Design, Construction, and Test of Compact, Distributed-Charge, X-Band Accelerator Systems that Enable Image-Guided, VHEE FLASH Radiotherapy.

The design and optimization of laser-Compton x-ray systems based on compact distributed charge accelerator structures can enable micron-scale imaging of disease and the concomitant production of beams of Very High Energy Electrons (VHEEs) capable of producing FLASH-relevant dose rates. The physics of laser-Compton x-ray scattering ensures that the scattered x-rays follow exactly the trajectory of the incident electrons, thus providing a route to image-guided, VHEE FLASH radiotherapy. The keys to a compact architecture capable of producing both laser-Compton x-rays and VHEEs are the use of X-band RF accelerator structures which have been demonstrated to operate with over 100 MeV/m acceleration gradients. The operation of these structures in a distributed charge mode in which each radiofrequency (RF) cycle of the drive RF pulse is filled with a low-charge, high-brightness electron bunch is enabled by the illumination of a high-brightness photogun with a train of UV laser pulses synchronized to the frequency of the underlying accelerator system. The UV pulse trains are created by a patented pulse synthesis approach which utilizes the RF clock of the accelerator to phase and amplitude modulate a narrow band continuous wave (CW) seed laser. In this way it is possible to produce up to 10 µA of average beam current from the accelerator. Such high current from a compact accelerator enables production of sufficient x-rays via laser-Compton scattering for clinical imaging and does so from a machine of "clinical" footprint. At the same time, the production of 1000 or greater individual micro-bunches per RF pulse enables > 10 nC of charge to be produced in a macrobunch of < 100 ns. The design, construction, and test of the 100-MeV class prototype system in Irvine, CA is also presented.

Quantitative trait loci and genomic prediction for grain sugar and mineral concentrations of cowpea [Vigna unguiculata (L.) Walp.].

Development of high yielding cowpea varieties coupled with good taste and rich in essential minerals can promote consumption and thus nutrition and profitability. The sweet taste of cowpea grain is determined by its sugar content, which comprises mainly sucrose and galacto-oligosaccharides (GOS) including raffinose and stachyose. However, GOS are indigestible and their fermentation in the colon can produce excess intestinal gas, causing undesirable bloating and flatulence. In this study, we aimed to examine variation in grain sugar and mineral concentrations, then map quantitative trait loci (QTLs) and estimate genomic-prediction (GP) accuracies for possible application in breeding. Grain samples were collected from a multi-parent advanced generation intercross (MAGIC) population grown in California during 2016-2017. Grain sugars were assayed using high-performance liquid chromatography. Grain minerals were determined by inductively coupled plasma-optical emission spectrometry and combustion. Considerable variation was observed for sucrose (0.6-6.9%) and stachyose (2.3-8.4%). Major QTLs for sucrose (QSuc.vu-1.1), stachyose (QSta.vu-7.1), copper (QCu.vu-1.1) and manganese (QMn.vu-5.1) were identified. Allelic effects of major sugar QTLs were validated using the MAGIC grain samples grown in West Africa in 2017. GP accuracies for minerals were moderate (0.4-0.58). These findings help guide future breeding efforts to develop mineral-rich cowpea varieties with desirable sugar content.

An accurate, reliable, and universal qPCR method to identify homozygous single insert T-DNA with the example of transgenic rice.

Early determination of transgenic plants that are homozygous for a single locus T-DNA insert is highly desirable in most fundamental and applied transgenic research. This study aimed to build on an accurate, rapid, and reliable quantitative real-time PCR (qPCR) method to fast-track the development of multiple homozygous transgenic rice lines in the T1 generation, with low copy number to single T-DNA insert for further analyses. Here, a well-established qPCR protocol, based on the OsSBE4 reference gene and the nos terminator, was optimized in the transgenic Japonica rice cultivar Nipponbare, to distinguish homozygous single-insert plants with 100% accuracy. This method was successfully adapted to transgenic Indica rice plants carrying three different T-DNAs, without any modifications to quickly develop homozygous rice plants in the T1 generation. The accuracy of this qPCR method when applied to transgenic Indica rice approached 100% in 12 putative transgenic lines. Moreover, this protocol also successfully detected homozygous single-locus T-DNA transgenic rice plants with two-transgene T-DNAs, a feature likely to become more popular in future transgenic research. The assay was developed utilizing universal primers targeting common sequence elements of gene cassettes (the nos terminator). This assay could therefore be applied to other transgenic plants carrying the nos terminator. All procedures described here use standardized qPCR reaction conditions and relatively inexpensive dyes, such as SYBR Green, thus the qPCR method could be cost-effective and suitable for lower budget laboratories that are involved in rice transgenic research.

Dietary Zn deficiency, the current situation and potential solutions.

Zinc (Zn) deficiency is a worldwide problem, and this review presents an overview of the magnitude of Zn deficiency with a particular emphasis on present global challenges, current recommendations for Zn intake, and factors that affect dietary requirements. The challenges of monitoring Zn status are clarified together with the discussion of relevant Zn bioaccessibility and bioavailability issues. Modern lifestyle factors that may exacerbate Zn deficiency and new strategies of reducing its effects are presented. Biofortification, as a potentially useful strategy for improving Zn status in sensitive populations, is discussed. The review proposes potential actions that could deliver promising results both in terms of monitoring dietary and physiological Zn status as well as in alleviating dietary Zn deficiency in affected populations.

Ecosystem services in connected catchment to coast ecosystems: Monitoring to detect emerging trends.

There is an increasing need for long-term monitoring of ecosystems and their services to inform on-ground management. The supply of many ecosystem services relies on connections that span multiple ecosystems. Monitoring the underlying condition of interconnected ecosystems is therefore required to track effectiveness of past interventions and identify impending change. Here we test the performance of indicators of ecosystem services with the aim of identifying the time-scales over which indicators of ecosystem services responded to change. We chose a case-study of a catchment in Northern Australia, where water resource development is a threat to the river flows that support vegetation growth and the life-cycle of coastal fishery species. We developed a novel approach to performance testing that drew on state-space modelling to capture ecological dynamics, and structural equation modelling to capture covariation in indicator time series. We first quantified covariation among three ecological indicators that had time-series data: pasture biomass, vegetation greenness and barramundi catch per unit effort. Higher values of all indicators occurred in years with greater river flow. We then predicted the emergence times for each indicator, as the time taken for a trend in an indicator to emerge from the background of natural variation. Emergence times were > 10 years in all cases, quantified at 80 % and higher confidence levels. Past trends and current status of ecosystem service flows are often used by decision makers to directly inform near-term actions, particularly for provisioning services (such as barramundi catch) due to their important contribution to regional economies. We found that ecological indicators could be used to assess historical performance over decadal timespans, but not as short-term indicators of recent change. More generally, we offer an approach to performance testing of indicators. This approach could be useful for quantifying timescales of ecosystem response in systems where cross-ecosystem connections are important.

Constructed Wetlands Suitability for Sugarcane Profitability, Freshwater Biodiversity and Ecosystem Services.

Freshwater ecosystems, such as wetlands, are among the most impacted by agricultural expansion and intensification through extensive drainage and pollution. There is a pressing need to identify ways of managing agricultural landscapes to ensure food and water security without jeopardising biodiversity and other environmental benefits. Here we examine the potential fish biodiversity and landholder financial benefits arising from the integration of constructed lagoons to improve drainage, flow regulation and habitat connectivity within a sugarcane dominated catchment in north Queensland, Australia. A hybrid approach was used, combining the findings of both fish ecological surveys and a financial cost-benefit analysis. We found that the constructed lagoons supported at least 36 native freshwater fishes (over half of all native freshwater fishes in the region), owing to their depth, vegetated margins, moderate water quality and high connectivity to the Tully River. In addition to biodiversity benefits, we estimated that surrounding sugarcane farms would have financially benefited from reduced flooding of cropland and the elevation of low-lying cropland with deposited spoil excavated from lagoon construction. Improved drainage and flow regulation allowed for improvement in sugarcane yield and elevated land increased gross margins from extending the length of the cane production cycle or enabling a switch from cattle grazing to cane production. Restoring or creating wetlands to reduce flooding in flood-prone catchments is a globally applicable model that could improve both agricultural productivity and aquatic biodiversity, while potentially increasing farm income by attracting payments for provision of ecosystem services.

How to build a cognitive map.

Learning and interpreting the structure of the environment is an innate feature of biological systems, and is integral to guiding flexible behaviors for evolutionary viability. The concept of a cognitive map has emerged as one of the leading metaphors for these capacities, and unraveling the learning and neural representation of such a map has become a central focus of neuroscience. In recent years, many models have been developed to explain cellular responses in the hippocampus and other brain areas. Because it can be difficult to see how these models differ, how they relate and what each model can contribute, this Review aims to organize these models into a clear ontology. This ontology reveals parallels between existing empirical results, and implies new approaches to understand hippocampal-cortical interactions and beyond.

Enteroendocrine cell types that drive food reward and aversion.

Animals must learn through experience which foods are nutritious and should be consumed, and which are toxic and should be avoided. Enteroendocrine cells (EECs) are the principal chemosensors in the GI tract, but investigation of their role in behavior has been limited by the difficulty of selectively targeting these cells in vivo. Here, we describe an intersectional genetic approach for manipulating EEC subtypes in behaving mice. We show that multiple EEC subtypes inhibit food intake but have different effects on learning. Conditioned flavor preference is driven by release of cholecystokinin whereas conditioned taste aversion is mediated by serotonin and substance P. These positive and negative valence signals are transmitted by vagal and spinal afferents, respectively. These findings establish a cellular basis for how chemosensing in the gut drives learning about food.

Dopamine subsystems that track internal states.

Food and water are rewarding in part because they satisfy our internal needs1,2. Dopaminergic neurons in the ventral tegmental area (VTA) are activated by gustatory rewards3-5, but how animals learn to associate these oral cues with the delayed physiological effects of ingestion is unknown. Here we show that individual dopaminergic neurons in the VTA respond to detection of nutrients or water at specific stages of ingestion. A major subset of dopaminergic neurons tracks changes in systemic hydration that occur tens of minutes after thirsty mice drink water, whereas different dopaminergic neurons respond to nutrients in the gastrointestinal tract. We show that information about fluid balance is transmitted to the VTA by a hypothalamic pathway and then re-routed to downstream circuits that track the oral, gastrointestinal and post-absorptive stages of ingestion. To investigate the function of these signals, we used a paradigm in which a fluid's oral and post-absorptive effects can be independently manipulated and temporally separated. We show that mice rapidly learn to prefer one fluid over another based solely on its rehydrating ability and that this post-ingestive learning is prevented if dopaminergic neurons in the VTA are selectively silenced after consumption. These findings reveal that the midbrain dopamine system contains subsystems that track different modalities and stages of ingestion, on timescales from seconds to tens of minutes, and that this information is used to drive learning about the consequences of ingestion.

Challenges in modelling the sediment retention ecosystem service to inform an ecosystem account - Examples from the Mitchell catchment in northern Australia.

A systems analysis perspective related to soil science is necessary to achieve many of the sustainability targets articulated by the United Nations Sustainable Development Goals (SDGs). The System of Environmental-Economic Accounting - Ecosystem Accounting (SEEA-EA) framework is the international statistical standard for quantifying both the contributions that ecosystems make to the economy, and the impacts of economic activity on ecosystems. However, due to the difficulty of obtaining empirical data on ecosystem service flows, in many cases such quantification is informed by ecosystem service models. Previous research on the Mitchell catchment, Queensland Australia provided a novel opportunity to quantify the implications of using a model of hillslope erosion and sediment delivery in isolation (as represented in one of the most frequently used ecosystem service models - InVEST), by comparing such estimates against multiple lines of local empirical data, and a more comprehensive representation of locally important erosion and deposition processes through a sediment budget model. Estimates of the magnitude of hillslope erosion modelled using an approach similar to InVEST and the calibrated sediment budget differed by an order of magnitude. If an uncalibrated InVEST-type model was used to inform the relative distribution of erosion magnitude, findings suggest the incorrect erosion process would be identified as the dominant contributor to suspended sediment loads. However, the sediment budget model could only be calibrated using data on sediment sources and sinks that had been collected through sustained research effort in the catchment. A comparable level of research investment may not be available to inform ecosystem service assessments elsewhere. Findings for the Mitchell catchment demonstrate that practitioners should exercise caution when using model-derived estimates of the sediment retention ecosystem service, which have not been calibrated and validated against locally collected empirical data, to inform an ecosystem account and progress towards achieving the SDGs.

Reinforcement learning: Dopamine ramps with fuzzy value estimates.

A new study in reinforcement learning theory shows that extending the temporal difference algorithm to unbiased learning under state uncertainty explains the observed ramping behaviour of dopamine neurons.

Calcium Biofortification of Crops-Challenges and Projected Benefits.

Despite Calcium (Ca) being an essential nutrient for humans, deficiency of Ca is becoming an ensuing public health problem worldwide. Breeding staple crops with higher Ca concentrations is a sustainable long-term strategy for alleviating Ca deficiency, and particular criteria for a successful breeding initiative need to be in place. This paper discusses current challenges and projected benefits of Ca-biofortified crops. The most important features of Ca nutrition in plants are presented along with explicit recommendations for additional exploration of this important issue. In order for Ca-biofortified crops to be successfully developed, tested, and effectively implemented in most vulnerable populations, further research is required.

Increasing the cost-effectiveness of nutrient reduction targets using different spatial scales.

In this paper, we investigate the potential gains in cost-effectiveness from changing the spatial scale at which nutrient reduction targets are set for the Baltic Sea, with particular focus on nutrient loadings from agriculture. The costs of achieving loading reductions are compared across five levels of spatial scale, namely the entire Baltic Sea; the marine basin level; the country level; the watershed level; and the grid square level. A novel highly-disaggregated model, which represents decreases in agricultural profits, changes in root zone N concentrations and transport to the Baltic Sea is used. The model includes 14 Baltic Sea marine basins, 14 countries, 117 watersheds and 19,023 10-by-10 km grid squares. The main result which emerges is that there is a large variation in the total cost of the program depending on the spatial scale of targeting: for example, for a 40% reduction in loads, the costs of a Baltic Sea-wide target is nearly three times lower than targets set at the smallest level of spatial scale (grid square). These results have important implications for both domestic and international policy design for achieving water quality improvements where non-point pollution is a key stressor of water quality.

Motivators and barriers to adoption of Improved Land Management Practices. A focus on practice change for water quality improvement in Great Barrier Reef catchments.

To protect and improve water quality in the Great Barrier Reef, the Queensland Government's Reef 2050 Water Quality Improvement Plan targets that 90% of sugarcane, horticulture, cropping and grazing lands in priority areas be managed using best management practices for sediment, nutrient and pesticides by 2025. Progress towards this target is insufficient and variable across catchments and industries. The motivation to adopt improvements in management practices is heavily influenced by social, economic, cultural and institutional dimensions. In this paper we synthesise the literature on how these human dimensions influence decision making for land management practice and highlight where future investment could be focussed. We highlight that focussing on -1) investigating systems to support landholder decision making under climate uncertainty (risk); 2) generating a better understanding of the extent and drivers of landholder transaction cost; 3) understanding if there are competing 'right' ways to farm; and 4) improving understanding of the social processes, trust and power dynamics within GBR industries and what these means for practice change- could improve practice change uptake in the future.

Single Cell Transcriptomic Analyses Reveal the Impact of bHLH Factors on Human Retinal Organoid Development.

The developing retina expresses multiple bHLH transcription factors. Their precise functions and interactions in uncommitted retinal progenitors remain to be fully elucidated. Here, we investigate the roles of bHLH factors ATOH7 and Neurog2 in human ES cell-derived retinal organoids. Single cell transcriptome analyses identify three states of proliferating retinal progenitors: pre-neurogenic, neurogenic, and cell cycle-exiting progenitors. Each shows different expression profile of bHLH factors. The cell cycle-exiting progenitors feed into a postmitotic heterozygous neuroblast pool that gives rise to early born neuronal lineages. Elevating ATOH7 or Neurog2 expression accelerates the transition from the pre-neurogenic to the neurogenic state, and expands the exiting progenitor and neuroblast populations. In addition, ATOH7 and Neurog2 significantly, yet differentially, enhance retinal ganglion cell and cone photoreceptor production. Moreover, single cell transcriptome analyses reveal that ATOH7 and Neurog2 each assert positive autoregulation, and both suppress key bHLH factors associated with the pre-neurogenic and states and elevate bHLH factors expressed by exiting progenitors and differentiating neuroblasts. This study thus provides novel insight regarding how ATOH7 and Neurog2 impact human retinal progenitor behaviors and neuroblast fate choices.

Land use conversion to improve water quality in high DIN risk, low-lying sugarcane areas of the Great Barrier Reef catchments.

Eutrophication of coastal and nearshore receiving environments downstream of intensive agricultural production areas is a global issue. The Reef 2050 Water Quality Improvement Plan (2017-2022) sets ambitious targets for reducing pollutant loads entering the Great Barrier Reef from contributing agricultural catchments. At a regional scale, the Wet Tropics end-of-catchment target load reduction for dissolved inorganic nitrogen (DIN) is 60% from the 2012-2013 anthropogenic load level. However, not even with the combined efforts of the Reef Regulations (December 2019) mandate and adoption of best practice nutrient management on farm, is it likely that these DIN targets will be reached. Thus, there is a need for innovative and cost-effective approaches to deliver further water quality improvement. Transitioning low-lying, marginal sugarcane land to alternative land uses that require lower or no nitrogen inputs, but still provide farmers with income streams, is a potentially attractive solution. In this study, a multi-criteria analysis was conducted to identify sites suitable for such alternative land uses. The cost-effectiveness of DIN reductions from these land use changes were calculated, accounting for reductions in annuity gross margins and land conversion cost. In certain locations (where conversion costs are low and DIN reductions are high) treatment wetlands and no-input cattle grazing offer cost-effective DIN reduction in the range of 20-26$/kg DIN. This compares favourably with existing agricultural extension-based approaches (c. $50/kg DIN reduction). Ecosystem service wetlands (i.e., wetland restoration for fish production) - again when appropriately situated - offer the prospect of even more cost-effective performance (11-14 $/kg DIN reduction). These results, in conjunction with best management practices, support the premise that alternative land uses are cost-effective options for improving water quality in certain areas of low-lying, low productivity sugarcane land. On-going investments by government in addition to private market funding mechanisms could be appropriate for supporting such land use transitions. These approaches need to be tested and refined via targeted pilot projects, as part of a whole-of-landscape approach to achieve broader reef water quality targets.

Horizontal Cell Feedback to Cone Photoreceptors in Mammalian Retina: Novel Insights From the GABA-pH Hybrid Model.

How neurons in the eye feed signals back to photoreceptors to optimize sensitivity to patterns of light appears to be mediated by one or more unconventional mechanisms. Via these mechanisms, horizontal cells control photoreceptor synaptic gain and enhance key aspects of temporal and spatial center-surround receptive field antagonism. After the transduction of light energy into an electrical signal in photoreceptors, the next key task in visual processing is the transmission of an optimized signal to the follower neurons in the retina. For this to happen, the release of the excitatory neurotransmitter glutamate from photoreceptors is carefully regulated via horizontal cell feedback, which acts as a thermostat to keep the synaptic transmission in an optimal range during changes to light patterns and intensities. Novel findings of a recently described model that casts a classical neurotransmitter system together with ion transport mechanisms to adjust the alkaline milieu outside the synapse are reviewed. This novel inter-neuronal messaging system carries feedback signals using two separate, but interwoven regulated systems. The complex interplay between these two signaling modalities, creating synaptic modulation-at-a-distance, has obscured it's being defined. The foundations of our understanding of the feedback mechanism from horizontal cells to photoreceptors have been long established: Horizontal cells have broad receptive fields, suitable for providing surround inhibition, their membrane potential, a function of stimulus intensity and size, regulates inhibition of photoreceptor voltage-gated Ca2+ channels, and strong artificial pH buffering eliminates this action. This review compares and contrasts models of how these foundations are linked, focusing on a recent report in mammals that shows tonic horizontal cell release of GABA activating Cl- and HCO3 - permeable GABA autoreceptors. The membrane potential of horizontal cells provides the driving force for GABAR-mediated HCO3 - efflux, alkalinizing the cleft when horizontal cells are hyperpolarized by light or adding to their depolarization in darkness and contributing to cleft acidification via NHE-mediated H+ efflux. This model challenges interpretations of earlier studies that were considered to rule out a role for GABA in feedback to cones.

The Tolman-Eichenbaum Machine: Unifying Space and Relational Memory through Generalization in the Hippocampal Formation.

The hippocampal-entorhinal system is important for spatial and relational memory tasks. We formally link these domains, provide a mechanistic understanding of the hippocampal role in generalization, and offer unifying principles underlying many entorhinal and hippocampal cell types. We propose medial entorhinal cells form a basis describing structural knowledge, and hippocampal cells link this basis with sensory representations. Adopting these principles, we introduce the Tolman-Eichenbaum machine (TEM). After learning, TEM entorhinal cells display diverse properties resembling apparently bespoke spatial responses, such as grid, band, border, and object-vector cells. TEM hippocampal cells include place and landmark cells that remap between environments. Crucially, TEM also aligns with empirically recorded representations in complex non-spatial tasks. TEM also generates predictions that hippocampal remapping is not random as previously believed; rather, structural knowledge is preserved across environments. We confirm this structural transfer over remapping in simultaneously recorded place and grid cells.

Vegetation and longitudinal coarse sediment connectivity affect the ability of ecosystem restoration to reduce riverbank erosion and turbidity in drinking water.

It is a substantial challenge to quantify the benefits which ecosystems provide to water supply at scales large enough to support policy making. This study tested the hypothesis that vegetation could reduce riverbank erosion, and therefore contribute to reducing turbidity and the cost of water supply, during a large magnitude flood along a 62 km riparian corridor where land cover differed substantially from natural conditions. Several lines of evidence were used to establish the benefits that vegetation provided to reducing eleven riverbank erosion processes over 1688 observations. The data and analyses confirmed that vegetation significantly reduced the magnitude of the riverbank erosion process which was the largest contributor to total erosion volume. For this process, a 1% increase in canopy cover of trees higher than five metres reduced erosion magnitude by between 2 and 3%. Results also indicate that riverbank erosion was likely to be affected by direct changes to the riparian corridor which influenced longitudinal coarse sediment connectivity. When comparing the impact of these direct changes on a relative basis, sand and gravel extraction was likely to be the dominant contributor to changed erosion rates. The locations where erosion rates had substantially increased were of limited spatial extent and in general substantial change in river form had not occurred. This suggests that the trajectory of river condition and increasing turbidity are potentially reversible if the drivers of river degradation are addressed through an ecosystem restoration policy.