Structure-Activity Relationship Explorations and Discovery of a Potent Antagonist for the Free Fatty Acid Receptor 2

Free fatty acid receptor 2 (FFA2) is a sensor for short-chain fatty acids that has been identified as an interesting potential drug target for treatment of metabolic and inflammatory diseases. Although several ligand series are known for the receptor, there is still a need for improved compounds. One of the most potent and frequently used antagonists is the amide-substituted phenylbutanoic acid known as CATPB ( 1 ). We here report the structure-activity relationship exploration of this compound, leading to the identification of homologues with increased potency. The preferred compound 37 (TUG-1958) was found, besides improved potency, to have high solubility and favorable pharmacokinetic properties.     

New Pilot Plant Studies at the Budapest Waterworks

The quality of water provided by the Budapest Waterworks should comply with the standards prescribed by the European Community. According to these provisions, on one of the major water-producing regions (Csepel Island), rows of wells of 60,000 m³/day yield have been closed recently, and in the immediate future further plants would have been closed because of the high iron and manganese content of the water.

The raw water obtained from 100 different wells will be purified by a water treatment plant of 150,000 m³/day capacity. Considering the high iron content (0.05–0.15 mg/L) and manganese content (0.05–0.2 mg/L), the raw water fails to comply with the requirements of the potable water standard.

Since 1990, over a period of three years, we conducted water purification experiments in several stages. In these, three methods of oxidizing as well as single and double layer open rapid filters were applied to oxidize the manganese (and, to a lesser extent, the water) present in dissolved form, resp., to destroy various living organisms.

In the course of the experiments, it became clear that the chlorine and chlorine + air methods are efficient in case of a small quantity of iron to be oxidized and only 20–25% of the dissolved manganese content could be oxidized.

Neither of the two methods could ensure firm management of microbiological and bacteriological characteristics. The best results were obtained by ozone oxidation, in which case the chemical oxidizing process was almost fully completed and even the chlorine-resistant living organisms could be destroyed.

On the basis of the experiments carried out, the investment program of the water treatment plant was worked out and the conditions of an international tender were compiled whose winner will be commissioned to build up the water works in the time period 1993–1996. One of the main steps of the proposed technology is the ozone treatment.     

Magneto-Inertial Fusion

In this community white paper, we describe an approach to achieving fusion which employs a hybrid of elements from the traditional magnetic and inertial fusion concepts, called magneto-inertial fusion (MIF). The status of MIF research in North America at multiple institutions is summarized including recent progress, research opportunities, and future plans.     

General factorization framework for context-aware recommendations

Context-aware recommendation algorithms focus on refining recommendations by considering additional information, available to the system. This topic has gained a lot of attention recently. Among others, several factorization methods were proposed to solve the problem, although most of them assume explicit feedback which strongly limits their real-world applicability. While these algorithms apply various loss functions and optimization strategies, the preference modeling under context is less explored due to the lack of tools allowing for easy experimentation with various models. As context dimensions are introduced beyond users and items, the space of possible preference models and the importance of proper modeling largely increases. In this paper we propose a general factorization framework (GFF), a single flexible algorithm that takes the preference model as an input and computes latent feature matrices for the input dimensions. GFF allows us to easily experiment with various linear models on any context-aware recommendation task, be it explicit or implicit feedback based. The scaling properties makes it usable under real life circumstances as well. We demonstrate the framework’s potential by exploring various preference models on a 4-dimensional context-aware problem with contexts that are available for almost any real life datasets. We show in our experiments—performed on five real life, implicit feedback datasets—that proper preference modelling significantly increases recommendation accuracy, and previously unused models outperform the traditional ones. Novel models in GFF also outperform state-of-the-art factorization algorithms. We also extend the method to be fully compliant to the Multidimensional Dataspace Model, one of the most extensive data models of context-enriched data. Extended GFF allows the seamless incorporation of information into the factorization framework beyond context, like item metadata, social networks, session information, etc. Preliminary experiments show great potential of this capability.     

The Interplay of Apoes with Syndecans in Influencing Key Cellular Events of Amyloid Pathology

Apolipoprotein E (ApoE) isoforms exert intricate effects on cellular physiology beyond lipid transport and metabolism. ApoEs influence the onset of Alzheimer’s disease (AD) in an isoform-dependent manner: ApoE4 increases AD risk, while ApoE2 decreases it. Previously we demonstrated that syndecans, a transmembrane proteoglycan family with increased expression in AD, trigger the aggregation and modulate the cellular uptake of amyloid beta (Aβ). Utilizing our previously established syndecan-overexpressing cellular assays, we now explore how the interplay of ApoEs with syndecans contributes to key events, namely uptake and aggregation, in Aβ pathology. The interaction of ApoEs with syndecans indicates isoform-specific characteristics arising beyond the frequently studied ApoE–heparan sulfate interactions. Syndecans, and among them the neuronal syndecan-3, increased the cellular uptake of ApoEs, especially ApoE2 and ApoE3, while ApoEs exerted opposing effects on syndecan-3-mediated Aβ uptake and aggregation. ApoE2 increased the cellular internalization of monomeric Aβ, hence preventing its extracellular aggregation, while ApoE4 decreased it, thus helping the buildup of extracellular plaques. The contrary effects of ApoE2 and ApoE4 remained once Aβ aggregated: while ApoE2 reduced the uptake of Aβ aggregates, ApoE4 facilitated it. Fibrillation studies also revealed ApoE4′s tendency to form fibrillar aggregates. Our results uncover yet unknown details of ApoE cellular biology and deepen our molecular understanding of the ApoE-dependent mechanism of Aβ pathology.     

Corrosion behaviour of as-cast ZK40 with CaO and Y additions

The microstructures of as-cast ZK40, ZK40 with 2% (mass fraction) CaO and ZK40 with 1% (mass fraction) Y were investigated, and the intermetallic phase morphology and the distribution were characterised. By having discrete intermetallic particles at the grain boundaries for the ZK40, the microstructure was modified to a semi-continuous network of intermetallic compounds along the grain boundaries for the ZK40 with CaO or Y additions. The CaO was not found in the microstructure. However, Ca was present in Ca₂Mg₆Zn₃ intermetallic compounds which were formed during casting. Hydrogen evolution and electrochemical impedance spectroscopy tests revealed that the addition of CaO slightly enhanced the corrosion resistance whereas Y had a negative effect on the corrosion resistance of ZK40. Immersion tests showed that severe localised corrosion as well as corrosion along the intermetallic compounds played an important role in the corrosion process of ZK40–Y whereas the localised corrosion was not pronounced for ZK40 or ZK40–CaO alloys. Micro-segregation in the α-Mg matrix was notably higher for the ZK40 alloy compared with the modified alloys. The combination of this effect with a possible formation of a more stable corrosion layer for the ZK40–CaO was attributed as the main reason for an improved corrosion resistance for the ZK40–CaO alloy.     

Polymer‐based nucleation for chemical vapour deposition of diamond

Chemical vapour deposition of diamond on foreign substrates is hindered due to its high surface energy. Therefore, nucleation treatment has to be employed to initialize the formation of diamond crystals. This article deals with diamond growth on silicon substrates coated with three types of polymers: (i) polystyrene (PS), (ii) polylactic‐co‐glycolic acid (PLGA), and (iii) polyvinyl alcohol (PVA) were applied in different forms, i.e., microspheres (PS, PLGA), monolayers (PLGA), multilayers (PLGA, PLGA/PS), and composites with embedded diamond nanoparticles (PLGA, PVA). Thin polymers and microsphere monolayers did not contribute to the diamond nucleation and/or growth. A thicker continuous polymer film (>750 nm) or thin polymer/microsphere layer led to a homogeneous and dense formation of diamond grains. In the case of nucleation using polymer composites, where the thin polymer film serves as a 3D carrier matrix for embedded diamond nanoparticles, a comparable nucleation density to the well‐established ultrasonic seeding method was achieved. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43688.