Metodologias alternativas no ensino de física

Screening a compound library of quinolinone derivatives identified compound 11a as a new P2X7 receptor antagonist. To optimize its activity, we assessed structure-activity relationships (SAR) at three different positions, R_1, R_2 and R_3, of the quinolinone scaffold. SAR analysis suggested that a carboxylic acid ethyl ester group at the R_1 position, an adamantyl carboxamide group at R_2 and a 4-methoxy substitution at the R_3 position are the best substituents for the antagonism of P2X7R activity. However, because most of the quinolinone derivatives showed low inhibitory effects in an IL-1β ELISA assay, the core structure was further modified to a quinoline skeleton with chloride or substituted phenyl groups. The optimized antagonists with the quinoline scaffold included 2-chloro-5-adamantyl-quinoline derivative (16c) and 2-(4-hydroxymethylphenyl)-5-adamantyl-quinoline derivative (17k), with IC_(50) values of 4 and 3 nM, respectively. In contrast to the quinolinone derivatives, the antagonistic effects of the quinoline compounds (16c and 17k) were paralleled by their ability to inhibit the release of the pro-inflammatory cytokine, IL-1β, from LPS/IFN-γ/BzATP-stimulated THP-1 cells (IC_(50) of 7 and 12 nM, respectively). In addition, potent P2X7R antagonists significantly inhibited the sphere size of TS15-88 glioblastoma cells

Search for the Sagittarius Tidal Stream of Axion Dark Matter around 4.55 μ\mueV

We report the first search for the Sagittarius tidal stream of axion dark matter around 4.55 $\mu$eV using CAPP-12TB haloscope data acquired in March of 2022. Our result excluded the Sagittarius tidal stream of Dine-Fischler-Srednicki-Zhitnitskii and Kim-Shifman-Vainshtein-Zakharov axion dark matter densities of $\rho_a\gtrsim0.184$ and $\gtrsim0.025$ GeV/cm$^{3}$, respectively, over a mass range from 4.51 to 4.59 $\mu$eV at a 90% confidence level.Comment: 6 pages, 7 Figures, PRD Letter accepte

PyNET-QxQ: A Distilled PyNET for QxQ Bayer Pattern Demosaicing in CMOS Image Sensor

The deep learning-based ISP models for mobile cameras produce high-quality images comparable to the professional DSLR camera. However, many of them are computationally expensive, which may not be appropriate for mobile environments. Also, the recent mobile cameras adopt non-Bayer CFAs (e.g., Quad Bayer, Nona Bayer, and QxQ Bayer) to improve image quality; however, most deep learning-based ISP models mainly focus on standard Bayer CFA. In this work, we propose PyNET-QxQ based on PyNET, a light-weighted ISP explicitly designed for the QxQ CFA pattern. The number of parameters of PyNET-QxQ is less than 2.5% of PyNET. We also introduce a novel knowledge distillation technique, progressive distillation, to train the compressed network effectively. Finally, experiments with QxQ images (obtained by an actual QxQ camera sensor, under development) demonstrate the outstanding performance of PyNET-QxQ despite significant parameter reductions.Comment: in revie

Synthesis and Structure–Activity Relationship Studies of Benzimidazole-4,7-dione-Based P2X3 Receptor Antagonists as Novel Anti-Nociceptive Agents

P2X3 receptors (P2X3R) are ATP-gated ion channels predominantly expressed in C- and Aδ-fiber primary afferent neurons and have been introduced as a novel therapeutic target for neurological disorders, including neuropathic pain and chronic cough. Because of its localized distribution, antagonism of P2X3R has been thoroughly considered, and the avoidance of issues related to CNS side effects has been proven in clinical trials. In this article, benzimidazole-4,7-dione-based derivatives were introduced as a new chemical entity for the development of P2X3R antagonists. Starting from the discovery of a hit compound from the screening of 8364 random library compounds in the Korea Chemical Bank, which had an IC50 value of 1030 nM, studies of structure–activity and structure–property relationships enabled further optimization toward improving the antagonistic activities as well as the drug’s physicochemical properties, including metabolic stability. As for the results, the final optimized compound 14h was developed with an IC50 value of 375 nM at P2X3R with more than 23-fold selectivity versus P2X2/3R, along with properties of metabolic stability and improved solubility. In neuropathic pain animal models evoked by either nerve ligation or chemotherapeutics in male Sprague-Dawley rats, compound 14h showed anti-nociceptive effects through an increase in the mechanical withdrawal threshold as measured by von Frey filament following intravenous administration

Reflux Esophagitis and Fatigue: Are They Related?

Gastroesophageal reflux disease (GERD) is a chronic, recurrent disease. Reflux esophagitis can interfere with sleep via acid reflux, which can cause daytime sleepiness or fatigue. However, little is known about the association between reflux esophagitis and fatigue. Objectives: We evaluated the association between fatigue and reflux esophagitis in subjects seen at health check-ups. Methods: Consecutive patients who were scheduled for screening endoscopies were enrolled prospectively at the Comprehensive Medical Examination Center of St. Vincent Hospital and Eunpyeong St. Mary’s Hospital, Korea. Three validated questionnaires were used to assess fatigue, daytime hypersomnolence, anxiety, and depression: the Multidimensional Fatigue Inventory—Korean version (MFI-K), Epworth Sleepiness Scale (ESS), and Hospital Anxiety and Depression Scale (HADS). Results: We investigated 497 consecutive eligible subjects. The reflux esophagitis and symptomatic GERD groups comprised 103 (20.7%) and 92 (18.5%) subjects, respectively. The MFI-K total, ESS, HADS-anxiety, and HADS-depression scores did not differ between the esophagitis and non-esophagitis groups (50.0 ± 11.5 vs. 49.7 ± 10.9, p = 0.661; 6.2 ± 2.8 vs. 6.1 ± 3.1, p = 0.987; 5.8 ± 3.1 vs. 5.2 ± 3.2, p = 0.060; 6.2 ± 3.6 vs. 6.0 ± 3.3, p = 0.561). However, the MFI-K total, ESS, HADS-anxiety, and HADS-depression scores were higher in the symptomatic group than in the non-symptomatic group (54.7 ± 12.7 vs. 48.6 ± 10.3, p < 0.001; 7.1 ± 3.5 vs. 5.9 ± 2.9, p = 0.002; 6.4 ± 3.3 vs. 5.1 ± 3.1, p < 0.001; 7.5 ± 4.0 vs. 5.7 ± 3.1, p < 0.001). Multiple regression analysis showed that the MFI-K total was correlated with GERD symptoms (p = 0.021), women (p = 0.001), anxiety (p < 0.001), and depression (p < 0.001). Conclusion: There was no statistically significant association in which reflux esophagitis could cause daytime sleepiness, fatigue, anxiety, or depression. However, fatigue was associated with GERD symptoms, women, anxiety, and depression. Further studies should clarify the association between fatigue and reflux esophagitis

Isoform Sequencing Provides a More Comprehensive View of the Panax ginseng Transcriptome

Korean ginseng (Panax ginseng C.A. Meyer) has been widely used for medicinal purposes and contains potent plant secondary metabolites, including ginsenosides. To obtain transcriptomic data that offers a more comprehensive view of functional genomics in P. ginseng, we generated genome-wide transcriptome data from four different P. ginseng tissues using PacBio isoform sequencing (Iso-Seq) technology. A total of 135,317 assembled transcripts were generated with an average length of 3.2 kb and high assembly completeness. Of those unigenes, 67.5% were predicted to be complete full-length (FL) open reading frames (ORFs) and exhibited a high gene annotation rate. Furthermore, we successfully identified unique full-length genes involved in triterpenoid saponin synthesis and plant hormonal signaling pathways, including auxin and cytokinin. Studies on the functional genomics of P. ginseng seedlings have confirmed the rapid upregulation of negative feed-back loops by auxin and cytokinin signaling cues. The conserved evolutionary mechanisms in the auxin and cytokinin canonical signaling pathways of P. ginseng are more complex than those in Arabidopsis thaliana. Our analysis also revealed a more detailed view of transcriptome-wide alternative isoforms for 88 genes. Finally, transposable elements (TEs) were also identified, suggesting transcriptional activity of TEs in P. ginseng. In conclusion, our results suggest that long-read, full-length or partial-unigene data with high-quality assemblies are invaluable resources as transcriptomic references in P. ginseng and can be used for comparative analyses in closely related medicinal plants

Three-Dimensional Fin-Structured Semiconducting Carbon Nanotube Network Transistor

Three-dimensional (3-D) fin-structured carbon nanotube field-effect transistors (CNT-FETs) with purified 99.9% semiconducting CNTs were demonstrated on a large scale 8 in. silicon wafer. The fabricated 3-D CNT-FETs take advantage of the 3-D geometry and exhibit enhanced electrostatic gate controllability and superior charge transport. A trigated structure surrounding the randomly networked single-walled CNT channel was formed on a fin-like 3-D silicon frame, and as a result, the effective packing density increased to almost 600 CNTs/μm. Additionally, highly sensitive controllability of the threshold voltage (<i>V</i>_TH) was achieved using a thin back gate oxide in the same silicon frame to control power consumption and enhance performance. Our results are expected to broaden the design margin of CNT-based circuit architectures for versatile applications. The proposed 3-D CNT-FETs can potentially provide a desirable alternative to silicon based nanoelectronics and a blueprint for furthering the practical use of emerging low-dimensional materials other than CNTs

Discovery of Potent Antiallodynic Agents for Neuropathic Pain Targeting P2X3 Receptors

Antagonism of the P2X3 receptor is one of the potential therapeutic strategies for the management of neuropathic pain because P2X3 receptors are predominantly localized on small to medium diameter C- and Aδ-fiber primary afferent neurons, which are related to the pain-sensing system. In this study, 5-hydroxy pyridine derivatives were designed, synthesized, and evaluated for their in vitro biological activities by two-electrode voltage clamp assay at hP2X3 receptors. Among the novel hP2X3 receptor antagonists, intrathecal treatment of compound <b>29</b> showed parallel efficacy with pregabalin (calcium channel modulator) and higher efficacy than AF353 (P2X3 receptor antagonist) in the evaluation of its antiallodynic effects in spinal nerve ligation rats. However, because compound <b>29</b> was inactive by intraperitoneal administration in neuropathic pain animal models due to low cell permeability, the corresponding methyl ester analogue, <b>28</b>, which could be converted to compound <b>29</b> in vivo, was investigated as a prodrug concept. Intravenous injection of compound <b>28</b> resulted in potent antiallodynic effects, with ED₅₀ values of 2.62 and 2.93 mg/kg in spinal nerve ligation and chemotherapy-induced peripheral neuropathy rats, respectively, indicating that new drug development targeting the P2X3 receptor could be promising for neuropathic pain, a disease with high unmet medical needs

Axion Dark Matter Search around 4.55 μeV with Dine-Fischler-Srednicki-Zhitnitskii Sensitivity

We report an axion dark matter search at Dine-Fischler-Srednicki-Zhitnitskii sensitivity with the CAPP-12TB haloscope, assuming axions contribute 100% of the local dark matter density. The search excluded the axion-photon coupling gaγγ down to about 6.2×10-16 GeV-1 over the axion mass range between 4.51 and 4.59 μeV at a 90% confidence level. The achieved experimental sensitivity can also exclude Kim-Shifman-Vainshtein-Zakharov axion dark matter that makes up just 13% of the local dark matter density. The CAPP-12TB haloscope will continue the search over a wide range of axion masses. © 2023 authors. Published by the American Physical Society.11Nsciescopu

Integrative epigenomic and transcriptomic analyses reveal metabolic switching by intermittent fasting in brain

10.1007/s11357-022-00537-zGEROSCIENCE4442171-219