Interim report on the ground-water resources of Seminole County, Florida

Salt-water encroachment is undoubtedly the problem of most concern to users of ground water in Florida. This is a problem in many coastal areas where water levels are lowered excessively by heavy pumping. It is a problem also in some inland areas where the water-bearing formations contain salty water at relatively shallow depths. Among the coastal areas where wells have become contaminated with salt water are Pinellas County and the Miami area of Dade County. Inland areas where wells are likely to become contaminated with salt water include Seminole County and the southwestern part of Volusia County. The purpose of the investigation is to make a detailed study of the geology and ground-water resources of the county with special emphasis on the problems associated with declining water levels and salt-water contamination. This report reviews briefly the progress of the investigation through February 1954. (PDF contains 43 pages.

Imipramine blue sensitively and selectively targets FLT3-ITD positive acute myeloid leukemia cells.

Aberrant cytokine signaling initiated from mutant receptor tyrosine kinases (RTKs) provides critical growth and survival signals in high risk acute myeloid leukemia (AML). Inhibitors to FLT3 have already been tested in clinical trials, however, drug resistance limits clinical efficacy. Mutant receptor tyrosine kinases are mislocalized in the endoplasmic reticulum (ER) of AML and play an important role in the non-canonical activation of signal transducer and activator of transcription 5 (STAT5). Here, we have tested a potent new drug called imipramine blue (IB), which is a chimeric molecule with a dual mechanism of action. At 200-300 nM concentrations, IB is a potent inhibitor of STAT5 through liberation of endogenous phosphatase activity following NADPH oxidase (NOX) inhibition. However, at 75-150 nM concentrations, IB was highly effective at killing mutant FLT3-driven AML cells through a similar mechanism as thapsigargin (TG), involving increased cytosolic calcium. IB also potently inhibited survival of primary human FLT3/ITD+ AML cells compared to FLT3/ITDneg cells and spared normal umbilical cord blood cells. Therefore, IB functions through a mechanism involving vulnerability to dysregulated calcium metabolism and the combination of fusing a lipophilic amine to a NOX inhibiting dye shows promise for further pre-clinical development for targeting high risk AML

The production and mapping of wheat-rye introgression lines exploiting Ph1

Wheat is a staple food source across the globe. To cope with the increasing problems of global food security, higher yielding, stress tolerant wheat cultivars are necessary. This thesis describes a method of introgressing rye chromatin into wheat to make beneficial rye traits available in wheat germplasm and thus to facilitate the use of rye traits in the breeding of elite wheat cultivars. A non-specific ‘shotgun’ method of incorporating wheat chromatin has been used and has successfully introgressed the whole rye genome into a wheat background. The Pairing homologue one locus, Ph1, is known to control homologous pairing in wheat and thus deletion mutants of Ph1 have been used to attempt to force recombination between wheat and rye. The amount of recombination between wheat and rye was lower than expected indicating a further barrier inhibiting recombination between wheat and rye. The introgression lines produced have been genotyped using a combination of genomic in situ hybridisation (GISH) and two single nucleotides polymorphism (SNP) based methods, i.e. the Axiom® 35K SNP wild relative array and a selection of KASP markers). Genotyping has enabled the identification and tracking of introgressions through successive generations of a crossing programme and has shown a range of novel introgression lines covering the whole rye genome. Using the SNP genotyping it was possible to produce a bin map of rye and compare this map to wheat, which has confirmed several structural changes in rye in comparison to wheat

Ecosystem approach to harvesting in the Arctic : walking the tightrope between exploitation and conservation in the Barents Sea

Funidng: This study was supported by the Changing Arctic Ocean project MiMeMo (NE/R012679/1) jointly funded by the UKRI Natural Environment Research Council (NERC) and the German Federal Ministry of Education and Research (BMBF/03F0801A). Brierley was also supported by ArcticPRIZE (NE/P005721/1).Projecting the consequences of warming and sea-ice loss for Arctic marine food web and fisheries is challenging due to the intricate relationships between biology and ice. We used StrathE2EPolar, an end-to-end (microbes-to-megafauna) food web model incorporating ice-dependencies to simulate climate-fisheries interactions in the Barents Sea. The model was driven by output from the NEMO-MEDUSA earth system model, assuming RCP 8.5 atmospheric forcing. The Barents Sea was projected to be > 95% ice-free all year-round by the 2040s compared to > 50% in the 2010s, and approximately 2 °C warmer. Fisheries management reference points (FMSY and BMSY) for demersal fish (cod, haddock) were projected to increase by around 6%, indicating higher productivity. However, planktivorous fish (capelin, herring) reference points were projected to decrease by 15%, and upper trophic levels (birds, mammals) were strongly sensitive to planktivorous fish harvesting. The results indicate difficult trade-offs ahead, between harvesting and conservation of ecosystem structure and function.Publisher PDFPeer reviewe

Synthetic shelf sediment maps for the Greenland Sea and Barents Sea

Seabed sediment maps underpin a variety of marine research endeavours. Seabed mapping data are available for many regions, but these usually provide discrete classifications which obscure underlying continuous properties of the sediments. Other areas are poorly surveyed, e.g., polar regions which are inaccessible due to ice cover. Here, we focus on the inaccessible North East Greenland shelf for which there are almost no seabed sediment data. We trained a random forest model to predict sediment classes from an existing map of the well-surveyed neighbouring Barents Sea, using data on bathymetry, currents and waves. We then used our model to predict the unknown sediment distributions off East Greenland. In the process, we generated some new spatial data on previously un-mapped properties of the Barents Sea, such as mean grain size, organic carbon and nitrogen content, porosity and permeability. The maps of both regions are available to support future research activities in the Arctic, e.g., the parameterization of benthic biogeochemistry in ecosystem models, or mapping species distributions

How is climate change affecting marine life in the Arctic?

Rising temperature is melting the ice that covers the Arctic Ocean, allowing sunlight into waters that have been dark for thousands of years. Previously barren ice-covered regions are being transformed into productive seas. Here we explain how computer modelling can be used to predict how this transformation will affect the food web that connects plankton to fish and top-predators like whales and polar bears. Images of starving polar bears have become symbolic of the effects of warming climate. Melting of the sea-ice is expected to reduce the bears’ ability to hunt for seals. However, at the same time, the food web upon which they depend is becoming more productive, so it is not completely clear what the eventual outcome will be for the bears. Computer models help us to understand these systems and inform policy decisions on the management of newly available Arctic resources

Cascaded- and Modular-Multilevel Converter Laboratory Test System Options: A Review

The increasing importance of cascaded multilevel converters (CMCs), and the sub-category of modular multilevel converters (MMCs), is illustrated by their wide use in high voltage DC connections and in static compensators. Research is being undertaken into the use of these complex pieces of hardware and software for a variety of grid support services, on top of fundamental frequency power injection, requiring improved control for non-traditional duties. To validate these results, small-scale laboratory hardware prototypes are often required. Such systems have been built by many research teams around the globe and are also increasingly commercially available. Few publications go into detail on the construction options for prototype CMCs, and there is a lack of information on both design considerations and lessons learned from the build process, which will hinder research and the best application of these important units. This paper reviews options, gives key examples from leading research teams, and summarizes knowledge gained in the development of test rigs to clarify design considerations when constructing laboratory-scale CMCs.This work was supported in part by The University of Manchester supported by the National Innovation Allowance project ``VSC-HVDC Model Validation and Improvement'' and Dr. Heath's iCASE Ph.D. studentship supported through Engineering and Physical Sciences Research Council (EPSRC) and National Grid, in part by the Imperial College London supported by EPSRC through the HubNet Extension under Grant EP/N030028/1, in part by an iCASE Ph.D. Studentship supported by EPSRC and EDF Energy and the CDT in Future Power Networks under Grant EP/L015471/1, in part by University of New South Wales (UNSW) supported by the Solar Flagships Program through the Education Infrastructure Fund (EIF), in part by the Australian Research Council through the Discovery Early Career Research Award under Grant DECRA_DE170100370, in part by the Basque Government through the project HVDC-LINK3 under Grant ELKARTEK KK-2017/00083, in part by the L2EP research group at the University of Lille supported by the French TSO (RTE), and in part by the Hauts-de-France region of France with the European Regional Development Fund under Grant FEDER 17007725

Huntingtin contains an ubiquitin-binding domain and regulates lysosomal targeting of mitochondrial and RNA-binding proteins

Understanding the normal function of the Huntingtin (HTT) protein is of significance in the design and implementation of therapeutic strategies for Huntington's disease (HD). Expansion of the CAG repeat in the HTT gene, encoding an expanded polyglutamine (polyQ) repeat within the HTT protein, causes HD and may compromise HTT's normal activity contributing to HD pathology. Here, we investigated the previously defined role of HTT in autophagy specifically through studying HTT's association with ubiquitin. We find that HTT interacts directly with ubiquitin in vitro. Tandem affinity purification was used to identify ubiquitinated and ubiquitin-associated proteins that copurify with a HTT N-terminal fragment under basal conditions. Copurification is enhanced by HTT polyQ expansion and reduced by mimicking HTT serine 421 phosphorylation. The identified HTT-interacting proteins include RNA-binding proteins (RBPs) involved in mRNA translation, proteins enriched in stress granules, the nuclear proteome, the defective ribosomal products (DRiPs) proteome and the brain-derived autophagosomal proteome. To determine whether the proteins interacting with HTT are autophagic targets, HTT knockout (KO) cells and immunoprecipitation of lysosomes were used to investigate autophagy in the absence of HTT. HTT KO was associated with reduced abundance of mitochondrial proteins in the lysosome, indicating a potential compromise in basal mitophagy, and increased lysosomal abundance of RBPs which may result from compensatory up-regulation of starvation-induced macroautophagy. We suggest HTT is critical for appropriate basal clearance of mitochondrial proteins and RBPs, hence reduced HTT proteostatic function with mutation may contribute to the neuropathology of HD