Studying mixture effects on uptake and tissue distribution of PFAS in zebrafish (Danio rerio) using physiologically based kinetic (PBK) modelling

Per- and polyfluoroalkyl substances (PFAS) are ubiquitously distributed in the aquatic environment. They include persistent, mobile, bioaccumulative, and toxic chemicals and it is therefore critical to increase our understanding on their adsorption, distribution, metabolism, excretion (ADME). The current study focused on uptake of seven emerging PFAS in zebrafish (Danio rerio) and their potential maternal transfer. In addition, we aimed at increasing our understanding on mixture effects on ADME by developing a physiologically based kinetic (PBK) model capable of handling co-exposure scenarios of any number of chemicals. All studied chemicals were taken up in the fish to varying degrees, whereas only perfluorononanoate (PFNA) and perfluorooctanoate (PFOA) were quantified in all analysed tissues. Perfluorooctane sulfonamide (FOSA) was measured at concerningly high concentrations in the brain (Cmax over 15 μg/g) but also in the liver and ovaries. All studied PFAS were maternally transferred to the eggs, with FOSA and 6:2 perfluorooctane sulfonate (6,2 FTSA) showing significant (p 85 % of predictions within a 10-fold error and 60 % of predictions within a 3-fold error. At studied levels of PFAS exposure, competitive binding was not a critical factor for PFAS kinetics. Gill surface pH influenced uptake for some carboxylates but not the sulfonates. The developed PBK model provides an important tool in understanding kinetics under complex mixture scenarios and this use of New Approach Methodologies (NAMs) is critical in future risk assessment of chemicals and early warning systems

The initial singularity of ultrastiff perfect fluid spacetimes without symmetries

We consider the Einstein equations coupled to an ultrastiff perfect fluid and prove the existence of a family of solutions with an initial singularity whose structure is that of explicit isotropic models. This family of solutions is `generic' in the sense that it depends on as many free functions as a general solution, i.e., without imposing any symmetry assumptions, of the Einstein-Euler equations. The method we use is a that of a Fuchsian reduction.Comment: 16 pages, journal versio

Combining in Silico Tools with Multicriteria Analysis for Alternatives Assessment of Hazardous Chemicals: A Case Study of Decabromodiphenyl Ether Alternatives

Alternatives assessment is applied for minimizing the risk of unintentionally replacing a hazardous chemical with another hazardous chemical. Central challenges are the diversity of properties to consider and the lack of high-quality experimental data. To address this, a novel alternatives assessment procedure was developed based on in silico data and multicriteria decision analysis (MCDA) methods. As a case study, 16 alternatives to the flame retardant decabromodiphenyl ether were considered. The hazard properties included persistence (P), bioaccumulation potential (B), toxicities (T), and mobility in water (M). Databases were consulted and 2866 experimental data points were collected for the target chemicals; however, these were mostly replicate data points for some hazard criteria for a subset of alternatives. Therefore, in silico data and three MCDA strategies were tested including heat mapping, multiattribute utility theory (MAUT), and Elimination Et Choix Traduisant la REalit\ue9 (ELECTRE III). The heat map clearly showed that none of the target chemicals are hazard-free, whereas MAUT and ELECTRE III agreed on ranking the "least worst" choices. This study identified several challenges and the complexity in the alternatives assessment processes motivating more case studies combining in silico and MCDA approaches

Collision Dynamics and Solvation of Water Molecules in a Liquid Methanol Film

Environmental molecular beam experiments are used to examine water interactions with liquid methanol films at temperatures from 170 K to 190 K. We find that water molecules with 0.32 eV incident kinetic energy are efficiently trapped by the liquid methanol. The scattering process is characterized by an efficient loss of energy to surface modes with a minor component of the incident beam that is inelastically scattered. Thermal desorption of water molecules has a well characterized Arrhenius form with an activation energy of 0.47{\pm}0.11 eV and pre-exponential factor of 4.6 {\times} 10^(15{\pm}3) s^(-1). We also observe a temperature dependent incorporation of incident water into the methanol layer. The implication for fundamental studies and environmental applications is that even an alcohol as simple as methanol can exhibit complex and temperature dependent surfactant behavior.Comment: 8 pages, 5 figure

Gene expression signatures in childhood acute leukemias are largely unique and distinct from those of normal tissues and other malignancies

<p>Abstract</p> <p>Background</p> <p>Childhood leukemia is characterized by the presence of balanced chromosomal translocations or by other structural or numerical chromosomal changes. It is well know that leukemias with specific molecular abnormalities display profoundly different global gene expression profiles. However, it is largely unknown whether such subtype-specific leukemic signatures are unique or if they are active also in non-hematopoietic normal tissues or in other human cancer types.</p> <p>Methods</p> <p>Using gene set enrichment analysis, we systematically explored whether the transcriptional programs in childhood acute lymphoblastic leukemia (ALL) and myeloid leukemia (AML) were significantly similar to those in different flow-sorted subpopulations of normal hematopoietic cells (n = 8), normal non-hematopoietic tissues (n = 22) or human cancer tissues (n = 13).</p> <p>Results</p> <p>This study revealed that e.g., the t(12;21) [<it>ETV6-RUNX1</it>] subtype of ALL and the t(15;17) [<it>PML-RARA</it>] subtype of AML had transcriptional programs similar to those in normal Pro-B cells and promyelocytes, respectively. Moreover, the 11q23/<it>MLL </it>subtype of ALL showed similarities with non-hematopoietic tissues. Strikingly however, most of the transcriptional programs in the other leukemic subtypes lacked significant similarity to ~100 gene sets derived from normal and malignant tissues.</p> <p>Conclusions</p> <p>This study demonstrates, for the first time, that the expression profiles of childhood leukemia are largely unique, with limited similarities to transcriptional programs active in normal hematopoietic cells, non-hematopoietic normal tissues or the most common forms of human cancer. In addition to providing important pathogenetic insights, these findings should facilitate the identification of candidate genes or transcriptional programs that can be used as unique targets in leukemia.</p

Weight of evidence evaluation of the metabolism disrupting effects of triphenyl phosphate using an expert knowledge elicitation approach

All partners acknowledge the contribution of their institutes for additional financial support. We would also like to acknowledge the scientific contributions from François Pouzaud, Sakina Mhaouty-Kodja and René Habert for the development of the EKE methodology within the frame of the Anses ED Expert group. Contributions from additional members of the GOLIATH consortium: Pierre-Etienne Toulemonde and Romane Multon from Anses are also acknowledged.Peer reviewe

Применение технологии набрызгбетонирования в Новоавстрийском Методе Туннелирования (NATM)

У статті проаналізовані суть і основні принципи Новоавстрійського Методу Тунелювання (NATM), що широко застосовується в зарубіжній практиці будівництва транспортних тунелів. Також розглянуто застосування технології торкретування, яка лежить в основі методу.Essence and basic principles of New Austrian Tunnelling Method (NATM), which widely used in foreign practice building of transport tunnels, is analysed in the article. Application of gunite technology, being the basis of method, is also considered