Probing Functional Heteromeric Chemokine Protein–Protein Interactions through Conformation‐Assisted Oxime Ligation

Protein–protein interactions (PPIs) govern most processes in living cells. Current drug development strategies are aimed at disrupting or stabilizing PPIs, which require a thorough understanding of PPI mechanisms. Examples of such PPIs are heteromeric chemokine interactions that are potentially involved in pathological disorders such as cancer, atherosclerosis, and HIV. It remains unclear whether this functional modulation is mediated by heterodimer formation or by the additive effects of mixed chemokines on their respective receptors. To address this issue, we report the synthesis of a covalent RANTES‐PF4 heterodimer (termed OPRAH) by total chemical synthesis and oxime ligation, with an acceleration of the final ligation step driven by PPIs between RANTES and PF4. Compared to mixed separate chemokines, OPRAH exhibited increased biological activity, thus providing evidence that physical formation of the heterodimer indeed mediates enhanced function.     

Verifying the attenuation of earplugs in situ: method validation using artificial head and numerical simulations

The use of in situ measurements of hearing protectors' (HPD's) attenuation following the microphone in real ear (MIRE) protocol is increasing. The attenuation is hereby calculated from the difference in sound levels outside the ear and inside the ear canal behind the HPD. Custom-made earplugs have been designed with an inner bore that allows inserting a miniature microphone. A thorough understanding of the difference, henceforth called transfer function, between the sound pressure of interest at the eardrum and the one measured at the inner bore of the HPD is indispensable for optimizing the MIRE technique and extending its field of application. This issue was addressed by measurements on a head-and-torso-simulator and finite difference time domain numerical simulations of the outer ear canal occluded by an earplug. Both approaches are in good agreement and reveal a clear distinction between the sound pressure at the MIRE microphone and at eardrum, but the measured transfer functions appear to be stable and reproducible. Moreover, the most striking features of the transfer functions can be traced down to the geometrical and morphological characteristics of the earplug and ear canal.     

Some potentials for the curvature tensor on three-dimensional manifolds

We study equations of Riemann–Lanczos type on three dimensional manifolds. Obstructions to global existence for global Lanczos potentials are pointed out. We check that the imposition of the original Lanczos symmetries on the potential leads to equations which do not have a determined type, leading to problems when trying to prove global existence. We show that elliptic equations can be obtained by relaxing those symmetry requirements in at least two different ways, leading to global existence of potentials under natural conditions. A second order potential for the Ricci tensor is introduced.     

Synthesis and Characterization of Ru-Loaded Anodized Aluminum Oxide for Hydrogenation Catalysis

Anodized aluminum oxides (AAOs) are synthesized and used as catalyst support in combination with Ru as metal in hydrogenation catalysis. SEM and TEM analysis of the as-synthesized AAOs reveal uniform, ordered nanotubes with pore diameters of 18 nm, which are further characterized with Kr physisorption, XRD and FTIR spectroscopy. After impregnation of the AAOs with Ru, the presence of Ru nanoparticles inside the tubular pores is evidenced clearly for the first time via HAADF-STEM-EDX. The Ru−AAOs have been tested for catalytic activity, which showed high conversion and selectivity for the hydrogenation of toluene and butanal.     

Using Schedule Risk Analysis with resource constraints for project control

Schedule Risk Analysis (SRA) has shown to provide reliable activity sensitivity information for taking corrective actions during project control. More precisely, by selecting a small subset of activities with high sensitivity values for taking corrective actions, the project outcome can be improved. In resource constrained projects, disrupted activities can affect both their successors as well as other activities when resource conflicts are induced. Since SRA focuses solely on the project network to determine the sensitivity of activities, the traditional SRA metrics do not accurately reflect the activity sensitivity for resource constrained projects. In this paper, the traditional SRA metrics are extended for resource constrained projects, and a novel resource-based sensitivity metric is introduced (RC-SRA metrics).A computational experiment is conducted to investigate the ability of the RC-SRA metrics to identify activities with higher sensitivity values. In addition, two activity selection strategies, defined as the normal strategy and sequential strategy, are designed to select activities for taking corrective actions. Further, two types of corrective actions are proposed to reduce the activity duration or resource demand in case of delays, respectively. Finally, the impact of dynamically updating the RC-SRA metrics during project execution is examined.The computational results show that the normal activity selection strategy is recommended for serial projects, while the sequential strategy is preferred for parallel projects. The results also indicate that reducing the activity durations performs better than reducing the resource demand of activities. Finally, it is shown that updating the RC-SRA metrics dynamically during project execution improves the efficiency of the corrective action taking process.     

Unraveling the Composition of Rembrandt's Impasto through the Identification of Unusual Plumbonacrite by Multimodal X‐ray Diffraction Analysis

Rembrandt (1606–1669) is renowned for his impasto technique, involving his use of lead white paint with outstanding rheological properties. This paint was obtained by combining lead white pigment (a mixture of cerussite PbCO₃ and hydrocerussite Pb₃(CO₃)₂(OH)₂) with an organic binding medium, but the exact formulation used by Rembrandt remains a mystery. A powerful combination of high‐angle and high‐lateral resolution x‐ray diffraction was used to investigate several microscopic paint samples from four Rembrandt masterpieces. A rare lead compound, plumbonacrite (Pb₅(CO₃)₃O(OH)₂), was detected in areas of impasto. This can be considered a fingerprint of Rembrandt's recipe and is evidence of the use of an alkaline binding medium, which sheds a new light on Rembrandt's pictorial technique.     

Structural Characterization of the Complex between Hen Egg‐White Lysozyme and ZrIV‐Substituted Keggin Polyoxometalate as Artificial Protease

Successful co‐crystallization of a noncovalent complex between hen egg‐white lysozyme (HEWL) and the monomeric Zr^IV‐substituted Keggin polyoxometalate (POM) (Zr1 K1), (Et₂NH₂)₃[Zr(PW₁₁O₃₉)] ( 1 ), has been achieved, and its single‐crystal X‐ray structure has been determined. The dimeric Zr^IV‐substituted Keggin‐type polyoxometalate (Zr1 K2), (Et₂NH₂)₁₀[Zr(PW₁₁O₃₉)₂] ( 2 ), has been previously shown to exhibit remarkable selectivity towards HEWL hydrolysis. The reported X‐ray structure shows that the hydrolytically active Zr^IV‐substituted Keggin POM exists as a monomeric species. Prior to hydrolysis, this monomer interacts with HEWL in the vicinity of the previously identified cleavage sites found at Trp28‐Val29 and Asn44‐Arg45, through water‐mediated H‐bonding and electrostatic interactions. Three binding sites are observed at the interface of the negatively charged Keggin POM and the positively charged regions of HEWL at: 1) Gly16, Tyr20, and Arg21; 2) Asn44, Arg45, and Asn46; and 3) Arg128.