Towards a dynamic assessment of raw materials criticality: linking agent-based demand--with material flow supply modelling approaches.

Emerging technologies such as information and communication-, photovoltaic- or battery technologies are expected to increase significantly the demand for scarce metals in the near future. The recently developed methods to evaluate the criticality of mineral raw materials typically provide a 'snapshot' of the criticality of a certain material at one point in time by using static indicators both for supply risk and for the impacts of supply restrictions. While allowing for insights into the mechanisms behind the criticality of raw materials, these methods cannot account for dynamic changes in products and/or activities over time. In this paper we propose a conceptual framework intended to overcome these limitations by including the dynamic interactions between different possible demand and supply configurations. The framework integrates an agent-based behaviour model, where demand emerges from individual agent decisions and interaction, into a dynamic material flow model, representing the materials' stocks and flows. Within the framework, the environmental implications of substitution decisions are evaluated by applying life-cycle assessment methodology. The approach makes a first step towards a dynamic criticality assessment and will enhance the understanding of industrial substitution decisions and environmental implications related to critical metals. We discuss the potential and limitation of such an approach in contrast to state-of-the-art methods and how it might lead to criticality assessments tailored to the specific circumstances of single industrial sectors or individual companies

Visual tests predict dementia risk in Parkinson's disease

OBJECTIVE To assess the role of visual measures and retinal volume to predict the risk of Parkinson disease (PD) dementia. METHODS In this cohort study, we collected visual, cognitive, and motor data in people with PD. Participants underwent ophthalmic examination, retinal imaging using optical coherence tomography, and visual assessment including acuity and contrast sensitivity and high-level visuoperception measures of skew tolerance and biological motion. We assessed the risk of PD dementia using a recently described algorithm that combines age at onset, sex, depression, motor scores, and baseline cognition. RESULTS One hundred forty-six people were included in the study (112 with PD and 34 age-matched controls). The mean disease duration was 4.1 (±2·5) years. None of these participants had dementia. Higher risk of dementia was associated with poorer performance in visual measures (acuity: ρ = 0.29, p = 0.0024; contrast sensitivity: ρ = −0.37, p < 0.0001; skew tolerance: ρ = −0.25, p = 0.0073; and biological motion: ρ = −0.26, p = 0.0054). In addition, higher risk of PD dementia was associated with thinner retinal structure in layers containing dopaminergic cells, measured as ganglion cell layer (GCL) and inner plexiform layer (IPL) thinning (ρ = −0.29, p = 0.0021; ρ = −0.33, p = 0.00044). These relationships were not seen for the retinal nerve fiber layer that does not contain dopaminergic cells and were not seen in unaffected controls. CONCLUSION Visual measures and retinal structure in dopaminergic layers were related to risk of PD dementia. Our findings suggest that visual measures and retinal GCL and IPL volumes may be useful to predict the risk of dementia in PD

Fluid Particle Accelerations in Fully Developed Turbulence

The motion of fluid particles as they are pushed along erratic trajectories by fluctuating pressure gradients is fundamental to transport and mixing in turbulence. It is essential in cloud formation and atmospheric transport, processes in stirred chemical reactors and combustion systems, and in the industrial production of nanoparticles. The perspective of particle trajectories has been used successfully to describe mixing and transport in turbulence, but issues of fundamental importance remain unresolved. One such issue is the Heisenberg-Yaglom prediction of fluid particle accelerations, based on the 1941 scaling theory of Kolmogorov (K41). Here we report acceleration measurements using a detector adapted from high-energy physics to track particles in a laboratory water flow at Reynolds numbers up to 63,000. We find that universal K41 scaling of the acceleration variance is attained at high Reynolds numbers. Our data show strong intermittency---particles are observed with accelerations of up to 1,500 times the acceleration of gravity (40 times the root mean square value). Finally, we find that accelerations manifest the anisotropy of the large scale flow at all Reynolds numbers studied.Comment: 7 pages, 4 figure

Reverse Transcriptase-Coupled Quantitative Real Time PCR Analysis of Cell-Free Transcription on the Chromatin-Assembled p21 Promoter

Background: Cell-free eukaryotic transcription assays have contributed tremendously to the current understanding of the molecular mechanisms that govern transcription at eukaryotic promoters. Currently, the conventional G-less cassette transcription assay is one of the simplest and fastest methods for measuring transcription in vitro. This method requires several components, including the radioisotope labelling of RNA product during the transcription reaction followed by visualization of transcripts using autoradiography. Methodology/Principal Findings: To further simplify and expedite the conventional G-less cassette transcription assay, we have developed a method to incorporate a reverse transcriptase-coupled quantitative real time PCR (RT-qPCR). By using DNA template depletion steps that include DNA template immobilization, Trizol extraction and DNase I treatment, we have successfully enriched p21 promoter-driven transcripts over DNA templates. The quantification results of RNA transcripts using the RT-qPCR assay were comparable to the results of the conventional G-less cassette transcription assay both in naked DNA and chromatin-assembled templates. Conclusions: We first report a proof-of-concept demonstration that incorporating RT-qPCR in cell-free transcription assays can be a simpler and faster alternative method to the conventional radioisotope-mediated transcription assays. This method will be useful for developing high throughput in vitro transcription assays and provide quantitative data for RNA transcript

Dual Space of a Lattice as the Completion of a Pervin Space

16th International Conference, RAMiCS 2017, Lyon, France, May 15-18, 2017, ProceedingsInternational audienceThis survey paper presents well-known results from a new angle. A Pervin space is a set X equipped with a set of subsets,called the blocks of the Pervin space. Blocks are closed under finite intersections and finite unions and hence form a lattice of subsets of X. Pervin spaces are thus easier to define than topological spaces or (quasi)-uniform spaces. As a consequence, most of the standard topological notions, like convergence and cluster points, specialisation order, filtersand Cauchy filters, complete spaces and completion are much easier to define for Pervin spaces. In particular, the completion of a Pervin space turns out to be the dual space (in the sense of Stone) of the original lattice.We show that any lattice of subsets can be described by a set of inequations of the form u ≤ v, where u and v are elements of its dual space. Applications to formal languages and complexity classes are given.Cet article de synthèse présente des résultats bien connus sous un nouvel angle. Un espace de Pervin est unensemble X équipé d'un ensemble de parties, appelé les blocs de l'espace de Pervin. Les blocs sont fermés par intersection finie et union finie et forment ainsi un treillis de parties de X. Les espaces de Pervin sont doncplus faciles à définir que les espaces topologiques ou les espaces (quasi-)uniformes. Par conséquent, la plupart des notions topologiques, comme la convergence et les points d'adhérence, l'ordre de spécialisation, les filtres de Cauchy, les espaces complets et la complétion sont beaucoup plus faciles à définir pour les espaces Pervin. En particulier, la complétion d'un espace Pervin s'avère être l'espace dual (au sens de Stone) du treillis de départ.Nous montrons que tout treillis de parties peut être décrit par un ensemble d'inéquations de la forme u ≤ v, où u et v sont des éléments de son espace dual. On donne des applications aux langages formels et aux classes de complexité

Purinergic receptors are part of a signalling system for proliferation and differentiation in distinct cell lineages in human anagen hair follicles

We investigated the expression of P2X5, P2X7, P2Y1 and P2Y2 receptor subtypes in adult human anagen hair follicles and in relation to markers of proliferation [proliferating cell nuclear antigen (PCNA) and Ki-67], keratinocyte differentiation (involucrin) and apoptosis (anticaspase-3). Using immunohistochemistry, we showed that P2X5, P2Y1 and P2Y2 receptors were expressed in spatially distinct zones of the anagen hair follicle: P2Y1 receptors in the outer root sheath and bulb, P2X5 receptors in the inner and outer root sheaths and medulla and P2Y2 receptors in living cells at the edge of the cortex/medulla. P2X7 receptors were not expressed. Colocalisation experiments suggested different functional roles for these receptors: P2Y1 receptors were associated with bulb and outer root sheath keratinocyte proliferation, P2X5 receptors were associated with differentiation of cells of the medulla and inner root sheaths and P2Y2 receptors were associated with early differentiated cells in the cortex/medulla that contribute to the formation of the hair shaft. The therapeutic potential of purinergic agonists and antagonists for controlling hair growth is discussed

Bedside Sublingual Video Imaging of Microcirculation in Assessing Bacterial Infection in Cirrhosis

Bacterial infections are common in cirrhosis and can lead to life-threatening complications. Sidestream dark-field (SDF) imaging has recently emerged as a noninvasive tool for capturing real-time video images of sublingual microcirculation in critically ill patients with sepsis. The objective of this study was to assess the utility of SDF in determining underlying infection in patients with cirrhosis. Sublingual microcirculation was compared among patients with compensated cirrhosis (Group A, n = 13), cirrhosis without sepsis (Group B, n = 18), cirrhosis with sepsis (Group C, n = 14), and sepsis only (Group D, n = 10). The blood flow was semi-quantitatively evaluated in four equal quadrants in small (10–25 mm); medium (26–50 mm); and large (51–100 mm) sublingual capillaries. The blood flow was described as no flow (0), intermittent flow (1), sluggish flow (2), and continuous flow (3). The overall flow score or microvascular flow index (MFI) was measured for quantitative assessment of microcirculation and predicting power for concurrent infection in cirrhosis. Marked impairment was observed at all levels of microvasculature in Groups B and C when compared with Group A. This effect was restricted to small vessels only when Group B was compared with Group C. MFI < 1.5 was found to have highest sensitivity (100%) and specificity (100%) for infection in decompensated cirrhosis. SDF imaging of sublingual microcirculation can be a useful bedside diagnostic tool to assess bacterial infection in cirrhosis

Intramolecular Folding in Human ILPR Fragment with Three C-Rich Repeats

Enrichment of four tandem repeats of guanine (G) rich and cytosine (C) rich sequences in functionally important regions of human genome forebodes the biological implications of four-stranded DNA structures, such as G-quadruplex and i-motif, that can form in these sequences. However, there have been few reports on the intramolecular formation of non-B DNA structures in less than four tandem repeats of G or C rich sequences. Here, using mechanical unfolding at the single-molecule level, electrophoretic mobility shift assay (EMSA), circular dichroism (CD), and ultraviolet (UV) spectroscopy, we report an intramolecularly folded non-B DNA structure in three tandem cytosine rich repeats, 5'-TGTC4ACAC4TGTC4ACA (ILPR-I3), in the human insulin linked polymorphic region (ILPR). The thermal denaturation analyses of the sequences with systematic C to T mutations have suggested that the structure is linchpinned by a stack of hemiprotonated cytosine pairs between two terminal C4 tracts. Mechanical unfolding and Br2 footprinting experiments on a mixture of the ILPR-I3 and a 5′-C4TGT fragment have further indicated that the structure serves as a building block for intermolecular i-motif formation. The existence of such a conformation under acidic or neutral pH complies with the strand-by-strand folding pathway of ILPR i-motif structures

The Contribution of Coevolving Residues to the Stability of KDO8P Synthase

The evolutionary tree of 3-deoxy-D-manno-octulosonate 8-phosphate (KDO8P) synthase (KDO8PS), a bacterial enzyme that catalyzes a key step in the biosynthesis of bacterial endotoxin, is evenly divided between metal and non-metal forms, both having similar structures, but diverging in various degrees in amino acid sequence. Mutagenesis, crystallographic and computational studies have established that only a few residues determine whether or not KDO8PS requires a metal for function. The remaining divergence in the amino acid sequence of KDO8PSs is apparently unrelated to the underlying catalytic mechanism.The multiple alignment of all known KDO8PS sequences reveals that several residue pairs coevolved, an indication of their possible linkage to a structural constraint. In this study we investigated by computational means the contribution of coevolving residues to the stability of KDO8PS. We found that about 1/4 of all strongly coevolving pairs probably originated from cycles of mutation (decreasing stability) and suppression (restoring it), while the remaining pairs are best explained by a succession of neutral or nearly neutral covarions.Both sequence conservation and coevolution are involved in the preservation of the core structure of KDO8PS, but the contribution of coevolving residues is, in proportion, smaller. This is because small stability gains or losses associated with selection of certain residues in some regions of the stability landscape of KDO8PS are easily offset by a large number of possible changes in other regions. While this effect increases the tolerance of KDO8PS to deleterious mutations, it also decreases the probability that specific pairs of residues could have a strong contribution to the thermodynamic stability of the protein