Phenotypic Discovery of SB1501, an Anti-obesity Agent,through Modulating Mitochondrial Activity

Obesity has become a pandemic that threatens the quality of life and discovering novel therapeutic agents that can reverse obesity and obesity-related metabolic disorders are necessary. Here, we aimed to identify new anti-obesity agents using a phenotype-based approach. We performed image-based high-content screening with a fluorogenic bioprobe (SF44), which visualizes cellular lipid droplets (LDs), to identify initial hit compounds. A structure-activity relationship study led us to yield a bioactive compound SB1501, which reduces cellular LDs in 3T3-L1 adipocytes without cytotoxicity. SB1501 induced the expression of gene products that regulate mitochondrial biogenesis and fatty acid oxidation in 3T3-L1 adipocytes. Daily treatment with SB1501 improved the metabolic states of db/db mice by reducing body fat mass, adipose tissue mass, food intake, and increasing glucose tolerance. The anti-obesity effect of SB1501 may result from perturbation of the PGC-1α–UCP1 regulatory axis in inguinal white adipose tissue and brown adipose tissue. These data suggest the therapeutic potential of SB1501 as an anti-obesity agent via modulating mitochondrial activities.     

Charge Transportation and Chirality in Liquid Crystalline Helical Network Phases of Achiral BTBT-Derived Polycatenar Molecules

First examples of multichain (polycatenar) compounds, based on the π-conjugated [1]benzothieno[3,2-b]benzothiophene unit are designed, synthesized, and their soft self-assembly and charge carrier mobility are investigated. These compounds, terminated by the new fan-shaped 2-brominated 3,4,5-trialkoxybenzoate moiety, form bicontinuous cubic liquid crystalline (LC) phases with helical network structure over extremely wide temperature ranges (>200 K), including ambient temperature. Compounds with short chains show an achiral cubic phase with the double network, which upon increasing the chain length, is at first replaced by a tetragonal 3D phase and then by a mirror symmetry is broken triple network cubic phase. In the networks, the capability of bypassing defects provides enhanced charge carrier mobility compared to imperfectly aligned columnar phases, and the charge transportation is non-dispersive, as only rarely observed for LC materials. At the transition to a semicrystalline helical network phase, the conductivity is further enhanced by almost one order of magnitude. In addition, a mirror symmetry broken isotropic liquid phase is formed beside the 3D phases, which upon chain elongation is removed and replaced by a hexagonal columnar LC phase.     

Evaluation of particle recovery from microalgae

Coccoliths are micro-structured biomineral particles found in cell protective covering layers of coccolithophore species. They are mainly composed of CaCO₃ and their individual crystal entities are arranged in such a way that they construct complex and unique structures. This complexity is found down to the individual particle level and appears to have promising properties to offer. This study focuses on the essential step prior to any kind of implementation, which is the recovery of the material. It summarizes cleaning protocols found in literature, compares them for the first time for the same freshly cultivated material and addresses challenges that still need to be overcome. Further, it highlight the advantages and disadvantages of the best cleaning protocols, suggests optimizations with promising results and uses size distribution measurements to analyse the recovery efficiency. To that end, further characterization techniques, new for coccoliths, are introduced and used to improve our current knowledge of the particles behaviour.     

Improving storability,physiological disorders,and antioxidant properties of ‘Bartlett’ and ‘d’Anjou’ pears (Pyrus communis L.) by pre-harvest 1-methylcyclopropene spraying

Ethylene continues to be a major factor influencing quality of European pears during storage. Although research has been done on the effect of pre-harvest 1-methylcyclopropene (1-MCP) on physiological characteristics in pears, a full understanding of cultivar response and antioxidant metabolism remains elusive. Spraying 1-MCP on ‘Bartlett’ and ‘d’Anjou’ pears was studied with respect to physiology, storage and eating quality, disorders, and antioxidant properties at two harvest date (H1 and H2) during storage and ripening. Treatment with 1-MCP extended the harvest window of ‘Bartlett’ and ‘d’Anjou’ pears 3 and 4 days, respectively, without reducing storage or eating quality. Treatment with 1-MCP reduced ethylene production (EPR) and respiration rates (RR), maintained fruit firmness and green colour during storage and retarded development of desirable melting texture in both cultivars. Additionally, 1-MCP lowered the incidence of disorders by alleviating membrane lipid peroxidation, retaining high total flavonoids (TF) and antioxidant capacity, and enhancing superoxide dismutase (SOD), catalase (CAT) and ascorbate peroxidase (APX) activity in both cultivars. Overall, pre-harvest 1-MCP applications could extend storage time of ‘Bartlett’ and ‘d’Anjou’ pears to 5 and 6 months, respectively, at −1.1 ± 0.5 °C, by reducing ethylene synthesis and enhancing antioxidant metabolism.     

Seismic behavior of geosynthetic-reinforced retaining walls backfilled with cohesive soil

This study investigates the seismic performance of geosynthetic-reinforced modular block retaining walls backfilled with cohesive, fine grained clay-sand soil mixture. Shaking table tests were performed for three ½ scaled (wall height 190 cm) and ¼ scaled model walls to investigate the effects of backfill type, the influence of reinforcement length and reinforcement stiffness effects. The El Centro and Kobe earthquake records of varying amplitudes were used as base acceleration. Displacement of the front wall, accelerations at different locations, strains on the reinforcements, and the visual observations of the facing and the backfill surface were used to evaluate the seismic performance of model walls. The model walls were subjected to rigorous shaking and the walls did not exhibit any stability problems or signs of impending failure. The maximum deformations observed on the models with cohesive backfill was less than half of the deformation of the sand model. The load transfers between the geogrid and cohesive soil was comparable to that of sand and hence the needed reinforcement length was similar as well. As a result; the model walls with cohesive backfills performed within acceptable limits under seismic loading conditions when compared with granular backfilled counterparts.     

Combination of nuclear magnetic resonance spectroscopy and nonlinear methods to analyze the copolymerization of phosphonic acid derivatives

We demonstrate in this study that the combination of modern inline monitoring methods [here: inline nuclear magnetic resonance (NMR)] with simulations gains more exact and profound kinetic results than previously used methods like linearization without that combination. The ¹H-NMR spectroscopic data (more than 100 data points) are used to construct the copolymerization diagram. The reactivity ratios are obtained applying the van Herks nonlinear least square method. The examination of the radical copolymerization of 2-hydroxyethyl methacrylate (HEMA) with (2-{[2-(ethoxycarbonyl)prop-2-en-1-yl]oxy}ethyl) phosphonic acid (ECPPA) as important adhesive monomer used in dentistry yields reactivity ratios of r_HEMA = 1.83; r_ECPPA = 0.42. The copolymerization diagram reflects nonideal, non-azeotropic copolymerization. The sequence distribution of the obtained by Monte Carlo simulation indicates the generation of statistical copolymers. As an important finding, it is demonstrated that the repeating units responsible for etching and adhesion are arranged over the whole polymer chain, which is necessary to achieve proper functionality. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 48256.     

On globally stable adaptive control providing l 1 tracking performance for linear discrete-time systems

Existing adaptive control algorithms at best guarantee that the tracking error is a l ₂ sequence. This paper presents globally stable adaptive control algorithms for linear discrete-time systems providing l ₁ tracking performance. Two algorithms with different degree of complexity are proposed, one for the case of known control directions, and a separate algorithm for the case of unknown control directions. It is demonstrated that in both cases the tracking error is l ₁ sequence, while the input and output signals are uniformly bounded.