Development of a Seafloor Community Classification for the New Zealand Region Using a Gradient Forest Approach

To support ongoing marine spatial planning in New Zealand, a numerical environmental classification using Gradient Forest models was developed using a broad suite of biotic and high-resolution environmental predictor variables. Gradient Forest modeling uses species distribution data to control the selection, weighting and transformation of environmental predictors to maximise their correlation with species compositional turnover. A total of 630,997 records (39,766 unique locations) of 1,716 taxa living on or near the seafloor were used to inform the transformation of 20 gridded environmental variables to represent spatial patterns of compositional turnover in four biotic groups and the overall seafloor community. Compositional turnover of the overall community was classified using a hierarchical procedure to define groups at different levels of classification detail. The 75-group level classification was assessed as representing the highest number of groups that captured the majority of the variation across the New Zealand marine environment. We refer to this classification as the New Zealand “Seafloor Community Classification” (SCC). Associated uncertainty estimates of compositional turnover for each of the biotic groups and overall community were also produced, and an added measure of uncertainty – coverage of the environmental space – was developed to further highlight geographic areas where predictions may be less certain owing to low sampling effort. Environmental differences among the deep-water New Zealand SCC groups were relatively muted, but greater environmental differences were evident among groups at intermediate depths in line with well-defined oceanographic patterns observed in New Zealand’s oceans. Environmental differences became even more pronounced at shallow depths, where variation in more localised environmental conditions such as productivity, seafloor topography, seabed disturbance and tidal currents were important differentiating factors. Environmental similarities in New Zealand SCC groups were mirrored by their biological compositions. The New Zealand SCC is a significant advance on previous numerical classifications and includes a substantially wider range of biological and environmental data than has been attempted previously. The classification is critically appraised and considerations for use in spatial management are discussed.

Network traits predict ecological strategies in fungi

Colonization of terrestrial environments by filamentous fungi relies on their ability to form networks that can forage for and connect resource patches. Despite the importance of these networks, ecologists rarely consider network features as functional traits because their measurement and interpretation are conceptually and methodologically difficult. To address these challenges, we have developed a pipeline to translate images of fungal mycelia, from both micro- and macro-scales, to weighted network graphs that capture ecologically relevant fungal behaviour. We focus on four properties that we hypothesize determine how fungi forage for resources, specifically: connectivity; relative construction cost; transport efficiency; and robustness against attack by fungivores. Constrained ordination and Pareto front analysis of these traits revealed that foraging strategies can be distinguished predominantly along a gradient of connectivity for micro- and macro-scale mycelial networks that is reminiscent of the qualitative ‘phalanx’ and ‘guerilla’ descriptors previously proposed in the literature. At one extreme are species with many inter-connections that increase the paths for multidirectional transport and robustness to damage, but with a high construction cost; at the other extreme are species with an opposite phenotype. Thus, we propose this approach represents a significant advance in quantifying ecological strategies for fungi using network information.

Genomic and Transcriptomic Underpinnings of Melanoma Genesis, Progression, and Metastasis

Melanoma is a deadly skin cancer with rapidly increasing incidence worldwide. The discovery of the genetic drivers of melanomagenesis in the last decade has led the World Health Organization to reclassify melanoma subtypes by their molecular pathways rather than traditional clinical and histopathologic features. Despite this significant advance, the genomic and transcriptomic drivers of metastatic progression are less well characterized. This review describes the known molecular pathways of cutaneous and uveal melanoma progression, highlights recently identified pathways and mediators of metastasis, and touches on the influence of the tumor microenvironment on metastatic progression and treatment resistance. While targeted therapies and immune checkpoint blockade have significantly aided in the treatment of advanced disease, acquired drug resistance remains an unfortunately common problem, and there is still a great need to identify potential prognostic markers and novel therapeutic targets to aid in such cases.

Plate Tectonics and Macrogeomorphology

The plate tectonics revolution was the most significant advance in our understanding of the Earth in the 20th century, but initially it had little impact on the discipline of geomorphology. Topography and landscape development were not considered to be important phenomena that deserved attention from the broader earth-science community in the context of the new model of global tectonics. This situation began to change from the 1980s as various technical innovations enabled landscape evolution to be modelled numerically at the regional to sub-continental scales relevant to plate tectonics, and rates of denudation to be quantified over geological time scales. These developments prompted interest amongst earth scientists from fields such as geophysics, geochemistry and geochronology in understanding the evolution of topography, the role of denudation in influencing patterns of crustal deformation, and the interactions between tectonics and surface processes. This trend was well established by the end of the century, and has become even more significant up to the present. In this chapter I review these developments and illustrate how plate tectonics has been related to landscape development, especially in the context of collisional orogens and passive continental margins. I also demonstrate how technical innovations have been pivotal to the expanding interest in macroscale landscape development in the era of plate tectonics, and to the significant enhancement of the status of the discipline of geomorphology in the earth sciences over recent decades.

Microstrip Array Ring FETs with 2D p-Ga2O3 Channels Grown by MOCVD

Gallium oxide (Ga2O3) thin films of various thicknesses were grown on sapphire (0001) substrates by metal organic chemical vapor deposition (MOCVD) using trimethylgallium (TMGa), high purity deionized water, and silane (SiH4) as gallium, oxygen, and silicon precursors, respectively. N2 was used as carrier gas. Hall measurements revealed that films grown with a lower VI/III ratio had a dominant p-type conduction with room temperature mobilities up to 7 cm2/Vs and carrier concentrations up to ~1020 cm−3 for thinner layers. High resolution transmission electron microscopy suggested that the layers were mainly κ phase. Microstrip field-effect transistors (FETs) were fabricated using 2D p-type Ga2O3:Si, channels. They achieved a maximum drain current of 2.19 mA and an on/off ratio as high as ~108. A phenomenological model for the p-type conduction was also presented. As the first demonstration of a p-type Ga2O3, this work represents a significant advance which is state of the art, which would allow the fabrication of p-n junction based devices which could be smaller/thinner and bring both cost (more devices/wafer and less growth time) and operating speed (due to miniaturization) advantages. Moreover, the first scaling down to 2D device channels opens the prospect of faster devices and improved heat evacuation.

Project Portfolio Selection of Solar Energy by Photovoltaic Generation Using Gini-CAPM Multi-Criteria and Considering ROI Covariations

For some time, renewable solar energy generations using cellular photovoltaic panels have stood out among the options, especially in the segment of micro and small companies, where the return on investment is usually higher. In this context, when micro and small companies do not have the capital for the enterprises, several others, mainly small ones, have emerged to finance. However, significant difficulties occur for financiers in selecting investment portfolios, especially when considering the trade-off between return and risk and the covariations of return on investment, which are very common. In this type of selection, the Capital Asset Pricing Model criteria using the Gini risk can help significantly because this one is a more robust risk coefficient for assessments of non-normal probability distributions. However, searches for methods that meet the selection needs using the adjacent criteria are unsuccessful. Thus, this work seeks to help minimize the gap by presenting a new method for selection using the criteria. Historical and simulations data stochastic evaluations indicate that the portfolios selected by the method are attractive options for implementations. These portfolios have reasonable probabilistic expectations and satisfactory protection to avoid mistakes caused for not considering covariations in return on investment, which indicates a significant advance on the current knowledge frontier and will likely allow the increased use of the concept. The method also presents theoretical contributions in adaptations of the benchmark models, which help to minimize the adjacent literary gap of similar methods.

Evaluation and space representation of the maximum surface runoff in watersheds

In Cuba, regardless of the advances made in hydrological and hydraulic investigations related to floods, there are limitations with the detailed knowledge of the true maximum surface runoff or maximum flow that characterizes these phenomena in the season of intense rains, for which it is necessary to carry out complex hydrological study that, with the help of professional software and statistical techniques, help to determine and model spatially with certain reliability, the maximum water surface drained in watersheds. The general objective was pursued: To determine and represent spatially with the use of Geographic Information Systems (GIS) and hydrological methods, the runoff or maximum flow produced by the intense rains in a watershed, selecting to exemplify the watershed from the Magdalena River to the south east of the Santiago de Cuba municipality. As a result was obtained in the first instance, that it is feasible to apply this procedure to know in a preliminary way what maximum flow is available at any point of a main river or tributary. This approximation constitutes a significant advance for subsequent work in other watersheds of Cuba or internationally.

Ice dynamics and ocean productivity during the Late Miocene, offshore Wilkes Land, East Antarctica

<p>The middle Miocene Climatic Transition (~14 Ma) is commonly interpreted to represent the significant advance of the East Antarctic Ice Sheet (EAIS), and the transition to a hyper-arid climate and a stable polar-styled ice sheet. However, an increasing number of studies provide evidence for continued instability and abundant meltwater processes influencing the low-lying margins of the EAIS during the Late Miocene (~11.6-5.3 Ma). The history of the EAIS during this period remains ambiguous due to the sparse number of records, and those that do exist have poor age resolution. This thesis investigates Integrated Ocean Drilling Program Site U1361 (64°24.5°S 143°53.1°E), located on the lowermost continental rise of the Wilkes Land margin. It aims to assess the variability of the EAIS and associated changes in palaeoceanography offshore one of the largest marine-based sectors of East Antarctica, the Wilkes Subglacial Basin, and to establish if the EAIS was responding to orbital forcings during the Late Miocene. The study period (~11.7 to 10.8 Ma) contains six intervals of nannofossil-rich mudstones, interbedded with laminated mudstones and diatom-rich mudstones. Nannofossils are absent elsewhere in core U1361A, which covers the past ~14 Ma. To identify the sedimentary and depositional processes which influenced this anomalous interval of calcareous biological productivity, a high-resolution record (using ~450 samples) of Iceberg Rafted Debris (IBRD), grain size analysis and bulk geochemistry XRF analysis have been developed. A lithofacies scheme has been established and used to provide an interpretation of the shifting sedimentary processes through time. Repeating cycles of faintly laminated mudstones were interpreted to represent the influence of bottom current activity on overbank turbidites, that spill onto a channel leeve, during glacial periods. The contouritic nature of the facies is likely associated with the low-relief channel-levee system at this time. Interglacial sedimentation is characterised by an increase in biogenic content, IBRD and bioturbation, with deposition occurring during biologically productive open marine conditions. Two types of biogenic productivity are present over the interval (silica and/or carbonate). The intervals of diatom-rich mud were interpreted to be associated with enhanced upwelling of Circumpolar Deep Water (CDW). While, the nannofossil-rich mudstones suggest a significantly warmer climate, with coccolithophore production proposed to represent the influence of meltwater and shifting Southern Ocean frontal systems, acting to restrict nutrient upwelling and increase water temperatures. Nannofossil-rich muds are only present for a short interval (700 kyr), suggesting that the anomalous depositional environment between ~11.7 to 11.0 Ma was potentially related to the significant retreat and surface meltwater processes at the EAIS margin. Interglacial sedimentation at Site U1361 is also accompanied by an increase in grain size (i.e. silt), interpreted to represent oceanic current intensification which acts to restrict the deposition of finer material, relative to glacial intervals. This intensification of ocean current strength may have resulted in increased heat delivery to the EAIS margin triggering a terrestrial based ice sheet, and the delivery of nutrients stimulating marine productivity. Spectral analysis of the mean grain size (MGS) and IBRD Mass Accumulation Rate (MAR) records revealed that during the Late Miocene (~11.7 to 10.8 Ma), the ice sheet was paced by ~100 kyr eccentricity cycles, and a low frequency ~20 kyr processional component. This is consistent with two Late Miocene 𝛿¹⁸O records that are also paced by eccentricity, suggesting that the Antarctic Ice Sheet was contributing a significant signal to the global 𝛿¹⁸O record during this interval of the Late Miocene. However, the presence of nannofossil suggests a warmer world, rather than the colder climate state that are often inferred to lead to eccentricity/precession variability. A recent hypothesis proposed by Levy et al., (2019) invokes that a warmer climate may lead to surface melt processes which at high latitudes are dominated by eccentricity/precession. Although this style of climate is commonly thought to have occurred prior to ~14 Ma in East Antarctica, the evidence presented in this study suggests such a state existed at the Wilkes Land margin until at least ~11.0 Ma.</p>

Ice dynamics and ocean productivity during the Late Miocene, offshore Wilkes Land, East Antarctica

<p>The middle Miocene Climatic Transition (~14 Ma) is commonly interpreted to represent the significant advance of the East Antarctic Ice Sheet (EAIS), and the transition to a hyper-arid climate and a stable polar-styled ice sheet. However, an increasing number of studies provide evidence for continued instability and abundant meltwater processes influencing the low-lying margins of the EAIS during the Late Miocene (~11.6-5.3 Ma). The history of the EAIS during this period remains ambiguous due to the sparse number of records, and those that do exist have poor age resolution. This thesis investigates Integrated Ocean Drilling Program Site U1361 (64°24.5°S 143°53.1°E), located on the lowermost continental rise of the Wilkes Land margin. It aims to assess the variability of the EAIS and associated changes in palaeoceanography offshore one of the largest marine-based sectors of East Antarctica, the Wilkes Subglacial Basin, and to establish if the EAIS was responding to orbital forcings during the Late Miocene. The study period (~11.7 to 10.8 Ma) contains six intervals of nannofossil-rich mudstones, interbedded with laminated mudstones and diatom-rich mudstones. Nannofossils are absent elsewhere in core U1361A, which covers the past ~14 Ma. To identify the sedimentary and depositional processes which influenced this anomalous interval of calcareous biological productivity, a high-resolution record (using ~450 samples) of Iceberg Rafted Debris (IBRD), grain size analysis and bulk geochemistry XRF analysis have been developed. A lithofacies scheme has been established and used to provide an interpretation of the shifting sedimentary processes through time. Repeating cycles of faintly laminated mudstones were interpreted to represent the influence of bottom current activity on overbank turbidites, that spill onto a channel leeve, during glacial periods. The contouritic nature of the facies is likely associated with the low-relief channel-levee system at this time. Interglacial sedimentation is characterised by an increase in biogenic content, IBRD and bioturbation, with deposition occurring during biologically productive open marine conditions. Two types of biogenic productivity are present over the interval (silica and/or carbonate). The intervals of diatom-rich mud were interpreted to be associated with enhanced upwelling of Circumpolar Deep Water (CDW). While, the nannofossil-rich mudstones suggest a significantly warmer climate, with coccolithophore production proposed to represent the influence of meltwater and shifting Southern Ocean frontal systems, acting to restrict nutrient upwelling and increase water temperatures. Nannofossil-rich muds are only present for a short interval (700 kyr), suggesting that the anomalous depositional environment between ~11.7 to 11.0 Ma was potentially related to the significant retreat and surface meltwater processes at the EAIS margin. Interglacial sedimentation at Site U1361 is also accompanied by an increase in grain size (i.e. silt), interpreted to represent oceanic current intensification which acts to restrict the deposition of finer material, relative to glacial intervals. This intensification of ocean current strength may have resulted in increased heat delivery to the EAIS margin triggering a terrestrial based ice sheet, and the delivery of nutrients stimulating marine productivity. Spectral analysis of the mean grain size (MGS) and IBRD Mass Accumulation Rate (MAR) records revealed that during the Late Miocene (~11.7 to 10.8 Ma), the ice sheet was paced by ~100 kyr eccentricity cycles, and a low frequency ~20 kyr processional component. This is consistent with two Late Miocene 𝛿¹⁸O records that are also paced by eccentricity, suggesting that the Antarctic Ice Sheet was contributing a significant signal to the global 𝛿¹⁸O record during this interval of the Late Miocene. However, the presence of nannofossil suggests a warmer world, rather than the colder climate state that are often inferred to lead to eccentricity/precession variability. A recent hypothesis proposed by Levy et al., (2019) invokes that a warmer climate may lead to surface melt processes which at high latitudes are dominated by eccentricity/precession. Although this style of climate is commonly thought to have occurred prior to ~14 Ma in East Antarctica, the evidence presented in this study suggests such a state existed at the Wilkes Land margin until at least ~11.0 Ma.</p>

Ponatinib, Lestaurtinib and mTOR/PI3K inhibitors are promising repurposing candidates against Entamoeba histolytica

Dysentery caused by Entamoeba histolytica affects millions of people annually. Current treatment regimens are based on metronidazole to treat invasive parasites combined with paromomycin for luminal parasites. Issues with treatment include significant side effects, inability to easily treat breastfeeding and pregnant women, the use of two sequential agents, and concern that all therapy is based on nitroimidazole agents with no alternatives if clinical resistance emerges. Thus, the need for new drugs against amebiasis is urgent. To identify new therapeutic candidates, we screened the ReFRAME library (11,948 compounds assembled for Repurposing, Focused Rescue, and Accelerated Medchem) against E. histolytica trophozoites. We identified 159 hits in the primary screen at 10 μM and 46 compounds were confirmed in secondary assays. Overall, 26 were selected as priority molecules for further investigation including 6 FDA approved, 5 orphan designation, and 15 which are currently in clinical trials (3 phase III, 7 phase II and 5 phase I). We found that all 26 compounds are active against metronidazole resistant E. histolytica and 24 are able to block parasite recrudescence after drug removal. Additionally, 14 are able to inhibit encystation and 2 (lestaurtinib and LY-2874455) are active against mature cysts. Two classes of compounds are most interesting for further investigations: the Bcr-Abl TK inhibitors, with the ponatinib (EC 50 0.39) as most potent and mTOR or PI3K inhibitors with 8 compounds in clinical development, of which 4 have nanomolar potency. Overall, these are promising candidates and represent a significant advance for drug development against E. histolytica .