Functional and chemical characterization of the aging process of an igniter

The igniter consisting of 34% Mg, 60% KNO₃, 3% KClO₄ and 3% organic binder was subjected to accelerated aging under the conditions of 85% relative humidity at 65°C, 75°C and 85°C, and at 75°C with 92% relative humidity. Chemical aging was followed through formation of Mg(OH)₂ and KNO₂. Functional characterization was accomplished in a device constructed to enable simultaneous determination of the heat of combustion and pressure-time recording of the combustion process of both fresh and aged samples. The maximum acceptable deterioration occured at different times depending upon the conditions. The acceleration factor for every 10°C at 85% relative humidity is on average 2.8, leading to a prediction of shelf life of not more than 4 years at 25°C. At the time when burning characteristics were significantly changed, the mixture suffered only slight chemical changes, with only about 1% Mg(OH)₂ and 0.5% KNO₂ being formed. Thus, no chemical changes should be tolerated in such formulations.     

Morphometry and Stiffness of Red Blood Cells—Signatures of Neurodegenerative Diseases and Aging

Human red blood cells (RBCs) are unique cells with the remarkable ability to deform, which is crucial for their oxygen transport function, and which can be significantly altered under pathophysiological conditions. Here we performed ultrastructural analysis of RBCs as a peripheral cell model, looking for specific signatures of the neurodegenerative pathologies (NDDs)—Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS) and Alzheimer’s disease (AD), utilizing atomic force (AFM) and conventional optical (OM) microscopy. We found significant differences in the morphology and stiffness of RBCs isolated from patients with the selected NDDs and those from healthy individuals. Neurodegenerative pathologies’ RBCs are characterized by a reduced abundance of biconcave discoid shape, lower surface roughness and a higher Young’s modulus, compared to healthy cells. Although reduced, the biconcave is still the predominant shape in ALS and AD cells, while the morphology of PD is dominated by crenate cells. The features of RBCs underwent a marked aging-induced transformation, which followed different aging pathways for NDDs and normal healthy states. It was found that the diameter, height and volume of the different cell shape types have different values for NDDs and healthy cells. Common and specific morphological signatures of the NDDs were identified.     

eDNA Inactivation and Biofilm Inhibition by the PolymericBiocide Polyhexamethylene Guanidine Hydrochloride (PHMG-Cl)

The choice of effective biocides used for routine hospital practice should consider the role of disinfectants in the maintenance and development of local resistome and how they might affect antibiotic resistance gene transfer within the hospital microbial population. Currently, there is little understanding of how different biocides contribute to eDNA release that may contribute to gene transfer and subsequent environmental retention. Here, we investigated how different biocides affect the release of eDNA from mature biofilms of two opportunistic model strains Pseudomonas aeruginosa ATCC 27853 (PA) and Staphylococcus aureus ATCC 25923 (SA) and contribute to the hospital resistome in the form of surface and water contaminants and dust particles. The effect of four groups of biocides, alcohols, hydrogen peroxide, quaternary ammonium compounds, and the polymeric biocide polyhexamethylene guanidine hydrochloride (PHMG-Cl), was evaluated using PA and SA biofilms. Most biocides, except for PHMG-Cl and 70% ethanol, caused substantial eDNA release, and PHMG-Cl was found to block biofilm development when used at concentrations of 0.5% and 0.1%. This might be associated with the formation of DNA–PHMG-Cl complexes as PHMG-Cl is predicted to bind to AT base pairs by molecular docking assays. PHMG-Cl was found to bind high-molecular DNA and plasmid DNA and continued to inactivate DNA on surfaces even after 4 weeks. PHMG-Cl also effectively inactivated biofilm-associated antibiotic resistance gene eDNA released by a pan-drug-resistant Klebsiella strain, which demonstrates the potential of a polymeric biocide as a new surface-active agent to combat the spread of antibiotic resistance in hospital settings.     

Peptides before and during the nucleotide world: an origins story emphasizing cooperation between proteins and nucleic acids

Recent developments in Origins of Life research have focused on substantiating the narrative of an abiotic emergence of nucleic acids from organic molecules of low molecular weight, a paradigm that typically sidelines the roles of peptides. Nevertheless, the simple synthesis of amino acids, the facile nature of their activation and condensation, their ability to recognize metals and cofactors and their remarkable capacity to self-assemble make peptides (and their analogues) favourable candidates for one of the earliest functional polymers. In this mini-review, we explore the ramifications of this hypothesis. Diverse lines of research in molecular biology, bioinformatics, geochemistry, biophysics and astrobiology provide clues about the progression and early evolution of proteins, and lend credence to the idea that early peptides served many central prebiotic roles before they were encodable by a polynucleotide template, in a putative ‘peptide-polynucleotide stage’. For example, early peptides and mini-proteins could have served as catalysts, compartments and structural hubs. In sum, we shed light on the role of early peptides and small proteins before and during the nucleotide world, in which nascent life fully grasped the potential of primordial proteins, and which has left an imprint on the idiosyncratic properties of extant proteins.     

Fluidization of spherical versus elongated particles: Experimental investigation using magnetic particle tracking

In biomass processing fluidized beds are used to process granular materials where particles typically possess elongated shapes. However, for simplicity, in computer simulations particles are often considered spherical, even though elongated particles experience more complex particle– particle interactions as well as different hydrodynamic forces. The exact effect of these more complex interactions in dense fluidized suspensions is still not well understood. In this study we use the magnetic particle tracking technique to compare the fluidization behavior of spherical particles to that of elongated particles. We found a considerable difference between fluidization behavior of spherical versus elongated particles in the time-averaged particle velocity field as well as in the time-averaged particle rotational velocity profile. Moreover, we studied the effect of fluid velocity and the particle's aspect ratio on the particle's preferred orientation in different parts of the bed, which provides new insight in the fluidization behavior of elongated particles.     

From miRNA Target Gene Network to miRNA Function: miR-375 Might Regulate Apoptosis and Actin Dynamics in the Heart Muscle via Rho-GTPases-Dependent Pathways

MicroRNAs (miRNAs) are short, single-stranded, non-coding ribonucleic acid (RNA) molecules, which are involved in the regulation of main biological processes, such as apoptosis or cell proliferation and differentiation, through sequence-specific interaction with target mRNAs. In this study, we propose a workflow for predicting miRNAs function by analyzing the structure of the network of their target genes. This workflow was applied to study the functional role of miR-375 in the heart muscle (myocardium), since this miRNA was previously shown to be associated with heart diseases, and data on its function in the myocardium are mostly unclear. We identified PIK3CA, RHOA, MAPK3, PAFAH1B1, CTNNB1, MYC, PRKCA, ERBB2, and CDC42 as key genes in the miR-375 regulated network and predicted the possible function of miR-375 in the heart muscle, consisting mainly in the regulation of the Rho-GTPases-dependent signaling pathways. We implemented our algorithm for miRNA function prediction into a Python module, which is available at GitHub.     

Synthetic Peroxides Promote Apoptosis of Cancer Cells by Inhibiting P-Glycoprotein ABCB5

This article discloses a new horizon for the application of peroxides in medical chemistry. Stable cyclic peroxides are demonstrated to have cytotoxic activity against cancer cells; in addition a mechanism of cytotoxic action is proposed. Synthetic bridged 1,2,4,5-tetraoxanes and ozonides were effective against HepG2 cancer cells and some ozonides selectively targeted liver cancer cells (the selectivity indexes for compounds 11 b and 12 a are 8 and 5, respectively). In some cases, tetraoxanes and ozonides were more selective than paclitaxel, artemisinin, and artesunic acid. Annexin V flow-cytometry analysis revealed that the active ozonides 22 a and 23 a induced cell death of HepG2 by apoptosis. Further study showed that compounds 22 a and 23 a exhibited a strong inhibitory effect on P-glycoprotein (P-gp/ABCB5)-overexpressing HepG2 cancer cells. ABCB5 is a key player in the multidrug-resistant phenotype of liver cancer. Peroxides failed to demonstrate a direct correlation between oxidative potential and their biological activity. To our knowledge this is the first time that peroxide diastereoisomers have been found to show stereospecific antimalarial action against the chloroquine-sensitive 3D7 strain of Plasmodium falciparum. Stereoisomeric ozonide 12 b is 11 times more active than stereoisomeric ozonide 12 a (IC₅₀=5.81 vs 65.18 μm ). Current findings mean that ozonides merit further investigation as potential therapeutic agents for drug-resistant hepatocellular carcinoma.     

Theory of competition between breakup and coalescence of droplets in flowing polymer blends

The Smoluchowski equation for the breakup and coalescence of dispersed droplets has been solved for flowing polymer blends. A scaling form for the distribution of droplet sized derived and published for a system of clusters with fragmentation and coagualation was used in our dervation. Equations are developed here for the average droplet size and for the characteristic time of transition to steady state flow of blends with a high content of the dispersed phase. Expressions reasonably describing the average size of droplets for all concentrations were obtained by a theory modification. Measured dependences of droplet size on the blend composition can be matched only if simultaneous collisions of three and more droplets are considered. The results of the theory indicate that the mechanism of droplet breakup (formation of pieces with the same or different volumes) has only a small effect on their average size in concentrated systems. The dependence of droplet size on the shear rate in flow is determined by properties of the blend components, and is generally nonmonotonic.     

COSMO‐based computer‐aided molecular/mixture design: A focus on reaction solvents

In this article, we investigate reaction solvent design using COSMO‐RS thermodynamics in conjunction with computer‐aided molecular design (CAMD) techniques. CAMD using COSMO‐RS has the distinct advantage of being a method based in quantum chemistry, which allows for the incorporation of quantum‐level information about transition states, reactive intermediates, and other important species directly into CAMD problems. This work encompasses three main additions to our previous framework for solvent design (Austin et al., Chem Eng Sci. 2017;159:93–105): (1) altering the group contribution method to estimate hydrogen‐bonding and non‐hydrogen‐bonding σ‐profiles; (2) ab initio modeling of strong solute/solvent interactions such as H‐bonding or coordinate bonding; and (3) solving mixture design problems limited to common laboratory and industrial solvents. We apply this methodology to three diverse case studies: accelerating the reaction rate of a Menschutkin reaction, controlling the chemoselectivity of a lithiation reaction, and controlling the chemoselectivity of a nucleophilic aromatic substitution reaction. We report improved solvents/mixtures in all cases. © 2017 American Institute of Chemical Engineers AIChE J, 63: 104–122, 2018