Targeted Delivery of siRNA‐Generating DNA Nanocassettes Using Multifunctional Nanoparticles

Molecular therapy using a small interfering RNA (siRNA) has shown promise in the development of novel therapeutics. Various formulations have been used for in vivo delivery of siRNAs. However, the stability of short double‐stranded RNA molecules in the blood and efficiency of siRNA delivery into target organs or tissues following systemic administration have been the major issues that limit applications of siRNA in human patients. In this study, multifunctional siRNA delivery nanoparticles are developed that combine imaging capability of nanoparticles with urokinase plasminogen activator receptor‐targeted delivery of siRNA expressing DNA nanocassettes. This theranostic nanoparticle platform consists of a nanoparticle conjugated with targeting ligands and double‐stranded DNA nanocassettes containing a U6 promoter and a shRNA gene for in vivo siRNA expression. Targeted delivery and gene silencing efficiency of firefly luciferase siRNA nanogenerators are demonstrated in tumor cells and in animal tumor models. Delivery of survivin siRNA expressing nanocassettes into tumor cells induces apoptotic cell death and sensitizes cells to chemotherapy drugs. The ability of expression of siRNAs from multiple nanocassettes conjugated to a single nanoparticle following receptor‐mediated internalization should enhance the therapeutic effect of the siRNA‐mediated cancer therapy.     

Viburnum mullaha D. DON fruit (Indian cranberry): A potential source of polyphenol with rich antioxidant,anti-elastase,anti-collagenase,and anti-tyrosinase activities

Viburnum mullaha (Buch.-Ham. Ex D. Don), is an underexplored wild edible fruit of Indian Himalayan region, analyzed for total polyphenol contents, antioxidant, anti-elastase, anti-collagenase, and anti-tyrosinase activities using in vitro assays. High values of total phenolic contents of 1257 ± 40 mg gallic acid equivalents/100 g fruit weight and total flavonoid contents of 3501 ± 203 mg catechin equivalents/100 g fruit weight were observed. V. mullaha fruit extracts showed outstanding antioxidant activities (ABTS⁺, 1,1-diphenyl-2-picrylhydrazyl, superoxide anion, linoleate peroxyl radicals scavenging, and ferric reducing activities) and remarkable anti-elastase, anti-collagenase, and anti-tyrosinase activities. High resolution liquid chromatography–mass spectroscopy analysis revealed presence of 15 phenolic compounds, namely, chlorogenic acid, acetyl salicylic acid, dihydrorobinetin, dihydromyricetin, 2-isoprenylemodin, rutin, cosmosiin hexaacetate, pectolinarin, dihydroquercetin, eriodictyol, iriginol hexaacetate, theaflavin, epicatechin-pentaacetate, lomatin, and peucenin in fruit extracts. This study recommends utilization of V. mullaha fruit as functional food with prospective pharmaceutical, nutraceutical, and cosmeceutical properties.     

大面积TFT-LCD市场增长迅猛

2003年第一季度,大面积(大于10英寸)薄膜工艺液晶显示器(TFT-LCD)的发货量超过预期,比前一季度上升了7％,比去年同期大幅上升了25％,出货量达到了两千万台。增长高于预期是由于各种显示器品牌厂家利用较低的面板价格,使液晶显示器面板的发货量大幅增加。 尽管大多数尺寸的大面积面板价格上涨,但2003年第二季度市场表现依然良好。2003年第二季度大面积产品的发货量同     

长江上游洪水与汉江洪水遭遇规律研究

长江干流与支流洪水互相遭遇容易形成长江流域特大洪水,为进一步优化三峡工程调度方案,充分发挥其巨大的防洪效益,从遭遇次数、遭遇时间、遭遇程度以及洪峰、洪量等角度,采用水文学分析法,重点研究了长江上游与汉江不同量级的洪水遭遇规律。研究表明,长江上游与汉江的中小量级的洪水遭遇频繁,遭遇时间主要发生在7,8,9三个月,洪水遭遇时各自的洪峰,最大7 d和15 d洪水过程无明显相应关系,遭遇后洪水过程重叠程度较高。     

Combinatorial strategies for targeting protein families: application to the proteases

Tens of thousands of proteins have been identified as a result of recent large scale genomic and proteomic efforts. With this large influx of new proteins, the formidable task of elucidating their function begins. However, this task becomes more manageable if proteins are divided into families based upon sequence homology, thereby allowing tools for their systematic study to be developed based upon their common structural and mechanistic characteristics. Combinatorial chemistry is ideally suited for the systematic study of protein families because a large amount of diversity can be readily displayed about a common scaffold designed to target a given protein family. Targeted combinatorial libraries have been particularly effective for the study of a ubiquitous family of proteins, the proteases. Substrate-specificity profiles of many proteases have been determined by using combinatorial libraries of appropriately labeled peptides. This specificity information been utilized to identify the physiological protein substrates of these enzymes and has facilitated inhibitor design efforts. Furthermore, combinatorial libraries of small molecules prepared with mechanism-based scaffolds have resulted in the identification of potent, small-molecule inhibitors of numerous proteases. Cell-permeable small-molecule inhibitors identified by these methods have served as powerful chemical tools to study protease function in vitro and in vivo and have served as leads for the development of therapeutic agents.     

Social viscosities: mapping social performance in public space

Abstract

This article evaluates locative media works that address a social consciousness; a public space of dynamic media linkages and improvised acts, where spontaneous formations of collective activity may proliferate through ‘social viscosities’ of space. What sorts of narrative space may be created within these linkages? As locative media become embedded in our environments, and become a part of our consciousness, to what types of dynamic social spaces do they contribute? Are these spaces vibrant with hidden sounds,images, narratives, and histories-affecting our sense of place? How do digital locative media contribute to a dialogue of emerging social communities in public space?     

Metal/Metal‐Oxide Interfaces: How Metal Contacts Affect the Work Function and Band Structure of MoO3

When transition metal oxides are used in practical applications, such as organic electronics or heterogeneous catalysis, they often must be in contact with a metal. Metal contacts can affect an oxide's chemical and electronic properties within the first few nanometers of the contact, resulting in changes to an oxide's chemical reactivity, conductivity, and energy‐level alignment properties. These effects can alter an oxide's ability to perform its intended function. Thus, the choice of contacting metal becomes an important design consideration when tailoring the properties of transition‐metal oxide thin films or nanoparticles. Here, metal/metal‐oxide interfaces involving a widely used oxide in organic electronics, MoO₃, are examined. It is demonstrated that metal contacts tend to reduce the Mo⁶⁺ cation to lower oxidation states and, consequently, alter MoO₃’s valence electronic structure and work function when the oxide layer is very thin (less than 10 nm). MoO₃ becomes semimetallic and has a lower work function near metal contacts. The observed behavior is attributed to two causes: 1) charge transfer from the metal Fermi level into MoO₃’s low‐lying conduction band and 2) an oxidation‐reduction reaction between the metal and MoO₃ that results in oxidation of the metal and reduction of MoO₃. These results illustrate how interfaces are important to an oxide's ability to provide energy‐level alignment.     

Materials for Immunotherapy

Breakthroughs in materials engineering have accelerated the progress of immunotherapy in preclinical studies. The interplay of chemistry and materials has resulted in improved loading, targeting, and release of immunomodulatory agents. An overview of the materials that are used to enable or improve the success of immunotherapies in preclinical studies is presented, from immunosuppressive to proinflammatory strategies, with particular emphasis on technologies poised for clinical translation. The materials are organized based on their characteristic length scale, whereby the enabling feature of each technology is organized by the structure of that material. For example, the mechanisms by which i) nanoscale materials can improve targeting and infiltration of immunomodulatory payloads into tissues and cells, ii) microscale materials can facilitate cell-mediated transport and serve as artificial antigen-presenting cells, and iii) macroscale materials can form the basis of artificial microenvironments to promote cell infiltration and reprogramming are discussed. As a step toward establishing a set of design rules for future immunotherapies, materials that intrinsically activate or suppress the immune system are reviewed. Finally, a brief outlook on the trajectory of these systems and how they may be improved to address unsolved challenges in cancer, infectious diseases, and autoimmunity is presented.