Recent Advances in Intracellular and In Vivo ROS Sensing: Focus on Nanoparticle and Nanotube Applications

Reactive oxygen species (ROS) are increasingly being implicated in the regulation of cellular signaling cascades. Intracellular ROS fluxes are associated with cellular function ranging from proliferation to cell death. Moreover, the importance of subtle, spatio-temporal shifts in ROS during localized cellular signaling events is being realized. Understanding the biochemical nature of the ROS involved will enhance our knowledge of redox-signaling. An ideal intracellular sensor should therefore resolve real-time, localized ROS changes, be highly sensitive to physiologically relevant shifts in ROS and provide specificity towards a particular molecule. For in vivo applications issues such as bioavailability of the probe, tissue penetrance of the signal and signal-to-noise ratio also need to be considered. In the past researchers have heavily relied on the use of ROS-sensitive fluorescent probes and, more recently, genetically engineered ROS sensors. However, there is a great need to improve on current methods to address the above issues. Recently, the field of molecular sensing and imaging has begun to take advantage of the unique physico-chemical properties of nanoparticles and nanotubes. Here we discuss the recent advances in the use of these nanostructures as alternative platforms for ROS sensing, with particular emphasis on intracellular and in vivo ROS detection and quantification.     

Effects of Ospemifene on Drug Metabolism Mediated by Cytochrome P450 Enzymes in Humans in Vitro and in Vivo

The objective of these investigations was to determine the possible effects of the novel selective estrogen receptor modulator, ospemifene, on cytochrome P450 (CYP)-mediated drug metabolism. Ospemifene underwent testing for possible effects on CYP enzyme activity in human liver microsomes and in isolated human hepatocytes. Based on the results obtained in vitro, three Phase 1 crossover pharmacokinetic studies were conducted in healthy postmenopausal women to assess the in vivo effects of ospemifene on CYP-mediated drug metabolism. Ospemifene and its main metabolites 4-hydroxyospemifene and 4′-hydroxyospemifene weakly inhibited a number of CYPs (CYP2B6, CYP2C9, CYP2C19, CYP2C8, and CYP2D6) in vitro. However, only CYP2C9 activity was inhibited by 4-hydroxyospemifene at clinically relevant concentrations. Induction of CYPs by ospemifene in cultured human hepatocytes was 2.4-fold or less. The in vivo studies showed that ospemifene did not have significant effects on the areas under the plasma concentration-time curves of the tested CYP substrates warfarin (CYP2C9), bupropion (CYP2B6) and omeprazole (CYP2C19), demonstrating that pretreatment with ospemifene did not alter their metabolism. Therefore, the risk that ospemifene will affect the pharmacokinetics of drugs that are substrates for CYP enzymes is low.     

Dynamic analysis of a bistable actuator for digital hydraulics

A fast and small electromagnetic actuator, which requires a small amount of work to switch between two stable positions, for the use in digital hydraulics, is presented. A dynamic study of the bistable actuator as part of a new kind of hydraulic on/off valve is carried out. A prototype is built and measured to verify the analysis. The results show that with careful elaboration the design is feasible. Furthermore, the response times depend on driving frequencies and an optimal current density for minimal energy consumption in cyclic action can be found. A single on/off valve is a critical part of a digital hydraulic system.     

A Dialogue with C. West Churchman

In 1996, the author attended a seminar on ethics given by C. West Churchman at the University of California, Berkeley. During that year, the author also interviewed Churchman several times regarding the future direction of information sciences in general and the information systems research field in particular. This article is a compilation of the seminar and the interviews. It is set in the context of both Churchman's earlier and his current views of a global god, good, kindness, and caring. C. West Churchman holds that global ethics should lead to the study and design of information systems to solve large and difficult problems of the humankind such as poverty, crime and disease. His Global Ethical Management (GEM) of information sciences translates into abandoning the current goals and boundaries of the information sciences fields and changing what constitutes valid research to globally ethical endeavors.     

Visual tests for measuring the picture quality of teleconsultations for medical purposes

Telemedicine provides a new way of delivering medical services. The good quality of the picture is, however, essential for a proper and reliable teleconsultation, especially in the cases when visual information about the patient's physical condition is of great importance as in ophthalmology and dermatology. Therefore real-time telemedical applications need standards for these procedures, e.g. minimum requirements for resolution, as well as contrast and color discrimination. The present study was carried out to test these parameters in a real environment. A panel of different resolution, contrast sensitivity and color discrimination tests was carried out for five test persons via PictureTel videoconference system by ISDN 128 kbit/s line speed and in a normal way. The good color discrimination of the teleconsultation system makes it possible to use the system in the evaluation of different skin lesions and exemas. However, the poor resolution and especially poor contrast sensitivity makes the use of the equipment valueless in the evaluation of diseases where the diagnoses are based on the discrimination of small details, like the biomicroscopical analysis of inflammatory cells in the aqua's humor in cases of intraocular inflammation. The authors are suggesting a simple panel of tests to optimize and standardize these parameters.     

Radio network planning process and methods for WCDMA

This paper describes the system dimensioning and the radio network planning methodology for a third generation wcdma system. The applicability of each method is demonstrated using examples of likely system scenarios. The challenges of modeling the multiservice environment are described and the implications to the system performance simulations are introduced.     

Electronic Commerce Internet Strategies and Business Models-A Survey

Today, any doubts about possibilities of significant profits over the Internet are a distant memory. Such has been the proliferation of Internet-based business on the public network. But electronic commerce has turned out to be more difficult to master than previously assumed. For many, ventures have been less lucrative than expected. The problem is that integrating business models with technology is a multifaceted and largely open question (Shaw, et al. 1997). How do businesses of various sizes and industries actually start their Internet activity and how do their business models change over time? More specifically, how do their different Internet strategies play out? This article is the result of a survey of the Internet strategies and business models of 280 companies that sell products and services on the public network. The results show that electronic commerce has penetrated companies of all sizes. Based on this survey it is apparent that while many companies have participated in electronic commerce for years, their business models are still in their infancy stages.     

Negative peer reactions from the perspective of the reactor.

Conducted 2 studies to examine negative social reactions from the perspective of rejecting peers. The purpose of Study 1 was to test an attributional model of negative peer reactions in which perceptions of responsibility and specific emotions mediate between deviant peer characteristics and negative social responses. The more children perceived atypical classmates to be responsible for their idiosyncrasies, the more anger and less sympathy they reported. Anger increased rejection and decreased social support, whereas sympathy facilitated social support. In Study 2, the effects of responsibility perceptions and affective reactions (annoyance) on social responses were tested with an experimental design. Perceived responsibility influenced liking and support, whereas annoyance affected sympathy, support, and rejection. The results are discussed with respect to intervention programs that would improve children's social acceptance. (PsycINFO Database Record (c) 2010 APA, all rights reserved)