A Versatile Strategy for Screening Custom-Designed Warhead-Armed Cyclic Peptide Inhibitors

Demand for peptide-based pharmaceuticals has been steadily increasing, but only limited success has been achieved to date. To expedite peptide-based drug discovery, we developed a general scheme for cell-based screening of cyclic peptide inhibitors armed with a user-designed warhead. We combined unnatural amino acid incorporation and split intein-mediated peptide cyclization techniques and integrated a yeast-based colorimetric screening assay to generate a new scheme that we call the custom-designed warhead-armed cyclic peptide screening platform (CWCPS). This strategy successfully discovered a potent inhibitor, CY5-6Q, that targets human histone deacetylase 8 (HDAC8) with a K_D value of 15 nM. This approach can be a versatile and general platform for discovering cyclic peptide inhibitors.     

Mercaptoamine-assisted Post-encapsulation of Metal Nanoparticles within Preformed Zeolites and their Analogues for Hydroisomerization and Methane Decomposition

We report a general synthetic strategy for post-encapsulation of metal nanoparticles within preformed zeolites using post-synthetic modification. Both anionic and cationic precursors to metal nanoparticle are supported on 8- and 10-membered ring zeolites and analogues during wet impregnation using 2-aminoethanethiol (AET) as a bi-grafting agent. Thiol groups are coordinated to metal centers, whereas amine moieties are dynamically attached to micropore walls via acid-base interactions. The dynamic acid-base interactions cause the even distribution of the metal-AET complex throughout the zeolite matrix. These processes encapsulate Au, Rh, and Ni precursors within the CHA, *MRE, MFI zeolite, and SAPO-34 zeolite analogues, for which small channel apertures preclude the post-synthesis impregnation of metal precursors. Sequential activation forms small and uniform nanoparticles (1–2.5 nm in diameter), as confirmed through electron microscopy and X-ray absorption spectroscopy. Containment within the small micropores protected the nanoparticles against harsh thermal sintering conditions and prevented the fouling of the metal surface by coke, thus resulting in a high catalytic performance in n-dodecane hydroisomerization and methane decomposition. The remarkable specificity of the thiol to metal precursors and the dynamic acid-base interaction make these protocols extendable to various metal-zeolite systems, suitable for shape-selective catalysts in challenging chemical environments.     

Development and validation of a sensitive ultra-high-performance liquid chromatography-tandem mass spectrometry method for quantitative analysis of bambermycin in livestock and aquatic products: Implications for food safety control and regulatory enforcement

A sensitive and accurate analytical method was developed and validated to detect bambermycin, a commonly used antibiotic in animal feed and livestock. The presence of bambermycin residues in food products can pose health risks to consumers, emphasizing the need for a sensitive and accurate analytical method. A reversed-phase analytical column was utilized with a mobile phase comprising 0.005 mol/L ammonium acetate in 5% acetonitrile (A) and 0.005 mol/L ammonium acetate in 95% acetonitrile (B) to achieve effective chromatographic separation. Quantitative determination of bambermycin in various samples, including beef, pork, chicken, milk, eggs, flatfish, eel, and shrimp, was performed using ultra-high-performance liquid chromatography-tandem mass spectrometry. Sample extraction involved a mixture of methanol and a 25% ammonium hydroxide solution, followed by low-temperature purification and phospholipid removal utilizing a Phree cartridge. The method exhibited a satisfactory recovery rate ranging from 69% to 100%. Validation results demonstrated the reliability, robustness, and accuracy of the method, exhibiting good linearity, precision, and recovery. This validated method can be applied for routine analysis of bambermycin residues, assisting in the development of effective monitoring and control measures to ensure the safety of livestock and aquatic products.     

Increasing Chemical Diversity of B2N2 Anthracene Derivatives by Introducing Continuous Multiple Boron-Nitrogen Units

Increasing the chemical diversity of organic semiconductors is essential to develop efficient electronic devices. In particular, the replacement of carbon-carbon (C−C) bonds with isoelectronic boron-nitrogen (B−N) bonds allows precise modulation of the electronic properties of semiconductors without significant structural changes. Although some researchers have reported the preparation of B₂N₂ anthracene derivatives with two B−N bonds, no compounds with continuous multiple BN units have been prepared yet. Herein, we report the synthesis and characterization of a B₂N₂ anthracene derivative with a BNBN unit formed by converting the BOBN unit at the zigzag edge. Compared to the all-carbon analogue 2-phenylanthracene, BNBN anthracene exhibits significant variations in the C−C bond length and a larger highest occupied molecular orbital–lowest unoccupied molecular orbital energy gap. The experimentally determined bond lengths and electronic properties of BNBN anthracene are confirmed through theoretical calculations. The BOBN anthracene organic light-emitting diode, used as a blue host, exhibits a low driving voltage. The findings of this study may facilitate the development of larger acenes with multiple BN units and potential applications in organic electronics.     

Projective normality of ruled surfaces

In this article we study normal generation of irrational ruled surfaces. When is a smooth curve of genus , Green and Lazarsfeld proved that a very ample line bundle    Pic with deg   Cliff is normally generated where Cliff denotes the Clifford index of the curve (Green and Lazarsfeld, 1986). We generalize this to line bundles on a ruled surface over .

     

The strong approximation property and the weak bounded approximation property

We show that the strong approximation property (strong AP) (respectively, strong CAP) and the weak bounded approximation property (respectively, weak BCAP) are equivalent for every Banach space. This gives a negative answer to Oja's conjecture. As a consequence, we show that each of the spaces _c0$c_0$ and _?1${?}_1$ has a subspace which has the AP but fails to have the strong AP.     

Leader‐following consensus problem of heterogeneous multi‐agent systems with nonlinear dynamics using fuzzy disturbance observer

This article considers the leader‐following consensus problem of heterogeneous multi‐agent systems. The proposed multi‐agent system is consisted of heterogeneous agents where each agents have their own nonlinear dynamic behavior. To overcome difficulty from heterogeneous nonlinear intrinsic dynamics of agents, a fuzzy disturbance observer is adopted. In addition, based on the Lyapunov stability theory, an adaptive control method is used to compensate the observation error caused by the difference between the unknown factor and estimated values. Two numerical examples are given to illustrate the effectiveness of the proposed method. © 2013 Wiley Periodicals, Inc. Complexity 19: 20–31, 2014     

Edge Singular Behavior for the Heat Equation on Polyhedral Cylinders in boldsymbol{mathbb{R}}^{bf 3}

We study the Heat equation in the polyhedral cylinder with a non-convex edge. We construct the singularity functions depending on the time and edge axis, and the coefficient of the singularity, called the stress intensity distributions, and show regularity results for the solution and the coefficient. The regularity is achieved in the (not weighted) Sobolev space in the L² and L ^q spaces, respectively. An application to the finite polyhedral cylinder is described.     

Toric origami manifolds and multi-fans

The notion of a toric origami manifold, which weakens the notion of a symplectic toric manifold, was introduced by A. Cannas da Silva, V. Guillemin and A.R. Pires. They showed that toric origami manifolds bijectively correspond to origami templates via moment maps, where an origami template is a collection of Delzant polytopes with some folding data. Like a fan is associated to a Delzant polytope, a multi-fan introduced by A. Hattori and M. Masuda can be associated to an oriented origami template. In this paper, we discuss their relationship and show that any simply connected compact smooth 4-manifold with a smooth action of T ² can be a toric origami manifold. We also characterize products of even dimensional spheres which can be toric origami manifolds.     

Generalized matching theorems for closed coverings of convex sets

In this paper we use fixed point and coincidence theorems due to Park [8] to give matching theorems concerning closed coverings of nonempty convex sets in a real topological vector space. Our new results extend previously given ones due to Ky Fan [2], [3], Shih [10], Shih and Tan [11], and Park [7].