The unsung heroes

This paper explores the roles played by local collectors, often little-known or rarely remembered, in the compilation of Britain’s Earlier (Lower and early Middle) Palaeolithic record, with reference to the work of C.E. (Charles) Bean at the Lower Palaeolithic site of Broom, and the activities of George Smith and Llewellyn and Mabel Treacher in the Middle Thames Valley. Their collecting practices, publication records, and archaeological knowledge and insights are reviewed, and their impacts assessed with reference to the activities of other contemporary collectors, and the regional archaeological records of the south-west and the Middle Thames. Their archives demonstrate that while the key sites and artefact assemblages sampled by Bean, Smith and the Treachers would not otherwise have been unknown, their work left important legacies in terms of rich artefact assemblages, site archives (Bean), and the long-term monitoring of key sites and fluvial terraces.

Challenges of operational river forecasting

Skillful and timely streamflow forecasts are critically important to water managers and emergency protection services. To provide these forecasts, hydrologists must predict the behavior of complex coupled human–natural systems using incomplete and uncertain information and imperfect models. Moreover, operational predictions often integrate anecdotal information and unmodeled factors. Forecasting agencies face four key challenges: 1) making the most of available data, 2) making accurate predictions using models, 3) turning hydrometeorological forecasts into effective warnings, and 4) administering an operational service. Each challenge presents a variety of research opportunities, including the development of automated quality-control algorithms for the myriad of data used in operational streamflow forecasts, data assimilation, and ensemble forecasting techniques that allow for forecaster input, methods for using human-generated weather forecasts quantitatively, and quantification of human interference in the hydrologic cycle. Furthermore, much can be done to improve the communication of probabilistic forecasts and to design a forecasting paradigm that effectively combines increasingly sophisticated forecasting technology with subjective forecaster expertise. These areas are described in detail to share a real-world perspective and focus for ongoing research endeavors.

Continental and global scale flood forecasting systems

Floods are the most frequent of natural disasters, affecting millions of people across the globe every year. The anticipation and forecasting of floods at the global scale is crucial to preparing for severe events and providing early awareness where local flood models and warning services may not exist. As numerical weather prediction models continue to improve, operational centres are increasingly using the meteorological output from these to drive hydrological models, creating hydrometeorological systems capable of forecasting river flow and flood events at much longer lead times than has previously been possible. Furthermore, developments in, for example, modelling capabilities, data and resources in recent years have made it possible to produce global scale flood forecasting systems. In this paper, the current state of operational large scale flood forecasting is discussed, including probabilistic forecasting of floods using ensemble prediction systems. Six state-of-the-art operational large scale flood forecasting systems are reviewed, describing similarities and differences in their approaches to forecasting floods at the global and continental scale. Currently, operational systems have the capability to produce coarse-scale discharge forecasts in the medium-range and disseminate forecasts and, in some cases, early warning products, in real time across the globe, in support of national forecasting capabilities. With improvements in seasonal weather forecasting, future advances may include more seamless hydrological forecasting at the global scale, alongside a move towards multi-model forecasts and grand ensemble techniques, responding to the requirement of developing multi-hazard early warning systems for disaster risk reduction.

MEF2C-MYOCD and leiomodin1 suppression by miRNA-214 promotes smooth muscle cell phenotype switching in pulmonary arterial hypertension

Background Vascular hyperproliferative disorders are characterized by excessive smooth muscle cell (SMC) proliferation leading to vessel remodeling and occlusion. In pulmonary arterial hypertension (PAH), SMC phenotype switching from a terminally differentiated contractile to synthetic state is gaining traction as our understanding of the disease progression improves. While maintenance of SMC contractile phenotype is reportedly orchestrated by a MEF2C-myocardin (MYOCD) interplay, little is known regarding molecular control at this nexus. Moreover, the burgeoning interest in microRNAs (miRs) provides the basis for exploring their modulation of MEF2C-MYOCD signaling, and in turn, a pro-proliferative, synthetic SMC phenotype. We hypothesized that suppression of SMC contractile phenotype in pulmonary hypertension is mediated by miR-214 via repression of the MEF2C-MYOCD-leiomodin1 (LMOD1) signaling axis. Methods and Results In SMCs isolated from a PAH patient cohort and commercially obtained hPASMCs exposed to hypoxia, miR-214 expression was monitored by qRT-PCR. miR-214 was upregulated in PAH- vs. control subject hPASMCs as well as in commercially obtained hPASMCs exposed to hypoxia. These increases in miR-214 were paralleled by MEF2C, MYOCD and SMC contractile protein downregulation. Of these, LMOD1 and MEF2C were directly targeted by the miR. Mir-214 overexpression mimicked the PAH profile, downregulating MEF2C and LMOD1. AntagomiR-214 abrogated hypoxia-induced suppression of the contractile phenotype and its attendant proliferation. Anti-miR-214 also restored PAH-PASMCs to a contractile phenotype seen during vascular homeostasis. Conclusions Our findings illustrate a key role for miR-214 in modulation of MEF2C-MYOCD-LMOD1 signaling and suggest that an antagonist of miR-214 could mitigate SMC phenotype changes and proliferation in vascular hyperproliferative disorders including PAH.