Correlation effects and spin dependent transport in carbon nanostructures

The impact of symmetry breaking perturbations on the spin dependent transport through carbon nanotube quantum dots in the Kondo regime is discussed.Comment: 10 pages, 6 figure

Serendipitous Discovery of Light-Induced \u3cem\u3e(In Situ)\u3c/em\u3e Formation of An Azo-Bridged Dimeric Sulfonated Naphthol as a Potent PTP1B Inhibito

Background Protein tyrosine phosphatases (PTPs) like dual specificity phosphatase 5 (DUSP5) and protein tyrosine phosphatase 1B (PTP1B) are drug targets for diseases that include cancer, diabetes, and vascular disorders such as hemangiomas. The PTPs are also known to be notoriously difficult targets for designing inihibitors that become viable drug leads. Therefore, the pipeline for approved drugs in this class is minimal. Furthermore, drug screening for targets like PTPs often produce false positive and false negative results. Results Studies presented herein provide important insights into: (a) how to detect such artifacts, (b) the importance of compound re-synthesis and verification, and (c) how in situ chemical reactivity of compounds, when diagnosed and characterized, can actually lead to serendipitous discovery of valuable new lead molecules. Initial docking of compounds from the National Cancer Institute (NCI), followed by experimental testing in enzyme inhibition assays, identified an inhibitor of DUSP5. Subsequent control experiments revealed that this compound demonstrated time-dependent inhibition, and also a time-dependent change in color of the inhibitor that correlated with potency of inhibition. In addition, the compound activity varied depending on vendor source. We hypothesized, and then confirmed by synthesis of the compound, that the actual inhibitor of DUSP5 was a dimeric form of the original inhibitor compound, formed upon exposure to light and oxygen. This compound has an IC50 of 36 μM for DUSP5, and is a competitive inhibitor. Testing against PTP1B, for selectivity, demonstrated the dimeric compound was actually a more potent inhibitor of PTP1B, with an IC50 of 2.1 μM. The compound, an azo-bridged dimer of sulfonated naphthol rings, resembles previously reported PTP inhibitors, but with 18-fold selectivity for PTP1B versus DUSP5. Conclusion We report the identification of a potent PTP1B inhibitor that was initially identified in a screen for DUSP5, implying common mechanism of inhibitory action for these scaffolds

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

FSHD myoblasts fail to downregulate intermediate filament protein vimentin during myogenic differentiation.

Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant hereditary neuromuscular disorder. The clinical features of FSHD include weakness of the facial and shoulder girdle muscles followed by wasting of skeletal muscles of the pelvic girdle and lower extremities. Although FSHD myoblasts grown in vitro can be induced to differentiate into myotubes by serum starvation, the resulting FSHD myotubes have been shown previously to be morphologically abnormal. Aim. In order to find the cause of morphological anomalies of FSHD myotubes we compared in vitro myogenic differentiation of normal and FSHD myoblasts at the protein level. Methods. We induced myogenic differentiation of normal and FSHD myoblasts by serum starvation. We then compared protein extracts from proliferating myoblasts and differentiated myotubes using SDS-PAGE followed by mass spectrometry identification of differentially expressed proteins. Results. We demonstrated that the expression of vimentin was elevated at the protein and mRNA levels in FSHD myotubes as compared to normal myotubes. Conclusions. We demonstrate for the first time that in contrast to normal myoblasts, FSHD myoblasts fail to downregulate vimentin after induction of in vitro myogenic differentiation. We suggest that vimentin could be an easily detectable marker of FSHD myotube

Magnetic translation groups in an n-dimensional torus

A charged particle in a uniform magnetic field in a two-dimensional torus has a discrete noncommutative translation symmetry instead of a continuous commutative translation symmetry. We study topology and symmetry of a particle in a magnetic field in a torus of arbitrary dimensions. The magnetic translation group (MTG) is defined as a group of translations that leave the gauge field invariant. We show that the MTG on an n-dimensional torus is isomorphic to a central extension of a cyclic group Z_{nu_1} x ... x Z_{nu_{2l}} x T^m by U(1) with 2l+m=n. We construct and classify irreducible unitary representations of the MTG on a three-torus and apply the representation theory to three examples. We shortly describe a representation theory for a general n-torus. The MTG on an n-torus can be regarded as a generalization of the so-called noncommutative torus.Comment: 29 pages, LaTeX2e, title changed, re-organized, to be published in Journal of Mathematical Physic

Evolutionary Multi-Objective Design of SARS-CoV-2 Protease Inhibitor Candidates

Computational drug design based on artificial intelligence is an emerging research area. At the time of writing this paper, the world suffers from an outbreak of the coronavirus SARS-CoV-2. A promising way to stop the virus replication is via protease inhibition. We propose an evolutionary multi-objective algorithm (EMOA) to design potential protease inhibitors for SARS-CoV-2's main protease. Based on the SELFIES representation the EMOA maximizes the binding of candidate ligands to the protein using the docking tool QuickVina 2, while at the same time taking into account further objectives like drug-likeliness or the fulfillment of filter constraints. The experimental part analyzes the evolutionary process and discusses the inhibitor candidates.Comment: 15 pages, 7 figures, submitted to PPSN 202

Application of Hansch’s Model to Capsaicinoids and Capsinoids: A Study Using the Quantitative Structure−Activity Relationship. A Novel Method for the Synthesis of Capsinoids

We describe a synthetic approach for two families of compounds, the capsaicinoids and capsinoids, as part of a study of the quantitative relationship between structure and activity

Simultaneous miRNA and mRNA transcriptome profiling of human myoblasts reveals a novel set of myogenic differentiation-associated miRNAs and their target genes

Background: miRNA profiling performed in myogenic cells and biopsies from skeletal muscles has previously identified miRNAs involved in myogenesis. Results: Here, we have performed miRNA transcriptome profiling in human affinity-purified CD56+ myoblasts induced to differentiate in vitro. In total, we have identified 60 miRNAs differentially expressed during myogenic differentiation. Many were not known for being differentially expressed during myogenic differentiation. Of these, 14 (miR-23b, miR-28, miR-98, miR-103, miR-107, miR-193a, miR-210, miR-324-5p, miR-324-3p, miR-331, miR-374, miR-432, miR-502, and miR-660) were upregulated and 6 (miR-31, miR-451, miR-452, miR-565, miR-594 and miR-659) were downregulated. mRNA transcriptome profiling performed in parallel resulted in identification of 6,616 genes differentially expressed during myogenic differentiation. Conclusions: This simultaneous miRNA/mRNA transcriptome profiling allowed us to predict with high accuracy target genes of myogenesis-related microRNAs and to deduce their functions