Deliberating performance targets workshop: Potential paths for emerging PM2.5 and O3 air sensor progress

The United States Environmental Protection Agency held an international two-day workshop in June 2018 to deliberate possible performance targets for non-regulatory fine particulate matter (PM2.5) and ozone (O3) air sensors. The need for a workshop arose from the lack of any market-wide manufacturer requirement for documented sensor performance evaluations, the lack of any independent third party or government-based sensor performance certification program, and uncertainty among all users as to the general usability of air sensor data. A multi-sector subject matter expert panel was assembled to facilitate an open discussion on these issues with multiple stakeholders. This summary provides an overview of the workshop purpose, key findings from the deliberations, and considerations for future actions specific to sensors. Important findings concerning PM2.5 and O3 sensors included the lack of consistent performance indicators and statistical metrics as well as highly variable data quality requirements depending on the intended use. While the workshop did not attempt to yield consensus on any topic, a key message was that a number of possible future actions would be beneficial to all stakeholders regarding sensor technologies. These included documentation of best practices, sharing quality assurance results along with sensor data, and the development of a common performance target lexicon, performance targets, and test protocols. Keywords: Low-cost air quality sensors, Performance targets, PM2.5, Ozon

Myocardial Induction of Nucleostemin in Response to Postnatal Growth and Pathological Challenge

Stem cell-specific proteins and regulatory pathways that determine self-renewal and differentiation have become of fundamental importance in understanding regenerative and reparative processes in the myocardium. One such regulatory protein, named nucleostemin, has been studied in the context of stem cells and several cancer cell lines, where expression is associated with proliferation and maintenance of a primitive cellular phenotype. We find nucleostemin is present in young myocardium and is also induced following cardiomyopathic injury. Nucleostemin expression in cardiomyocytes is induced by fibroblast growth factor-2 and accumulates in response to Pim-1 kinase activity. Cardiac stem cells also express nucleostemin that is diminished in response to commitment to a differentiated phenotype. Overexpression of nucleostemin in cultured cardiac stem cells increases proliferation while preserving telomere length, providing a mechanistic basis for potential actions of nucleostemin in promotion of cell survival and proliferation as seen in other cell types

Myocardial induction of nucleostemin in response to postnatal growth and pathological challenge

Stem cell - specific proteins and regulatory pathways that determine self-renewal and differentiation have become of fundamental importance in understanding regenerative and reparative processes in the myocardium. One such regulatory protein, named nucleostemin, has been studied in the context of stem cells and several cancer cell lines, where expression is associated with proliferation and maintenance of a primitive cellular phenotype. We find nucleostemin is present in young myocardium and is also induced following cardiomyopathic injury. Nucleostemin expression in cardiomyocytes is induced by fibroblast growth factor-2 and accumulates in response to Pim-1 kinase activity. Cardiac stem cells also express nucleostemin that is diminished in response to commitment to a differentiated phenotype. Overexpression of nucleostemin in cultured cardiac stem cells increases proliferation while preserving telomere length, providing a mechanistic basis for potential actions of nucleostemin in promotion of cell survival and proliferation as seen in other cell types

Deliberating performance targets workshop: Potential paths for emerging PM2.5 and O3 air sensor progress.

The United States Environmental Protection Agency held an international two-day workshop in June 2018 to deliberate possible performance targets for non-regulatory fine particulate matter (PM2.5) and ozone (O3) air sensors. The need for a workshop arose from the lack of any market-wide manufacturer requirement for Ozone documented sensor performance evaluations, the lack of any independent third party or government-based sensor performance certification program, and uncertainty among all users as to the general usability of air sensor data. A multi-sector subject matter expert panel was assembled to facilitate an open discussion on these issues with multiple stakeholders. This summary provides an overview of the workshop purpose, key findings from the deliberations, and considerations for future actions specific to sensors. Important findings concerning PM2.5 and O3 sensors included the lack of consistent performance indicators and statistical metrics as well as highly variable data quality requirements depending on the intended use. While the workshop did not attempt to yield consensus on any topic, a key message was that a number of possible future actions would be beneficial to all stakeholders regarding sensor technologies. These included documentation of best practices, sharing quality assurance results along with sensor data, and the development of a common performance target lexicon, performance targets, and test protocols

The effect of transient oxygenation on stem cell mobilization and ischemia/reperfusion heart injury

For general anesthesia, pre-oxygenation is routinely performed prior to intubation. It is well-known that ischemic/hypoxic preconditioning induces stem cell mobilization and protects against ischemia/reperfusion (I/R) injury. In this study, we investigated the effect of transient oxygenation on stem cell mobilization and I/R injury of the heart. Mice were exposed to 100% oxygen for 5 or 20 minutes. We evaluated the number of c-kit+ stem/progenitor cells and the levels of SDF-1α and VEGF in peripheral blood at 1, 3, 6, and 24 hours after oxygenation. We also induced I/R injury of the heart at 3 hours post-oxygenation for 5 minutes and then examined stem cell recruitment and fibrotic changes in the heart 3 or 14 days later. The number of c-kit+ cells in peripheral blood was significantly increased at 1 or 24 hours after oxygenation for either 5 or 20 minutes. Oxygenation for 5 or 20 minutes did not significantly change the SDF-1α level measured in plasma. However, the plasma VEGF level was decreased at 3 hours post-oxygenation for 20 minutes (p = 0.051). Oxygenation for 5 minutes did not significantly alter the fibrotic area or cell apoptosis. Although oxygenation for 5 minutes increased the number of c-kit+ cells in hearts damaged by I/R injury, this difference was not significant between groups due to large variation between individuals (p = 0.14). Although transient oxygenation induces stem cell mobilization, it does not appear to protect against I/R injury of the heart in mice

Nuclear Calcium/Calmodulin-dependent Protein Kinase II Signaling Enhances Cardiac Progenitor Cell Survival and Cardiac Lineage Commitment

Ca(2+)/Calmodulin-dependent protein kinase II (CaMKII) signaling in the heart regulates cardiomyocyte contractility and growth in response to elevated intracellular Ca(2+). The δB isoform of CaMKII is the predominant nuclear splice variant in the adult heart and regulates cardiomyocyte hypertrophic gene expression by signaling to the histone deacetylase HDAC4. However, the role of CaMKIIδ in cardiac progenitor cells (CPCs) has not been previously explored. During post-natal growth endogenous CPCs display primarily cytosolic CaMKIIδ, which localizes to the nuclear compartment of CPCs after myocardial infarction injury. CPCs undergoing early differentiation in vitro increase levels of CaMKIIδB in the nuclear compartment where the kinase may contribute to the regulation of CPC commitment. CPCs modified with lentiviral-based constructs to overexpress CaMKIIδB (CPCeδB) have reduced proliferative rate compared with CPCs expressing eGFP alone (CPCe). Additionally, stable expression of CaMKIIδB promotes distinct morphological changes such as increased cell surface area and length of cells compared with CPCe. CPCeδB are resistant to oxidative stress induced by hydrogen peroxide (H(2)O(2)) relative to CPCe, whereas knockdown of CaMKIIδB resulted in an up-regulation of cell death and cellular senescence markers compared with scrambled treated controls. Dexamethasone (Dex) treatment increased mRNA and protein expression of cardiomyogenic markers cardiac troponin T and α-smooth muscle actin in CPCeδB compared with CPCe, suggesting increased differentiation. Therefore, CaMKIIδB may serve as a novel modulatory protein to enhance CPC survival and commitment into the cardiac and smooth muscle lineages