ARCaDia: single-round screening of a DNA-type targeted covalent binder possessing a latent warhead.

A covalent binder for a target protein was obtained by a direct single-round screening of a latent-warhead-modified DNA library affinity/reactivity-based co-selection of aptameric deoxyribonucleic acid (ARCaDia), followed by a top -mer analysis. The optimal position of the conjugated warhead on the selected aptamer was simultaneously identified.

Atomic structure of the Se-passivated GaAs(001) surface revisited.

We present a combined experimental and theoretical study of the Se-treated GaAs(001)-([Formula: see text]) surface. The ([Formula: see text]) structure with the two-fold coordinated Se atom at the outermost layer and the three-fold coordinated Se atom at the third layer was found to be energetically stable and agrees well with the experimental data from scanning tunneling microscopy, low energy electron diffraction, and x-ray photoelectron spectroscopy. This atomic geometry accounts for the improved stability of the Se-treated surface against the oxidation.

bioTCIs: Middle-to-Macro Biomolecular Targeted Covalent Inhibitors Possessing Both Semi-Permanent Drug Action and Stringent Target Specificity as Potential Antibody Replacements.

Monoclonal antibody therapies targeting immuno-modulatory targets such as checkpoint proteins, chemokines, and cytokines have made significant impact in several areas, including cancer, inflammatory disease, and infection. However, antibodies are complex biologics with well-known limitations, including high cost for development and production, immunogenicity, a limited shelf-life because of aggregation, denaturation, and fragmentation of the large protein. Drug modalities such as peptides and nucleic acid aptamers showing high-affinity and highly selective interaction with the target protein have been proposed alternatives to therapeutic antibodies.

Relative Nuclease Resistance of a DNA Aptamer Covalently Conjugated to a Target Protein.

A major obstacle to the therapeutic application of an aptamer is its susceptibility to nuclease digestion. Here, we confirmed the acquisition of relative nuclease resistance of a DNA-type thrombin binding aptamer with a warhead (TBA) by covalent binding to a target protein in the presence of serum/various nucleases. When the thrombin-inhibitory activity of TBA on thrombin was reversed by the addition of the complementary strand, the aptamer was instantly degraded by the nucleases, showing that the properly folded/bound aptamer conferred the resistance.

Solvatochromic peptidic binder obtained via extended phage display acts as a fluororeporter for fragment-based drug discovery (FBDD).

We have previously established a selection system to obtain a solvatochromic protein binder from a peptidic fluoroprobe library via the extended T7 phage display. Here, we use the peptidic binder as a fluororeporter in this proof-of-concept study of fragment-based screening approach to drug discovery. The binder is released from the target protein on mixing with an appropriate lead compound, thereby altering its fluorescence color/intensity under 365 nm ultraviolet wavelength irradiation.

Size Optimization of a N-Doped Graphene Nanocluster for the Oxygen Reduction Reaction.

N-Doped graphene nanoclusters (N-GNCs) are promising electrocatalysts for the oxygen reduction reaction (ORR) at the cathode of fuel cells. In this study, the dependence of the ORR activity on the size of N-GNCs was investigated using first-principles calculations based on density functional theory. The maximum electrode potential ( ) was estimated from the free energy of the reaction intermediates of the ORR.

Statistical and Criticality Analysis of the Lower Ionosphere Prior to the 30 October 2020 Samos (Greece) Earthquake (M6.9), Based on VLF Electromagnetic Propagation Data as Recorded by a New VLF/LF Receiver Installed in Athens (Greece).

In this work we present the statistical and criticality analysis of the very low frequency (VLF) sub-ionospheric propagation data recorded by a VLF/LF radio receiver which has recently been established at the University of West Attica in Athens (Greece). We investigate a very recent, strong (M6.9), and shallow earthquake (EQ) that occurred on 30 October 2020, very close to the northern coast of the island of Samos (Greece).

High Accuracy Heartbeat Detection from CW-Doppler Radar Using Singular Value Decomposition and Matched Filter.

Heart rate measurement using a continuous wave Doppler radar sensor (CW-DRS) has been applied to cases where non-contact detection is required, such as the monitoring of vital signs in home healthcare. However, as a CW-DRS measures the speed of movement of the chest surface, which comprises cardiac and respiratory signals by body motion, extracting cardiac information from the superimposed signal is difficult. Therefore, it is challenging to extract cardiac information from superimposed signals.

Direct screening of a target-specific covalent binder: stringent regulation of warhead reactivity in a matchmaking environment.

A peptide-type covalent binder for a target protein was obtained by direct and stringent screening of a warhead-modified peptide library on the robust T7 phage. The aryl fluorosulfate (fosylate) warhead was activated only in a matchmaking microenvironment created between the target protein and an appropriate peptide during the reactivity/affinity-based co-selection process of extended phage display.

Inhibition of thrombin activity by a covalent-binding aptamer and reversal by the complementary strand antidote.

Alleviating the potential risk of irreversible adverse drug effects has been an important and challenging issue for the development of covalent drugs. Here we created a DNA-aptamer-type covalent drug by introducing a sulfonyl fluoride warhead at appropriate positions of the thrombin binding aptamer to create weaponized covalent drugs. We showed the de-activation of thrombin by the novel modality, followed by its re-activation by the complementary strand antidote at an arbitrary time.

Natural Time Analysis of Global Navigation Satellite System Surface Deformation: The Case of the 2016 Kumamoto Earthquakes.

In order to have further evidence of the atmospheric oscillation channel of the lithosphere-atmosphere-ionosphere coupling (LAIC), we have studied criticality in global navigation satellite system (GNSS) surface deformation as a possible agent for exciting atmospheric gravity waves (AGWs) in the atmosphere and GNSS fluctuations in the frequency range of AGWs with the use of the natural time (NT) method. The target earthquake (EQ) is the 2016 Kumamoto EQ with its main shock on 15 April 2016 (M = 7.3, universal time).

Gravity Wave Activity in the Stratosphere before the 2011 Tohoku Earthquake as the Mechanism of Lithosphere-atmosphere-ionosphere Coupling.

The precursory atmospheric gravity wave (AGW) activity in the stratosphere has been investigated in our previous paper by studying an inland Kumamoto earthquake (EQ). We are interested in whether the same phenomenon occurs or not before another major EQ, especially an oceanic EQ. In this study, we have examined the stratospheric AGW activity before the oceanic 2011 Tohoku EQ (M 9.

Ultrafast spectroscopy on water-processable PCBM: rod-coil block copolymer nanoparticles.

Using ultrafast spectroscopy, we investigate the photophysics of water-processable nanoparticles composed of a block copolymer electron donor and a fullerene derivative electron acceptor. The block copolymers are based on a poly[2,6-(4,4-bis-(2-ethylhexyl)-4H-cyclopenta[2,1-b;3,4-b']dithiophene)-alt-4,7-(2,1,3-benzothiadiazole)] rod, which is covalently linked with 2 or 100 hydrophilic coil units. In both samples the photogenerated excitons in the blend nanoparticles migrate in tens of ps to a donor/acceptor interface to be separated into free charges.

A medium-firm drug-candidate library of cryptand-like structures on T7 phage: design and selection of a strong binder for Hsp90.

We designed and synthesized a medium-firm drug-candidate library of cryptand-like structures possessing a randomized peptide linker on the bacteriophage T7. From the macrocyclic library with a 109 diversity, we obtained a binder toward a cancer-related protein (Hsp90) with an antibody-like strong affinity (KD = 62 nM) and the binding was driven by the enthalpy. The selected supramolecular ligand inhibited Hsp90 activity by site-specific binding outside of the well-known ATP-binding pocket on the N-terminal domain (NTD).

Edge-State-Induced Stacking of Zigzag Graphene Nanoribbons.

We have investigated the structural stabilities and electronic properties for AA and the Bernal-stacked AB bilayer zigzag graphene nanoribbons (ZZGNRs) using first-principles calculations within density functional theory. The AB-stacked ZZGNR exhibits the spin-polarized state, while the AA-stacked ZZGNR has the nonmagnetic ground state, being more energetically stable than the AB-stacked one. For the AA-stacked ZZGNR, the interaction between the so-called edge states rather than the van der Waals (vdW) interaction plays an important role: the occupied up-spin and the unoccupied down-spin states at one end of ZZGNR interact with each other, and vice versa at the other end, forming the non-spin-polarized bonding and antibonding states at the zigzag edge.

Effect of Water on the Manifestation of the Reaction Selectivity of Nitrogen-Doped Graphene Nanoclusters toward Oxygen Reduction Reaction.

We investigated the selectivity of N-doped graphene nanoclusters (N-GNCs) toward the oxygen reduction reaction (ORR) using first-principles calculations within the density functional theory. The results show that the maximum electrode potentials ( ) for the four-electron (4e) pathway are higher than those for the two-electron (2e) pathway at almost all of the reaction sites. Thus, the N-GNCs exhibit high selectivity for the 4e pathway, that is, the 4e reduction proceeds preferentially over the 2e reduction.

Facile and Efficient Chemoenzymatic Semisynthesis of Fc-Fusion Compounds for Half-Life Extension of Pharmaceutical Components.

The formation of Fc-fusions, in which biologically active molecules and the Fc fragment of antibodies are linked to each other, is one of the most efficient and successful half-life extension technologies to be developed and applied to peptide and protein pharmaceuticals thus far. Fc-fusion compounds are generally produced by recombinant methods. However, these cannot be applied to artificial middle molecules, such as peptides with non-natural amino acids, unnatural cyclic peptides, or pharmaceutical oligonucleotides.

Micro-Hall Sensors Based on Two-Dimensional Molybdenum Diselenide.

Sensors and electronic devices based on semiconductors in their two-dimensional forms have many advantages. In this paper, we studied micro-Hall sensors based on two-dimensional molybdenum diselenide for the first time. The micro-Hall sensor based on a Ti/MoSe₂/Ti structure clearly showed a linear dependence of the Hall voltage as a function of the magnetic field, with a magnetic sensitivity of ∼16 V/AT.

Fluorescent "keep-on" type pharmacophore obtained from dynamic combinatorial library of Schiff bases.

We established a novel principle for fluorescence detection of a target protein. A low-molecular-weight fluorescent pharmacophore, as a targeted probe, was selected from a dynamic combinatorial library of Schiff bases. The pharmacophore retains its fluorescence when bound to the hydrophobic site of the target, whereas it loses it because of hydrolysis when unbound.

Combinatorially Screened Peptide as Targeted Covalent Binder: Alteration of Bait-Conjugated Peptide to Reactive Modifier.

A peptide-type covalent binder for a target protein was obtained by combinatorial screening of fluoroprobe-conjugated peptide libraries on bacteriophage T7. The solvatochromic fluoroprobe works as a bait during the affinity selection process of phage display. To obtain the targeted covalent binder, the bait in the selected consensus peptide was altered into a reactive warhead possessing a sulfonyl fluoride.

Criticality Analysis of the Lower Ionosphere Perturbations Prior to the 2016 Kumamoto (Japan) Earthquakes as Based on VLF Electromagnetic Wave Propagation Data Observed at Multiple Stations.

The perturbations of the ionosphere which are observed prior to significant earthquakes (EQs) have long been investigated and could be considered promising for short-term EQ prediction. One way to monitor ionospheric perturbations is by studying VLF/LF electromagnetic wave propagation through the lower ionosphere between specific transmitters and receivers. For this purpose, a network of eight receivers has been deployed throughout Japan which receive subionospheric signals from different transmitters located both in the same and other countries.

Atomic structure and passivated nature of the Se-treated GaAs(111)B surface.

We have systematically studied the atomic structure and electronic properties of the Se-treated GaAs(111)B surface using scanning tunneling microscopy, reflection high-energy electron diffraction, x-ray photoelectron spectroscopy, and first-principles calculations. We have found that Se atoms substitute [Formula: see text] monolayer of As atoms at the outermost layer of the ideal (111)B surface. Charge transfer from Se to As eliminates all of unsaturated dangling bonds, so that the surface is electronically stabilized, leaving no surface states in the mid-gap region.

Novel and Simple Ultrasonographic Methods for Estimating the Abdominal Visceral Fat Area.

Objectives: To evaluate the abdominal visceral fat area (VFA), we developed novel ultrasonographic (US) methods for estimating.

Methods: 100 male volunteers were recruited, and their VFA was calculated by two novel US methods, the triangle method and the ellipse method. The VFA calculated by these methods was compared with the VFA calculated by CT.