Evidence for the formation of magnetic moments in the cuprate superconductor Hg0.8_{0.8}Cu0.2_{0.2}Ba2_2Ca2_2Cu3_3O8+δ_{8+\delta} below TcT_c seen by NQR

We report pure zero field nuclear magnetic resonance (NQR) measurements on the optimally doped three layer high-$T_{c}$-compounds HgBaCaCuO and HgBaCaCuO(F) with $T_c$ 134 K. Above $T_{c}$ two Cu NQR line pairs are observed in the spectra corresponding to the two inequivalent Cu lattice sites. Below $T_{c}$ the Cu NQR spectra show additional lines leading to the extreme broadened Cu NQR spectra at 4.2 K well known for the HgBaCaCuO compounds. The spin-lattice relaxation curves follow a triple exponential function with coefficients depend onto the saturation time (number of saturation pulses), whereas the spin-spin relaxation curve is described by a single exponential function. From the spin-lattice relaxation we deduced a complete removal of the Kramers degeneracy of the Cu quadrupole indicating that the additional lines are due to a Zeemann splitting of the $^{63/65}$Cu lines due to the spontaneous formation of magnetic moments within the CuO layers. Below 140 K, the spectra are well fitted by a number of 6 $^{63/65}$Cu line pairs. From the number of the Cu lines, the position of the lines relative to each other and the complete removal of the Kramers degeneracy we deduced an orientation of the magnetic moments parallel to the symmetry axis of the electric field gradient tensor with magnitudes of the order of 1000 G. We also discuss the possible microscopic origin of the observed internal magnetic fields.Comment: 11 pages, 12 figure

Філософія популізму як варіант сучасної філософії

We have previously reported on the functional interaction of Lipid II with human alpha-defensins, a class of antimicrobial peptides. Lipid II is an essential precursor for bacterial cell wall biosynthesis and an ideal and validated target for natural antibiotic compounds. Using a combination of structural, functional and in silico analyses, we present here the molecular basis for defensin-Lipid II binding. Based on the complex of Lipid II with Human Neutrophil peptide-1, we could identify and characterize chemically diverse low-molecular weight compounds that mimic the interactions between HNP-1 and Lipid II. Lead compound BAS00127538 was further characterized structurally and functionally; it specifically interacts with the N-acetyl muramic acid moiety and isoprenyl tail of Lipid II, targets cell wall synthesis and was protective in an in vivo model for sepsis. For the first time, we have identified and characterized low molecular weight synthetic compounds that target Lipid II with high specificity and affinity. Optimization of these compounds may allow for their development as novel, next generation therapeutic agents for the treatment of Gram-positive pathogenic infections

Estudo da cadeia produtiva como subsídio para pesquisa e desenvolvimento do agronegócio do sisal na Paraíba /

Tese (Doutorado) - Universidade Federal de Santa Catarina, Centro Tecnológico

株券発行会社の株式の譲受人が譲渡人の株券発行会社に対する株券発行請求権を代位行使すること及び当該株券を譲受人に直接交付するように求めることの可否 -最判令和6年4月19日LEX/DB 文献番号25573475-

departmental bulletin pape

フランス古法における債権者代位権の実相(4・完)

departmental bulletin pape

In vitro modeling to determine mutation specificity of EGFR tyrosine kinase inhibitors against clinically relevant EGFR mutants in non-small-cell lung cancer

EGFR mutated lung cancer accounts for a significant subgroup of non-small-cell lung cancer (NSCLC). Over the last decade, multiple EGFR tyrosine kinase inhibitors (EGFR-TKIs) have been developed to target mutated EGFR. However, there is little information regarding mutation specific potency of EGFR-TKIs against various types of EGFR mutations. The purpose of this study is to establish an in vitro model to determine the “therapeutic window” of EGFR-TKIs against various types of EGFR mutations, including EGFR exon 20 insertion mutations. The potency of 1st (erlotinib), 2nd (afatinib) and 3rd (osimertinib and rociletinib) generation EGFR-TKIs was compared in vitro for human lung cancer cell lines and Ba/F3 cells, which exogenously express mutated or wild type EGFR. An in vitro model of mutation specificity was created by calculating the ratio of IC50 values between mutated and wild type EGFR. The in vitro model identified a wide therapeutic window of afatinib for exon 19 deletions and L858R and of osimertinib and rociletinib for T790M positive mutations. The results obtained with our models matched well with previously reported preclinical and clinical data. Interestingly, for EGFR exon 20 insertion mutations, most of which are known to be resistant to 1st and 2nd generation EGFR-TKIS, osimertinib was potent and presented a wide therapeutic window. To our knowledge, this is the first report that has identified the therapeutic window of osimertinib for EGFR exon 20 insertion mutations. In conclusion, this model will provide a preclinical rationale for proper selection of EGFR-TKIs against clinically-relevant EGFR mutations

The RNA acetyltransferase driven by ATP hydrolysis synthesizes N4-acetylcytidine of tRNA anticodon

The wobble base of Escherichia coli elongator tRNAMet is modified to N4-acetylcytidine (ac4C), which is thought to ensure the precise recognition of the AUG codon by preventing misreading of near-cognate AUA codon. By employing genome-wide screen of uncharacterized genes in Escherichia coli (‘ribonucleome analysis'), we found the ypfI gene, which we named tmcA (tRNAMet cytidine acetyltransferase), to be responsible for ac4C formation. TmcA is an enzyme that contains a Walker-type ATPase domain in its N-terminal region and an N-acetyltransferase domain in its C-terminal region. Recombinant TmcA specifically acetylated the wobble base of E. coli elongator tRNAMet by utilizing acetyl-coenzyme A (CoA) and ATP (or GTP). ATP/GTP hydrolysis by TmcA is stimulated in the presence of acetyl-CoA and tRNAMet. A mutation study revealed that E. coli TmcA strictly discriminates elongator tRNAMet from the structurally similar tRNAIle by mainly recognizing the C27–G43 pair in the anticodon stem. Our findings reveal an elaborate mechanism embedded in tRNAMet and tRNAIle for the accurate decoding of AUA/AUG codons on the basis of the recognition of wobble bases by the respective RNA-modifying enzymes

A physicochemical descriptor-based scoring scheme for effective and rapid filtering of kinase-like chemical space

<p>Abstract</p> <p>Background</p> <p>The current chemical space of known small molecules is estimated to exceed 10⁶⁰structures. Though the largest physical compound repositories contain only a few tens of millions of unique compounds, virtual screening of databases of this size is still difficult. In recent years, the application of physicochemical descriptor-based profiling, such as Lipinski's rule-of-five for drug-likeness and Oprea's criteria of lead-likeness, as early stage filters in drug discovery has gained widespread acceptance. In the current study, we outline a kinase-likeness scoring function based on known kinase inhibitors.</p> <p>Results</p> <p>The method employs a collection of 22,615 known kinase inhibitors from the ChEMBL database. A kinase-likeness score is computed using statistical analysis of nine key physicochemical descriptors for these inhibitors. Based on this score, the kinase-likeness of four publicly and commercially available databases, i.e., National Cancer Institute database (NCI), the Natural Products database (NPD), the National Institute of Health's Molecular Libraries Small Molecule Repository (MLSMR), and the World Drug Index (WDI) database, is analyzed. Three of these databases, i.e., NCI, NPD, and MLSMR are frequently used in the virtual screening of kinase inhibitors, while the fourth WDI database is for comparison since it covers a wide range of known chemical space. Based on the kinase-likeness score, a kinase-focused library is also developed and tested against three different kinase targets selected from three different branches of the human kinome tree.</p> <p>Conclusions</p> <p>Our proposed methodology is one of the first that explores how the narrow chemical space of kinase inhibitors and its relevant physicochemical information can be utilized to build kinase-focused libraries and prioritize pre-existing compound databases for screening. We have shown that focused libraries generated by filtering compounds using the kinase-likeness score have, on average, better docking scores than an equivalent number of randomly selected compounds. Beyond library design, our findings also impact the broader efforts to identify kinase inhibitors by screening pre-existing compound libraries. Currently, the NCI library is the most commonly used database for screening kinase inhibitors. Our research suggests that other libraries, such as MLSMR, are more kinase-like and should be given priority in kinase screenings.</p

RESCIMENTO E PRODUÇÃO DE BIOMASSA DO ALECRIM EM AMBIENTE URBANO

O alecrim, Rosmarinus officinalis, é uma planta da família Lamiaceae, com propriedades estomacais, estimulantes, antiespasmódica, emenagogas e cicatrizantes. Assim, considerando a carência de informações do cultivo de R. officinalis no ambiente urbano, este estudo teve por objetivo avaliar o efeito de duas doses de adubação orgânica no crescimento e produção de biomassa do alecrim. Os tratamentos foram constituídos por duas doses de adubação orgânica de esterco bovino (1 L e 3 L cova-1) em quatro épocas de avaliação (128, 149, 170 e 191 dias após o plantio). As plantas submetidas aos dois tratamentos de adubação orgânica não apresentaram diferenças significativas em todas as épocas de avaliação nas variáveis avaliadas. Entretanto, no tratamento de 3 L de adubação orgânica cova-1 as plantas apresentaram maior produção de biomassa. No tratamento com 3 L de adubação orgânica a produção de biomassa fresca permite estimar uma produtividade de 3,9 t ha-1. A partir dos resultados obtidos no presente estudo, constatou-se que a produção de alecrim apresentou grande potencial para ser implementada em pequenas áreas urbanas ou nas residências dos consumidores com a redução do custo de transporte e do produto final