Photodynamic therapy (PDT) is a cancer treatment modality that requires three components, namely light, dioxygen and a photosensitizing agent. After light excitation, the photosensitizer (PS) in its excited state transfers its energy to oxygen, which leads to photooxidation reactions. In order to improve the selectivity of the treatment, research has focused on the design of PS covalently attached to a tumor-targeting moiety. In this paper, we describe the synthesis and the physico-chemical and photophysical properties of six new peptide-conjugated photosensitizers designed for targeting the neuropilin-1 (NRP-1) receptor. We chose a TPC (5-(4-carboxyphenyl)-10,15, 20-triphenyl chlorine as photosensitizer, coupled via three different spacers (aminohexanoic acid, 1-amino-3,6-dioxaoctanoic acid, and 1-amino-9-aza-3,6,12,15-tetraoxa-10-on-heptadecanoic acid) to two different peptides (DKPPR and TKPRR). The affinity towards the NRP-1 receptor of the conjugated chlorins was evaluated along with in vitro and in vivo stability levels. The tissue concentration of the TPC-conjugates in animal model shows good distribution, especially for the DKPPR conjugates. The novel peptide–PS conjugates proposed in this study were proven to have potential to be further developed as future NRP-1 targeting photodynamic therapy agent. 相似文献
The static bending behavior of porous functionally graded (PFG) micro-plate under the geometrically nonlinear analysis is studied in this article. A small-scale nonlinear solution is established using the Von-Kármán hypothesis and the modified couple stress theory (MCST). To obtain the deflection of the plate, the Reddy higher-order plate theory coupled with isogeometric analysis (IGA) is utilized. The distribution of porosities is assumed to be even and uneven across the plate’s thickness and the effective material properties of porous functionally graded micro-plate are calculated using the refined rule-of-mixture hypothesis. The influence of power index, porosity parameter and material length scale parameter on the nonlinear behaviors of static bending of porous FGM micro-plates are also investigated using several numerical examples.
Vibration-based damage detection methods have become widely used because of their advantages over traditional methods. This paper presents a new approach to identify the crack depth in steel beam structures based on vibration analysis using the Finite Element Method (FEM) and Artificial Neural Network (ANN) combined with Butterfly Optimization Algorithm (BOA). ANN is quite successful in such identification issues, but it has some limitations, such as reduction of error after system training is complete, which means the output does not provide optimal results. This paper improves ANN training after introducing BOA as a hybrid model (BOA-ANN). Natural frequencies are used as input parameters and crack depth as output. The data are collected from improved FEM using simulation tools (ABAQUS) based on different crack depths and locations as the first stage. Next, data are collected from experimental analysis of cracked beams based on different crack depths and locations to test the reliability of the presented technique. The proposed approach, compared to other methods, can predict crack depth with improved accuracy. 相似文献
Hydrogen can be cited as prospective source of clean power. In this work hydrogen rich syn-gas generated from the agro-waste, empty cotton bolls was injected into an IC engine in continuous mode along with gasoline. At the air-fuel ratio of 23.40, specific fuel consumption of 0.35 kg kWh?1, the engine could be operated with higher efficiency than with gasoline alone. A distinct reduction in emission characteristics could also be seen. Empty cotton bolls derived after removal of cotton from the flower in field, was first studied for fuel properties. The reasonably high heating value (HHV) of 17.54 MJ kg?1 suggested that it could be a precursor to hydrogen via two stepped thermo-chemical process. The first step involved slow pyrolysis of the biomass at 500 °C for 60 min at a heating rate of 10 °C min?1 yielding 39.71% bio-char by weight. The C, H, N, S and O contents of the produced bio-char was 59.91, 2.91, 0.72, 0.47 and 35.99% respectively and its HHV was 26.7 MJ kg?1. Steam gasification of this bio-char, at 700 °C and water flowrate of 7 mL min?1 exhibited maximum hydrogen yield of 67.42% (v/v) in the syn-gas mixture. Subsequent enrichment of the gas using ethanolamine/ethylene diamine and KMnO4 solutions resulted in more than 90% (v/v) hydrogen in the combustible gas mixture and the test engine could be effectively operated. 相似文献
Supply chain risk management (SCRM) encompasses a wide variety of strategies aiming to identify, assess, mitigate and monitor unexpected events or conditions which might have an impact, mostly adverse, on any part of a supply chain. SCRM strategies often depend on rapid and adaptive decision-making based on potentially large, multidimensional data sources. These characteristics make SCRM a suitable application area for artificial intelligence (AI) techniques. The aim of this paper is to provide a comprehensive review of supply chain literature that addresses problems relevant to SCRM using approaches that fall within the AI spectrum. To that end, an investigation is conducted on the various definitions and classifications of supply chain risk and related notions such as uncertainty. Then, a mapping study is performed to categorise existing literature according to the AI methodology used, ranging from mathematical programming to Machine Learning and Big Data Analytics, and the specific SCRM task they address (identification, assessment or response). Finally, a comprehensive analysis of each category is provided to identify missing aspects and unexplored areas and propose directions for future research at the confluence of SCRM and AI. 相似文献
Ionic liquids (ILs) and deep eutectic solvents have shown great promise in drug delivery applications. Choline‐based ILs, in particular choline and geranic acid (CAGE), have been used to enhance the transdermal delivery of several small and large molecules. However, detailed studies outlining the design principles of ILs for transdermal drug delivery are still lacking. Using two model drugs of differing hydrophilicities, acarbose and ruxolitinib and 16 ILs, the dependence of skin penetration on the chemical properties of ILs is examined. First, the impact of ion stoichiometry on skin penetration of drugs is assessed using CAGE, which evidences that a molar ratio of 1:2 of choline to geranic acid yields the highest delivery. Subsequently, variants of CAGE are prepared using anions with structural similarity to geranic acid and cations with structural similarity to choline at a ratio of 1:2. Mechanistic studies reveal that the potency of ILs in enhancing transdermal drug delivery correlates inversely with the inter‐ionic interactions as determined by 2D NMR spectroscopy. Using this understanding, a new IL is designed, and it provides the highest delivery of ruxolitinib of all ILs tested here. Overall, these studies provide a generalized framework for optimizing ILs for enhancing skin permeability. 相似文献
An exact solution for the postbuckling configurations of composite beams is presented. The equations governing the axial and transverse deformations of a composite laminated beam accounting for the midplane stretching are derived. The inplane inertia and damping are neglected, and hence the two equations are reduced to a single nonlinear fourth-order partial–integral–differential equation governing the transverse deformations. We find out that the governing equation for the postbuckling of symmetric or asymmetric composite beams has the same form as that of beams made of an isotropic material. Composite beams with fixed–fixed, fixed–hinged, and hinged–hinged boundary conditions are considered. A closed-form solution for the postbuckling deformation is obtained as a function of the applied axial load, which is beyond the critical buckling load. To study the vibrations that take place in the vicinity of a buckled equilibrium position, we exactly solved the linear vibration problem around the first buckled configuration. Solving the resulting eigen-value problem results in the natural frequencies and their associated mode shapes. Both the static response represented by the postbuckling analysis and the dynamic response represented by the free vibration analysis in the postbuckling domain strongly depend on the lay-up of the laminate. Variations of the beam’s midspan rise and the fundamental natural frequency of the postbuckling domain vibrations with the applied axial load are presented for a variety of lay-up laminates. The ratio of the axial stiffness to the bending stiffness was found to be a crucial parameter in the analysis. This control parameter, through the selection of the appropriate lay-up, can be manipulated to help design and optimize the static and dynamic behavior of composite beams. 相似文献