A critical crevice solution and IR drop crevice corrosion model

This paper presents a mechanistic model describing the dynamic concentration profiles and corrosion currents within a corroding crevice. The model couples anodic areas within the crevice with cathodic areas on the bold surface. It also incorporates the combined effects of the chemical attack of the crevice solution along with the electric potential changes in the crevice and over the bold surface. The mathematical model is used to predict the dynamic crevice pH profile and remarkable agreement with experimental data is evident. Three crevice corrosion phases were determined that correspond to the evolution of the electric potential drop within the crevice.     

N.J. court committee requires most out-of-state lawyers to register for ADR

A New Jersey Supreme Court committee issues an unauthorized practice of law opinion that calls into question who can represent a party in private ADR matters. Based on recent-vintage changes to attorneys' model conduct rules, the move, while extreme, also may be part of a larger trend nationwide     

Sterically Enhanced Control of Enzyme-Assisted DNA Assembly**

Traditional methods for the assembly of functionalised DNA structures, involving enzyme restriction and modification, present difficulties when working with small DNA fragments (<100 bp), in part due to a lack of control over enzymatic action during the DNA modification process. This limits the design flexibility and range of accessible DNA structures. Here, we show that these limitations can be overcome by introducing chemical modifications into the DNA that spatially restrict enzymatic activity. This approach, sterically controlled nuclease enhanced (SCoNE) DNA assembly, thereby circumvents the size limitations of conventional Gibson assembly (GA) and allows the preparation of well-defined, functionalised DNA structures with multiple probes for specific analytes, such as IL-6, procalcitonin (PCT), and a biotin reporter group. Notably, when using the same starting materials, conventional GA under typical conditions fails. We demonstrate successful analyte capture based on standard and modified sandwich ELISA and also show how the inclusion of biotin probes provides additional functionality for product isolation.     

Modulating the RAGE-Induced Inflammatory Response: Peptoids as RAGE Antagonists

While the primary pathology of Alzheimer's disease (AD) is defined by brain deposition of amyloid-β (Aβ) plaques and tau neurofibrillary tangles, chronic inflammation has emerged as an important factor in AD etiology. Upregulated cell surface expression of the receptor for advanced glycation end-products (RAGE), a key receptor of innate immune response, is reported in AD. In parallel, RAGE ligands, including Aβ aggregates, HMGB1, and S100B, are elevated in AD brain. Activation of RAGE by these ligands triggers release of inflammatory cytokines and upregulates cell surface RAGE. Despite such observation, there are currently no therapeutics that target RAGE for treatment of AD-associated neuroinflammation. Peptoids, a novel class of potential AD therapeutics, display low toxicity, facile blood-brain barrier permeability, and resistance to proteolytic degradation. In the current study, peptoids were designed to mimic Aβ, a ligand that binds the V-domain of RAGE, and curtail RAGE inflammatory activation. We reveal the nanomolar binding capability of peptoids JPT1 and JPT1a to RAGE and demonstrate their ability to attenuate lipopolysaccharide-induced pro-inflammatory cytokine production as well as upregulation of RAGE cell surface expression. These results support RAGE antagonist peptoid-based mimics as a prospective therapeutic strategy to counter neuroinflammation in AD and other neurodegenerative diseases.     

Using Holographic Microscopy To Measure the Effect of Confinement on Crowding Agents in Lipid Vesicles

The hydrodynamic effects of macromolecular crowding inside cells are often studied in vitro by using polymers as crowding agents. Confinement of polymers inside cell-sized droplets has been shown to affect the diffusion of small molecules. Here we develop a method, based on digital holographic microscopy, to measure the diffusion of polystyrene microspheres that are confined within lipid vesicles containing a high concentration of solute. We apply the method to three solutes of varying complexity: sucrose, dextran, and PEG, prepared at ∼7 % (w/w). We find that diffusion inside and outside the vesicles is the same when the solute is sucrose or dextran that is prepared below the critical overlap concentration. For poly(ethylene glycol), which is present at a concentration higher than the critical overlap concentration, the diffusion of microspheres inside vesicles is slower, hinting at the potential effects of confinement on crowding agents.     

Rigidity-Activity Relationships of bisQPC Scaffolds against Pathogenic Bacteria

Biscationic quaternary phosphonium compounds (bisQPCs) represent a promising class of antimicrobials, displaying potent activity against both Gram-negative and Gram-positive bacteria. In this study, we explored the effects of structural rigidity on the antimicrobial activity of QPC structures bearing a two-carbon linker between phosphonium groups, testing against a panel of six bacteria, including multiple strains harboring known disinfectant resistance mechanisms. Using simple alkylation reactions, 21 novel compounds were prepared, although alkene isomerization as well as an alkyne reduction were observed during the respective syntheses. The resulting bisQPC compounds showed strong biological activity, but were hampered by diminished solubility of their iodide salts. One compound (P2P-10,10 I) showed single-digit micromolar activity against the entire panel of bacteria. Overall, intriguing biological activity was observed, with less rigid structures displaying better efficacy against Gram-negative strains and more rigid structures demonstrating slightly increased efficacy against S. aureus strains.     

Mapping the Chemical Space of Active-Site Targeted Covalent Ligands for Protein Tyrosine Phosphatases**

Protein tyrosine phosphatases (PTPs) are an important class of enzymes that modulate essential cellular processes through protein dephosphorylation and are dysregulated in various disease states. There is demand for new compounds that target the active sites of these enzymes, for use as chemical tools to dissect their biological roles or as leads for the development of new therapeutics. In this study, we explore an array of electrophiles and fragment scaffolds to investigate the required chemical parameters for covalent inhibition of tyrosine phosphatases. Our analysis juxtaposes the intrinsic electrophilicity of these compounds with their potency against several classical PTPs, revealing chemotypes that inhibit tyrosine phosphatases while minimizing excessive, potentially non-specific reactivity. We also assess sequence divergence at key residues in PTPs to explain their differential susceptibility to covalent inhibition. We anticipate that our study will inspire new strategies to develop covalent probes and inhibitors for tyrosine phosphatases.     

Switchable DNA-Based Peroxidases Controlled by a Chaotropic Ion**

Here we demonstrate a switchable DNA electron-transfer catalyst, enabled by selective destabilization of secondary structure by the denaturant, perchlorate. The system is comprised of two strands, one of which can be selectively switched between a G-quadruplex and duplex or single-stranded conformations. In the G-quadruplex state, it binds hemin, enabling peroxidase activity. This switching ability arises from our finding that perchlorate, a chaotropic Hofmeister ion, selectively destabilizes duplex over G-quadruplex DNA. By varying perchlorate concentration, we show that the DNA structure can be switched between states that do and do not catalyze electron-transfer catalysis. State switching can be achieved in three ways: thermally, by dilution, or by concentration.     

Impact of post-pyrolysis wash on biochar properties

Washing biochar modifies its properties for use as a soil amendment. The important biochar properties for use as a soil amendment are hydrophilicity, adsorption, and stability. Biochar was obtained with intermediate pyrolysis at 400°C of three different feedstocks: woodchips, Bayview Flowers Digestate, and Storm Fisher Digestate biomass. A simple wash with an aqueous surfactant solution improved the properties of the biochar for soil amendment, with a non-ionic surfactant combined with oxidizing hydrogen peroxide being the most effective. The improved properties included the removal of tars and possible modification of surface properties that increased hydrophilicity and adsorption and decreased leaching of any hydrocarbons that could negatively impact the surroundings. As a result, the washed biochar will exhibit better water retention and a more hospitable environment for the growth of beneficial microorganisms. In addition, by making the biochar more hydrophilic, a wash will make its granulation easier, reducing dust emissions during its application and allowing its formulation with enhancement additives. Although many post-pyrolysis treatments of biochars have been investigated, the proposed wash is simple and effective, with beneficial advantages for downstream processing and application as a soil amendment.     

Reproducibility of diffusion tensor imaging-derived parameters: implications for the streptozotocin-induced type 1 diabetic rats

Magnetic Resonance Materials in Physics, Biology and Medicine - Diffusion tensor imaging (DTI) is a useful approach for studying neuronal integrity in animals. However, the test–retest...