reduced. Thereby, the drying losses increase and the overall plant efficiency decrease slightly. Elements contained within the used biomass need to be specified to avoid an undesired enrichment of pollutants in the cellulose process. In a worst case scenario the maximum amount of each element has been determined, which is transported by the product gas into the lime kiln. From an economic point of view a public funding and/or a higher plant capacity are required to realize this concept.The second feasibility study analyses the product gas production from paper fibre residues and rejects for partial replacement of natural gas in gas turbines. The simulation of a defined design point shows a conversion of 10 530 kW paper fibre residues, 5 130 kW rejects, 970 kW electric energy and 200 kW solvent into a product gas with a chemical power of 10 000 kW and a sensible heat power content of 230 kW. In addition, 3 290 kW of exportable heat are available. The plant performance diagram shows a strong increase for the amount of fuel with rising fuel water content after dryer. Fuel water content should be reduced at least 30 m-% to ensure a stable plant operation without auxiliary firing. Practical experiments are advised concerning flue gas emissions for all pollutants except mercury, to define a potentially required additional flue gas cleaning. Heavy metal contamination of the ash is expected to be low in comparison with reference values for soils according ÖNORM L 1075, only copper and nickel exceed the values. An economic consideration shows quite a high potential for the realization of the investigated concept. Beforehand gasification experiments in a laboratory plant are recommended, because so far no practical experience for dual fluidized bed steam gasification of paper fibre residues and rejects exists.The feasibility studies carried out in the present thesis discover new promising ways for the integration of the dual fluidized bed steam gasification process in pulp and paper industry. Achieved results offer the possibility to assess the recommended plant concepts in detail from energetic, technical and economical points of view

Wenn Fehler helfen – Fallbeispiel: First Attempt in Learning

Jeder Fehler ist der erste Schritt, um etwas Neues zu lernen. Nach diesem Prinzip arbeitet das Gehen Verstehen®-Konzept, in dem sogenannte FAILs (First Attempt In Learning) positiv belegt sind. Im Fallbeispiel kann der Läufer David P. nach langjähriger Schmerzgeschichte wieder beschwerdefrei seinen Sport ausüben, obwohl seine Therapie mit einem Fehler der Therapeutin in der Ursachenhypothese begann. </jats:p

The reliability of satellite-based lighttrends for dark sky areas in Austria

Globally, light pollution is a phenomenon rising in its appearance and threatening human health and natural habitats for flora and fauna. Consequently, there is a great interest in interdisciplinary communities to keep an eye on its occurrence and development. One possibility to obtain meaningful data are satellite-based observations, coming mainly from the Visible Infrared Imaging Radiometer Suite (VIIRS) capturing top-of-the -atmosphere radiance levels originating from Earth's surface. Tools designed to easily inspect monthly averaged data of this instrument are web applications. In this work, we focus on dark sky areas in Austria, namely 47 nature parks, and investigate collected data from such application and their reliability in making statements about the development of artificial light at night on the ground. Including atmospheric variations and other limitations, our results lead to a detection limit in radiance change by a minimum of +/- 10%. Below this value, detected changes in surface brightness must not be traced back to changes of ground-based artificial light according to a specified statistical significance of three sigma. In total, 38 of 47 nature parks are examinable, showing an increase in radiance by similar to 42 percent over ten years in average, more than double compared to the entire national territory. As a conclusion, satellite data as analysed must be available for large periods, in order to decrease detection thresholds and make accurate statements about the development of light pollution. However, for detailed analytical research, it is highly recommended that especially dark areas globally establish ground-based light monitoring networks in their areas