利用深部非弹反应对Z≈56,N≈80区核激发态的探索性研究

通过410MeV ⁸²Se轰击天然Ba靶引起的深部非弹反应布居产生了类弹和类靶余核的激发态,利用在束γ谱学方法测量了它们的退激γ.通过γ–γ符合测量估计了类弹、类靶余核激发态的产生截面,在多个类靶余核中观测到了新γ跃迁,并建立了¹³⁶Ba的新能级纲图,说明利用深部非弹反应研究Z≈56,N≈80区高自旋态是有效、可行的.     

Dual‐Targeting Dual‐Action Platinum(IV) Platform for Enhanced Anticancer Activity and Reduced Nephrotoxicity

A novel and highly efficient dual‐targeting platform was designed to ensure targeted in vivo delivery of dual‐action Pt^IV prodrugs. The dual targeting was established by liposomal encapsulation of Pt^IV complexes, thereby utilizing the enhanced permeability and retention (EPR) effect as the first stage of targeting to attain a high accumulation of the drug‐loaded liposomes in the tumor. After the release of the Pt^IV prodrug inside cancer cells, a second stage of targeting directed a portion of the Pt^IV prodrugs to the mitochondria. Upon intracellular reduction, these Pt^IV prodrugs released two bioactive molecules, acting both on the mitochondrial and on the nuclear DNA. Our Pt^IV system showed excellent activity in vitro and in vivo, characterized by a cytotoxicity in a low micromolar range and complete tumor remission, respectively. Notably, marked in vivo activity was accompanied by reduced kidney toxicity, highlighting the unique therapeutic potential of our novel dual‐targeting dual‐action platform.     

Systemic Brain Delivery of Antisense Oligonucleotides across the Blood–Brain Barrier with a Glucose‐Coated Polymeric Nanocarrier

Current antisense oligonucleotide (ASO) therapies for the treatment of central nervous system (CNS) disorders are performed through invasive administration, thereby placing a major burden on patients. To alleviate this burden, we herein report systemic ASO delivery to the brain by crossing the blood–brain barrier using glycemic control as an external trigger. Glucose‐coated polymeric nanocarriers, which can be bound by glucose transporter‐1 expressed on the brain capillary endothelial cells, are designed for stable encapsulation of ASOs, with a particle size of about 45 nm and an adequate glucose‐ligand density. The optimized nanocarrier efficiently accumulates in the brain tissue 1 h after intravenous administration and exhibits significant knockdown of a target long non‐coding RNA in various brain regions, including the cerebral cortex and hippocampus. These results demonstrate that the glucose‐modified polymeric nanocarriers enable noninvasive ASO administration to the brain for the treatment of CNS disorders.     

Vibration analysis and non-destructive testing with real-time shearography

Real-time laser speckle shearography coupled with vibration stressing is shown to be an effective means of vibration analysis and non-destructive testing. The shearograms are modulated by a system of live fringes. These fringes are shown to be described by the zeroth-order Bessel function of the first kind and their visibility decreases with increasing fringe order. In vibration analysis, the instantaneous fringe pattern depicts the out-of-plane surface displacement gradient of the object surface at various resonance modes. In non-destructive testing, the flaw depth in a component can be determined without having to determine fringe orders. There is good agreement between the results obtained using the method and those from theory and time-average holography. A major advantage of real-time shearography is its facility for continuous assessment of a vibrating object without the need for secondary shearogram reconstruction.     

Computational analysis of ligand recognition mechanisms by prostaglandin E2 (subtype 2) and D2 receptors

The eight members of the prostanoid receptor family belong to the class A G protein-coupled receptors. We investigated the evolutionary relationship of the eight members by a molecular phylogenetic analysis and found that prostaglandin E₂ receptor subtype 2 (EP₂) and prostaglandin D₂ receptor (DP) were closely related. The structures of the ligands for the two receptors are similar to each other but are distinguished by the exchanged locations of the carbonyl oxygen and the hydroxy group in the cyclopentane ring. The ligand recognition mechanisms of the receptors were examined by an integrated approach using several computational methods, such as amino acid sequence comparison, homology modeling, docking simulation, and molecular dynamics simulation. The results revealed the similar location of the ligand between the two receptors. The common carboxy group of the ligands interacts with the Arg residue on the seventh transmembrane (TM) helix, which is invariant among the prostanoid receptors. EP₂ uses a Ser on TM1 to recognize the carbonyl oxygen in the cyclopentane ring of the ligand. The Ser is specifically conserved within EP₂. On the other hand, DP uses a Lys on TM2 to recognize the hydroxy group of the ?? chain of the ligand. The Lys is also specifically conserved within DP. The interaction network between the D(E)RY motif and TM6 was found in EP₂. However, DP lacked this network, due to the mutation in the D(E)RY motif. Based on these observations and the previously published mutational studies on the motif, the possibility of another activation mechanism that does not involve the interaction between the D(E)RY motif and TM6 will be discussed.     

Membrane interactive alpha-helices in GPCRs as a novel drug target

G-Protein Coupled Receptors (GPCRs) are one of the most important targets for pharmaceutical drug design. Over the past 30 years, mounting evidence has suggested the existence of homo and hetero dimers or higher-order complexes (oligomers) that are involved in signal transduction and some diseases. The number of reports describing GPCR oligomerization has increased, and in 2003, the organization of mouse rhodopsin into two-dimensional arrays of dimers was determined by an atomic force microscopic analysis. The analysis of the mouse rhodopsin complex has enabled us to discuss the oligomerization based on structural data. Although many unsolved problems still remains, the idea that GPCRs directly interact to form oligomers has been gradually accepted. One of the recent findings in the GPCR investigations is the clarification of the mechanisms of GPCR oligomerization at a molecular level. Most of these studies have suggested the importance of transmembrane alpha-helices for GPCR oligomerization. In this review, we will first summarize the importance of GPCR oligomerization and the functions of GPCRs. Then, we will explain the involvement of transmembrane alpha-helices in the oligomerization and a drug design strategy that targets these regions for GPCR oligomerization. Considering the current drug design methods, which are based on the modification of the protein-protein interactions of soluble regions of proteins, a "peptide mimic approach" that targets the transmembrane alpha-helices constituting the interfaces would be promising in drug discovery for GPCR oligomerization. For that purpose, we must know the positions of the interfaces. However, problems specific to membrane proteins have made it difficult to identify the positions of the interfaces experimentally. Therefore, information about the interfaces predicted by bioinformatics approaches is valuable. At the end of this review, several bioinformatics approaches toward interface prediction for oligomerization are introduced. The benefits and the pitfalls of these approaches are also discussed.     

‘Nano-impacts’: An Electrochemical Technique for Nanoparticle Sizing in Optically Opaque Solutions

Typical laser-dependent methods such as nanoparticle tracking analysis (NTA) and dynamic light scattering (DLS) are not able to detect nanoparticles in an optically opaque medium due to scattering or absorption of light. Here, the electrochemical technique of ‘nano-impacts’ was used to detect nanoparticles in solution in the presence of high levels of alumina particulates causing a milky white suspension. Using the ‘nano-impacts’ method, silver nanoparticles were successfully detected and sized in the model opaque medium. The results obtained compared well with those using transmission electron microscopy (TEM), an ex situ method for nanoparticle size determination. The ability to use the ‘nano-impacts’ method in media unmeasurable to competitor techniques confers a significant advantage on the electrochemical approach.     

187Pt的转动带性质研究

利用在束γ谱学技术和¹⁷³Yb(¹⁸O, 4n)熔合蒸发反应研究了¹⁸⁷Pt的高自旋态能级结构. 建立了包括3个转动带的¹⁸⁷Pt高自旋态能级纲图. 基于¹⁸⁷Pt周围核结构的系统学和比较带内B(M1)/B(E2)比率的实验值和理论值, 建议上述3个转动带的组态 分别为11/2⁺[615], 7/2^－[503]和1/2^－[521]. 对各转动带的带交叉频率、顺排增益、旋称劈裂等进行了讨论.     

An introduction to a class of matrix cone programming

In this paper, we define a class of linear conic programming (which we call matrix cone programming or MCP) involving the epigraphs of five commonly used matrix norms and the well studied symmetric cone. MCP has recently been found to have many important applications, for example, in nuclear norm relaxations of affine rank minimization problems. In order to make the defined MCP tractable and meaningful, we must first understand the structure of these epigraphs. So far, only the epigraph of the Frobenius matrix norm, which can be regarded as a second order cone, has been well studied. Here, we take an initial step to study several important properties, including its closed form solution, calm Bouligand-differentiability and strong semismoothness, of the metric projection operator over the epigraph of the $l_1,\,l_\infty $ , spectral or operator, and nuclear matrix norm, respectively. These properties make it possible to apply augmented Lagrangian methods, which have recently received a great deal of interests due to their high efficiency in solving large scale semidefinite programming, to this class of MCP problems. The work done in this paper is far from comprehensive. Rather it is intended as a starting point to call for more insightful research on MCP so that it can serve as a basic tool to solve more challenging convex matrix optimization problems in years to come.     

Identification of a New Band and Its Signature Inversion in ^174Re

High spin states in ^174Re are investigated via the ^152Sm（^27 AL,5nγ）^174Re reaction and γ - γ coincidence relationships are analysed carefully. A new band is identified due to its spectroscopic connection with the known π1/2^-[541] × ν1/2^-[521] band. This band is proposed to be the ground-state band built on the π1/2^-[541]× ,ν5/2^-[512] configuration in view of the low-lying intrinsic states in the neighbouring odd-mass nuclei. It is of particular interesting that the new band exhibits a phenomenon of low-spin signature inversion, providing a new situation for theoretical investigations.