22 research outputs found
Surface plasmon polaritons assisted diffraction in periodic subwavelength holes of metal films with reduced interplane coupling
Metal films grown on Si wafer perforated with a periodic array of
subwavelength holes have been fabricated and anomalous enhanced transmission in
the mid-infrared regime has been observed. High order transmission peaks up to
Si(2,2) are clearly revealed due to the large dielectric constant contrast of
the dielectrics at the opposite interfaces. Si(1,1) peak splits at oblique
incidence both in TE and TM polarization, which confirms that anomalous
enhanced transmission is a surface plasmon polaritons (SPPs) assisted
diffraction phenomenon. Theoretical transmission spectra agree excellently with
the experimental results and confirm the role of SPPs diffraction by the
lattice.Comment: 4 pages, 5 figures, 26 reference
Spin-Charge Coupling in lightly doped NdCeCuO
We use neutron scattering to study the influence of a magnetic field on spin
structures of NdCuO. On cooling from room temperature, NdCuO
goes through a series of antiferromagnetic (AF) phase transitions with
different noncollinear spin structures. While a c-axis aligned magnetic field
does not alter the basic zero-field noncollinear spin structures, a field
parallel to the CuO plane can transform the noncollinear structure to a
collinear one ("spin-flop" transition), induce magnetic disorder along the
c-axis, and cause hysteresis in the AF phase transitions. By comparing these
results directly to the magnetoresistance (MR) measurements of
NdCeCuO, which has essentially the same AF structures
as NdCuO, we find that a magnetic-field-induced spin-flop transition,
AF phase hysteresis, and spin c-axis disorder all affect the transport
properties of the material. Our results thus provide direct evidence for the
existence of a strong spin-charge coupling in electron-doped copper oxides.Comment: 12 pages, 12 figure
Identifying adolescents' gaming preferences for a tobacco prevention social game: A qualitative study.
IntroductionConsidering the dangers of adolescent tobacco use, the successful design of behavioral programs is crucial for tobacco prevention. According to preliminary research, social game interventions can improve adolescent tobacco outcomes. The current qualitative study aims to (1) uncover the gaming elements that adolescents deem important for a positive learning experience, and (2) confirm these gaming elements with adolescents who are presented with a tobacco prevention game concept that applies these elements.MethodsFindings from this study are drawn from two phases. Phase 1 involved in-person focus group discussions (n = 15) and Phase 2 included three online focus groups and a paired interview with another set of adolescents (n = 15). The study was conducted under a project that aimed to design and test a social game-based tobacco prevention program for adolescents (Storm-Heroes). With open coding and thematic analysis, two research team members identified repeated topics and relevant quotes to organize them into themes. The themes evolved as new content was identified during the process. This process was repeated until thematic saturation was reached.ResultsThematic analysis across Phase 1 and Phase 2 revealed four major themes: 1) Balance during gaming challenges, 2) Healthy social interaction, 3) Performance and creative freedom, and 4) Fictional world and game mechanics for tobacco prevention.ConclusionThis study identified specific intervention features that best fit the needs of adolescents in the context of a social game for tobacco prevention. For future research, we will use a participatory approach to allow adolescents to take part in the design process, improve Storm-Heroes, and develop health promotional messages that can be incorporated into the program. Ultimately, a board game for tobacco prevention is expected to bring adolescents together to create lasting memories that nudge them away from tobacco use and the harm it can cause
Rapid discovery and crystallography study of highly potent and selective butylcholinesterase inhibitors based on oxime-containing libraries and conformational restriction strategies
22 p.-9 fig.-8 tab.Butyrylcholinesterase is regarded as a promising drug target in advanced Alzheimer’s disease. In order to identify highly selective and potent BuChE inhibitors, a 53-membered compound library was constructed via the oxime-based tethering approach based on microscale synthesis. Although A2Q17 and A3Q12 exhibited higher BuChE selectivity versus acetylcholinesterase, the inhibitory activities were unsatisfactory and A3Q12 did not inhibit Aβ1-42 peptide self-induced aggregation. With A2Q17 and A3Q12 as leads, a novel series of tacrine derivatives with nitrogen-containing heterocycles were designed based on conformation restriction strategy. The results demonstrated that 39 (IC50 = 3.49 nM) and 43 (IC50 = 7.44 nM) yielded much improved hBuChE inhibitory activity compared to the lead A3Q12 (IC50 = 63 nM). Besides, the selectivity indexes (SI = AChE IC50 / BChE IC50) of 39 (SI = 33) and 43 (SI = 20) were also higher than A3Q12 (SI = 14). The results of the kinetic study showed that 39 and 43 exhibited a mixed-type inhibition against eqBuChE with respective Ki values of 1.715 nM and 0.781 nM. And 39 and 43 could inhibit Aβ1-42 peptide self-induced aggregation into fibril. X-ray crystallography structures of 39 or 43 complexes with BuChE revealed the molecular basis for their high potency. Thus, 39 and 43 are deserve for further study to develop potential drug candidates for the treatment of Alzheimer’s disease.We gratefully acknowledge financial support from the Shandong Provincial Key Research and Development Project (No. 2019JZZY021011), Science Foundation for Outstanding Young Scholars of Shandong Province (ZR2020JQ31), Foreign Cultural and Educational Experts Project (GXL20200015001), Qilu Young Scholars Program of Shandong University, Distinguished Young and Middle-aged Scholar of Shandong University, the Taishan Scholar Program at Shandong Province, and MINECO (Grants SAF2016-76693-R to A.M), F.C., F.N. and X.B. were supported by the French Ministry of Armed Forces (Direction Générale de l'Armement and Service de Santé des Armées, NBC-5-C-4210). Authors would like to thank the ESRF for long-term beamtime access (MX2329 IBS BAG).Peer reviewe
Covalently Targeted Highly Conserved Tyr318 to Improve the Drug Resistance Profiles of HIV-1 NNRTIs: A Proof-of-Concept Study
This study presents proof of concept for designing a novel HIV-1 covalent inhibitor targeting the highly conserved Tyr318 in the HIV-1 non-nucleoside reverse transcriptase inhibitors binding pocket to improve the drug resistance profiles. The target inhibitor ZA-2 with a fluorosulfate warhead in the structure was found to be a potent inhibitor (EC50 = 11–246 nM) against HIV-1 IIIB and a panel of NNRTIs-resistant strains, being far superior to those of NVP and EFV. Moreover, ZA-2 was demonstrated with lower cytotoxicity (CC50 = 125 µM). In the reverse transcriptase inhibitory assay, ZA-2 exhibited an IC50 value of 0.057 µM with the ELISA method, and the MALDI-TOF MS data demonstrated the covalent binding mode of ZA-2 with the enzyme. Additionally, the molecular simulations have also demonstrated that compounds can form covalent binding to the Tyr318
Influence of a Coronary Artery Disease-Associated Genetic Variant on FURIN Expression and Effect of Furin on Macrophage Behavior.
OBJECTIVE: Genome-wide association studies have revealed a robust association between genetic variation on chromosome 15q26.1 and coronary artery disease (CAD) susceptibility; however, the underlying biological mechanism is still unknown. The lead CAD-associated genetic variant (rs17514846) at this locus resides in the FURIN gene. In advanced atherosclerotic plaques, furin is expressed primarily in macrophages. We investigated whether this CAD-associated variant alters FURIN expression and whether furin affects monocyte/macrophage behavior. APPROACH AND RESULTS: A quantitative reverse transcription polymerase chain reaction analysis showed that leukocytes from individuals carrying the CAD risk allele of rs17514846 had increased FURIN expression. A chromatin immunoprecipitation assay revealed higher RNA polymerase II occupancy in the FURIN gene in mononuclear cells of individuals carrying this allele. A reporter gene assay in transiently transfected monocytes/macrophages indicated that the CAD risk allele had higher transcriptional activity than the nonrisk allele. An analysis of isogenic monocyte cell lines created by CRISPR-mediated genome editing showed that isogenic cells with the A/A genotype for rs17514846 had higher FURIN expression levels than the isogenic cells with the C/C genotype. An electrophoretic mobility shift assay exhibited preferential binding of a nuclear protein to the risk allele. Studies of monocytes/macrophages with lentivirus-mediated furin overexpression or shRNA-induced furin knockdown showed that furin overexpression promoted monocyte/macrophage migration, increased proliferation, and reduced apoptosis whereas furin knockdown had the opposite effects. CONCLUSIONS: Our study shows that the CAD-associated genetic variant increases FURIN expression and that furin promotes monocyte/macrophage migration and proliferation while inhibiting apoptosis, providing a biological mechanism for the association between variation at the chromosome 15q26.1 locus and CAD risk