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Adaptive active Brownian particles searching for targets of unknown positions
<p>Developing behavioral policies designed to efficiently solve target-search problems is a crucial issue both in nature and in the nanotechnology of the 21st century. Here, we characterize the target-search strategies of simple microswimmers in a homogeneous environment containing sparse targets of unknown positions. The microswimmers are capable of controlling their dynamics by switching between Brownian motion and an active Brownian particle and by selecting the time duration of each of the two phases. The specific conduct of a single microswimmer depends on an internal decision-making process determined by a simple neural network associated with the agent itself. Starting from a population of individuals with random behavior, we exploit the genetic algorithm NeuroEvolution of Augmenting Topologies to show how an evolutionary pressure based on the target-search performances of single individuals helps to find the optimal duration of the two different phases. Our findings reveal that the optimal policy strongly depends on the magnitude of the particle's self-propulsion during the active phase and that a broad spectrum of network topology solutions exists, differing in the number of connections and hidden nodes.</p>
Investigations into Simplified Analogues of the Herbicidal Natural Product (+)-Cornexistin
UIBK_Avalanche
<p>Labeled avalanche images.</p><p>Folder annotations with glide, loose and slab avalanches.</p><p>Training: train.txt. Test: test.txt</p>
Effect of curcuminoids on cell-free 5-lipoxygenase activity
<p>Human semi-purified or purified 5-lipoxygenase (5-LOX) enzyme was pre-treated with DMSO or curcuminoids, 5-LOX product formation was initiated by arachidonic acid and 5-LOX products (et-LTB4, t-LTB4 and 5-H(p)ETE) were analyzed by RP-UV-HPLC.</p><p>Raw data including the absolute values (ng) and normalized data (% of control) of all individual experiments was uploaded.</p><p>The methods and results were published in Rao et al., Biochem Pharmacol. 2022 Sep:203:115202. doi: 10.1016/j.bcp.2022.115202 </p><p>To determine 5-LOX activity, semi-purified 5-LOX (0.5 µg) was pre-treated with vehicle (DMSO), test compounds or the selective 5-LOX inhibitor BWA4C (0.1 μM, Merck) in 1 mL PBS pH 7.4 plus EDTA (1 mM) and ATP (1 mM) for 10 min at 4 °C. The mixture was pre-warmed for 30 s at 37 °C before 5-LOX product formation was initiated by the addition of AA (20 μM or as indicated, Cayman Chemical) and CaCl2 (2 mM). After 10 min incubation at 37 °C, the reaction was stopped with an equal volume of ice-cold methanol containing the internal standard PGB1 (2 ng, Cayman Chemical). Lipid mediators formed were extracted by solid phase extraction using Sep-Pak C18 35 cc Vac Cartridges (Waters, Milford, MA). Major 5-LOX products (all-trans isomers of LTB4 and 5-H(p)ETE) were analyzed by RP-UV-HPLC using a Nova-Pak C18 Radial-Pak Column (4 μm, 5 × 100 mm, Waters) under isocratic conditions (73 % methanol/27 % water/0.007 % trifluoroacetic acid) at a flow rate of 1.2 mL/min and detected at 235 nm (for 5-H(p)ETE) or 280 nm (all-trans isomers of LTB4). The 5-LOX reference inhibitor BWA4C (0.1 μM, Merck) inhibited 5-LOX product formation by 87.6 ± 1.7 %.</p><p>For the AA competition studies shown in <a href="https://www.sciencedirect.com/science/article/pii/S0006295222002969?via%3Dihub#f0005">Fig. 1</a><strong>E-G</strong>, human recombinant 5-LOX (Cayman Chemical, 25–50 units in 1 mL PBS pH 7.4 with 1 mM EDTA and 1 mM ATP) was pre-incubated with vehicle (DMSO), compound <strong>1a</strong>, <strong>3b,</strong> or <strong>2f</strong> for 10 min on ice. Product formation was initiated by the addition of AA (10 µM, 20 µM or 40 µM, Cayman Chemical) and CaCl2 (2 mM) followed by incubation at 37 °C. After 10 min, the reaction was stopped by the addition of ice-cold methanol (1 mL) containing PGB1 (2 ng, Cayman Chemical) as internal standard. PBS pH 7.4 (498.2 µL) acidified with HCl (1 M, 31.8 µL) was added to the samples, which were centrifuged (750 × g, 10 min, 4 °C) and subjected to solid phase extraction. Clean-Up C-18 Endcapped SPE cartridges (100 mg, 10 mL, UCT, Bristol, PA) were washed twice with methanol and pre-conditioned with water (1 mL each). Supernatants were loaded onto the cartridges, which were washed with 1 mL water and 1 mL water/methanol (75/25, v/v) prior to elution of 5-LOX products with 300 µL methanol. After addition of 120 µL water, samples were centrifuged (21,000xg, 10 min, 4 °C) and supernatants subjected to UPLC-photodiode array detector (PDA) analysis.</p><p>Chromatographic separation of 5-LOX products (all-<i>trans</i> isomers of LTB4 and 5-H(p)ETE) was performed at 40 °C on a Kinetex C-18 LC column (100 Å, 1.3 μm, 2.1 × 50 mm, Phenomenex, Torrance, CA) using a Nexera X2 UHPLC system (Shimadzu, Kyoto, Japan) that was coupled to a PDA (SPD-M20A, Shimadzu). The UHPLC system was operated at a flow rate of 0.45 mL/min using buffer A (50 % methanol/50 % water/0.05 % trifluoroacetic acid) and buffer B (100 % methanol/0.05 % trifluoroacetic acid). Following sample injection (10 µL), the initial mobile phase composition (A/B = 86/14) was kept constant for 2 min before it was stepwise decreased to A/B = 54/46 (2 min) and then to A/B = 10/90 (another 2 min).</p><p>For 5-H(p)ETE analysis, the wavelength was set to 235 nm, whereas PGB1 (internal standard, Cayman Chemical) and the all-<i>trans</i> isomers of LTB4 were detected at 280 nm. Chromatograms were acquired and processed using LabSolutions (version 5.97, Shimadzu).</p>
Analysis of the phosphatidylcholine fatty acid composition in α-T-13′-COOH-treated macrophages
<p>RAW264.7 cells were incubated with vehicle (DMSO, 'w/o') or 0.5 or 5.0 µM α-T-13′-COOH for 24 h. The fatty acid distribution of phosphatidylcholine was then analyzed by UPLC-MS/MS.</p><p>Raw analyst files (.wiff and .wiff.scan) of the UPLC-MS/MS results were uploaded, together with an Excel file for the sample list.</p><p>The methods and results were published in Liao et al., Int J Mol Sci, 2023 May 25;24(11):9229. doi: 10.3390/ijms24119229.</p><p>Lipids were extracted from RAW264.7 cell pellets by the successive addition of methanol, PBS (pH 7.4), chloroform, and saline (final ratio: 34:14:35:17). After the evaporation of the organic solvent, the remaining lipid fraction was dissolved in methanol, stored at −20 °C, and analyzed by UPLC-MS/MS. Internal standards: 1,2-dimyristoyl-<i>sn</i>-glycero-3-phosphatidylcholine (DMPC), 1,2-dimyristoyl-<i>sn</i>-glycero-3-phosphatidyl-ethanolamine (DMPE).</p><p>Phospholipids (PC, PE, PI, PS, PG) were separated on an Acquity UPLC BEH C8 column (130 Å, 1.7 μm, 2.1 × 100 mm; Waters, Milford, MA, USA) using an Acquity UPLC system (Waters), which was coupled to a QTRAP 5500 mass spectrometer (Sciex, Framingham, MA, USA) equipped with a Turbo V Ion Source and an electrospray ionization probe. Chromatographic separation was performed at a flow rate of 0.75 mL/min and at a column temperature of 45 °C. The mobile phase was composed of eluent A (acetonitrile/water, 95/5, with 2 mM ammonium acetate) and eluent B (water/acetonitrile, 90/10, with 2 mM ammonium acetate). The gradient was ramped from 70% to 80% A within 5 min and to 100% A within 2 min, followed by isocratic elution for another 2 min. Eluted phospholipids were detected upon the fragmentation of parental ions (PC: [M+OAc]−, all other phospholipids: [M-H]−) to fatty acid anions derived from <i>sn</i>-1 and <i>sn</i>-2 positions by multiple reaction monitoring using a QTRAP 5500 mass spectrometer. The ion spray voltage was set to −4500 V, the curtain gas to 30 psi, the collision gas to medium, and the heated capillary temperature to either 350 °C (PC), 500 °C (PI), 550 °C (PS, PG), or 650 °C (PE). The sheath gas pressure was set to 45 (PS) or 55 psi (PC, PE, PI, PG) and the auxiliary gas pressure was set to either to 75 psi (PC, PE, PI, PG) or 80 psi (PS). The declustering potential was set to −40 V (PS), −44 V (PC), −45 V (PG), or −50 V (PE, PI), the entrance potential to −10 eV (PC; PE, PI, PS, PG), the collision energy to −38 eV (PE), −46 eV (PC), −52 eV (PG), −56 eV (PS), or −62 eV (PI), and the collision cell exit potential to −11 V (PC, PI), −12 V (PE), −18 V (PG), or −20 V (PS).</p><p>The instruments were either operated with Analyst 1.6.2 (QTRAP 5500, Sciex) or Analyst 1.7.1 (QTRAP 6500+, Sciex). </p>
Effect of curcuminoids on DPPH radical scavenging
<p>Scavenging of 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals by <strong>3b</strong>, cysteine, and ascorbic acid (2–200 µM).</p><p>Raw data including the absolute values (absorbance subtract ethanol blank) and normalized data (% of control) of all individual experiments was uploaded.</p><p>The methods and results were published in Rao et al., Biochem Pharmacol. 2022 Sep:203:115202. doi: 10.1016/j.bcp.2022.115202 </p><p>Vehicle (ethanol), compound <strong>3b</strong>, cysteine hydrochloride (reference compound, Merck) or ascorbic acid (reference compound, Caesar & Loretz GmbH, Hilden, Germany) were incubated with 2,2-diphenyl-1-picrylhydrazyl (Merck; 50 µM) under shaking in the dark. After 30 min, the absorbance was measured at 520 nm using a Multiskan Spectrum Microplate Reader (Thermo Fisher Scientific).</p>
Effect of curcuminoids on 5-lipoxygenase product formation in activated neutrophils
<p>Human polymorphonuclear leukocytes (PMNL) were pre-treated with DMSO or curcuminoids, 5-LOX product formation was initiated by arachidonic acid (AA, 20 µM) and A23187 (2.5 µM) and 5-LOX products (LTB4, its isomers et-LTB4, t-LTB4, and 5-H(p)ETE) were analyzed by RP-UV-HPLC. </p><p>Raw data including the absolute values (ng) and normalized data (% of control) of all individual experiments was uploaded.</p><p>The methods and results were published in Rao et al., Biochem Pharmacol. 2022 Sep:203:115202. doi: 10.1016/j.bcp.2022.115202 </p><p>Freshly isolated human PMNL (6 × 106 cells/mL) were resuspended in PBS pH 7.4 with glucose (1 mg/mL) and CaCl2 (1 mM). Cells were first pre-treated with vehicle (DMSO), test compounds or zileuton (3 μM, Cayman Chemical) for 10 min and then co-incubated with AA (20 μM) and calcium ionophore (A23187, 2.5 μM, Merck) for another 10 min at 37 °C. The reaction was terminated with an equal volume of ice-cold methanol containing the internal standard PGB1 (2 ng, Cayman Chemical). Formed lipid mediators were extracted by solid phase extraction using Sep-Pak C18 35 cc Vac Cartridges (Waters), and major 5-LOX products (LTB4, its all-trans isomers and 5-H(p)ETE) were analyzed by RP-UV-HPLC as described for the determination of cell-free 5-LOX activity. The 5-LOX reference inhibitor zileuton (3 μM, Cayman Chemical) suppressed 5-LOX product formation by 50.0 ± 20.5%.</p>
A Divergent Polyene Cyclization for the Total Synthesis of Greenwayodendrines, Greenwaylactams, Polysin and Polyveoline
Networks of Anglophone LGBTQ+ Exile Writers from 1900 to 1969
<p>Data sets on meetings and creative exchanges between Anglophone LGBTQ+ writers (1900-69) for series of network visulalizations (graphs, maps, and timeline).</p><p>Austrian Science Fund (FWF): 10.55776/P35199</p>