Selective Monovalent Galectin-8 Ligands Based on 3-Lactoylgalactoside

Galectin-8 has gained attention as a potential new pharmacological target for the treatment of various diseases, including cancer, inflammation, and disorders associated with bone mass reduction. To that end, new molecular probes are needed in order to better understand its role and its functions. Herein we aimed to improve the affinity and target selectivity of a recently published galectin-8 ligand, 3-O-[1-carboxyethyl]-β-d -galactopyranoside, by introducing modifications at positions 1 and 3 of the galactose. Affinity data measured by fluorescence polarization show that the most potent compound reached a K_D of 12 μM. Furthermore, reasonable selectivity versus other galectins was achieved, making the highlighted compound a promising lead for the development of new selective and potent ligands for galectin-8 as molecular probes to examine the protein's role in cell-based and in vivo studies.     

Verhalten von hochduktilem Beton unter Impaktbelastung

In diesem Aufsatz wird das Materialverhalten von Hochduktilem Beton (engl.: Strain Hardening Cementitious Composite – SHCC) bei Impaktbelastung beschrieben. Dazu werden Ergebnisse aus hochdynamischen Spallations‐Experimenten an einem Hopkinson‐ Bar mit Dehnraten > 140 1/s den Resultaten aus quasi‐statischen, zentrischen Zugversuchen mit Dehnraten von 0,001 1/s gegenübergestellt. Die Auswirkungen hoher Dehnraten auf das Materialverhalten erfolgt anhand eines Vergleiches der zentrischen Zugfestigkeit, des E‐Moduls sowie der Bruchenergie. Die experimentellen Ergebnisse werden zudem mit den Kennwerten anderer Betone in Beziehung gesetzt. Unterschiede im Materialverhalten werden auf Grundlage von Phänomenen der Rissbildung und des Faserauszuges erklärt. Mechanical Behaviour of SHCC under Impact This paper describes the material behaviour of Strain Hardening Cementitious Composite (SHCC) at high strain rates. The results of high dynamic spall experiments using a Hopkinson Bar at strain rates > 140/sec were arrayed against the results of quasistatic, centric tensile tests at strain rates of 0,001/sec. This comparison is based on the parameters of tensile strength, elastic modulus, and fracture energy of the specimens. In addition, the experimental results of SHCC are related to the characteristic values of other concrete types. Differences in material behaviour are explained by the phenomena of crack formation and fibre pullout force.     

Analysis of light scattering in amorphous Si:H solar cells by a one‐dimensional semi‐coherent optical model

A one‐dimensional semi‐coherent optical model for thin‐film solar cells is presented. The optical circumstances at flat interfaces are addressed and the situation at rough interfaces in the model is described for the case of direct (coherent) incident and scattered (incoherent) incident light. After the model has been experimentally verified, analysis of the light scattering process in hydrogenated amorphous silicon (a‐Si:H) p–i–n solar cells is carried out. The influence of the interface root‐mean‐square roughness and the effect of different angular distribution functions of diffused light on quantum efficiency and short‐circuit current are investigated by the optical model. Copyright © 2002 John Wiley & Sons, Ltd.     

An Intriguing Array of Extrudate Patterns in Long-Chain Branched Polymers During Extrusion

The present study highlights a range of surface and volume extrudate patterns that can be detected during the extrusion flow of long-chain branched polymers. Thus, four linear low-density polyethylenes (LDPEs) have been extruded using a single-screw extruder coupled to an inline optical imaging system. The selected LDPEs are selected to outline the influence of molecular weight and long-chain branching on the types of melt flow extrusion instabilities (MFEI). Through the inline imaging system, space–time diagrams are constructed and analyzed via Fourier-transformation using a custom moving window procedure. Based on the number of characteristic frequencies, peak broadness, and whether they are surface or volume distortions, three main MFEI types, distinct from those typically observed in linear and short-chain branched polymers, are identified. The higher molecular weight, low long-chain branching LDPEs exhibited all three instability types, including a special type volume instability. Independently of the molecular weight, higher long-chain branching appeared to have a stabilizing effect on the transition sequences by suppressing volume extrudate distortions or limiting surface patters to a form of weak intensity type.     

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.     

A benchmark analysis of data-driven and geometric approaches for robot ego-motion estimation

In the last decades, ego-motion estimation or visual odometry (VO) has received a considerable amount of attention from the robotic research community, mainly due to its central importance in achieving robust localization and, as a consequence, autonomy. Different solutions have been explored, leading to a wide variety of approaches, mostly grounded on geometric methodologies and, more recently, on data-driven paradigms. To guide researchers and practitioners in choosing the best VO method, different benchmark studies have been published. However, the majority of them compare only a small subset of the most popular approaches and, usually, on specific data sets or configurations. In contrast, in this work, we aim to provide a complete and thorough study of the most popular and best-performing geometric and data-driven solutions for VO. In our investigation, we considered several scenarios and environments, comparing the estimation accuracies and the role of the hyper-parameters of the approaches selected, and analyzing the computational resources they require. Experiments and tests are performed on different data sets (both publicly available and self-collected) and two different computational boards. The experimental results show pros and cons of the tested approaches under different perspectives. The geometric simultaneous localization and mapping methods are confirmed to be the best performing, while data-driven approaches show robustness with respect to nonideal conditions present in more challenging scenarios.     

Sol–gel synthesis and characterization of lithium aluminate (L–A–H) and lithium aluminosilicate (L–A–S–H) gels

Hydrous lithium aluminosilicate (L–A–S–H) and lithium aluminate (L–A–H) gels are candidate precursors for glass-ceramics and ceramics with potential advantages over conventional processing routes. However, their structure before calcination remained largely unknown, despite the importance of precursor structure on the properties of the resulting materials. In the present study, it is demonstrated that L–A–S–H and L–A–H gels with Li/Al ≤ 1 can be produced via an organic steric entrapment route, while higher Li/Al ratios lead to crystallization of gibbsite or nordstrandite. The composition and the structure of the gels was studied by thermogravimetric analysis, X-ray diffraction, ²⁷Al and ²⁹Si magic-angle spinning nuclear magnetic resonance, and Raman spectroscopy. Aluminium was found to be almost exclusively in six-fold coordination in both the L–A–H and the L–A–S–H gels. Silicon in the L–A–S–H gels was mainly in Q⁴ sites and to a lesser extent in Q³ sites (four-fold coordination with no Si–O–Al bonds). The results thus indicate that silica-rich and aluminium-rich domains formed in these gels.     

Repurposing of 8-Hydroxyquinoline-Based Butyrylcholinesterase and Cathepsin B Ligands as Potent Nonpeptidic Deoxyribonuclease I Inhibitors

A library of 31 butyrylcholinesterase (BChE) and cathepsin B (CatB) inhibitors was screened in vitro for inhibition of deoxyribonuclease I (DNase I). Compounds 22 , 8 and 7 are among the most potent synthetic non-peptide DNase I inhibitors reported to date. Three 8-hydroxyquinoline analogues inhibited both DNase I and BChE with IC₅₀ values below 35 μM and 50 nM, respectively, while two nitroxoline derivatives inhibited DNase I and Cat B endopeptidase activity with IC₅₀ values below 60 and 20 μM. Selected derivatives were screened for various co-target binding affinities at dopamine D₂ and D₃, histamine H₃ and H₄ receptors and inhibition of 5-lipoxygenase. Compound 8 bound to the H₃ receptor and is highlighted as the most promising multifunctional ligand with a favorable pharmacokinetic profile and one of the most potent non-peptide DNase I inhibitors. The present study demonstrates that 8-hydroxyquinoline is a structural fragment critical for DNase I inhibition in the presented series of compounds.     

Interactive Depixelization of Pixel Art through Spring Simulation

We introduce an approach for converting pixel art into high-quality vector images. While much progress has been made on automatic conversion, there is an inherent ambiguity in pixel art, which can lead to a mismatch with the artist's original intent. Further, there is room for incorporating aesthetic preferences during the conversion. In consequence, this work introduces an interactive framework to enable users to guide the conversion process towards high-quality vector illustrations. A key idea of the method is to cast the conversion process into a spring-system optimization that can be influenced by the user. Hereby, it is possible to resolve various ambiguities that cannot be handled by an automatic algorithm.