Protein Surface Mimetics: Understanding How Ruthenium Tris(Bipyridines) Interact with Proteins

Protein surface mimetics achieve high‐affinity binding by exploiting a scaffold to project binding groups over a large area of solvent‐exposed protein surface to make multiple cooperative noncovalent interactions. Such recognition is a prerequisite for competitive/orthosteric inhibition of protein–protein interactions (PPIs). This paper describes biophysical and structural studies on ruthenium(II) tris(bipyridine) surface mimetics that recognize cytochrome (cyt) c and inhibit the cyt c/cyt c peroxidase (CCP) PPI. Binding is electrostatically driven, with enhanced affinity achieved through enthalpic contributions thought to arise from the ability of the surface mimetics to make a greater number of noncovalent interactions than CCP with surface‐exposed basic residues on cyt c. High‐field natural abundance ¹H,¹⁵N HSQC NMR experiments are consistent with surface mimetics binding to cyt c in similar manner to CCP. This provides a framework for understanding recognition of proteins by supramolecular receptors and informing the design of ligands superior to the protein partners upon which they are inspired.     

The formalism underlying EASYMAP: A precompiler for refinement-based exploration of hierarchical data organizations

In the computer science community, data structure design is mainly conducted at a high level of abstraction under the implicit assumption that the platform contains a monolithic memory. Exploiting platform-related knowledge such as available on-chip and off-chip memory sizes, the cache size, and the number of banks is mainly conducted in the system engineering community when the refined data structure has already been chosen. A convergence of both communities is desirable since this can lead to powerful optimizations.To achieve the convergence mentioned above, data-related transformations have been researched extensively in the recent past. Many of these transformations have a direct and large impact on memory footprint, execution time and energy consumption. Unfortunately, however, the most effective transformations are applied manually (e.g. in C code) and these result in a very time-consuming and error-prone design process. To overcome this burden, our general research goal is to develop a computer-aided design tool, called , that helps the designer to correctly construct the C code of an efficient but difficult-to-understand data structure. The formal design of is the topic of this article with the emphasis on , the internal language of . is based on a novel extension of Separation Logic’s spatial conjunction operator (∗), allowing it to concisely describe access operations of an irregularly accessed complex data organization. is the basic building block of ; it serves the purpose of automating ’s refinement process and proving that it is correct by construction.     

Determination of CaO–SiO2–MgO–Al2O3–CrOx Liquidus

In this work, the liquidus of synthetic CaO–SiO₂–MgO–Al₂O₃–CrO _x slags is evaluated in the industrially relevant compositional domain. Equilibrium experiments are carried out at 1500°C and partial oxygen pressure ( p _O2) 10^−11.04 atm, and at 1600°C and p _O2=10^−10.16 and 10^−9.36 atm. The studied basicities (CaO/SiO₂) are 1.2 and 0.5. Al₂O₃ levels range from 0 to 30 wt%. Oversaturated liquid is sampled and phase relations are measured with quantitative electron probe microanalysis–wavelength dispersive spectroscopy (EPMA–WDS). The results are compared with the commercially available FactSage thermodynamic databases. Qualitative agreement is always obtained. Also a good quantitative agreement is found at the higher basicity, especially for the spinel liquidus. A minor but systematic deviation can be observed for the eskolaite liquidus. At the lower basicity, the calculated phase diagram deviates strongly from the experimental results, probably due to missing ternary interactions in the database.     

Gastric Helicobacter suis Infection Partially Protects against Neurotoxicity in A 6-OHDA Parkinson’s Disease Mouse Model

The exact etiology of Parkinson’s disease (PD) remains largely unknown, but more and more research suggests the involvement of the gut microbiota. Interestingly, idiopathic PD patients were shown to have at least a 10 times higher prevalence of Helicobacter suis (H. suis) DNA in gastric biopsies compared to control patients. H. suis is a zoonotic Helicobacter species that naturally colonizes the stomach of pigs and non-human primates but can be transmitted to humans. Here, we investigated the influence of a gastric H. suis infection on PD disease progression through a 6-hydroxydopamine (6-OHDA) mouse model. Therefore, mice with either a short- or long-term H. suis infection were stereotactically injected with 6-OHDA in the left striatum and sampled one week later. Remarkably, a reduced loss of dopaminergic neurons was seen in the H. suis/6-OHDA groups compared to the control/6-OHDA groups. Correspondingly, motor function of the H. suis-infected 6-OHDA mice was superior to that in the non-infected 6-OHDA mice. Interestingly, we also observed higher expression levels of antioxidant genes in brain tissue from H. suis-infected 6-OHDA mice, as a potential explanation for the reduced 6-OHDA-induced cell loss. Our data support an unexpected neuroprotective effect of gastric H. suis on PD pathology, mediated through changes in oxidative stress.     

Molecular dynamics study of dipalmitoylphosphatidylcholine lipid layer self-assembly onto a single-walled carbon nanotube

Single-walled carbon nanotubes (SWNTs) are possible nano-injectors and delivery vehicles of molecular probes and drugs into cells. In order to explore the interaction between lipid membranes and carbon nanotubes, we investigate the binding mechanism of dipalmitoylphosphatidylcholine (DPPC) with SWNTs by molecular dynamics. In low concentration range simulations, the DPPC molecules form a supramolecular two-layered cylindrical structure wrapped around the carbon nanotube surface. The hydrophobic part of DPPC is adsorbed on the surface of the nanotube, and the hydrophilic top is oriented towards the aqueous phase. For higher concentration ranges, the DPPC molecules are found to form a supramolecular multi-layered structure wrapped around the carbon nanotube surface. At the saturation point a membrane-like structure is self-assembled with a width of 41.4 Å, which is slightly larger than the width of a cell membrane. Our study sheds light on the existing conflicting simulation data on adsorption of single-chained phospholipids.      

Visualization and simulation of the transfer process of index‐matched silica microparticle inks for gravure printing

A combined experimental and computational study of the transfer of transparent index‐matched silica‐particle inks between two flat plates is presented for gravure printing applications. The influence of printing speed and initial ink droplet size on the ability to accurately transfer ink during the printing process is explored systematically. Smooth interface volume of fluid simulations show the same trends as the ink transfer observed in experiments over a wide range of printing speeds and for inks having different silica particle loadings. Our calculations indicate that for ink droplets with characteristic dimensions in the vicinity of 10 μm, which are of particular interest for gravure printing applications, ink transfer improves significantly due to the diminishing effect of gravity, and the increased importance of capillary forces at small length scales. © 2016 American Institute of Chemical Engineers AIChE J, 63: 1419–1429, 2017