A Novel Neurofilament Light Chain ELISA Validated in Patients with Alzheimer’s Disease,Frontotemporal Dementia,and Subjective Cognitive Decline,and the Evaluation of Candidate Proteins for Immunoassay Calibration

Neurofilament light chain (Nf-L) is a well-known biomarker for axonal damage; however, the corresponding circulating Nf-L analyte in cerebrospinal fluid (CSF) is poorly characterized. We therefore isolated new monoclonal antibodies against synthetic peptides, and these monoclonals were characterized for their specificity on brain-specific intermediate filament proteins. Two highly specific antibodies, ADx206 and ADx209, were analytically validated for CSF applications according to well-established criteria. Interestingly, using three different sources of purified Nf-L proteins, a significant impact on interpolated concentrations was observed. With a lower limit of analytical sensitivity of 100 pg/mL using bovine Nf-L as the calibrator, we were able to quantify the Nf-L analyte in each sample, and these Nf-L concentrations were highly correlated to the Uman diagnostics assay (Spearman rho = 0.97, p < 0.001). In the clinical diagnostic groups, the new Nf-L ELISA could discriminate patients with Alzheimer’s disease (AD, n = 20) from those with frontotemporal lobe dementia (FTD, n = 20) and control samples with subjective cognitive decline (SCD, n = 20). Henceforth, this novel Nf-L ELISA with well-defined specificity and epitopes can be used to enhance our understanding of harmonizing the use of Nf-L as a clinically relevant marker for neurodegeneration in CSF.     

Introduction to the Special Issue on Meta-Learning

Recent advances in meta-learning are providing the foundations to construct meta-learning assistants and task-adaptive learners. The goal of this special issue is to foster an interest in meta-learning by compiling representative work in the field. The contributions to this special issue provide strong insights into the construction of future meta-learning tools. In this introduction we present a common frame of reference to address work in meta-learning through the concept of meta-knowledge. We show how meta-learning can be simply defined as the process of exploiting knowledge about learning that enables us to understand and improve the performance of learning algorithms.     

Chelating Polymers for Targeted Decontamination of Actinides: Application of PEI-MP to Hydroxyapatite-Th(IV)

In case of an incident in the nuclear industry or an act of war or terrorism, the dissemination of plutonium could contaminate the environment and, hence, humans. Human contamination mainly occurs via inhalation and/or wounding (and, less likely, ingestion). In such cases, plutonium, if soluble, reaches circulation, whereas the poorly soluble fraction (such as small colloids) is trapped in alveolar macrophages or remains at the site of wounding. Once in the blood, the plutonium is delivered to the liver and/or to the bone, particularly into its mineral part, mostly composed of hydroxyapatite. Countermeasures against plutonium exist and consist of intravenous injections or inhalation of diethylenetetraminepentaacetate salts. Their effectiveness is, however, mainly confined to the circulating soluble forms of plutonium. Furthermore, the short bioavailability of diethylenetetraminepentaacetate results in its rapid elimination. To overcome these limitations and to provide a complementary approach to this common therapy, we developed polymeric analogs to indirectly target the problematic retention sites. We present herein a first study regarding the decontamination abilities of polyethyleneimine methylcarboxylate (structural diethylenetetraminepentaacetate polymer analog) and polyethyleneimine methylphosphonate (phosphonate polymeric analog) directed against Th(IV), used here as a Pu(IV) surrogate, which was incorporated into hydroxyapatite used as a bone model. Our results suggest that polyethylenimine methylphosphonate could be a good candidate for powerful bone decontamination action.     

Compressive and Tensile Behaviours of PLLA Matrix Composites Reinforced with Randomly Dispersed Flax Fibres

Nowadays, the ecological footprint of a material is becoming tremendously important. The Poly l-Lactide Acid (PLLA) matrix composites reinforced by randomly scattered flax fibres have mechanical properties similar to polyester/glass composites [1], lower environmental impacts and can be compost at the end of their lives. In this study, the mechanical characterization of biocomposites has been pushed further with the determination of the compressive and tensile properties. Furthermore, the mechanical properties of single flax fibres have been measured and implemented in a micro-mechanical estimation of the composite elastic modulus. Tensile and compressive stiffness determined by the mechanical analyses show very good correlations with the mathematical estimation.     

Multiproject lineage management: Bridging project management and design-based innovation strategy

Innovation-based strategies are widely recognized as key drivers to maintain competitive advantage. The design and strategic literature underline the possibility of triggering a multiproduct value-expansion dynamic based on the creation of new concepts dynamically twinned with corporate strategy. However, the multiproject-management literature—portfolio, program, and platform—lags behind and remains focused on ex ante coordination, resource allocation and selectionism. Thus, there are still few indications of the processes that stimulate and orient continuous, profitable multiproject creative expansion. Bridging the multiproject-management literature and design theory, we propose a model of multiproject lineage management (MPLM), which focuses on the key processes that drive exploration efforts and shape innovation trajectory. We conduct a multiple longitudinal case analysis in the automobile sector. Based on this analysis, we expose the principles of MPLM, mapping the roles of corporate, program and project management within a global expansion project. Finally, we highlight our contributions to managerial practices and the related literature.     

Mechanistic investigation and selectivity of the grafting onto C60 of macroradicals prepared by cobalt-mediated radical polymerization

The grafting mechanism of poly(vinyl acetate) macroradicals prepared by cobalt-mediated radical polymerization onto C₆₀ is investigated. The experimental conditions directly impact the nature and stability of the PVAc/C₆₀ adducts. In the presence of residual initiating radicals that can compete with PVAc° macroradicals for addition onto C₆₀, mixtures of PVAc/C₆₀ adducts having between one and eight polymer chains per C₆₀ are formed. PVAc/C₆₀ adducts prepared with low [PVAc]:[C₆₀] ratios may contain weak C₆₀–C₆₀ bonds that further dissociate and account for the instability of the products. The formation of such dimers can be lessened by increasing the temperature from 30 °C to 100 °C. The temperature increase also allows a complete dissociation of the PVAc-Co dormant species into PVAc° macroradicals and an almost quantitative grafting of eight PVAc chains onto C₆₀, leading to well-defined C₆₀(PVAc)₈ octa-adducts. These results might shed new light on the grafting onto C₆₀ of macroradicals prepared by other CRP techniques.     

PLLA/Flax Mat/Balsa Bio-Sandwich—Environmental Impact and Simplified Life Cycle Analysis

In the present paper the environmental impact of biocomposites and bio-sandwich materials production are evaluated, using simplified Life Cycle Analysis (LCA) following the procedure recommended in the ISO 14044 standard. The materials are dimensioned and evaluated by comparing with reference materials, glass mat reinforced unsatured polyester and glass mat/unsatured polyester/balsa sandwich. The results indicate that bio-sandwich materials are very attractive in terms environmental impact. However further improvements in biocomposite and bio-sandwich mechanical strength are necessary if they are to be used in transport application compared to glass/polyester and glass/polyester/balsa sandwich.