Reforming American Higher Education: The University of Rhode Island International Engineering Program

The goal of this paper is to explore how American higher education may be better adapted to the needs of today’s global society by means of a more integrated curriculum, one that rigorously partners the “hard skills” of math, the sciences, and engineering (the STEM and professional disciplines) with those supposedly “softer” ones derived through the arts and humanities. The authors believe that students will be better prepared for the challenges of the contemporary workplace through an education equally grounded in the sciences and the arts, including the study of varied sets of value systems, by pursuing dual degrees across those disciplines. Having pioneered one such effective and well-known model for the internationalization of engineering education, the five year dual degree (BA/BS) International Engineering Program (IEP) at the University of Rhode Island, Berka and Grandin propose the marriage of engineering and language/culture as a model or template for a meaningful and productive partnership between science and technology, the humanities, and society as a whole, potentially adaptable to all comprehensive institutions of higher education and to a broad range of disciplines. As the United States seeks answers to a growing crisis of cost and relevance in higher education, therefore, the IEP will be presented here as an inspiration and a model for much needed reform, made possible by the creative reorganization and integration of subject areas which formerly went their separate ways, but benefitted enormously by finding their common ground

NADPH oxidase, NOX1, mediates vascular injury in ischemic retinopathy

<b>Aims:</b> Ischemic retinal diseases such as retinopathy of prematurity are major causes of blindness due to damage to the retinal microvasculature. Despite this clinical situation, retinopathy of prematurity is mechanistically poorly understood. Therefore, effective preventative therapies are not available. However, hypoxic-induced increases in reactive oxygen species (ROS) have been suggested to be involved with NADPH oxidases (NOX), the only known dedicated enzymatic source of ROS. Our major aim was to determine the contribution of NOX isoforms (1, 2, and 4) to a rodent model of retinopathy of prematurity. <b>Results:</b> Using a genetic approach, we determined that only mice with a deletion of NOX1, but not NOX2 or NOX4, were protected from retinal neovascularization and vaso-obliteration, adhesion of leukocytes, microglial accumulation, and the increased generation of proangiogenic and proinflammatory factors and ROS. We complemented these studies by showing that the specific NOX inhibitor, GKT137831, reduced vasculopathy and ROS levels in retina. The source of NOX isoforms was evaluated in retinal vascular cells and neuro-glial elements. Microglia, the immune cells of the retina, expressed NOX1, 2, and 4 and responded to hypoxia with increased ROS formation, which was reduced by GKT137831. <b>Innovation:</b> Our studies are the first to identify the NOX1 isoform as having an important role in the pathogenesis of retinopathy of prematurity. <b>Conclusions:</b> Our findings suggest that strategies targeting NOX1 have the potential to be effective treatments for a range of ischemic retinopathie

Candesartan Attenuates Diabetic Retinal Vascular Pathology by Restoring Glyoxalase-I Function

This is an uncopyedited electronic version of an article accepted for publication in Diabetes. The American Diabetes Association, publisher of Diabetes, is not responsible for any errors or omissions in this version of the manuscript or any version derived from it by third parties. The definitive publisher-authenticated version will be available in a future issue of Diabetes in print and online a

Nasal Epithelial Cells of Donor Origin after Allogeneic Hematopoietic Cell Transplantation are Generated at a Faster Rate in the First 3 Months Compared with Later Posttransplantation

Detection of donor-type epithelial cells (ECs) after allogeneic hematopoietic cell transplantation (allo-HCT) using XY chromosome fluorescein in situ hybridization (FISH) has suggested that hematopoietic stem cells carry a degree of developmental plasticity. This is controversial, given artifacts of XY-based detection and the possibility of hematopoietic–nonhematopoietic cell fusion. Moreover, the kinetics of donor-type ECs (quantity at different time points after transplant) is unknown. Here, we document unequivocally the existence of donor-type ECs using a method obviating the artifacts of XY-FISH and study their kinetics. Nasal scrapings and blood specimens were collected from 60 allo-HCT survivors between 7 days and 22 years posttransplantation. DNA extracted from laser-captured nasal ECs (ie, CK+CD45− cells) and blood leukocytes was polymerase chain reaction–amplified for a panel of 16 short tandem repeat markers. The median percentage of donor-type ECs (among nasal ECs) was 0% on day 7 posttransplantation, 2.8% at 3 months posttransplantation, and 8.5% at 12-22 years posttransplantation. Cell fusion was ruled out by FISH analysis for two autosomes. We conclude that donor-type nasal ECs exist after HCT, and that their percentage rises rapidly in the first 3 months posttransplantation and more slowly thereafter

Perylene Diimide as a Precise Graphene-like Superoxide Dismutase Mimetic

Here we show that the active portion of a graphitic nanoparticle can be mimicked by a perylene diimide (PDI) to explain the otherwise elusive biological and electrocatalytic activity of the nanoparticle construct. Development of molecular analogues that mimic the antioxidant properties of oxidized graphenes, in this case the poly(ethylene glycolated) hydrophilic carbon clusters (PEG–HCCs), will afford important insights into the highly efficient activity of PEG–HCCs and their graphitic analogues. PEGylated perylene diimides (PEGn–PDI) serve as well-defined molecular analogues of PEG–HCCs and oxidized graphenes in general, and their antioxidant and superoxide dismutase-like (SOD-like) properties were studied. PEGn–PDIs have two reversible reduction peaks, which are more positive than the oxidation peak of superoxide (O2•–). This is similar to the reduction peak of the HCCs. Thus, as with PEG–HCCs, PEGn–PDIs are also strong single-electron oxidants of O2•–. Furthermore, reduced PEGn–PDI, PEGn–PDI•–, in the presence of protons, was shown to reduce O2•– to H2O2 to complete the catalytic cycle in this SOD analogue. The kinetics of the conversion of O2•– to O2 and H2O2 by PEG8–PDI was measured using freeze-trap EPR experiments to provide a turnover number of 133 s–1; the similarity in kinetics further supports that PEG8–PDI is a true SOD mimetic. Finally, PDIs can be used as catalysts in the electrochemical oxygen reduction reaction in water, which proceeds by a two-electron process with the production of H2O2, mimicking graphene oxide nanoparticles that are otherwise difficult to study spectroscopically

Determination of ππ\pi\pi scattering lengths from measurement of π+π−\pi^+\pi^- atom lifetime

The DIRAC experiment at CERN has achieved a sizeable production of $\pi^+\pi^-$ atoms and has significantly improved the precision on its lifetime determination. From a sample of 21227 atomic pairs, a 4% measurement of the S-wave $\pi\pi$ scattering length difference $|a_0-a_2| = (.0.2533^{+0.0080}_{-0.0078}|_\mathrm{stat}.{}^{+0.0078}_{-0.0073}|_\mathrm{syst})M_{\pi^+}^{-1}$ has been attained, providing an important test of Chiral Perturbation Theory.Comment: 6 pages, 6 figure

Effect of NADPH oxidase 1 and 4 blockade in activated human retinal endothelial cells

© 2018 Royal Australian and New Zealand College of Ophthalmologists. This author accepted manuscript is made available following 12 month embargo from date of publication (January 2018) in accordance with the publisher's archiving policy.Background Over‐production of reactive oxygen species (ROS) and resulting oxidative stress contribute to retinal damage in vascular diseases that include diabetic retinopathy, retinopathy of prematurity and major retinal vessel occlusions. NADPH oxidase (Nox) proteins are professional ROS‐generating enzymes, and therapeutic targeting in these diseases has strong appeal. Pharmacological inhibition of Nox4 reduces the severity of experimental retinal vasculopathy. We investigated the potential application of this drug approach in humans. Methods Differential Nox enzyme expression was studied by real‐time‐quantitative polymerase chain reaction in primary human retinal endothelial cell isolates and a characterized human retinal endothelial cell line. Oxidative stress was triggered chemically in endothelial cells, by treatment with dimethyloxalylglycine (DMOG; 100 μM); Nox4 and vascular endothelial growth factor (VEGFA) transcript were measured; and production of ROS was detected by 2′,7′‐dichlorofluorescein. DMOG‐stimulated endothelial cells were treated with two Nox1/Nox4 inhibitors, GKT136901 and GKT137831; cell growth was monitored by DNA quantification, in addition to VEGFA transcript and ROS production. Results Nox4 (isoform Nox4A) was the predominant Nox enzyme expressed by human retinal endothelial cells. Treatment with DMOG significantly increased endothelial cell expression of Nox4 over 72 h, accompanied by ROS production and increased VEGFA expression. Treatment with GKT136901 or GKT137831 significantly reduced DMOG‐induced ROS production and VEGFA expression by endothelial cells, and the inhibitory effect of DMOG on cell growth. Conclusions Our findings in experiments on activated human retinal endothelial cells provide translational corroboration of studies in experimental models of retinal vasculopathy and support the therapeutic application of Nox4 inhibition by GKT136901 and GKT137831 in patients with retinal vascular diseases

Analysis of Stochastic Strategies in Bacterial Competence: A Master Equation Approach

Competence is a transiently differentiated state that certain bacterial cells reach when faced with a stressful environment. Entrance into competence can be attributed to the excitability of the dynamics governing the genetic circuit that regulates this cellular behavior. Like many biological behaviors, entrance into competence is a stochastic event. In this case cellular noise is responsible for driving the cell from a vegetative state into competence and back. In this work we present a novel numerical method for the analysis of stochastic biochemical events and use it to study the excitable dynamics responsible for competence in Bacillus subtilis. Starting with a Finite State Projection (FSP) solution of the chemical master equation (CME), we develop efficient numerical tools for accurately computing competence probability. Additionally, we propose a new approach for the sensitivity analysis of stochastic events and utilize it to elucidate the robustness properties of the competence regulatory genetic circuit. We also propose and implement a numerical method to calculate the expected time it takes a cell to return from competence. Although this study is focused on an example of cell-differentiation in Bacillus subtilis, our approach can be applied to a wide range of stochastic phenomena in biological systems