COMPUTE A CELIS-DENNIS-TAPIA STEP

In this paper,we present an algorithm for the CDT subproblem.This problem stemsfrom computing a trust region step of an algorithm,which was first proposed by Celis,Dennis and Tapia for equality constrained optimization.Our algorithm considers generalcase of the CDT subproblem,convergence of the algorithm is proved.Numerical examplesare also provided.     

Generation of carbohydrate-deficient transferrin by enzymatic deglycosylation of human transferrin

Carbohydrate-deficient transferrin (CDT) molecules are transferrin isoforms that lack one or both of the carbohydrate groups attached to a normal human transferrin molecule. CDT has been reported to be a sensitive and specific marker for diagnosing alcoholism. This report demonstrates the in vitro generation of CDT molecules that can potentially be used as the standard in measuring CDT concentrations. This was achieved by deglycosylation of human transferrin with the enzyme Endo-β-N-acetylglucosaminidase F₂ (Endo-F₂). The enzyme was immobilized on sepharose beads, which were packed into a column. The immobilization of the enzyme not only eliminated the Endo-F₂ contamination of CDT, but also rendered the enzyme suitable for repetitive use. In this manner, it was possible to obtain at least 200 mg of CDT over a period of more than 3 mo, without any noticeable decrease of enzyme activity, using only 3.0 μg of enzyme. This proved to be an efficient method for generating CDT.     

Computing a Celis-Dennis-Tapia trust-region step for equality constrained optimization

We study an approach for minimizing a convex quadratic function subject to two quadratic constraints. This problem stems from computing a trust-region step for an SQP algorithm proposed by Celis, Dennis and Tapia (1985) for equality constrained optimization. Our approach is to reformulate the problem into a univariate nonlinear equation()=0 where the function() is continuous, at least piecewise differentiable and monotone. Well-established methods then can be readily applied. We also consider an extension of our approach to a class of non-convex quadratic functions and show that our approach is applicable to reduced Hessian SQP algorithms. Numerical results are presented indicating that our algorithm is reliable, robust and has the potential to be used as a building block to construct trust-region algorithms for small-sized problems in constrained optimization.This research was performed while the author was on a postdoctoral appointment in the Department of Mathematical Sciences, Rice University, Houston, TX, USA and was supported in part by AFOSR 85-0243 and DOE DEFG05-86ER 25017.     

On KKT points of Celis-Dennis-Tapia subproblem

The Celis-Dennis-Tapia(CDT) problem is a subproblem of the trust region algorithms for the constrained optimization. CDT subproblem is studied in this paper. It is shown that there exists the KKT point such that the Hessian matrix of the Lagrangian is positive semidefinite, if the multipliers at the global solution are not unique. Next the second order optimality conditions are also given, when the Hessian matrix of Lagrange at the solution has one negative eigenvalue. And furthermore, it is proved that all feasible KKT points satisfying that the corresponding Hessian matrices of Lagrange have one negative eigenvalue are the local optimal solutions of the CDT subproblem.     

Synthesis of cleavable peptides with authentic C-termini: an application for fully automated SPOT synthesis

A simple method for the synthesis of carboxyl-free peptides on cellulose membranes was improved and adapted for fully automated SPOT synthesis. Using 1,1′-carbonyl-di-imidazole (CDI) or 1,1′-carbonyl-di-(1,2,4-triazole) (CDT) as an activator within a defined period of time, we were able to reduce the formation of di- or oligomerization of the C-terminal amino acid. The soluble peptides are obtained in a purity range of 60-95% and could be used directly for different biological assays (e.g., CD8 T-cell epitope) that require authentic C-termini.     

GSH/ROS Dual-Responsive Supramolecular Nanoparticles Based on Pillar[6]arene and Betulinic Acid Prodrug for Chemo–Chemodynamic Combination Therapy

Chemodynamic therapy (CDT) based on intracellular Fenton reactions is attracting increasing interest in cancer treatment. A simple and novel method to regulate the tumor microenvironment for improved CDT with satisfactory effectiveness is urgently needed. Therefore, glutathione (GSH)/ROS (reactive oxygen species) dual-responsive supramolecular nanoparticles (GOx@BNPs) for chemo–chemodynamic combination therapy were constructed via host–guest complexation between water-soluble pillar[6]arene and the ferrocene-modified natural anticancer product betulinic acid (BA) prodrug, followed by encapsulation of glucose oxidase (GOx) in the nanoparticles. The novel supramolecular nanoparticles could be activated by the overexpressed GSH and ROS in the tumor microenvironment (TME), not only accelerating the dissociation of nanoparticles—and, thus, improving the BA recovery and release capability in tumors—but also showing the high-efficiency conversion of glucose into hydroxyl radicals (·OH) in succession through intracellular Fenton reactions. Investigation of antitumor activity and mechanisms revealed that the dramatic suppression of cancer cell growth induced by GOx@BNPs was derived from the elevation of ROS, decrease in ATP and mitochondrial transmembrane potential (MTP) and, finally, cell apoptosis. This work presents a novel method for the regulation of the tumor microenvironment for improved CDT, and the preparation of novel GSH/ROS dual-responsive supramolecular nanoparticles, which could exert significant cytotoxicity against cancer cells through the synergistic interaction of chemodynamic therapy, starvation therapy, and chemotherapy (CDT/ST/CT).     

The potential of mass spectrometry to study iron-containing proteins used in clinical diagnosis

Many proteins contain iron as metal ion either within their own structures or bound to their active sites. These iron-containing proteins are involved in numerous biological processes and some of them serve as biomarkers of clinical pathologies, not only related to iron homeostasis but also to other physiological disorders. Thus, a variety of analytical strategies have been developed over the last years in order to conduct studies on Fe-containing proteins. Among them, mass spectrometric (MS) methods still remain as preferred tools since they provide the capabilities of structure elucidation together with quantitative possibilities. Therefore, in this work we have tried to summarize the most recent applications of elemental and molecular mass spectrometric-based methods for the characterization (mostly qualitative but quantitative in some cases) of the high abundant Fe-containing proteins used for clinical diagnosis.     

基于CDT和Self-trapping的8×8光交叉连接特性数值研究

采用相干隧穿破坏(CDT)理论和自囚禁(self-trapping)效应相结合的方法实现光信号的交叉连接功能.在标量场和傍轴近似下,进一步采用紧束缚近似,得到周期性调制光纤中光信号传播的耦合模方程组.只考虑相邻光纤耦合作用情况下,数值模拟全光交叉连接功能实现过程并获得各种变换所需条件.在器件输出端引入可调谐滤波器可实现光信号的广播发送、光路变换和上下路等功能,能推广到任意N×N光交叉连接设计中,有效地解决波分复用光网络中光信号时延和容量需求问题.     

A Supramolecular Photosensitizer System Based on Nano-Cu/ZIF-8 Capped with Water-Soluble Pillar[6]arene and Methylene Blue Host–Guest Complexations

Photodynamic therapy (PDT) as a safe, non-invasive modality for cancer therapy, in which the low oxygen and high glutathione in the tumor microenvironment reduces therapeutic efficiency. In order to overcome these problems, we prepared a supramolecular photosensitive system of O₂-Cu/ZIF-8@ZIF-8@WP6–MB (OCZWM), which was loaded with oxygen to increase the oxygen concentration in the tumor microenvironment, and the Cu²⁺ in the system reacted with glutathione (GSH) to reduce the GSH concentration to generate Cu⁺. It is worth noting that the generated Cu⁺ can produce the Fenton reaction, thus realizing the combination therapy of PDT and chemodynamic therapy (CDT) to achieve the purpose of significantly improving the anti-cancer efficiency.