BRAF Gene and Melanoma: Back to the Future

As widely acknowledged, 40–50% of all melanoma patients harbour an activating BRAF mutation (mostly BRAF V600E). The identification of the RAS–RAF–MEK–ERK (MAP kinase) signalling pathway and its targeting has represented a valuable milestone for the advanced and, more recently, for the completely resected stage III and IV melanoma therapy management. However, despite progress in BRAF-mutant melanoma treatment, the two different approaches approved so far for metastatic disease, immunotherapy and BRAF+MEK inhibitors, allow a 5-year survival of no more than 60%, and most patients relapse during treatment due to acquired mechanisms of resistance. Deep insight into BRAF gene biology is fundamental to describe the acquired resistance mechanisms (primary and secondary) and to understand the molecular pathways that are now being investigated in preclinical and clinical studies with the aim of improving outcomes in BRAF-mutant patients.     

Natural and Designed Toxins for Precise Therapy: Modern Approaches in Experimental Oncology

Cancer cells frequently overexpress specific surface receptors providing tumor growth and survival which can be used for precise therapy. Targeting cancer cell receptors with protein toxins is an attractive approach widely used in contemporary experimental oncology and preclinical studies. Methods of targeted delivery of toxins to cancer cells, different drug carriers based on nanosized materials (liposomes, nanoparticles, polymers), the most promising designed light-activated toxins, as well as mechanisms of the cytotoxic action of the main natural toxins used in modern experimental oncology, are discussed in this review. The prospects of the combined therapy of tumors based on multimodal nanostructures are also discussed.     

Discovery–Versus Hypothesis–Driven Detection of Protein–Protein Interactions and Complexes

Protein complexes are the main functional modules in the cell that coordinate and perform the vast majority of molecular functions. The main approaches to identify and quantify the interactome to date are based on mass spectrometry (MS). Here I summarize the benefits and limitations of different MS-based interactome screens, with a focus on untargeted interactome acquisition, such as co-fractionation MS. Specific emphasis is given to the discussion of discovery- versus hypothesis-driven data analysis concepts and their applicability to large, proteome-wide interactome screens. Hypothesis-driven analysis approaches, i.e., complex- or network-centric, are highlighted as promising strategies for comparative studies. While these approaches require prior information from public databases, also reviewed herein, the available wealth of interactomic data continuously increases, thereby providing more exhaustive information for future studies. Finally, guidance on the selection of interactome acquisition and analysis methods is provided to aid the reader in the design of protein-protein interaction studies.     

A UNIFIED FRAMEWORK OF TARGETED MARKETING USING CUSTOMER PREFERENCES

One of the fundamental tasks of targeted marketing is to elicit associations between customers and products. Based on the results from information retrieval and utility theory, this article proposes a unified framework of targeted marketing. The customer judgments of products are formally described by preference relations and the connections of customers and products are quantitatively measured by market value functions. Two marketing strategies, known as the customer‐oriented and product‐oriented marketing strategies, are investigated. Four marketing models are introduced and examined. They represent, respectively, the relationships between a group of customers and a group of products, between a group of customers and a single product, between a single customer and a group of products, and between a single customer and a single product. Linear and bilinear market value functions are suggested and studied. The required parameters of a market value function can be estimated by exploring three types of information, namely, customer profiles, product profiles, and transaction data. Experiments on a real‐world data set are performed to demonstrate the effectiveness of the proposed framework.     

一种靶向蛋白质超声微泡的制备及表征

以氟碳气体为超声造影剂,通过接枝纳米磁性颗粒-RGD多肽,构建靶向蛋白质超声微泡,制备一种可同时用于超声造影和磁共振成像(MRI)的双模态造影增强剂。通过显微镜对磁性蛋白超声微泡形貌进行观察,利用红外光谱、分光光度法分析纳米磁性颗粒接枝牛血清蛋白的接枝率,并通过细胞实验评价磁性蛋白微泡的生物相容性。     

Aperture-Adjustable and Repairable Metal-Based MOFs Catalysis Membrane for Water Purification

Precise adjustment of the pore size, damage repair, and efficient cleaning is all challenges for the wider application of inorganic membranes. This study reports a simple strategy of combining dry-wet spinning and electrosynthesis to fabricate stainless-steel metal–organic framework composite membranes characterized by customizable pore sizes, targeted reparability, and high catalytic activity for membrane cleaning. The membrane pore size can be precisely customized in the range of 14–212 nm at nanoscale, and damaged membranes can be repaired by targeted treatment in 120 s. In addition, advanced oxidation processes can be used to quickly clean the membrane and achieve 98% flux recovery. The synergistic actions of the membrane matrix and the selective layer increase the adsorption energy of active sites to oxidant, shorten the electron transfer cycle, and enhance the overall catalytic performance. This study can provide a new direction for the development of advanced membranes for water purification and high-efficiency membrane cleaning methods.     

Immobilization of Photo‐Immunoconjugates on Nanoparticles Leads to Enhanced Light‐Activated Biological Effects

The past three decades have witnessed notable advances in establishing photosensitizer–antibody photo‐immunoconjugates for photo‐immunotherapy and imaging of tumors. Photo‐immunotherapy minimizes damage to surrounding healthy tissue when using a cancer‐selective photo‐immunoconjugate, but requires a threshold intracellular photosensitizer concentration to be effective. Delivery of immunoconjugates to the target cells is often hindered by I) the low photosensitizer‐to‐antibody ratio of photo‐immunoconjugates and II) the limited amount of target molecule presented on the cell surface. Here, a nanoengineering approach is introduced to overcome these obstacles and improve the effectiveness of photo‐immunotherapy and imaging. Click chemistry coupling of benzoporphyrin derivative (BPD)–Cetuximab photo‐immunoconjugates onto FKR560 dye‐containing poly(lactic‐co‐glycolic acid) nanoparticles markedly enhances intracellular photo‐immunoconjugate accumulation and potentiates light‐activated photo‐immunotoxicity in ovarian cancer and glioblastoma. It is further demonstrated that co‐delivery and light activation of BPD and FKR560 allow longitudinal fluorescence tracking of photoimmunoconjugate and nanoparticle in cells. Using xenograft mouse models of epithelial ovarian cancer, intravenous injection of photo‐immunoconjugated nanoparticles doubles intratumoral accumulation of photo‐immunoconjugates, resulting in an enhanced photoimmunotherapy‐mediated tumor volume reduction, compared to “standard” immunoconjugates. This generalizable “carrier effect” phenomenon is attributed to the successful incorporation of photo‐immunoconjugates onto a nanoplatform, which modulates immunoconjugate delivery and improves treatment outcomes.     

Privacy‐preserving targeted mobile advertising: requirements,design and a prototype implementation

With the continued proliferation of mobile devices, the collection of information associated with such devices and their users—such as location, installed applications and cookies associated with built‐in browsers—has become increasingly straightforward. By analysing such information, organisations are often able to deliver more relevant and better focused advertisements. Of course, such targeted mobile advertising gives rise to a number of concerns, with privacy‐related concerns being prominent. In this paper, we discuss the necessary balance that needs to be struck between privacy and utility in this emerging area and propose privacy‐preserving targeted mobile advertising as a solution that tries to achieve that balance. Our aim is to develop a solution that can be deployed by users but is also palatable to businesses that operate in this space. This paper focuses on the requirements and design of privacy‐preserving targeted mobile advertising and also describes an initial prototype. We also discuss how more detailed technical aspects and a complete evaluation will underpin our future work in this area. Copyright © 2016 John Wiley & Sons, Ltd.     

α放射性核素靶向治疗研究进展:α核素的制备与分离北大核心CSCD

α放射性核素靶向治疗(targeted alpha therapy,TAT)技术作为一种很有前景的肿瘤放疗手段近些年来正不断发展。因α放射性核素具有线性传能密度(linear energy transfer,LET)高、射程短、放射生物学效应和细胞毒性强等特点,TAT在微小肿瘤、散在性肿瘤及发生微转移肿瘤的治疗上展现出了独特的优势。但是,由于可用于TAT的α核素来源非常有限,且其制备和纯化也十分困难,这就导致α核素的获取成为了制约TAT技术发展的主要因素之一。针对α放射性核素靶向治疗中α核素的获取问题,本文从核素的性质、制备技术及分离方法的角度对几种适用于靶向治疗的α放射性核素(^(225)Ac、^(213)Bi、^(212)Pb、^(212)Bi、^(227)Th、^(223)Ra、^(230)U、^(226)Th、^(211)At、^(149)Tb)的研究现状进行了概述。