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Gene therapies have greatly changed the outlook in spinal muscular atrophy (SMA), and this disorder provides a rare opportunity to study longitudinal biomarker changes correlated with reduced disease burden and improved clinical outcomes. Recent work suggests clinical response to correlate with declining cerebrospinal fluid (CSF) levels of the neurodegenerative marker neurofilament light chain (NfL) in children receiving serial anti-sense oligonucleotide therapy. However, change in CSF NfL levels is no longer a practical biomarker as more children undergo single-dose gene replacement therapy. Here we leverage serial CSF samples (median of 4 per child) collected in 13 children with SMA undergoing anti-sense oligonucleotide therapy to characterize the longitudinal profiles of NfL as well as inflammatory and neuronal proteins. In contrast to neurodegeneration in adults, we found NfL levels to first decrease following initiation of treatment but then increase upon further treatment and improved motor functions. We then examined additional CSF inflammatory and neuronal markers for linear association with motor function during SMA treatment. We identified longitudinal IL-8 levels to inversely correlate with motor functions determined by clinical examination (F(1, 47) = 12.903, p = 0.001) or electromyography in the abductor pollicis brevis muscle (p = 0.064). In keeping with this, lower baseline IL-8 levels were associated with better longitudinal outcomes, even though this difference diminished over 2 years in the younger group. We thus propose CSF IL-8 as a biomarker for baseline function and short-term treatment response in SMA, and a candidate biomarker for future treatment trials in other neurodegenerative disorders. [ABSTRACT FROM AUTHOR]

Pretreatment and hydrolysis of lignocellulosic biomass are affected by several uncertainties, which must be systematically considered for a robust process design. In this work, stochastic simulations for expected uncertainties in feedstock composition, kinetic parameter values, and operational parameter values for these two steps were performed. The results indicated that these uncertainties significantly impacted the concentration profiles, which could also affect the optimal batch time. Global sensitivity analysis was then used to identify the critical uncertain parameters. In the feedstock components, cellulose and xylan fractions for acid pretreatment and cellulose fraction for enzymatic hydrolysis were important. Temperature was the most sensitive operating parameter for both acid pretreatment and hydrolysis. The activation energies for different reactions were ranked in terms of their impact on process output. The selected parameters were used to develop stochastic process models using Ito process and mean reverting process for feed composition and kinetic parameter uncertainty. [ABSTRACT FROM AUTHOR]

Abstract: This paper examines the effect of mixer size on the density of the propellant and it also explores the role of the propellant density with regards to burning rate and burn rate pressure index. Propellant samples were prepared in the four different size (15, 70, 200 and 1000g) mixers with identical input of ingredients to examine the effect of mixer size on density and burning rate of the composite solid propellant. It was noticed that density and burning rate of the propellant changes significantly with change in the mixer size from 15g to 1000g. This is because for the smaller mixers the surface area to volume ratio is large and the actual percentage of aluminum and ammonium perchlorate (especially coarse) that goes into the propellant reduces. High burning rate with decrease in mixer size is also accompanied with increase in burn rate pressure index. The composition analysis was also carried out and it is noticed that the actual percentage of the ingredients is different from the intended percentage of the ingredients and percentage change is more when the mixer size decreases. [Copyright &y& Elsevier]

Abstract: This paper reports the discovery of activated charcoal as an effective burn rate enhancer of aluminized composite solid propellant. Experiments were carried out using a strand burner at pressures ranging from 10 to 70bar with varying fractions of activated charcoal. The results show that with the addition of activated charcoal in an aluminized composite propellant higher burn rates (in excess of 25mm/s at 70bar) were obtained. This paper also explores the possibility of further enhancing the burn rates of aluminized composite propellant by using iron oxide along with activated charcoal. Burn rates recorded with iron oxide and activated charcoal both present in the propellant were in excess of 50mm/s at 70bar. It was noticed that these high burn rates were accompanied by a higher (0.65) pressure index of combustion. A series of experiments were designed to understand the burn rate enhancement with activated charcoal in aluminized composite propellant. TGA and DSC tests were carried out on AP pellets with and without activated charcoal to detect any condensed phase activity of activated charcoal. These tests did not show any significant difference between the AP pellets with and without activated charcoal. The AP pellets with and without activated charcoal were also burnt in a strand burner to understand if any gas phase reaction was being catalyzed by activated charcoal. AC does not enhance any gas phase activity while addition of AC in AP increased the LPDL of AP and reduced the burn rate. Lastly, sandwich propellant with activated charcoal at the interface was prepared to determine if interface reactions were being affected with the addition of activated charcoal. It has been observed that with the addition of activated charcoal at the AP–binder interface the burn rates are higher than those recorded without activated charcoal at the AP–binder interface. [Copyright &y& Elsevier]