Update on optimized purification and characterization of natural milk allergens

Highly purified allergens namely cow's milk alpha-lactalbumin (ALA). (Bos d 4), beta-lactoglobulin (BLG) (Bos d 5) and casein (Bos d 8) and goat's milk casein were prepared from the raw milk from a single animal with a known genetic background. Consequently the natural isoforms are limited, constant and characterized. Purification included selective precipitations and chromatographical steps. Characterization of structure and allergenic activity assessment of milk allergens were carried out using physicochemical and immunochemical methods. Taken together data demonstrated the absence of impurities and of contamination by other milk allergens in each preparation. NMR and circular dichroism analyses confirmed the native conformation and proper folding of ALA and BLG and the expected absence of folding of bovine and caprine casein. Enzyme immuno assays confirmed the native conformation of BLG and the purity and immunoreactivity of all the proteins. The allergenic activity, e. g. the IgE binding capacity, of purified proteins was identical as that of those proteins when present in milk. The purified proteins also demonstrated the ability to provoke the degranulation of humanized rat basophilic leukaemia cells. All the data thus confirm the purity, identity, structural conformation and functionality of the prepared milk allergens.     

Novel Tacrine‐Grafted Ugi Adducts as Multipotent Anti‐Alzheimer Drugs: A Synthetic Renewal in Tacrine–Ferulic Acid Hybrids

Herein we describe the design, multicomponent synthesis, and biological, molecular modeling and ADMET studies, as well as in vitro PAMPA‐blood–brain barrier (BBB) analysis of new tacrine–ferulic acid hybrids (TFAHs). We identified (E)‐3‐(hydroxy‐3‐methoxyphenyl)‐N‐{8[(7‐methoxy‐1,2,3,4‐tetrahydroacridin‐9‐yl)amino]octyl}‐N‐[2‐(naphthalen‐2‐ylamino)2‐oxoethyl]acrylamide (TFAH 10 n ) as a particularly interesting multipotent compound that shows moderate and completely selective inhibition of human butyrylcholinesterase (IC₅₀=68.2 nM ), strong antioxidant activity (4.29 equiv trolox in an oxygen radical absorbance capacity (ORAC) assay), and good β‐amyloid (Aβ) anti‐aggregation properties (65.6 % at 1:1 ratio); moreover, it is able to permeate central nervous system (CNS) tissues, as determined by PAMPA‐BBB assay. Notably, even when tested at very high concentrations, TFAH 10 n easily surpasses the other TFAHs in hepatotoxicity profiling (59.4 % cell viability at 1000 μM ), affording good neuroprotection against toxic insults such as Aβ_1–40, Aβ_1–42, H₂O₂, and oligomycin A/rotenone on SH‐SY5Y cells, at 1 μM . The results reported herein support the development of new multipotent TFAH derivatives as potential drugs for the treatment of Alzheimer′s disease.     

REACTION KINETICS PARAMETERS DESCRIBING DISPLACEMENT BY ACIDS OF STRUCTURAL METALLIC IONS FROM CLAY MINERALS

Chemical kinetics parameters describing reactions of naturally-occurring clay minerals with acids were determined using batch reaction and analytical techniques. Clay minerals included sodium montmo-rillonite, kaolinite, and illite, reacting with hydrochloric acid, nitric acid, and sulfuric acid. Two acid concentrations were examined at 50 and 70^°C. Displacement by acids of aluminum and magnesium from clays was found to follow pseudo-first order kinetics. Data analysis verified the batch reaction technique for determining kinetics parameters of acid-clay reactions and demonstrated acid neutralization by naturally-occurring clays. For reactions of sodium montmorillonite with hydrochloric acid, nitric acid, and sulfuric acid, reaction rate coefficients for displacement of aluminum ranged from 1·73 × 10^-4 kg/mol-hr at 50^°C to 3·02 × 10^-3 kg/mol-hr at 70^°C. Displacement of magnesium from sodium montmorillonite by these acids occurred at rates ranging from 3·68 × 10^-4 kg/mol-hr at 50^°C to 1·12 × 10^-2 kg/mol-hr at 70^°C. Activation energies for displacement by acids of aluminum from sodium montmorillonite were calculated to range from 31,000J/mol to 112,000J/mol, while activalion energies for displacement of magnesium from sodium montmorillonite ranged from 36.000 J/mol to 103,000 J/mol. For reactions of illite with acids, reaction rate coefficients for displacement of aluminum were determined to be 1·45×10^-4Kg/mol-hr at 50^°C to 1·7×10^-3kg/mol-hr at 70^°C. Displacement of magneisum by acids from illite occurred at rates from 6·06 × 10^-4 kg/mol-hr at 50^°C to 5·97 × 10^-3 kg/mol-hr. Activation energies for reactions of acids with illite ranged from 33,000 J/mol to 62,000 J/mol for displacement of aluminum and from 9,400 J/mol to 29,000 J/mol for displacement of magnesium.     

Fragmentation and film growth in supersonic nanoaggregate aerosol deposition

Aerosol deposition with gas phase-synthesized chain-like nanoaggregates can yield dense coatings from the impaction of particles on a substrate; however, dense coating formation is not well understood. Here, we study coating consolidation at the single nanoaggregate level. Flame spray pyrolysis-made tin oxide nanoaggregates are mobility (size) filtered, accelerated through a de Laval nozzle, and impacted on alumina substrates. TEM images obtained from low velocity collection and supersonic deposition are compared via quantitative image analysis, which reveals that upon supersonic impact nanoaggregates fragment into smaller aggregates. This suggests that fragmentation is a key step in producing coatings denser than the depositing nanoaggregates themselves. We supplement experiments with detailed particle trajectory calculations, which show that the impact energies per atom during nanoaggregate deposition are below 0.2 eV/molecule. These results suggest that fragmentation can only occur at locations where nanoaggregates bonded by van der Waals and capillary interactions.     

Long-Term Measures of Dyslipidemia,Inflammation, and Oxidative Stress in Rats Fed a High-Fat/High-Fructose Diet

Inflammation and oxidative stress are thought to be involved in, or associated with, the development of obesity, dyslipidemia, hepatic steatosis, and insulin resistance. This work was designed to determine the evolution of inflammation and oxidative stress during onset and progression of hepatic steatosis and glucose intolerance. Seventy-five male Wistar rats were divided to control and high-fat high-fructose (HFHFr) groups. A subgroup of each group was sacrificed at 4, 8, 12, 16, and 20 weeks. HFHFr-fed rats exhibited overweight, glucose intolerance, and hepatic steatosis with increased contents of hepatic diacylglycerols and ceramides. The HFHFr diet increased hepatic interleukin 6 (IL-6) protein and adipose tissue CCL5 gene expression and hepatic nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity but not mitochondrial reactive oxygen species (ROS) production. The HFHFr diet decreased plasma and liver levels of isoprostanoid metabolites as well as plasma thiobarbituric acid-reactive substance (TBARS) levels. Hepatic glutathione content was decreased with a moderate decrease in superoxide dismutase (SOD) and glutathione peroxidase (GPx) with the HFHFr diet. Overall, HFHFr diet led to hepatic lipid accumulation and glucose intolerance, which were accompanied by only moderate inflammation and oxidative stress. Most of these changes occurred at the same time and as early as 8 or 12 weeks of diet treatment. This implies that oxidative stress may be the result, not the cause, of these metabolic alterations, and suggests that marked hepatic oxidative stress should probably occur at the end of the steatotic stage to result in frank insulin resistance and steatohepatitis. These findings need to be further evaluated in other animal species as well as in human studies.     

Effects of chloride and sulfate on the rate of oxidation of ferrous ion by H2O2

The rates of oxidation of Fe(II) by H(2)O(2) in the presence of sodium perchlorate, sodium nitrate, sodium chloride and sodium sulfate salts (0-1M) have been compared in the study. Experiments were carried out in a batch reactor, in the dark, at pH <3, 25+/-0.5 degrees C and at controlled ionic strength (< or =1M). The experimental results showed that the rates of oxidation of Fe(II) in the presence of chloride, nitrate and perchlorate were identical. In the presence of sulfate, the rate of oxidation of Fe(II) was faster and depended on the pH and the concentration of sulfate. The pseudo second-order rate constants for the reaction of H(2)O(2) with Fe(2+), FeCl(+) and FeSO(4) were determined as 55+/-1, 55+/-1 and 78+/-3 M(-1) s(-1), respectively.     

韧性概念的重新审视

自《2005—2015兵库行动框架》被采纳以来,受灾社区的恢复力紧密取决于受灾社区的韧性,已经成为灾害风险控制项目的共同特征。现在人们越来越多地关注受灾社区在灾难发生后不依靠或少依靠外部援助而"反弹"或恢复的能力。与其仅仅关注受灾对象的需求和弱点,不如把着眼点放在应对灾难的韧性上,这突出了灾害风险控制领域需要转变。然而在灾害学界的研究和学术领域,对韧性这一概念达成共识依然是个挑战。本文梳理了不同情况下韧性的定义,脆弱性在韧性主题中所扮演的角色和意义,以及脆弱性和韧性之间的差异。文章最后探讨和总结了韧性思维在我们认识和应对灾害时所具有的指导意义。     

Modelling complex manufacturing systems using discrete event simulation

This paper presents an approach in simulating complex manufacturing systems. The approach is founded on developing several general purpose simulation generators for an assembly station, a manufacturing cell, and an inventory transfer function. These simulation generators can then be linked together to create a model of a complex manufacturing system. A typical manufacturing system is modelled using these simulation generators and the results summarized.     

Effect of Bimodal Grain Size Distribution on the Strain Hardening Behavior of a Medium-Entropy Alloy

The evolution of strain hardening behavior of the Fe_(50)(CoCrMnNi)_(50) medium-entropy alloy as a function of the fraction of recrystallized microstructure and the grain size was studied using the Hollomon and Ludwigson equations.The specimens under study were partially recrystallized,fully recrystallized with ultrafine-grained microstructure,and fully recrystallized with coarse grains.The yield strength decreases steadily as the fraction of recry stallized micro structure and grain size increases due to the recovery process and the Hall-Petch effect.Interestingly,the bimodal grain distribution was found to have a significant impact on strain hardening during plastic deformation.For instance,the highest ultimate tensile strength was exhibited by a 0.97 μm specimen,which was observed to contain a bimodal grain distribution.Furthermore,using the Ludwigson equation,the effect of the bimodal grain distribution was established from the behavior of K_2 and n1 curves.These curves tend to show very high values in the specimens with a bimodal grain distribution compared to those that show a homogenous grain distribution.Additionally,the bimodal grain distribution contributes to the extensive L(u|")ders strain observed in the 0.97 μm specimen,which induces a significant deviation of the Hollomon equation at lower strains.     

Image segmentation by a contrario simulation

Segmenting an image into homogeneous regions generally involves a decision criterion to establish whether two adjacent regions are similar. Decisions should be adaptive to get robust and accurate segmentation algorithms, avoid hazardous a priori and have a clear interpretation. We propose a decision process based on a contrario reasoning: two regions are meaningfully different if the probability of observing such a difference in pure noise is very low. Since the existing analytical methods are intractable in our case, we extend them to allow a mixed use of analytical computations and Monte-Carlo simulations. The resulting decision criterion is tested experimentally through a simple merging algorithm, which can be used as a post-filtering and validation step for existing segmentation methods.