The Tropospheric Ozone Assessment Report (TOAR) is an activity of the International Global Atmospheric Chemistry Project. This paper is a component of the report, focusing on the present-day distribution and trends of tropospheric ozone relevant to climate and global atmospheric chemistry model evaluation. Utilizing the TOAR surface ozone database, several figures present the global distribution and trends of daytime average ozone at 2702 non-urban monitoring sites, highlighting the regions and seasons of the world with the greatest ozone levels. Similarly, ozonesonde and commercial aircraft observations reveal ozone’s distribution throughout the depth of the free troposphere. Long-term surface observations are limited in their global spatial coverage, but data from remote locations indicate that ozone in the 21st century is greater than during the 1970s and 1980s. While some remote sites and many sites in the heavily polluted regions of East Asia show ozone increases since 2000, many others show decreases and there is no clear global pattern for surface ozone changes since 2000. Two new satellite products provide detailed views of ozone in the lower troposphere across East Asia and Europe, revealing the full spatial extent of the spring and summer ozone enhancements across eastern China that cannot be assessed from limited surface observations. Sufficient data are now available (ozonesondes, satellite, aircraft) across the tropics from South America eastwards to the western Pacific Ocean, to indicate a likely tropospheric column ozone increase since the 1990s. The 2014–2016 mean tropospheric ozone burden (TOB) between 60˚N–60˚S from five satellite products is 300 Tg ± 4%. While this agreement is excellent, the products differ in their quantification of TOB trends and further work is required to reconcile the differences. Satellites can now estimate ozone’s global long-wave radiative effect, but evaluation is difficult due to limited in situ observations where the radiative effect is greatest.

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Block copolymer micelles have become accepted as a viable strategy for drug formulation and delivery. Block copolymer micelles may serve as solubilizers and/or true drug carriers depending on their drug retention properties in vivo. Indeed the formulation of hydrophobic drugs in these micelle systems has been shown to provide up to a 30,000 fold increase in the water solubility of some compounds. In addition, the administration of drugs in copolymer micelles has been shown to reduce their toxicity and improve their therapeutic efficacy. The present review is focused on the drug loading and release properties of block copolymer micelles. Specifically, the properties of the drug, properties of the micelle core and the presence of interactions between the drug and the core-forming block are discussed in terms of their influence on the drug loading and release properties of the micelles. The various methods employed to prepare drug-loaded micelles are reviewed and the in vitro release assays used to predict the in vivo release characteristics of the formulations are discussed. The balance between drug loading and micelle stability is highlighted as a critical factor in the optimization of micelle-based formulations. The in vivo performance of micelles as delivery systems is evaluated by comparing the pharmacokinetics of free drug and drug administered in micelle-based formulations. Overall, the composition-property and property-performance relationships outlined in this review may aid in guiding the rational design of block copolymer micelles for drug delivery. In addition, suggestions for future research in this area are provided as a means to assist in furthering block copolymer micelles as one of the leading advanced drug delivery technologies for the systemic administration of drugs.

The signaling pathways by which intermittent strain (60 cycles/min, 15 min/h) regulates proliferation of mixed fetal rat lung cell in vitro have been investigated. Adenosine 3',5'-cyclic monophosphate (cAMP) content and cAMP-dependent protein kinase (PKA) activity were not affected by strain. The stimulatory effect of strain on DNA synthesis was also not influenced by the cyclic nucleotide-dependent protein kinase inhibitors H-8 or HA-1004, the adenylate cyclase inhibitor SQ-22536, or a PKA inhibitor and cAMP antagonist, adenosine 3',5'-cyclic monophosphothioate (Rp-cAMPS). In contrast, intracellular concentrations of two second messengers, inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG), were dramatically increased after a short period of strain. This increase in second messengers was accompanied by an increased tyrosine phosphorylation of phospholipase C-gamma 1. Phospholipase D activity was also increased by strain. Mechanical strain elicited a shift in the subcellular distribution of PKC activity from cytosol to membranes shortly after the onset of strain. The specific activity of PKC in the membranes increased 6- to 10-fold within 5-15 min and remained increased throughout a 48-h period of intermittent strain. Strain-induced PKC activation and DNA synthesis were blocked by the PKC inhibitors H-7, staurosporine, and calphostin C, as well as by the phospholipase C inhibitor U-73,122. We conclude that mechanical strain of mixed fetal rat lung cells activates phospholipid turnover via phospholipases, followed by PKC activation, which then triggers the downstream events that lead to cell proliferation.