Toward Rigorous Materials Production: New Approach Methodologies Have Extensive Potential to Improve Current Safety Assessment Practices

Advanced material development, including at the nanoscale, comprises costly and complex challenges coupled to ensuring human and environmental safety. Governmental agencies regulating safety have announced interest toward acceptance of safety data generated under the collective term New Approach Methodologies (NAMs), as such technologies/approaches offer marked potential to progress the integration of safety testing measures during innovation from idea to product launch of nanomaterials. Divided in overall eight main categories, searchable databases for grouping and read across purposes, exposure assessment and modeling, in silico modeling of physicochemical structure and hazard data, in vitro high‐throughput and high‐content screening assays, dose‐response assessments and modeling, analyses of biological processes and toxicity pathways, kinetics and dose extrapolation, consideration of relevant exposure levels and biomarker endpoints typify such useful NAMs. Their application generally agrees with articulated stakeholder needs for improvement of safety testing procedures. They further fit for inclusion and add value in nanomaterials risk assessment tools. Overall 37 of 50 evaluated NAMs and tiered workflows applying NAMs are recommended for considering safer‐by‐design innovation, including guidance to the selection of specific NAMs in the eight categories. An innovation funnel enriched with safety methods is ultimately proposed under the central aim of promoting rigorous nanomaterials innovation.     

Long-term impact of acid resin waste deposits on soil quality of forest areas I. Contaminants and abiotic properties

Acid resins are residues characterised by elevated concentrations of hydrocarbons and trace elements, which were produced by mineral oil industries in Central Europe during the first half of the last century. Due to the lack of environmental legislation at that time, these wastes were dumped into excavated ponds in public areas without further protection. In this work, the long-term effects of such resin deposits on soil quality of two forest areas (Bayern, Germany) were assessed. We evaluated the distribution and accumulation of contaminants in the surroundings of the deposits, where the waste was disposed of about 60 years ago. General soil chemical properties such as pH, C, N and P content were also investigated. Chemical analysis of resin waste from the deposits revealed large amounts of potential contaminants such as hydrocarbons (93 g kg(-1)), As (63 mg kg(-1)), Cd (24 mg kg(-1)), Cu (1835 mg kg(-1)), Pb (8100 mg kg(-1)) and Zn (873 mg kg(-1)). Due to the location of the deposits on a hillside and the lack of adequate isolation, contaminants have been released downhill despite the solid nature of the waste. Five zones were investigated in each site: the deposit, three affected zones along the plume of contamination and a control zone. In affected zones, contaminants were 2 to 350 times higher than background levels depending on the site. In many cases, contaminants exceeded the German environmental guidelines for the soil-groundwater path and action levels based on extractable concentrations. Resin contamination yielded larger total C/total N ratios in affected zones, but no clear effect was observed on absolute C, N and P concentrations. In general, no major acidification effect was reported in affected zones.     

Long-term impact of acid resin waste deposits on soil quality of forest areas II. Biological indicators

In this study, we evaluated the effects of two acid resin deposits on the soil microbiota of forest areas by means of biomass, microbial activity-related estimations and simple biological ratios. The determinations carried out included: total DNA yield, basal respiration, intracellular enzyme activities (dehydrogenase and catalase) and extracellular enzyme activities involved in the cycles of C (beta-glucosidase and chitinase), N (protease) and P (acid-phosphatase). The calculated ratios were: total DNA/total N; basal respiration/total DNA; dehydrogenase/total DNA and catalase/total DNA. Total DNA yield was used to estimate soil microbial biomass. Results showed that microbial biomass and activity were severely inhibited in the deposits, whilst resin effects on contaminated zones were variable and site-dependant. Correlation analysis showed no clear effect of contaminants on biomass and activities outside the deposits, but a strong interdependence with natural organic matter related parameters such as total N. In contrast, by using simple ratios we could detect more stressful conditions in terms of organic matter turnover and basal metabolism in contaminated areas compared to their uncontaminated counterparts. These results stress that developed ecosystems such as forests can buffer the effects of pollutants and preserve high functionality via natural attenuation mechanisms, but also that acid resins can be toxic to biological targets negatively affecting soil dynamics. Acid resin deposits can therefore act as contaminant sources adversely altering soil processes and reducing the environmental quality of affected areas despite the solid nature of these wastes.     

Semi-natural grassland continuity, long-term land-use change and plant species richness in an agricultural landscape on Öland, Sweden

The study characterizes historical land-use change and the development of semi-natural grassland habitats, over 274 years, within a mosaic agricultural landscape (22 km²) on the island of Öland (Sweden). We also explore the relationship between previous land-use, habitat continuity and present-day vascular plant species richness in grassland patches. Land-cover maps, based on cadastral maps and aerial photographs, were produced for six time-periods between 1723/1733 and 1994/1997. In 1723/1733, the landscape was dominated by grasslands, with arable land surrounding the villages. The grassland area decreased throughout the study period and grassland patches became progressively more fragmented. Present-day grasslands represent 18% of the grassland area in 1723/1733. The land-use structure of the early 18th century is still evident in the modern landscape. The majority of the present-day grasslands are situated on former common grazing land and have had a continuity of at least 274 years: the remaining grasslands are younger and developed during the 20th century on arable or forested land. The proportion of plant species that depend on grazing and are characteristic of semi-natural grasslands significantly reflects the continuity and previous land-use of grassland sites. The study illustrates the way in which information on historical land-use and habitat continuity can help to explain the structuring of plant assemblages in semi-natural grasslands within the modern landscape.     

提高大坝安全性能的一种方法——溢洪道维修案例分析(英文)

瑞典新的洪水设计及大坝安全指南对全国水库大坝的安全提出了更高的要求。指南对每一条河流情况进行了复核并找到了较好的解决方案,即储水和提高溢洪道泄洪能力相结合的方案。为了符合指南的要求,瑞典全国上下都在实施一个大坝安全计划,对大量的水库大坝提高其安全性能,以满足更高的洪水设计(及其它方面)的要求。技术方案包括大坝加固、溢洪道泄洪能力提升和临时储水设施。Stenkullafor 水库大坝设有一个 2 闸控制的敞开式溢洪道。该水库修改后的设计洪水将比现有溢洪道泄洪能力提高 40%。根据成本效益分析,提高溢洪道泄流能力的主要措施是降低其中一个闸门顶高程,以适应需要提高的泄洪能力。通过水工模型试验,一方面优化溢洪道顶部轮廓,另一方面降低溢洪道顶部改造和新闸门的成本。溢洪道右侧闸门底高程降低 4.3 m,并新安装一扇更高的闸门。现在,大坝的安全性能已得到提高。对水工模型试验和施工时的洪水风险,施工过程及其遇到的困难进行了介绍,并对坝体加固、上游坡新的侵蚀防护、下游消能及下游行洪渠道等工程措施进行了描述。     

Thoracic and lumbar spinal impact tolerance

INTRODUCTION: Thoracolumbar injuries resulting from motor vehicle accidents, falls, and assaults have a high risk of morbidity and mortality. However, there are no biomechanically based standards that address this problem. METHODS: This study used four cadaveric porcine specimens as a model for direct spinal impact injuries to humans to determine an appropriate injury tolerance value. The anthropometric parameters of these specimens are compared with values found in a large human cadaveric dataset. Each specimen was subjected to five impacts on the dorsal surface of the lower thorax and abdomen. RESULTS: The injuries ranged from mild spinous process fractures to endplate fractures with anterior longitudinal ligament (ALL) transactions with a maximum AIS=3. The average peak reaction force for the thoracic failure tests was 4720+/-1340 N, and the average peak reaction force for the lumbar failure tests was 4650+/-1590 N. DISCUSSION: When scaled to human values using anthropometric parameters determined in this study, the force at which there is a 50% risk of injury is 10,200+/-3900 N. This value favorably compares to that found in the existing literature on isolated vertebral segments. SUMMARY: After demonstrating that the porcine model can be used as a spinal impact model for the human, the resulting injury risk value can be used in determining new standards for human injury risk or in guiding the design of safety equipment for the back.     

Masculinity causes speeding in young men

The goal of this study was to examine if masculinity is causally responsible for speeding in young men. Participants (83 males) were randomly assigned to a masculine, feminine, or neutral priming condition. Priming consisted in active listening to either masculine, feminine, or neutral words coming from the car radio while driving in a high-end driving simulator. Results showed that when the concept of masculinity was activated by priming, participants' driving speed increased significantly from the beginning to the end of the driving simulation as compared to the neutral and the feminine condition. Results are discussed with respect to real life health implications.     

Multivariate analysis applied to the study of spatial distributions found in drug-eluting stent coatings by confocal Raman microscopy

Multivariate data analysis was applied to confocal Raman measurements on stents coated with the polymers and drug used in the CYPHER Sirolimus-eluting Coronary Stents. Partial least-squares (PLS) regression was used to establish three independent calibration curves for the coating constituents: sirolimus, poly(n-butyl methacrylate) [PBMA], and poly(ethylene-co-vinyl acetate) [PEVA]. The PLS calibrations were based on average spectra generated from each spatial location profiled. The PLS models were tested on six unknown stent samples to assess accuracy and precision. The wt % difference between PLS predictions and laboratory assay values for sirolimus was less than 1 wt % for the composite of the six unknowns, while the polymer models were estimated to be less than 0.5 wt % difference for the combined samples. The linearity and specificity of the three PLS models were also demonstrated with the three PLS models. In contrast to earlier univariate models, the PLS models achieved mass balance with better accuracy. This analysis was extended to evaluate the spatial distribution of the three constituents. Quantitative bitmap images of drug-eluting stent coatings are presented for the first time to assess the local distribution of components.     

NMR-detected conformational exchange observed in a computationally designed variant of protein Gbeta1

Detailed biophysical characterization of computationally designed proteins has become increasingly important in order to thoroughly understand the properties of these variants compared with wild-type and to apply this knowledge to future designs. The protein dynamics and structural properties of a computationally designed variant (Delta1.5) of the beta1 domain of streptococcal protein G (Gbeta1) were measured using multinuclear NMR methods. Results from relaxation, diffusion and hydrogen exchange experiments indicate that the variant weakly self-associates at NMR concentrations, with evidence for multiple binding sites. Although comparison of fast (ps-ns) timescale motions shows only small differences in dynamics between Delta1.5 and wild-type, results from the measurement of intermediate (mus-ms) timescale motions are very different. Significant backbone conformational exchange has been observed in the variant at positions all along the sequence, whereas the wild-type Gbeta1 shows little evidence for this type of motion. This increased conformational exchange in Delta1.5 has been attributed to core overpacking resulting from the incorporation of two large hydrophobic side chains and the loss of an aromatic T-stacking interaction. These data highlight, in detail, the potential consequences of incorporating major perturbations in the core of a protein and the need to carry out more detailed analyses of the biophysical properties of designed proteins in order to better understand and predict the effects of mutations.