Pattern enrichment analysis for phage selection of stapled peptide ligands

Phage display is the most widely used technique to discover de novo peptides that bind to target proteins. However, it is associated with some challenges such as compositional bias. In this study, to overcome these difficulties, we devised a ‘pattern enrichment analysis.’ In this method, two samples (one obtained by affinity selection, the other simply amplified without selection) are prepared, and the two sequence datasets read on next-generation sequencer are compared to find the three-residue pattern most enriched in the selected sample. This allows us to compare two sequence datasets with high coverage and facilitates the identification of peptide sequences and the key residues for binding. We also demonstrated that this approach in the combination with structured peptide libraries allowed spatial mapping of the enriched sequence patterns. Here, we prepared a phage library displaying chemically stapled helical peptides with the X₁C₂X₃X₄X₅X₆X₇X₈C₉X₁₀ sequence, where X is any amino acid. To validate our method, we performed screening against the HDM2 protein. The results showed that the hydrophobic residues (Phe, Tyr, Trp and Leu) that are key to interactions with HDM2 were clearly identified by the pattern enrichment analysis. We also performed selection targeting the SARS-CoV-2 spike RBD in the same manner. The results showed that similar patterns were enriched among the hit peptides that inhibited the protein–protein interaction.

To effectively identify helical peptide binders from a phage library, we developed “pattern enrichment analysis,” which finds the enriched three-residue patterns by comparison with a control sample.     

Formation of rectangular packing and one-dimensional lines of C60 on 11-phenoxyundecanethiol self-assembled monolayers on Au(111)

The behavior of C(60) molecules deposited onto 11-phenoxyundecanethiol (phenoxy) self-assembled monolayers (SAMs) is studied using ultrahigh vacuum scanning tunneling microscopy (UHV-STM) and spectroscopy. We observe that after thermally annealing between 350 and 400 K in vacuum a combination of hexagonally close-packed islands, rectangularly packed islands, and isolated single lines of C(60) is observed when the C(60) is initially deposited on an unannealed phenoxy SAM. However, only rectangularly packed islands are found when they are deposited on a preannealed phenoxy SAM. We determine the rectangular packing to have a (2√3 × 4) rectangular unit cell with respect to the underlying Au(111) substrate. This type of C(60) structure has not been observed previously for multicomponent self-assemblies on a surface. We discuss the possible causes for the formation of this structure as well as the differences between starting on an unannealed SAM and an annealed one. This study demonstrates the capability of functionalized alkanethiol SAMs to control the growth and structure of C(60) islands during annealing depending on the structural changes of the SAM itself; by preannealing the SAM, the motion of the C(60) can be confined and unique structures resulting from interactions between the SAM molecules and C(60) can be produced.     

Benzothiadiazole-based dyes that emit red light in solution,solid, and liquid state

In this paper, we report the preparation and red-light-emitting behavior of benzothiadiazole–tris(alkyloxy)phenylethene dyes. In solution, we observed an efficient red light emission with high fluorescence quantum yields (up to 0.78). With increase in solvent polarity, the emission bands shifted to longer wavelengths accompanied by a large Stokes shift of up to 152 nm. A moderate fluorescence quantum yield of 0.52 could be achieved even in the polar solvent dimethylformamide. Red light emission with good fluorescence quantum yields (up to 0.50) was also observed in the bulk solid, liquid, and film state.     

Intermittent transport associated with the geodesic acoustic mode near the critical gradient regime

Turbulent transport near the critical gradient in toroidal plasmas is studied based on global Landau-fluid simulations and an extended predator-prey theoretical model of ion temperature gradient turbulence. A new type of intermittent transport associated with the emission and propagation of a geodesic acoustic mode (GAM) is found near the critical gradient regime, which is referred to as GAM intermittency. The intermittency is characterized by new time scales of trigger, damping, and recursion due to GAM damping. During the recursion of intermittent bursts, stationary zonal flow increases with a slow time scale due to the accumulation of undamped residues and eventually quenches the turbulence, suggesting that a nonlinear upshift of the critical gradient, i.e., Dimits shift, is established through such a dynamical process.     

Fabrication of BDD quantum node switches on embedded GaAs quantum wires grown by selective MBE

In view of applications to hexagonal binary decision diagram (BDD) LSIs, a first attempt is made to form quantum BDD node switches on selectively grown (SG) embedded quantum wires (QWRs) by molecular beam epitaxy (MBE). SG branch switches controlled by a Schottky wrap gate (WPG) were successfully fabricated by MBE growth and subsequent device processing. Gate control characteristics were studied by gate-dependent Shubnikov–de-Haas measurements, and the behavior was found to be similar to that of devices fabricated on wires by etching. The switch exhibited clear conductance quantization at low temperature, and temperature dependence of the voltage slope of conductance jump was clarified. A Y-branch BDD node device using two SG branch switches was successfully fabricated, and realized clear path switching characteristics.     

Core electron excitation spectra of diamond,graphite, and glassy carbon

Low-energy electron energy loss spectra in theC(1s) core electron excitation region have been measured in diamond, graphite and glassy carbon in the non-differentiated form. The background subtractedN(E) spectrum has been proved to reflect the density-of-states (DOS) of the conduction band well, and the conduction band structures of these materials have been elucidated. The energy positions of the symmetry points in their conduction bands have been determined from the second-derivative spectra, which were obtained by numerical differentiation of the measuredN(E) spectra.