An Engineered sgsh Mutant Zebrafish Recapitulates Molecular and Behavioural Pathobiology of Sanfilippo Syndrome A/MPS IIIA

Mucopolysaccharidosis IIIA (MPS IIIA, Sanfilippo syndrome type A), a paediatric neurological lysosomal storage disease, is caused by impaired function of the enzyme N-sulfoglucosamine sulfohydrolase (SGSH) resulting in impaired catabolism of heparan sulfate glycosaminoglycan (HS GAG) and its accumulation in tissues. MPS IIIA represents a significant proportion of childhood dementias. This condition generally leads to patient death in the teenage years, yet no effective therapy exists for MPS IIIA and a complete understanding of the mechanisms of MPS IIIA pathogenesis is lacking. Here, we employ targeted CRISPR/Cas9 mutagenesis to generate a model of MPS IIIA in the zebrafish, a model organism with strong genetic tractability and amenity for high-throughput screening. The sgsh^Δex5−6 zebrafish mutant exhibits a complete absence of Sgsh enzymatic activity, leading to progressive accumulation of HS degradation products with age. sgsh^Δex5−6 zebrafish faithfully recapitulate diverse CNS-specific features of MPS IIIA, including neuronal lysosomal overabundance, complex behavioural phenotypes, and profound, lifelong neuroinflammation. We further demonstrate that neuroinflammation in sgsh^Δex5−6 zebrafish is largely dependent on interleukin-1β and can be attenuated via the pharmacological inhibition of Caspase-1, which partially rescues behavioural abnormalities in sgsh^Δex5−6 mutant larvae in a context-dependent manner. We expect the sgsh^Δex5−6 zebrafish mutant to be a valuable resource in gaining a better understanding of MPS IIIA pathobiology towards the development of timely and effective therapeutic interventions.     

The effective diffusivities in porous media with and without nonlinear reactions

The question of whether effective diffusivities in porous materials under reactive and nonreactive conditions are equal is addressed. Previous studies had considered the problem with first-order reactions. We study the issue with two nonlinear reactions—a second-order reaction and one governed by the Michaelis-Menten kinetics. Pore network and continuum models of porous media are utilized to estimate the effective diffusivities under reactive and nonreactive conditions. We show that the two effective diffusivities are significantly different. The difference is due to the heterogeneities of the porous material, and the fluctuations that they cause in the spatially varying local concentrations and diffusivities, and can be as large as a few orders of magnitude. Theoretical analysis of diffusion and reactions in porous media is also presented that supports the results of the simulations. In particular, it is shown that the results of pore network simulations cannot be fitted to the classical continuum equation of diffusion and reaction, and that a more complex continuum equation should be used for this purpose.     

Scientific basis for establishing country greenhouse gas estimates for rice-based agriculture: An Indian case study

A comprehensive scientific assessment of CH₄ budget estimation for Indian rice paddies, based on a decade of measurements in India, is presented. Indian paddy cultivation areas contain soils that have low to medium levels of soil organic carbon. The average seasonally integrated CH₄ flux (E _sif) values calculated from these measurements were 15.3 ± 2.6 g m^–2 for continuously flooded (CF), 6.9 ± 4.3 g m^–2 for intermittently flooded (IF) single aeration (SA) and 2.2 ± 1.5 g m^–2 for IF multiple aeration (MA) rice ecosystems. For CF and IF (MA) rice ecosystems having high soil organic carbon, without organic amendments, the CH₄ flux (E _sif) may be increased by 1.7 times relative to low soil organic carbon, whereas it may enhance by 5.3 for CF if amended organically. Organic amendment and high soil organic carbon paddy areas do not alter the methane budget estimates for India (3.6±1.4 TgY^–1) much, due to their small paddy harvested area. Methane estimated using average emission factors (E _sif) for all paddy water regimes, which include harvested areas having soils with high organic carbon and organic amendments, may give a budget of 5 TgY^–1 for India.     

Precautious-RM: a predictable non-preemptive scheduling algorithm for harmonic tasks

A major requirement of many real-time embedded systems is to have time-predictable interaction with the environment. More specifically, they need fixed or small sampling and I/O delays, and they cannot cope with large delay jitters. Non-preemptive execution is a known method to reduce the latter delay; however, the corresponding scheduling problem is NP-Hard for periodic tasks. In this paper, we present Precautious-RM as a predictable linear-time online non-preemptive scheduling algorithm for harmonic tasks which can also deal with the former delay, namely sampling delay. We derive conditions of optimality of Precautious-RM and show that satisfying those conditions, tight bounds for best- and worst-case response times of the tasks can be calculated in polynomial-time. More importantly, response time jitter of the tasks is analyzed and it is proven that under specific conditions, each task has either one or two values for response time, which leads to improving the predictability of the system interaction with the environment. Simulation results demonstrate efficiency of Precautious-RM in increasing accuracy of control applications.     

Anisotropy of X-ray structural parameters of the three phase model in cellulose I

Anisotropy of X-ray structural parameters of the three phase model proposed by Mitra and Mukherjee (ref.2), has been investigated in the case of cellulose fibres of ramie, hemp and jute. The structural parameters have been determined separately from each of the observable equatorial reflections. It has been found that the parameter degree of crystallinity as defined in the model is in fact anisotropic at least in the samples studied. The parameter degree of paracrystallinity introduced by Mitra and Mukherjee was also found to be anisotropic. Several important correlations between the structural parameters have been drawn. It has been observed, in agreement with the recent findings of Hosemann and Balta Calleja (ref.10) that the greater the paracrystalline distortion, the smaller the ‘paracrystallite size’.     

ShapeSynth: Parameterizing model collections for coupled shape exploration and synthesis

Recent advances in modeling tools enable non‐expert users to synthesize novel shapes by assembling parts extracted from model databases. A major challenge for these tools is to provide users with relevant parts, which is especially difficult for large repositories with significant geometric variations. In this paper we analyze unorganized collections of 3D models to facilitate explorative shape synthesis by providing high‐level feedback of possible synthesizable shapes. By jointly analyzing arrangements and shapes of parts across models, we hierarchically embed the models into low‐dimensional spaces. The user can then use the parameterization to explore the existing models by clicking in different areas or by selecting groups to zoom on specific shape clusters. More importantly, any point in the embedded space can be lifted to an arrangement of parts to provide an abstracted view of possible shape variations. The abstraction can further be realized by appropriately deforming parts from neighboring models to produce synthesized geometry. Our experiments show that users can rapidly generate plausible and diverse shapes using our system, which also performs favorably with respect to previous modeling tools.     

Pore network model of deactivation of immobilized glucose isomerase in packed-bed reactors II: three-dimensional simulation at the particle level

Immobilized glucose isomerase is widely used for converting glucose to fructose by enzymatic isomerization. The process takes place in a packed-bed reactor consisting of mesoporous particles with distributed pore sizes and interconnectivities. Its efficiency is, however, significantly affected by deactivation of the mesoporous particles. In this paper, we study deactivation of the mesoporous particles using a three-dimensional pore network model of the pore space with distributed pore sizes and interconnectivities, and investigate several plausible mechanisms of deactivation of the porous particles. The results of the present study, which will be used as the input for simulation of the phenomenon at the reactor level, demonstrates the strong effect of the particles’ morphology on the deactivation process.     

Design and fabrication of 3D‐plotted polymeric scaffolds in functional tissue engineering

Regenerating the load‐bearing tissues requires 3D scaffolds that balance the temporary mechanical function with the biological requirements. In functional tissue engineering, designing scaffolds with biomimetic mechanical properties could promote tissue ingrowth since the cells are sensitive to their local mechanical environment. This work aims to design scaffolds that mimic the mechanical response of the biological tissues under physiological loading conditions. Poly(L ‐lactide) (PLLA) scaffolds with varying porosities and pore sizes were made by the 3D‐plotting technique. The scaffolds were tested under unconfined ramp compression to compare their stress profile under load with that of bovine cartilage. A comparison between the material parameters estimated for the scaffolds and for the bovine cartilage based on the biphasic theory enabled the definition of an optimum window for the porosity and pore size of these constructs. Moreover, the finite element prediction for the stress distribution inside the scaffolds, surrounded by the host cartilaginous tissue, demonstrated a negligible perturbation of the stress field at the site of implantation. The finite element modeling tools in combination with the developed methodology for optimal porosity/pore size determination can be used to improve the design of biomimetic scaffolds. POLYM. ENG. SCI., 47:608–618, 2007. © 2007 Society of Plastics Engineers.     

Analysing the patterns of spatial contrast discontinuities in natural images for robust edge detection

Pattern Analysis and Applications - The pattern of spatial contrast discontinuities in natural images has been analysed in the present work, and based on it, a new adaptive model of the...     

Influence of a mixed Al2O3+Cr2O3 superficial coating on the non-isothermal oxidation behavior of Fe and Fe-Cr alloys

The non-isothermal oxidation behavior of electrolytic-grade iron and Fe-Cr alloys in dry air has been studied using linear heating rates of 6 K/min, 10 K/ min, and 15 K/min up to a final temperature of 1273–1473 K. Some of the iron and iron-chromium alloy samples were given a surface treatment by dipping them in an aqueous solution containing both Cr and Al ions before their oxidation studies. This pretreatment has resulted in improved oxidation resistance and scale adherence as depicted by no scale rupture even after a second thermal cycle. Mass changes were recorded gravimetrically, and scales have been characterized by SEM, EPMA, and x-ray diffraction analyses.