Apurinic/Apyrimidinic Endonuclease 1 Regulates Inflammatory Response in Macrophages

The multi-functional apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) DNA repair and redox signaling protein has been shown to have a role in cancer growth and survival, however, little has been investigated concerning its role in inflammation. In this study, an APE1 redox-specific inhibitor (E3330) was used in lypopolysaccharide (LPS)-stimulated macrophages (RAW264.7). E3330 clearly suppressed secretion of inflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin (IL-6) and IL-12 and inflammatory mediators nitric oxide (NO) as well as prostaglandin E2 (PGE2) from the LPS-stimulated RAW264.7 cells. These data were supported by the down-regulation of the LPS-dependent expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) genes in the RAW264.7 cells. The effects of E3330 were mediated by the inhibition of transcription factors nuclear factor-κB (NF-κB) and activator protein 1 (AP-1) in the LPS-stimulated macrophages, both known targets of APE1. In conclusion, pharmacological inhibition of APE1 by E3330 suppresses inflammatory response in activated macrophages and can be considered as a novel therapeutic strategy for the inhibition of tumor-associated macrophages

Development of Entrepreneurial Attitudes Assessment Instrument for Freshman Students

An increasing population of university programs and quantity of curricular content focused on entrepreneurship poses both enormous opportunities for student growth, and numerous practical challenges. Prior work has largely focused on pre-post assessment of student learning, shifts in‘mindset’, activity effectiveness, mapping of student outcomes, and implications of student learning on career success. A baseline of freshman student attitudes towards entrepreneurship,outside of specifically focused entrepreneurial leaning, has significant potential to identify and inform programming in entrepreneurship, as well as general curriculums and pedagogy. An improved understanding of student’s constructive and cognitive influences in entrepreneurial education will serve to better inform the way entrepreneurship education in engineering is historically and currently discussed. Improving entrepreneurship education models begins with understanding student backgrounds comprised of different experiences, knowledge, and preconceptions. When looking longitudinally, migratory information can better inform entrepreneurial programming to provide data and support for more organized and integrated approaches to entrepreneurship education.This work in progress provides initial results and validation on the quantitative instrument portion of a mixed methods study developed for assessing and tracking entrepreneurial behaviors, experiences, and attitudes in a way identifiable to engineering and business freshman.The instrument is modified from the Entrepreneurial Attitude Orientation (EAO) survey instrument developed by Robbins in the early 1990s. Additionally, a section for gathering student socioeconomic status and gender, using elements of the Academic Pathways of People Learning Engineering Survey (APPLES) is included. Based on the difficulties in operationalization of student socioeconomic status self-identification, normalizing question are added as suggested by Donaldson and Sheppard from results in the APPLES instrument development process.The quantitative portion, discussed here, survey will be deployed during winter of 2015, to business and engineering freshman at a large Midwestern university. The initial deployment will allow validation against prior uses of the EAO instrument. Results will be presented in the paper and conference presentation comparing gender and socioeconomic correlations to entrepreneurial attitudes with previous publications. The survey instrument is being developed as the quantitative element of a mixed method longitudinal study tracking student entrepreneurial attitudes, focus, and growth over student college experiences. Follow-on efforts are intended to help better inform educators about the nature of student construction and growth in an university space increasingly influenced by a move towards entrepreneurship education

Analysis of cylindrical wrap-around and doubly conformal patch antennas by way of the finite element-artificial absorber method

The goal of this project was to develop analysis codes for computing the scattering and radiation of antennas on cylindrically and doubly conformal platforms. The finite element-boundary integral (FE-BI) method has been shown to accurately model the scattering and radiation of cavity-backed patch antennas. Unfortunately extension of this rigorous technique to coated or doubly curved platforms is cumbersome and inefficient. An alternative approximate approach is to employ an absorbing boundary condition (ABC) for terminating the finite element mesh thus avoiding use of a Green's function. A FE-ABC method is used to calculate the radar cross section (RCS) and radiation pattern of a cavity-backed patch antenna which is recessed within a metallic surface. It is shown that this approach is accurate for RCS and antenna pattern calculations with an ABC surface displaced as little as 0.3 lambda from the cavity aperture. These patch antennas may have a dielectric overlay which may also be modeled with this technique

Optimizing University Mobility : An Internal Navigation and Crowd Management System

In the evolving landscape of educational technology, the article explores the critical frontier of indoor navigation systems, focusing on universities. Traditional approaches in higher education often fall short of meeting dynamic user expectations, necessitating revolutionary solutions. This research introduces an innovative internal navigation and crowd management system that seamlessly integrates augmented reality, natural language processing, machine learning, and image processing technologies. The Android platform serves as the foundation, harnessing augmented reality's transformative capabilities to provide real-time visual cues and personalized wayfinding experiences. The voice interaction module, backed by NLP and ML, creates an intelligent, context-aware assistant. The crowd management module, employing advanced image processing, delivers real-time crowd density insights. Personalized recommendations, powered by NLP and ML, offer tailored canteen suggestions based on user preferences. The agmented reality navigation module, using Mapbox, Unity Hub, AR Core, and Vuforia, enriches the user experience with dynamic visual cues. Results reveal the success of each module: the voice interaction module showcases continuous learning, user-centric feedback, contextual guidance excellence, robust security, and multimodal interaction flexibility. The crowd management module excels in video feed processing, image processing with OpenCV, and real-time availability information retrieval. The personalized recommendations module demonstrates high accuracy, equilibrium, and robust performance. The AR navigation module impresses with precision, enriched navigation, and tailored routes through machine learning. This cohesive system sets new benchmarks for user-centric technology in universities. Future work includes multi-university integration, intelligent spatial design, and real-time decision support, paving the way for more efficient, user-centered university experiences and contributing to the advancement of smart university environments. The research serves as a pivotal force in reshaping interactions within university spaces, envisioning a future where technology seamlessly enhances the essence of human interaction in educational environments

Characterization plan for Fort St. Vrain and Peach Bottom graphite fuels

Part of Fort St. Vrain (FSV) and most of the Peach Bottom (PB) reactor spent fuels are currently stored at INEL and may remain in storage for many years before disposal. Three disposal pathways have been proposed: intact disposal, fuels partially disassembled and the high-level waste fraction conditioned prior to disposal, and fuels completed disassembled and conditioned prior to disposal. Many options exist within each of these pathways. PNL evaluated the literature and other reference to develop a fuels characterization plan for these fuels. This plan provides guidance for the characteristics of the fuel which will be needed to pursue any of the storage or disposal pathways. It also provides a suggested fuels monitoring program for the current storage facilities. This report recommends a minimum of 7 fuel elements be characterized: PB Core 1 fuel: one Type II nonfailed element, one Type II failed element, and one Type III nonfailed element; PB Core 2 fuel: two Type II nonfailed fuel elements; and FSV fuel: at least two fuel blocks from regions of high temperature and fluence and long in-reactor performance (preferably at reactor end-of- life). Selection of PB fuel elements should focus on these between radial core position 8 and 14 and on compacts between compact numbers 10 and 20. Selection of FSV fuel elements should focus on these from Fuel Zones II and III, located in Core Layers 6, 7, and possibly 8

ReishiMax, mushroom based dietary supplement, inhibits adipocyte differentiation, stimulates glucose uptake and activates AMPK

<p>Abstract</p> <p>Background</p> <p>Obesity is a health hazard which is closely associated with various complications including insulin resistance, hypertension, dyslipidemia, atherosclerosis, type 2 diabetes and cancer. In spite of numerous preclinical and clinical interventions, the prevalence of obesity and its related disorders are on the rise demanding an urgent need for exploring novel therapeutic agents that can regulate adipogenesis. In the present study, we evaluated whether a dietary supplement ReishiMax (RM), containing triterpenes and polysaccharides extracted from medicinal mushroom <it>Ganoderma lucidum</it>, affects adipocyte differentiation and glucose uptake in 3T3-L1 cells.</p> <p>Methods</p> <p>3T3-L1 pre-adipocytes were differentiated into adipocytes and treated with RM (0-300 μg/ml). Adipocyte differentiation/lipid uptake was evaluated by oil red O staining and triglyceride and glycerol concentrations were determined. Gene expression was evaluated by semi-quantitative RT-PCR and Western blot analysis. Glucose uptake was determined with [³H]-glucose.</p> <p>Results</p> <p>RM inhibited adipocyte differentiation through the suppresion of expression of adipogenic transcription factors peroxisome proliferator-activated receptor-γ (PPAR-γ), sterol regulatory element binding element protein-1c (SREBP-1c) and CCAAT/enhancer binding protein-α (C/EBP-α). RM also suppressed expression of enzymes and proteins responsible for lipid synthesis, transport and storage: fatty acid synthase (FAS), acyl-CoA synthetase-1 (ACS1), fatty acid binding protein-4 (FABP4), fatty acid transport protein-1 (FATP1) and perilipin. RM induced AMP-activated protein kinase (AMPK) and increased glucose uptake by adipocytes.</p> <p>Conclusion</p> <p>Our study suggests that RM can control adipocyte differentiation and glucose uptake. The health benefits of ReishiMax warrant further clinical studies.</p

NAHA, a Novel Hydroxamic Acid-Derivative, Inhibits Growth and Angiogenesis of Breast Cancer In Vitro and In Vivo

BACKGROUND: We have recently synthesized novel N-alkylated amino acid-derived hydroxamate, 2-[Benzyl-(2-nitro-benzenesulfonyl)-amino]-N-hydroxy-3-methyl-N-propyl-butyramide (NAHA). Here, we evaluate the anticancer activity of NAHA against highly invasive human breast cancer cells MDA-MB-231 in vitro and in vivo. METHODOLOGY/PRINCIPAL FINDINGS: Cell growth was evaluated by MTT and soft agar assays. Protein expression was determined by DNA microarray and Western blot analysis. Metastatic potential was evaluated by cell adhesion, migration, invasion, capillary morphogenesis, and ELISA assays. The anticancer activity in vivo was evaluated in mouse xenograft model. NAHA inhibited proliferation and colony formation of MDA-MB-231 cells together with the down-regulation of expression of Cdk2 and CDC20 proteins. NAHA inhibited cell adhesion, migration, and invasion through the suppression of secretion of uPA. NAHA suppressed secretion of VEGF from MDA-MB-231 cells and inhibited capillary morphogenesis of human aortic endothelial cells (HAECs). Finally, NAHA at 50 mg/kg was not toxic and decreased tumor volume and tumor weight in vivo. This suppression of tumor growth was associated with the inhibition of mitotic figures and induction of apoptosis, and the reduction of CD31 and VEGF positive cells in tumors. CONCLUSION: NAHA could be a novel promising compound for the development of new drugs for the therapy of invasive breast cancers

Phellinus linteus suppresses growth, angiogenesis and invasive behaviour of breast cancer cells through the inhibition of AKT signalling

The antitumour activity of a medicinal mushroom Phellinus linteus (PL), through the stimulation of immune system or the induction of apoptosis, has been recently described. However, the molecular mechanisms responsible for the inhibition of invasive behaviour of cancer cells remain to be addressed. In the present study, we demonstrate that PL inhibits proliferation (anchorage-dependent growth) as well as colony formation (anchorage-independent growth) of highly invasive human breast cancer cells. The growth inhibition of MDA-MB-231 cells is mediated by the cell cycle arrest at S phase through the upregulation of p27Kip1 expression. Phellinus linteus also suppressed invasive behaviour of MDA-MB-231 cells by the inhibition of cell adhesion, cell migration and cell invasion through the suppression of secretion of urokinase-plasminogen activator from breast cancer cells. In addition, PL markedly inhibited the early event in angiogenesis, capillary morphogenesis of the human aortic endothelial cells, through the downregulation of secretion of vascular endothelial growth factor from MDA-MB-231 cells. These effects are mediated by the inhibition of serine-threonine kinase AKT signalling, because PL suppressed phosphorylation of AKT at Thr308 and Ser473 in breast cancer cells. Taken together, our study suggests potential therapeutic effect of PL against invasive breast cancer

Intervention effects of Ganoderma lucidum spores on epileptiform discharge hippocampal neurons and expression of Neurotrophin-4 and N-Cadherin

Epilepsy can cause cerebral transient dysfunctions. Ganoderma lucidum spores (GLS), a traditional Chinese medicinal herb, has shown some antiepileptic effects in our previous studies. This was the first study of the effects of GLS on cultured primary hippocampal neurons, treated with Mg2+ free medium. This in vitro model of epileptiform discharge hippocampal neurons allowed us to investigate the anti-epileptic effects and mechanism of GLS activity. Primary hippocampal neurons from <1 day old rats were cultured and their morphologies observed under fluorescence microscope. Neurons were confirmed by immunofluorescent staining of neuron specific enolase (NSE). Sterile method for GLS generation was investigated and serial dilutions of GLS were used to test the maximum non-toxic concentration of GLS on hippocampal neurons. The optimized concentration of GLS of 0.122 mg/ml was identified and used for subsequent analysis. Using the in vitro model, hippocampal neurons were divided into 4 groups for subsequent treatment i) control, ii) model (incubated with Mg2+ free medium for 3 hours), iii) GLS group I (incubated with Mg2+ free medium containing GLS for 3 hours and replaced with normal medium and incubated for 6 hours) and iv) GLS group II (neurons incubated with Mg2+ free medium for 3 hours then replaced with a normal medium containing GLS for 6 hours). Neurotrophin-4 and N-Cadherin protein expression were detected using Western blot. The results showed that the number of normal hippocampal neurons increased and the morphologies of hippocampal neurons were well preserved after GLS treatment. Furthermore, the expression of neurotrophin-4 was significantly increased while the expression of N-Cadherin was decreased in the GLS treated group compared with the model group. This data indicates that GLS may protect hippocampal neurons by promoting neurotrophin-4 expression and inhibiting N-Cadherin expression