Review of Lung Particle Overload, Rat Lung Cancer, and the Conclusions of the Edinburgh Expert Panel—It's Time to Revisit Cancer Hazard Classifications for Titanium Dioxide and Carbon Black

Chronic inhalation of titanium dioxide or carbon black by rats at concentrations which overload lung particle clearance can result in lung cancer. Based on this rat lung response, IARC, NIOSH, and ECHA classified titanium dioxide, and IARC classified carbon black, as potential human carcinogens. These classifications have been questioned based on an extensive data base demonstrating: the rat lung cancer occurred only under conditions of extreme lung particle overload; the lung cancer response in rats has not been seen in other animal species; and studies in titanium dioxide and carbon black exposed human populations have not shown an increased incidence of cancer. In 2019 an international panel of science and regulatory experts was convened to document the state of the science on lung particle overload and rat lung cancer after exposure to poorly soluble low toxicity particles. Regarding hazard identification, the expert panel concluded, in the absence of supporting data from other species, lung particle overload-associated rat lung cancer does not imply a cancer hazard for humans. Regarding high to low dose extrapolation, the expert panel concluded rat lung tumors occurring only under conditions of lung particle overload are not relevant to humans exposed under non-overloading conditions. The conclusions of the Edinburgh Expert Panel directly conflict with IARC, ECHA and NIOSH's extrapolation of lung particle overload associated rat lung cancer to hazard for humans. The hazard classifications for titanium dioxide and carbon black inhalation should be assessed considering the state-of-the-science on lung particle overload and rat lung cancer

Considerations in Assuring Safety of Increasingly Autonomous Systems

Recent technological advances have accelerated the development and application of increasingly autonomous (IA) systems in civil and military aviation. IA systems can provide automation of complex mission tasks-ranging across reduced crew operations, air-traffic management, and unmanned, autonomous aircraft-with most applications calling for collaboration and teaming among humans and IA agents. IA systems are expected to provide benefits in terms of safety, reliability, efficiency, affordability, and previously unattainable mission capability. There is also a potential for improving safety by removal of human errors. There are, however, several challenges in the safety assurance of these systems due to the highly adaptive and non-deterministic behavior of these systems, and vulnerabilities due to potential divergence of airplane state awareness between the IA system and humans. These systems must deal with external sensors and actuators, and they must respond in time commensurate with the activities of the system in its environment. One of the main challenges is that safety assurance, currently relying upon authority transfer from an autonomous function to a human to mitigate safety concerns, will need to address their mitigation by automation in a collaborative dynamic context. These challenges have a fundamental, multidimensional impact on the safety assurance methods, system architecture, and V&V capabilities to be employed. The goal of this report is to identify relevant issues to be addressed in these areas, the potential gaps in the current safety assurance techniques, and critical questions that would need to be answered to assure safety of IA systems. We focus on a scenario of reduced crew operation when an IA system is employed which reduces, changes or eliminates a human's role in transition from two-pilot operations

Maintaining surface-phase purity is key to efficient open air fabricated cuprous oxide solar cells

This is the final published version. It first appeared at http://scitation.aip.org/content/aip/journal/aplmater/3/2/10.1063/1.4913442.Electrochemically deposited Cu 2O solar cells are receiving growing attention owing to a recent doubling in efficiency. This was enabled by the controlled chemical environment used in depositing doped ZnO layers by atomic layer deposition, which is not well suited to large-scale industrial production. While open air fabrication with atmospheric pressure spatial atomic layer deposition overcomes this limitation, we find that this approach is limited by an inability to remove the detrimental CuO layer that forms on the Cu 2O surface. Herein, we propose strategies for achieving efficiencies in atmospherically processed cells that are equivalent to the high values achieved in vacuum processed cells.The authors acknowledge funding from the Cambridge Commonwealth, European and International Trusts (R.L.Z.H. and Y.I.), Rutherford Foundation of New Zealand (R.L.Z.H.), an NSF Graduate Research Fellowship (R.E.B.), EPSRC of the UK (S.H.), University of Cambridge EPSRC Centre for Doctoral Training in Nanoscience (S.H.), Girton College Cambridge (K.P.M.), an NSF CAREER Award ECCS-1150878 (T.B.), the National Research Foundation Singapore through the Singapore Massachusetts Institute of Technology Alliance for Research and Technology’s Low Energy Electronics Systems research program (T.B.), and an ERC Advanced Investigator Grant, Novox, ERC-2009-adG247276 (J.L.D.)

The Grizzly, December 1, 1989

Curriculum in Transition • Armstrong\u27s Talk a Trauma • Letters: Maturity Decides Right Choice; Everybody\u27s a Critic; Championship Cycling; PDA Pooh-Poohed; Pro-Choice Rally Ironic • Aquatic Lady Bears Stroke Strongly • Hoopsters Hopeful • Women\u27s Track Looks to Season • Congrats to Athletes • Shoudt to Return Next Fall • X-Country Wrap-Up • Swimmers Victorious • Down with Frats • Faith-Leaps Abound • EPA: Not a Joking Matter • What Can Clamer Claim? • Victims of Fishy Business • Corsonites Fashion Comatose • Greeks Promote Sexism • U.C. Honors Spotlight • Final Exam Schedulehttps://digitalcommons.ursinus.edu/grizzlynews/1248/thumbnail.jp

Lipidoid-Coated Iron Oxide Nanoparticles for Efficient DNA and siRNA delivery

The safe, targeted and effective delivery of gene therapeutics remains a significant barrier to their broad clinical application. Here we develop a magnetic nucleic acid delivery system composed of iron oxide nanoparticles and cationic lipid-like materials termed lipidoids. Coated nanoparticles are capable of delivering DNA and siRNA to cells in culture. The mean hydrodynamic size of these nanoparticles was systematically varied and optimized for delivery. While nanoparticles of different sizes showed similar siRNA delivery efficiency, nanoparticles of 50–100 nm displayed optimal DNA delivery activity. The application of an external magnetic field significantly enhanced the efficiency of nucleic acid delivery, with performance exceeding that of the commercially available lipid-based reagent, Lipofectamine 2000. The iron oxide nanoparticle delivery platform developed here offers the potential for magnetically guided targeting, as well as an opportunity to combine gene therapy with MRI imaging and magnetic hyperthermia.National Heart, Lung, and Blood InstituteNational Institutes of Health (U.S.) (Program of Excellence in Nanotechnology (PEN) Award, Contract #HHSN268201000045C

Report of the Particulate Matter Research Strategies Workshop, Park City, Utah, April 29–30, 1996

An informal one-and-a-half-day workshop devoted to research needs on the health effects of airborne particulate matter (PM) was held in Park City, Utah, on April 29 and 30,1996, in conjunction with the Second Colloquium on Particulate Air Pollution and Health at Park City, Utah, on May 1-3,1996. The objective of the workshop was to prepare a holistic assessment of knowledge gaps and research opportunities for presentation at the penultimate session of the colloquium. The workshop reviewed the research progress made since the first PM colloquium (Irvine, California, January 1994) and the findings of recent major reviews of the PM literature by the World Health Organization-European Region, the U.K. Health Department, the National Institute of Public Health in the Netherlands, and the U.S. Environmental Protection Agency. It then discussed (1) the nature of ambient PM, (2) population segments at special risk, (3) the nature of the health effects of concern, (4) the sources of ambient air PM, and (5) the implications of ambient air PM health effects on occupational exposure limits and occupational cohorts. The workshop concluded that: A primary focus for fuaher research should be on accumulation mode aerosol with the objective of disentangling the roles of its chemical constituents, as well as their interactive effects with each other and with coexisting gaseous criteria pollutants. Research is also urgently needed on the health effects of both the coarse-mode PM10 and the ultrafine particles in the nuclei-mode aerosol. There should be a continued focus on infants, the elderly, and people with preexisting cardiopulmonary diseases. Further development and validation of animal models for human sensitive groups warrants high priority. Validated animal models are needed for target human populations in order to investigate: (1) the roles of specific constituents of PM mixtures, (2) the roles of exposure concentrations and durations on responses, (3) some of the risk factors that predispose individuals to be responsive to PM exposures, and (4) physiological, biochemical, molecular, and pathological correlates of mortality, tissue and organ damage, and chronic disease development. © 1998, Taylor & Francis Group, LLC. All rights reserved

The Lantern, 2017-2018

On Dissociation • Untouchable • After Rocket Man • The Science Fair • Cardinal Rule at Stephen J. Memorial • Quentin & Sylvie • Cabello • The Get Out • Painting Day • Black, White and Grey • Family Pruning • How to Remove a Stain • Becoming Ourselves • Wonderbread U • Overture • Pescadero • Gross • Stage Fright • Lucky Daddy • Sarah • Rumble • Silvermine • The Green Iguana • A Poem for Ghost Children • A Poem for Lost Boys • Mother • Drop of Grease • Don\u27t Wanna be White • I • Amelia Earhart Disappeared Into My Vagina: An Ode to Cunts, Menstrual Cups and All Things Woman • Suburban Summer • Nightmares and Dreams Induced by My Mother • Teacups, Skins, etc. • Three Thoughts About My Bedroom • Dear Siri • 2 Queens (Beyonce in Reference to Sonia Sanchez) • Voyeurs • In Front of the Bathroom Mirror • To a Rose • Howl • Mice • Mirror • Language Accordion Volcano Mouth • Lucky Woman • Butterscotch • To Persephone • Wolf • Notes Never Passed • Topple • Bust • Kyoto • Identity • Sunflower • Tornabuoni Bubbles • Olympia • Decayed Hall • Perspectivehttps://digitalcommons.ursinus.edu/lantern/1186/thumbnail.jp

Automated High-Content Live Animal Drug Screening Using C. elegans Expressing the Aggregation Prone Serpin α1-antitrypsin Z

The development of preclinical models amenable to live animal bioactive compound screening is an attractive approach to discovering effective pharmacological therapies for disorders caused by misfolded and aggregation-prone proteins. In general, however, live animal drug screening is labor and resource intensive, and has been hampered by the lack of robust assay designs and high throughput work-flows. Based on their small size, tissue transparency and ease of cultivation, the use of C. elegans should obviate many of the technical impediments associated with live animal drug screening. Moreover, their genetic tractability and accomplished record for providing insights into the molecular and cellular basis of human disease, should make C. elegans an ideal model system for in vivo drug discovery campaigns. The goal of this study was to determine whether C. elegans could be adapted to high-throughput and high-content drug screening strategies analogous to those developed for cell-based systems. Using transgenic animals expressing fluorescently-tagged proteins, we first developed a high-quality, high-throughput work-flow utilizing an automated fluorescence microscopy platform with integrated image acquisition and data analysis modules to qualitatively assess different biological processes including, growth, tissue development, cell viability and autophagy. We next adapted this technology to conduct a small molecule screen and identified compounds that altered the intracellular accumulation of the human aggregation prone mutant that causes liver disease in α1-antitrypsin deficiency. This study provides powerful validation for advancement in preclinical drug discovery campaigns by screening live C. elegans modeling α1-antitrypsin deficiency and other complex disease phenotypes on high-content imaging platforms