Energy dissipation in sheared wet granular assemblies

Energy dissipation in sheared dry and wet granulates is considered in the presence of an externally applied confining pressure. Discrete element simulations reveal that for sufficiently small confining pressures, the energy dissipation is dominated by the effects related to the presence of cohesive forces between the particles. The residual resistance against shear can be quantitatively explained by a combination of two effects arising in a wet granulate: (i) enhanced friction at particle contacts in the presence of attractive capillary forces and (ii) energy dissipation due to the rupture and reformation of liquid bridges. Coulomb friction at grain contacts gives rise to an energy dissipation which grows linearly with increasing confining pressure for both dry and wet granulates. Because of a lower Coulomb friction coefficient in the case of wet grains, as the confining pressure increases the energy dissipation for dry systems is faster than for wet ones

Developing integrated PBPK/PD coupled mechanistic pathway model (miRNA-BDNF): An approach towards system toxicology

Integration of a dynamic signal transduction pathway into the tissue dosimetry model is a major advancement in the area of computational toxicology. This paper illustrates the ways to incorporate the use of existing system biological model in the field of toxicology via its coupling to the Physiological based Pharmacokinetics and Pharmacodynamics (PBPK/PD) model. This expansion framework of integrated PBPK/PD coupled mechanistic system pathway model can be called as system toxicology that describes the kinetics of both - the chemicals and - biomolecules, help us to understand the dynamic and steady-state behaviors of molecular pathways under perturbed condition. The objective of this article is to illustrate a system toxicology based approach by developing an integrated PBPK/PD coupled miRNA-BDNF pathway model and to demonstrate its application by taking a case study of the PFOS mediated neurotoxicity. System dynamic involves miRNA-mediated BDNF regulation, which plays an important role in the control of neuronal cell proliferation, differentiation, and survivability

Active Site Mapping of Xylan-Deconstructing Enzymes with Arabinoxylan Oligosaccharides Produced by Automated Glycan Assembly

Xylan-degrading enzymes are crucial for the deconstruction of hemicellulosic biomass, making the hydrolysis products available for various industrial applications such as the production of biofuel. To determine the substrate specificities of these enzymes, we prepared a collection of complex xylan oligosaccharides by automated glycan assembly. Seven differentially protected building blocks provided the basis for the modular assembly of 2-substituted, 3-substituted, and 2-/3-substituted arabino- and glucuronoxylan oligosaccharides. Elongation of the xylan backbone relied on iterative additions of C4-fluorenylmethoxylcarbonyl (Fmoc) protected xylose building blocks to a linker-functionalized resin. Arabinofuranose and glucuronic acid residues have been selectively attached to the backbone using fully orthogonal 2-(methyl)naphthyl (Nap) and 2-(azidomethyl)benzoyl (Azmb) protecting groups at the C2 and C3 hydroxyls of the xylose building blocks. The arabinoxylan oligosaccharides are excellent tools to map the active site of glycosyl hydrolases involved in xylan deconstruction. The substrate specificities of several xylanases and arabinofuranosidases were determined by analyzing the digestion products after incubation of the oligosaccharides with glycosyl hydrolases.Fil: Senf, Deborah. Max Planck Institut für Kolloid und Grenzflächenforschung; Alemania. Freie Universität; AlemaniaFil: Ruprecht, Colin. Max Planck Institut für Kolloid und Grenzflächenforschung; AlemaniaFil: de Kruijff, Goswinus H. M.. Max Planck Institut für Kolloid und Grenzflächenforschung; Alemania. Freie Universität; Alemania. University Mainz. Institute of Institute of Organic Chemistry, Johannes Gutenberg; AlemaniaFil: Simonetti, Sebastián Osvaldo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina. Max Planck Institut für Kolloid und Grenzflächenforschung; AlemaniaFil: Schuhmacher, Frank. Max Planck Institut für Kolloid und Grenzflächenforschung; Alemania. Freie Universität; AlemaniaFil: Seeberger, Peter H.. Max Planck Institut für Kolloid und Grenzflächenforschung; Alemania. Freie Universität; AlemaniaFil: Pfrengle, Fabian. Max Planck Institut für Kolloid und Grenzflächenforschung; Alemania. Freie Universität; Alemani

Automated glycan assembly of oligosaccharides related to arabinogalactan proteins

Arabinogalactan proteins are heavily glycosylated proteoglycans in plants. Their glycan portion consists of type-II arabinogalactan polysaccharides whose heterogeneity hampers the assignment of the arabinogalactan protein function. Synthetic chemistry is key to the procurement of molecular probes for plant biologists. Described is the automated glycan assembly of 14 oligosaccharides from four monosaccharide building blocks. These linear and branched glycans represent key structural features of natural type-II arabinogalactans and will serve as tools for arabinogalactan biology

Comparative In Vitro Toxicity Evaluation of Heavy Metals (Lead, Cadmium, Arsenic, and Methylmercury) on HT-22 Hippocampal Cell Line

Heavy metals are considered some of the most toxic environmental pollutants. Exposure to heavy metals including lead (Pb), cadmium (Cd), arsenic (As), and methyl mercury (MeHg) has long been known to cause damage to human health. Many recent studies have supported the hippocampus as the major target for these four metals for inflicting cognitive dysfunction. In the present study, we proposed hippocampal relevant in vitro toxicity of Pb, Cd, As, and MeHg in HT-22 cell line. This study reports, initially, cytotoxic effects in acute, subchronic, chronic exposures. We further investigated the mechanistic potency of DNA damage and apoptosis damage with the observed cytotoxicity. The genotoxicity and apoptosis were measured by using the comet assay, annexin-V FTIC / propidium iodide (PI) assay, respectively. The results of cytotoxicity assay clearly demonstrated significant concentration and time-dependent effects on HT-22 cell line. The genotoxic and apoptosis effects also concentration-dependent fashion with respect to their potency in the range of IC10-IC30, maximal level of damage observed in MeHg. In conclusion, the obtained result suggests concentration and potency-dependent response; the maximal level of toxicity was observed in MeHg. These novel findings support that Pb, Cd, As, and MeHg induce cytotoxic, genotoxic, and apoptotic effects on HT-22 cells in potency-dependent manner; MeHg> As> Cd> Pb. Therefore, the toxicity of Pb, Cd, As, and MeHg could be useful for knowing the common underlying molecular mechanism, and also for estimating the mixture impacts on HT-22 cell line

Pre-clinical evaluation of advanced nerve guide conduits using a novel 3D in vitro testing model

Autografts are the current gold standard for large peripheral nerve defects in clinics despite the frequentlyoccurring side effects like donor site morbidity. Hollow nerve guidance conduits (NGC) are proposed alternatives toautografts, but failed to bridge gaps exceeding 3 cm in humans. Internal NGC guidance cues like microfibresare believed to enhance hollow NGCs by giving additional physical support for directed regeneration of Schwann cellsand axons. In this study, we report a new 3D in vitro model that allows the evaluation of different intraluminal fibrescaffolds inside a complete NGC. The performance of electrospun polycaprolactone (PCL) microfibres inside 5 mmlong polyethylene glycol (PEG) conduits were investigated in neuronal cell and dorsal root ganglion (DRG) cultures invitro. Z-stack confocal microscopy revealed the aligned orientation of neuronal cells along the fibres throughout thewhole NGC length and depth. The number of living cells in the centre of the scaffold was not significantly different tothe tissue culture plastic (TCP) control. For ex vivo analysis, DRGs were placed on top of fibre-filled NGCs to simulatethe proximal nerve stump. In 21 days of culture, Schwann cells and axons infiltrated the conduits along the microfibreswith 2.2 ± 0.37 mm and 2.1 ± 0.33 mm, respectively. We conclude that this in vitro model can help define internal NGCscaffolds in the future by comparing different fibre materials, composites and dimensions in one setup prior to animaltesting

Localization Recall Precision (LRP): A New Performance Metric for Object Detection

Average precision (AP), the area under the recall-precision (RP) curve, is the standard performance measure for object detection. Despite its wide acceptance, it has a number of shortcomings, the most important of which are (i) the inability to distinguish very different RP curves, and (ii) the lack of directly measuring bounding box localization accuracy. In this paper, we propose 'Localization Recall Precision (LRP) Error', a new metric which we specifically designed for object detection. LRP Error is composed of three components related to localization, false negative (FN) rate and false positive (FP) rate. Based on LRP, we introduce the 'Optimal LRP', the minimum achievable LRP error representing the best achievable configuration of the detector in terms of recall-precision and the tightness of the boxes. In contrast to AP, which considers precisions over the entire recall domain, Optimal LRP determines the 'best' confidence score threshold for a class, which balances the trade-off between localization and recall-precision. In our experiments, we show that, for state-of-the-art object (SOTA) detectors, Optimal LRP provides richer and more discriminative information than AP. We also demonstrate that the best confidence score thresholds vary significantly among classes and detectors. Moreover, we present LRP results of a simple online video object detector which uses a SOTA still image object detector and show that the class-specific optimized thresholds increase the accuracy against the common approach of using a general threshold for all classes. At https://github.com/cancam/LRP we provide the source code that can compute LRP for the PASCAL VOC and MSCOCO datasets. Our source code can easily be adapted to other datasets as well.Comment: to appear in ECCV 201

Analysis of the uncertainty in the monetary valuation of ecosystem services - a case study at the river basin scale

Ecosystem services provide multiple benefits to human wellbeing and are increasingly considered by 18 policy-makers in environmental management. However, the uncertainty related with the monetary 19 valuation of these benefits is not yet adequately defined or integrated by policy-makers. Given this 20 background, our aim was to quantify different sources of uncertainty when performing monetary 21 valuation of ecosystem services, in order to provide a series of guidelines to reduce them. With an 22 example of 4 ecosystem services (i.e., water provisioning, waste treatment, erosion protection, and 23 habitat for species) provided at the river basin scale, we quantified the uncertainty associated with 24 the following sources: (1) the number of services considered, (2) the number of benefits considered 25 for each service, (3) the valuation metrics (i.e. valuation methods) used to value benefits, and (4) the 26 uncertainty of the parameters included in the valuation metrics. Results indicate that the highest 27 uncertainty was caused by the number of services considered, as well as by the number of benefits 28 considered for each service, whereas the parametric uncertainty was similar to the one related to the 29 selection of valuation metric, thus suggesting that the parametric uncertainty, which is the only 30 uncertainty type commonly considered, was less critical than the structural uncertainty, which is in 31 turn mainly dependent on the decision-making context. Given the uncertainty associated to the 32 valuation structure, special attention should be given to the selection of services, benefits and 33 metrics according to a given context