No abstract

Cell-penetrating peptides (CPPs) are short peptides which can carry various types of molecules into cells; however, although most CPPs rapidly penetrate cells in vitro, their in vivo tissue-targeting specificities are low. Herein, we describe cell-binding, internalization, and targeting characteristics of a newly identified 10-residue CPP, denoted ECP32–41, derived from the core heparin-binding motif of human eosinophil cationic protein (ECP). Besides traditional emphasis on positively charged residues, the presence of cysteine and tryptophan residues was demonstrated to be essential for internalization. ECP32–41 entered Beas-2B and wild-type CHO-K1 cells, but not CHO cells lacking of cell-surface glycosaminoglycans (GAGs), indicating that binding of ECP32–41 to cell-surface GAGs was required for internalization. When cells were cultured with GAGs or pre-treated with GAG-digesting enzymes, significant decreases in ECP32–41 internalization were observed, suggesting that cell-surface GAGs, especially heparan sulfate proteoglycans were necessary for ECP32–41 attachment and penetration. Furthermore, treatment with pharmacological agents identified two forms of energy-dependent endocytosis, lipid-raft endocytosis and macropinocytosis, as the major ECP32–41 internalization routes. ECP32–41 was demonstrated to transport various cargoes including fluorescent chemical, fluorescent protein, and peptidomimetic drug into cultured Beas-2B cells in vitro, and targeted broncho-epithelial and intestinal villi tissues in vivo. Hence this CPP has the potential to serve as a novel vehicle for intracellular delivery of biomolecules or medicines, especially for the treatment of pulmonary or gastrointestinal diseases.

Analyzing the reasonable service life of buildings is a critical step to evaluate the decision for building utilization, reuse, or disposal. If buildings manifest service value, sustainable refurbishment and reuse methods can be employed to extend their service life. Previous studies on building service life largely focused on physical obsolescence. Few studies have analyzed other aspects. The objective of the present study was to propose a systematic approach to evaluate and predict the reasonable service life of buildings. First, the Fuzzy-Delphi Method (FDM) and analytical hierarchy process (AHP) were adopted to determine the final evaluation criteria and weights. Second, a mathematical model for predicting building service life was developed by combining the evaluation criteria, six obsolescence factors, and diagnostic scores. Finally, the model was applied to four case studies. The results produced by the model were consistent with those determined by an expert panel, verifying its effectiveness as a tool for decision making for formulating favorable suggestions concerning asset disposal, urban renewal, and renovation. Later obsolescence of buildings can be reduced by taking into account the proposed obsolescence criteria in the construction of new buildings to avoid implementing designs that are prone to obsolescence, thereby enhancing building service life.

As heparan sulfate proteoglycans (HSPGs) are known as co-receptors to interact with numerous growth factors and then modulate downstream biological activities, overexpression of HS/HSPG on cell surface acts as an increasingly reliable prognostic factor in tumor progression. Cell penetrating peptides (CPPs) are short-chain peptides developed as functionalized vectors for delivery approaches of impermeable agents. On cell surface negatively charged HS provides the initial attachment of basic CPPs by electrostatic interaction, leading to multiple cellular effects. Here a functional peptide (CPPecp) has been identified from critical HS binding region in hRNase3, a unique RNase family member with in vitro antitumor activity. In this study we analyze a set of HS-binding CPPs derived from natural proteins including CPPecp. In addition to cellular binding and internalization, CPPecp demonstrated multiple functions including strong binding activity to tumor cell surface with higher HS expression, significant inhibitory effects on cancer cell migration, and suppression of angiogenesis in vitro and in vivo. Moreover, different from conventional highly basic CPPs, CPPecp facilitated magnetic nanoparticle to selectively target tumor site in vivo. Therefore, CPPecp could engage its capacity to be developed as biomaterials for diagnostic imaging agent, therapeutic supplement, or functionalized vector for drug delivery.

Today, automotive design has to face numerous exciting challenges. The growing globalization causes an intensified competition amongst car manufacturers and forces them to reduce the required development time in order to shorten time to market, to appear first with attractive new products. Efficient and flexible processes and tools are necessary to handle the arising complexity efficiently. Parametric-associative 3D-CAD systems offer ideal conditions to face this challenge in virtual development. The present paper focusses on a special issue in automotive concept phasethe vehicle architecture layout process and required parameterization strategies. In most cases, parametric-associative relations defined within 3D-CAD models are of rigid kind. This implies that a formula, which is defined within a 3D-CAD model in order to evaluate a specific parameter, cannot change the input/output situation of involved parameters. In most application cases, this disadvantage can be neglected, but not in case of vehicle layouting in the early concept phase. Since geometric boundary conditions which define the geometric base of a vehicle concept can vary significantly, a rigid model parameterization is not the proper solution and prevents efficient reuse of 3D-CAD models. Additionally, rigid parameterization concepts lack of the required flexibility when having to manage multiple design variants in a single model. Therefore, the present paper outlines a possible strategy, which enables the use of advantages of parametric-associative design, while allowing changes of relations-evaluation behavior in context of respective technical issues and simultaneously preserving necessary geometrical model consistency.