176 research outputs found

    Application of Self-Monitoring for Situational Awareness

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    Self-monitoring devices and services are used for physical wellness, personal tracking and self-improvement. These individual devices and services can only provide information based on what they can measure directly or historically without an intermediate system. This paper proposes a self-monitoring system to perform situational awareness which may extend into providing insight into predictable behaviors. Knowing an individual’s current state and likelihood of particular behaviors occurring is a general solution. This knowledge-based solution derived from sensory data has many applications. The proposed system could monitor current individual situational status, automatically provide personal status as it changes, aid personal improvement, contribute to other self-monitoring systems, and enhance other life-tracking objectives

    AN OVERVIEW OF SELF-MONITORING SYSTEMS

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    The advancement of mobile devices, battery longevity, and low cost sensors is a confluence of enabling technologies, which have led to the creation of self-monitoring systems. This paper is a review of technologies within the field of self-monitoring or Quantified Self systems. Additionally, an original framework is presented for classifying such systems. The framework is intended to aid in evaluation of existing or proposed systems, managing research, and applications of self-monitoring systems. Technology gaps and applications are then addressed to highlight what topics are under-developed or covered by existing work. Knowing these topics could then be used to direct research and development to a certain degree

    Effects of Silver Nanoparticles on Primary Mixed Neural Cell Cultures: Uptake, Oxidative Stress and Acute Calcium Responses

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    In the body, nanoparticles can be systemically distributed and then may affect secondary target organs, such as the central nervous system (CNS). Putative adverse effects on the CNS are rarely investigated to date. Here, we used a mixed primary cell model consisting mainly of neurons and astrocytes and a minor proportion of oligodendrocytes to analyze the effects of well-characterized 20 and 40 nm silver nanoparticles (SNP). Similar gold nanoparticles served as control and proved inert for all endpoints tested. SNP induced a strong size-dependent cytotoxicity. Additionally, in the low concentration range (up to 10 μg/ml of SNP), the further differentiated cultures were more sensitive to SNP treatment. For detailed studies, we used low/medium dose concentrations (up to 20 μg/ml) and found strong oxidative stress responses. Reactive oxygen species (ROS) were detected along with the formation of protein carbonyls and the induction of heme oxygenase-1. We observed an acute calcium response, which clearly preceded oxidative stress responses. ROS formation was reduced by antioxidants, whereas the calcium response could not be alleviated by antioxidants. Finally, we looked into the responses of neurons and astrocytes separately. Astrocytes were much more vulnerable to SNP treatment compared with neurons. Consistently, SNP were mainly taken up by astrocytes and not by neurons. Immunofluorescence studies of mixed cell cultures indicated stronger effects on astrocyte morphology. Altogether, we can demonstrate strong effects of SNP associated with calcium dysregulation and ROS formation in primary neural cells, which were detectable already at moderate dosages

    Cyclosporine exacerbates ketamine toxicity in zebrafish: Mechanistic studies on drug–drug interaction

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    Cyclosporine A (CsA) is an immunosuppressive drug commonly used in organ transplant patients to prevent allograft rejections. Ketamine is a pediatric anesthetic that noncompetitively inhibits the calcium-permeable N-methyl-D-aspartic acid receptors. Adverse drug–drug interaction effects between ketamine and CsA have been reported in mammals and humans. However, the mechanism of such drug–drug interaction is unclear. We have previously reported adverse effects of combination drugs, such as verapamil/ketamine and shown the mechanism through intervention by other drugs in zebrafish embryos. Here, we show that ketamine and CsA in combination produce developmental toxicity even leading to lethality in zebrafish larvae when exposure began at 24h post-fertilization (hpf ), whereas CsA did not cause any toxicity on its own. We also demonstrate that acetyl L-carnitine (ALCAR) completely reversed the adverse effects. Both ketamine and CsA are CYP3A4 substrates. Although ketamine and CsA independently altered the expression of the hepatic marker CYP3A65, a zebrafish ortholog of human CYP3A4, both drugs together induced further increase in CYP3A65 expression. In the presence of ALCAR, however, CYP3A65 expression was normalized. ALCAR has been shown to prevent ketamine toxicity in mammal and zebrafish. In conclusion, CsA exacerbated ketamine toxicity and ALCAR reversed the effects. These results, providing evidence for the first time on the reversal of the adverse effects of CsA/ketamine interaction by ALCAR, would prove useful in addressing potential occurrences of such toxicities in humans

    Novel Gemcitabine Conjugated Albumin Nanoparticles: a Potential Strategy to Enhance Drug Efficacy in Pancreatic Cancer Treatment

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    Purpose: The present study reports a novel conjugate of gemcitabine (GEM) with bovine serum albumin (BSA) and thereof nanoparticles (GEM-BSA NPs) to potentiate the therapeutic efficacy by altering physicochemical properties, improving cellular uptake and stability of GEM. Methods: The synthesized GEM-BSA conjugate was extensively characterized by NMR, FTIR, MALDI-TOF and elemental analysis. Conjugation mediated changes in structural conformation and physicochemical properties were analysed by fluorescence, Raman and CD spectroscopy, DSC and contact angle analysis. Further, BSA nanoparticles were developed from BSA-GEM conjugate and extensively evaluated against in-vitro pancreatic cancer cell lines to explore cellular uptake pathways and therapeutic efficacy. Results: Various characterization techniques confirmed covalent conjugation of GEM with BSA. GEM-BSA conjugate was then transformed into NPs via high pressure homogenization technique with particle size 147.2 ± 7.3, PDI 0.16 ± 0.06 and ZP -19.2 ± 1.4. The morphological analysis by SEM and AFM revealed the formation of smooth surface spherical nanoparticles. Cellular uptake studies in MIA PaCa-2 (GEM sensitive) and PANC-1 (GEM resistant) pancreatic cell lines confirmed energy dependent clathrin internalization/endocytosis as a primary mechanism of NPs uptake. In-vitro cytotoxicity studies confirmed the hNTs independent transport of GEM in MIA PaCa-2 and PANC-1 cells. Moreover, DNA damage and annexin-V assay revealed significantly higher apoptosis level in case of cells treated with GEM-BSA NPs as compared to free GEM. Conclusions: GEM-BSA NPs were found to potentiate the therapeutic efficacy by altering physicochemical properties, improving cellular uptake and stability of GEM and thus demonstrated promising therapeutic potential over free drug

    COMPARISON OF DRUG EFFLUX TRANSPORT KINETICS IN VARIOUS BLOOD-BRAIN BARRIER MODELS

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    Vegetation and Moisture Controls on Soil C Mineralization in Semi-Arid Environments

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    Mechanisms of vegetation control on C mineralization in semiarid ecosystems are not well understood. We developed a series of model predictions for beneath the native shrub Wyoming big sagebrush [Artemisia tridentata (Nutt.) ssp. wyomingensis], the invasive annual grass cheatgrass (Bromus tectorum L.), and the exotic introduced perennial grass crested wheatgrass [Agropyron desertorum (L.) Gaertn.]. Soil samples (0–10 cm) collected biweekly for two growing seasons were analyzed in the laboratory for: water content, CO2 from intact soil cores and CO2 from soils sieved and wetted to 23%, total organic C, total N, and microbial biomass C. Our results suggest that different vegetation types in the Great Basin affect C mineralization primarily through modification of soil moisture and, secondarily, the amount of labile C. Soils beneath cheatgrass and sagebrush canopy retained more water after high‐and moderate‐intensity rainfalls than soils beneath crested wheatgrass and sagebrush interspace. Sagebrush canopy probably intercepts more incoming precipitation without significant throughfall to the soil surface below than cheatgrass or crested wheatgrass. At the same time, soils beneath cheatgrass had 8% more labile C and 36% higher C mineralization rates than sagebrush. Regression analysis showed that soil water content alone explained nearly 84% of the variation, and adding information on labile C accounted for nearly 88% of the variation in soil C mineralization rates. With increasing variability of precipitation in this region, the continuously increasing presence of cheatgrass in the semiarid and arid western United States may significantly impact the CO2 contributions to overall greenhouse gas emissions
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