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Extracellular vesicles and exomere nanoparticles are under intense investigation as sources of clinically relevant cargo. Here we report the discovery of a distinct extracellular nanoparticle, termed supermere. Supermeres are morphologically distinct from exomeres and display a markedly greater uptake in vivo compared with small extracellular vesicles and exomeres. The protein and RNA composition of supermeres differs from small extracellular vesicles and exomeres. Supermeres are highly enriched with cargo involved in multiple cancers (glycolytic enzymes, TGFBI, miR-1246, MET, GPC1 and AGO2), Alzheimer's disease (APP) and cardiovascular disease (ACE2, ACE and PCSK9). The majority of extracellular RNA is associated with supermeres rather than small extracellular vesicles and exomeres. Cancer-derived supermeres increase lactate secretion, transfer cetuximab resistance and decrease hepatic lipids and glycogen in vivo. This study identifies a distinct functional nanoparticle replete with potential circulating biomarkers and therapeutic targets for a host of human diseases.

In New York City, LGBTQ people from different generations have had few opportunities to connect. They have splintered into age-segregated micro-communities, robbing them of opportunities to weave a common history and share strategies that community members have used to survive and thrive. "Bridging the Gap" was a community-based intergenerational theatre project designed to address this problem. It was developed and facilitated by a team of three candidates for The City University of New York (CUNY) School of Professional Studies' MA in Applied Theatre. The project was a partnership between CUNY and SAGE (Services and Advocacy for Gay, Lesbian, Bisexual & Transgender Elders) and culminated in a live performance of "Step Right Up!", an original devised theatre piece. In this paper, we explore our application of the drama strategy, "Role on the Wall", in an intergenerational LGBTQ context. Our various adaptations of the activity allowed for age-related stereotypes to be identified, confronted and disrupted. We further incorporated "Role on the Wall" into the culminating performance. Our dramatisation of the perceptions revealed by "Role on the Wall" allowed us not only to start a dialogue about pertinent subjects within our group, but also to share our dialogue with a wider audience during the performance. (Contains 1 figure and 4 notes.)

An analysis of differential charging between dielectric surface materials and the frame of a DSCS-III geosynchronous spacecraft is presented. Charging levels measured by surface potential monitors (SPMs) covered with samples of Kapton and Astroquartz have been recorded for one half of a solar cycle. Both seasonal and solar cycle effects are seen in the daily peak levels of the SPM voltages, with local maxima occurring near the equinoxes and a general trend increasing as solar max is approached. Charge neutralization by an onboard Xe plasma contactor was demonstrated to be effective throughout the mission, with a mean voltage reduction of 86% for Astroquartz and 74% for Kapton. Though a statistical analysis shows a general correlation between the fluence of charging electrons with SPM voltages, the event-specific correlation contains enough variance to cast doubt on the usefulness of an electron sensor as a differential charging alarm. We have found that a Kapton-covered SPM may be better suited than an electron sensor as a differential charging alarm. Index Terms--Geosynchronous orbit, satellite charging, space environmental effects, space weather.

The Compact Environmental Anomaly Sensor (CEASE) is an instrument designed to provide real-time space environment hazard warnings to the host spacecraft. In this paper, we report on the first year of on-orbit operation of this instrument and describe its performance with particular emphasis on its engineering, hazard-warning function. Index Terms--Dosimetry, proton radiation effects, radiation detectors, satellites.

The solar cycle dependence of dose rates in the low-altitude 'horns' of the outer zone electron belt is examined using data from TSX5/CEASE (solar maximum epoch) and APEX/PASP+ (solar minimum epoch). It is found, after normalizing the dose rates to account for the different shielding geometries, that the ratio of PASP to CEASE dose rates is ~4 for L > 4. This is contrary to the equal dose rates predicted by the NASA AE8MIN and AE8MAX models. Index Terms--Electron dose, low earth orbit, radiation belt, solar cycle variation.

Background & Aims: Heparin-binding epidermal growth factor–like growth factor (HB-EGF) is produced as a type-I, single-pass transmembrane protein that can be cleaved to release a diffusible peptide. HB-EGF, often overexpressed in damaged or diseased epithelium, is normally expressed in pancreatic islets, but its function is not understood. Methods: To understand the function of each isoform of HB-EGF, we made transgenes expressing either a constitutively transmembrane or a constitutively secreted protein. Results: The transmembrane isoform was not an inert precursor protein, but a functional molecule, downregulating the glucose-sensing apparatus of pancreatic islets. Conversely, the secreted form of HB-EGF improved islet function, but had severe fibrotic and neoplastic effects on surrounding tissues. Each isoform had a more severe phenotype than that of full-length HB-EGF, even though the full-length protein was efficiently cleaved, thus producing both isoforms, suggesting that a level of regulation was lost by separating the isoforms. Conclusions: This work demonstrates that islet function depends on the ratio of cleaved to uncleaved HB-EGF and that the transmembrane intermediate, while deleterious to islet function, is necessary to restrict action of soluble HB-EGF away from surrounding tissue. [Copyright &y& Elsevier]