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The effects of the consumption of an extract of the brown seaweed Ascophyllum nodosum (BSW) on postprandial glucose and insulin response to white bread were investigated in an acute, randomized, double-blind, three-arm, crossover, controlled trial in healthy, normoglyacemic subjects. Sixteen subjects were administrated either control white bread (50 g total digestible carbohydrates), or white bread with either 500 mg or 1000 mg of BSW extract. Biochemical parameters were measured in venous blood over 3h. Significant inter-individual variation in the glycaemic response to white bread was observed. Analysis of the response of all subjects to either 500 mg or 1000 mg of BSW extract versus control revealed no significant effects of treatments. The variation in response to the control was used to classify individuals into glyacemic responders and non-responders. In the sub-cohort of 10 subjects with peak glucose levels after white bread above 1mmol/L we observed a significant decrease in maximum levels of plasma glucose after the intervention meal with 1000 mg of extract, compared with control. No adverse effects were reported. Further work defining all factors that determine “responders” to the effects of brown seaweed extracts and identify the cohort that would benefit the most from their consumption, is warranted.

Salinity stress is a major problem affecting plant growth and crop productivity. While plant biostimulants have been reported to be an effective solution to tackle salinity stress in different crops, the key genes and metabolic pathways involved in these tolerance processes remain unclear. This study focused on integrating phenotypic, physiological, biochemical and transcriptome data obtained from different tissues of Solanum lycopersicum L. plants (cv. Micro-Tom) subjected to a saline irrigation water program for 61 days (EC: 5.8 dS/m) and treated with a combination of protein hydrolysate and Ascophyllum nodosum-derived biostimulant, namely PSI-475. The biostimulant application was associated with the maintenance of higher K+/Na+ ratios in both young leaf and root tissue and the overexpression of transporter genes related to ion homeostasis (e.g., NHX4, HKT1;2). A more efficient osmotic adjustment was characterized by a significant increase in relative water content (RWC), which most likely was associated with osmolyte accumulation and upregulation of genes related to aquaporins (e.g., PIP2.1, TIP2.1). A higher content of photosynthetic pigments (+19.8% to +27.5%), increased expression of genes involved in photosynthetic efficiency and chlorophyll biosynthesis (e.g., LHC, PORC) and enhanced primary carbon and nitrogen metabolic mechanisms were observed, leading to a higher fruit yield and fruit number (47.5% and 32.5%, respectively). Overall, it can be concluded that the precision engineered PSI-475 biostimulant can provide long-term protective effects on salinity stressed tomato plants through a well-defined mode of action in different plant tissues.

The effects of the consumption of an extract of the brown seaweed Ascophyllum nodosum (BSW) on postprandial glucose and insulin responses to white bread were investigated in an acute, randomized, double-blind, three-arm, crossover, controlled trial in healthy, normoglycemic subjects. Sixteen subjects were administered either control white bread (50 g total digestible carbohydrates) or white bread with 500 mg or 1000 mg of BSW extract. Biochemical parameters were measured in venous blood over 3 h. Significant inter-individual variation in the glycaemic response to white bread was observed. Analysis of the responses of all subjects to either 500 mg or 1000 mg of BSW extract versus control revealed no significant effects of treatments. The variation in response to the control was used to classify individuals into glycaemic responders and non-responders. In the sub-cohort of 10 subjects with peak glucose levels after white bread above 1 mmol/L, we observed a significant decrease in maximum levels of plasma glucose after the intervention meal with 1000 mg of extract compared with the control. No adverse effects were reported. Further work is warranted to define all factors that determine “responders” to the effects of brown seaweed extracts and identify the cohort that would benefit the most from their consumption.

Background and Aims: Besides the crucial role in the treatment of acute ischemic stroke (AIS), mechanical thrombectomy represents a unique opportunity for researchers to study the retrieved clots, with the possibility of unveiling biological patterns linked to stroke pathophysiology and etiology. We aimed to develop a shotgun proteomic approach to study and compare the proteome of formalin-fixed paraffin-embedded (FFPE) cardioembolic and large artery atherosclerotic (LAA) clots. Methods: We used 16 cardioembolic and 15 LAA FFPE thrombi from 31 AIS patients. The thrombus proteome was analyzed by label-free quantitative liquid chromatography-tandem mass spectrometry (LC-MS/MS). MaxQuant v1.5.2.8 and Perseus v.1.6.15.0 were used for bioinformatics analysis. Protein classes were identified using the PANTHER database and the STRING database was used to predict protein interactions. Results: We identified 1,581 protein groups as part of the AIS thrombus proteome. Fourteen significantly differentially abundant proteins across the two etiologies were identified. Four proteins involved in the ubiquitin-proteasome pathway, blood coagulation or plasminogen activating cascade were identified as significantly abundant in LAA clots. Ten proteins involved in the ubiquitin proteasome-pathway, cytoskeletal remodeling of platelets, platelet adhesion or blood coagulation were identified as significantly abundant in cardioembolic clots. Conclusion: Our results outlined a set of 14 proteins for a proof-of-principle characterization of cardioembolic and LAA FFPE clots, advancing the proteome profile of AIS human thrombi and understanding the pathophysiology of ischemic stroke. This publication has emanated from research conducted with the financial support of Science Foundation Ireland (SFI) and is co-funded under the European Regional Development Fund under Grant No. 13/RC/2073_2. Furthermore, the authors declare that this study received funding from Cerenovus. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication. peer-reviewed

Reduction in the emissions of the greenhouse gas nitrous oxide and nitrogen (N) pollution of ground water by improving nitrogen use efficiency (NUE) in crops is urgently required in pursuit of a sustainable agricultural future. Utilising an engineered biostimulant (PSI-362) derived from the brown seaweed Ascophyllum nodosum, we examined its effect on wheat seedling growth dynamics and mechanistic spatiotemporal changes at transcriptional and biochemical levels in relation to N uptake, assimilation and NUE. PSI-362-mediated biomass increase was associated with increased nitrate uptake and N assimilation in the form of glutamate, glutamine, free amino acids, soluble proteins and total chlorophyll. Phenotypical and biochemical analysis were supported by evaluation of differential expression of genetic markers involved in nitrate perception and transport (TaNRT1.1/NPF6.3), and assimilation (TaNR1 and TaNiR1, TaGDH2, TaGoGAT, TaGS1). Finally, a comparative analysis of the PSI-362 and two generic Ascophyllum nodosum extracts (ANEs) demonstrated that the NUE effect greatly differs depending on the ANE biostimulant used. In the current context of climate warming the transition of agriculture to a more sustainable model is urgently required. Application and adoption of precision biostimulants creates an opportunity for sustainable crop management, reduced production cost and environmental pollution, while maintaining yields.

Reduction in the greenhouse gas (GHG) emissions and nitrogen (N) pollution of ground water by improving nitrogen use efficiency (NUE) in crops has become an intensively investigated research topic in pursuit of a more sustainable future. Although, distinct solutions have been proposed there are only a few reports documenting the detailed interplay between observed plant growth dynamics and changes in plant N related transcriptional and biochemical changes. It was previously demonstrated that the application of a formulated biostimulant (PSI-362) derived from Ascophyllum nodosum (ANE) improves N uptake in Arabidopsis thaliana and in barley. In this study, the effect of PSI-362 on the growth dynamics of wheat seedlings was evaluated at different biostimulant and N supplementation rates. Wheat grown on N deficient MS medium was also analysed from the first hour of the treatment until the depletion of the nutrients in the medium 9 days later. During this time the biomass increase measured for PSI-362 treated plants versus untreated controls was associated with increased nitrate uptake, with surplus N assimilated by the biomass in the form of glutamate, glutamine, free amino acids, soluble proteins, and chlorophyll. Phenotypical and biochemical analysis were supported by evaluation of differential expression of genetic markers involved in nitrate perception and transport (TaNRT1.1/NPF6.3), nitrate and nitrite reduction (TaNR1 and TaNiR1) and assimilation (TaGDH2, TaGoGAT, TaGS1). Finally, a comparative analysis of the precision biostimulant PSI-362 and two generic ANEs demonstrated that the NUE effect greatly differs depending on the ANE formulation used.

Intensive agricultural production utilizes large amounts of nitrogen (N) mineral fertilizers that are applied to the soil to secure high crop yields. Unfortunately, up to 65% of this N fertilizer is not taken up by crops and is lost to the environment. To compensate these issues, growers usually apply more fertilizer than crops actually need, contributing significantly to N pollution and to GHG emissions. In order to combat the need for such large N inputs, a better understanding of nitrogen use efficiency (NUE) and agronomic solutions that increase NUE within crops is required. The application of biostimulants derived from extracts of the brown seaweed Ascophyllum nodosum has long been accepted by growers as a sustainable crop production input. However, little is known on how Ascophyllum nodosum extracts (ANEs) can influence mechanisms of N uptake and assimilation in crops to allow reduced N application. In this work, a significant increase in nitrate accumulation in Arabidopsis thaliana 6 days after applying the novel proprietary biostimulant PSI-362 was observed. Follow-up studies in barley crops revealed that PSI-362 increases NUE by 29.85–60.26% under 75% N input in multi-year field trials. When PSI-362 was incorporated as a coating to the granular N fertilizer calcium ammonium nitrate and applied to barley crop, a coordinated stimulation of N uptake and assimilation markers was observed. A key indicator of biostimulant performance was increased nitrate content in barley shoot tissue 22 days after N fertilizer application (+17.9–72.2%), that was associated with gene upregulation of root nitrate transporters (NRT1.1, NRT2.1, and NRT1.5). Simultaneously, PSI-362 coated fertilizer enhanced nitrate reductase and glutamine synthase activities, while higher content of free amino acids, soluble protein and photosynthetic pigments was measured. These biological changes at stem elongation stage were later translated into enhanced NUE traits in harvested grain. Overall, our results support the agronomic use of this engineered ANE that allowed a reduction in N fertilizer usage while maintaining or increasing crop yield. The data suggests that it can be part of the solution for the successful implementation of mitigation policies for water quality and GHG emissions from N fertilizer usage.

Soybean is one of the most valuable commercial crops because of its high protein, carbohydrate, and oil content. The land area cultivated with soybean in subtropical regions, such as Brazil, is continuously expanding, in some instances at the expense of carbon storing natural habitats. Strategies to decrease yield/seed losses and increase production efficiency are urgently required to meet global demand for soybean in a sustainable manner. Here, we evaluated the effectiveness of an Ascophyllum nodosum extract (ANE), SealicitTM, in increasing yields of different soybean varieties, in two geographical regions (Canada and Brazil). In addition, we investigated the potential of SealicitTM to reduce pod shattering at the trials in Brazil. Three different concentrations of SealicitTM were applied to pod shatter-susceptible (SS) UFUS 6901 and shatter-resistant (SR) UFUS 7415 varieties to assess their impact on pod firmness. SS variety demonstrated a significant decrease in pod shattering, which coincided with deregulation of GmPDH1.1 and GmSHAT1–5 expression, genes that determine pod dehiscence, and higher seed weight per pod. SealicitTM application to the SR variety did not significantly alter its inherent pod shatter resistance, but provided higher increases in seed yield at harvest. This yield increase maybe associated with to other yield components stimulated by the biostimulant. This work demonstrates that SealicitTM, which has previously been shown to improve pod firmness in Arabidopsis and selected commercial oilseed rape varieties through IND gene down-regulation, also has the potential to improve pod resistance and seed productivity in soybean, a member of the legume family sharing a similar strategy for seed dispersal.

A novel technique of phytoactive water-soluble chitooligosaccharide (COS) production in low-temperature plasma is described. Design, operation, and control of plasma chemical reactors used to produce COS from the powder of high molecular weight chitosan are presented. The electron beam plasma is strongly non-equilibrium and chemically active, plasma was excited by injecting the scanning electron beam into reaction volume filled with aerosol, containing oxygen and chitosan powder. Plasma chemical processes, responsible for the raw chitosan destruction and techniques of these processes to obtain control of products of optimal molecular weight, are considered. COS, in amounts sufficient for laboratory tests with some plants, were produced. Tests showed that the addition of COS into the liquid growing medium at 0.25 and 1 mg/mL stimulates root growth in Arabidopsis thaliana seedlings (Col-0) by up to 40%, with respect to control plants. Foliar application of these COS formulations at 0.25 mg/mL on tomato plants (cv. Micro-Tom) also resulted in increases between 11.9% and 36% in two important plant productivity indicators (flower and fruit numbers) compared to the control plants. Being environmentally friendly (and resource saving) the electron beam plasma technology of renewable natural biopolymer processing can be considered as a competitive way to produce biostimulants for commercial agriculture.

Type II diabetes is considered the most common metabolic disorder in the developed world and currently affects about one in ten globally. A therapeutic target for the management of type II diabetes is the inhibition of α- glucosidase, an essential enzyme located at the brush border of the small intestinal epithelium. The inhibition of α-glucosidase results in reduced digestion of carbohydrates and a decrease in postprandial blood glucose. Although pharmaceutical synthetic inhibitors are available, these are usually associated with significant gastrointestinal side effects. In the present study, the impact of inhibitors derived from edible brown algae is being investigated and compared for their effect on glycaemic control. Carbohydrate- and polyphenolic-enriched extracts derived from Ascophyllum nodosum, Fucus vesiculosus and Undaria pinnatifida were characterised and screened for their inhibitory effects on maltase and sucrase enzymes. Furthermore, enzyme kinetics and the mechanism of inhibition of maltase and sucrase were determined using linear and nonlinear regression methods. All tested extracts showed a dose-dependent inhibitory effect of α-glucosidase with IC50 values ranging from 0⋅26 to 0⋅47 mg/ml for maltase; however, the only extract that was able to inhibit sucrase activity was A. nodosum, with an IC50 value of 0⋅83 mg/ml. The present study demonstrates the mechanisms in which different brown seaweed extracts with varying composition and molecular weight distribution differentially inhibit α-glucosidase activities. The data highlight that all brown seaweed extracts are not equal in the inhibition of carbohydrate digestive enzymes involved in postprandial glycaemia.

Most vegetable crops are salt sensitive, growing inadequately in salinised soils due to the accumulation of toxic ions from prolonged irrigation regimes. Plant biostimulants are a potential tool that can be used to counteract salinity stress and increase crop yield. The aim of this study was to investigate the ability of the proprietary protein hydrolysate and Ascophyllum nodosum-derived biostimulant PSI-475 to activate salinity stress tolerance responses in plants. After characterising PSI-475 composition, initial biostimulant activity screening was performed using Arabidopsis thaliana. PSI-475 stimulated primary root growth (+5.5–20.0%) and photosynthetic pigments content (18.8–63.0%) under unstressed and salinity stressed conditions. Subsequently, PSI-475 was assessed by foliar application on tomato plants (cv. Micro-Tom) that received a saline irrigation water program, which caused a significant decrease in fruit yield (−37.5%). Stressed plants treated with PSI-475 increased this parameter by 31.8% versus the stressed control. Experimental data suggest that PSI-475 can alleviate the negative effects of saline irrigation by improving osmotic adjustment and ion homeostasis markers. PSI-475 was also able to provide significant yield benefits in unstressed plants (+16.9%) that were associated with improved leaf biochemical markers. The data presented support the use of this precision biostimulant to target the negative effects of salinity stress from irrigation.

Nitrogen (N) is the most important macronutrient used in modern agricultural systems to enhance crop yields; however, a significant amount of applied N is not taken up by the crop and is lost to the environment. Improving the nitrogen use efficiency (NUE) of crops can curb these environmental losses while concurrently delivering economic gains. Plant biostimulants have potential to improve NUE in agronomic settings. In this research, a granular N-containing fertilizer coated with the biostimulant PSI-362, an extract from the brown seaweed Ascophyllum nodosum, was applied to grass managed under different production systems to assess its impact on NUE. The role of soil type, pH, phosphorus (P) and potassium (K) on the efficacy of the biostimulant in improving NUE was assessed using lysimeters filled with six different soils. A significant increase in grass yield (29%) was found with PSI-362 addition at a 75% N rate over the 75% N control (8478 kg of dry matter (DM) ha−1 vs. 6772 kg of DM ha−1) over two years of trials under a simulated grazing platform of six rotations. The NUE increased to 96.6% for the PSI-362-treated grass compared to 82.8% for controls. Field-based evaluations demonstrated no decrease in yield and quality from harvested and grazed grass treated with the biostimulant when the N rate was reduced by 20 to 25%. Based on these results, the application of PSI-362 allows a reduction in nitrogen input by up to 25% without losses of grass yield or quality.

The application of biostimulants derived from extracts of the brown seaweed Ascophyllum nodosum has long been accepted by growers to have productivity benefits in stressed crops. The impact of the processing method of the A. nodosum biomass is also known to affect compositional and physicochemical properties. However, the identification of the mechanisms by which processing parameters of Ascophyllum nodosum extracts (ANEs) affect biostimulant performance in abiotically stressed crops is still poorly understood. In this study, we performed a comparative analysis of two carbohydrate-rich formulations derived from A. nodosum: C129, an ANE obtained at low temperatures through a gentle extraction and the novel proprietary PSI-494 extracted under high temperatures and alkaline conditions. We tested the efficiency of both ANEs in unstressed conditions as well as in mitigating long-term moderate heat stress in tomato (Lycopersicon esculentum, cv. Micro Tom) during the reproductive stage. Both ANEs showed significant effects on flower development, pollen viability, and fruit production in both conditions. However, PSI-494 significantly surpassed the heat stress tolerance effect of C129, increasing fruit number by 86% compared to untreated plants growing under heat stress conditions. The variation in efficacy was associated with different molecular mass distribution profiles of the ANEs. Specific biochemical and transcriptional changes were observed with enhanced thermotolerance. PSI-494 was characterized as an ANE formulation with lower molecular weight constituents, which was associated with an accumulation of soluble sugars, and gene transcription of protective heat shock proteins (HSPs) in heat stressed tomato flowers before fertilization. These findings suggest that specialized ANE biostimulants targeting the negative effects of periods of heat stress during the important reproductive stage can lead to significant productivity gains.

Prevalence of type 2 diabetes mellitus has significantly increased in the last three decades and currently affects about 1 in 10 globally. A common therapeutic target for type 2 diabetes is α- glucosidase, an essential enzyme located at the brush border of the small intestinal epithelium. The inhibition of α-glucosidase results in a reduced digestion of carbohydrates and a decrease of postprandial blood glucose. Although, synthetic inhibitors are available in the market, these are usually associated with significant gastrointestinal side effects. In this study, natural inhibitors derived from edible brown algae are being investigated as an alternative.Polysaccharide- and polyphenolic-enriched extracts from Ascophyllum nodosum and Fucus vesiculosus were characterized and screened for their inhibitory effects against α-glucosidase obtained from rat intestine using maltose, sucrose, and p-nitrophenyl (pNPG) as substrates. Acarbose was used as a synthetic inhibitor. Furthermore, enzyme kinetics and mechanism of inhibition of α- glucosidase were determined using linear and non-linear regression methods (GraphPad Prism ver. 6, GraphPad Software, La Jolla California USA).All tested extracts showed a dose-dependent inhibitory effect against α-glucosidase. However, the type of inhibition varied between the extracts. Most importantly, the composition analysis showed that the seaweed extracts had different polysaccharide and phenolic contents, suggesting different mode of actions against α-glucosidase. The relation between chemical composition and inhibitory activity of the compounds are discussed.In summary, the current study demonstrates the mechanisms in which different brown seaweed extracts with various composition effectively inhibit α-glucosidase. Therefore, this natural inhibitor can be considered as a potential candidate for the management of type 2 diabetes mellitus.

Objectives Timely implementation of influenza infection control and treatment can significantly reduce the impact on Hospital resources and patient management when demand is at peak. Turnaround times of Laboratory based screening tests for the diagnosis of influenza may have an impact on the implementation of infection control measures and treatment. In this study the objectives included determining the correlation between the Abbott ID NOW point-of-care testing (POCT) instrument using the Influenza A&B2 test and the laboratory based GeneXpert Flu+RSV kit. In addition the impact of the POCT instrument on the prescription of antivirals and antibiotics was evaluated by comparing with practice when the instrument was not in place. Results The results of the correlation study with a cohort of 54 patients revealed the Abbott ID NOW POCT has 92% sensitivity for the detection of Influenza A, while specificity was 100% for both Influenza A and B. The impact of the POCT instrument on the frequency of prescription of antivirals and amount of antibiotics consumed (33% reduction in antibiotic consumption in a cohort of 65 (2017) and 61 (2018)) was significant. In addition the average patient length of Hospital stay was significantly reduced from 5.26 days to 3.73 days.

The yield of podded crops such as oilseed rape (OSR) is limited by evolutionary adaptations of the plants for more efficient and successful seed dispersal for survival. These plants have evolved dehiscent dry fruits that shatter along a specifically developed junction at carpel margins. A number of strategies such as pod sealants, GMOs and hybrids have been developed to mitigate the impact of pod shatter on crop yield with limited success. Plant biostimulants have been shown to influence plant development. A challenge in plant biostimulant research is elucidating the mechanisms of action. Here we have focused on understanding the effect of an Ascophyllum nodosum based biostimulant (Sealicit) on fruit development and seed dispersal trait in Arabidopsis and OSR at genetic and physiological level. The results indicate that Sealicit is affecting the expression of the major regulator of pod shattering, INDEHISCENT, as well as disrupting the auxin minimum. Both factors influence the formation of the dehiscence zone and consequently reduce pod shattering. Unravelling the mode of action of this unique biostimulant provides data to support its effectiveness in reducing pod shatter and highlights its potential for growers to increase seed yield in a number of OSR varieties.

Chitosans with defined characteristics have been shown to possess reproducible bioactivities for numerous applications. A promising approach for producing chitosans with defined degrees of polymerization (DP), degrees of acetylation (DA), and patterns of acetylation (PA) involves using chitin-modifying enzymes. One such enzyme, the chitinase Tv-ECH1 belonging to the glycoside hydrolase (GH) family 18, seems to have an important role in the biocontrol properties of the fungus Trichoderma virens, suggesting its potential in generating novel chitosans for plant health applications. In this study, the Tv-ECH1 enzyme was overexpressed in the methylotrophic yeast Pichia pastoris, yielding large amounts (up to 2mgmL-1) of purified recombinant enzyme of high activity, high purity, and high stability, making the system promising for industrial production of Tv-ECH1. The purified Tv-ECH1 chitinase displayed a wide optimal pH range from 4.5 to 6 and an optimal temperature of 37°C. Detailed subsite specificity analyses revealed high preference for acetylated residues at all four subsites analyzed (-2, -1, +1, +2), making Tv-ECH1 a promising candidate for the biotechnological production of specific chitosan oligomers and for the characterization of chitosan polymers via enzymatic fingerprinting.

Global changes in climate are leading to increased occurrence and duration of drought episodes with concurrent reduction in crop yields. Expansion of the irrigated land area does not appear to be a viable solution in many regions to deliver crop productivity. The development of crop drought tolerance traits by either genetic modification or plant breeding represent the principal approaches to meeting this challenge to date. Biostimulants are an emerging category of crop management products which can enhance crop productivity under abiotic stress conditions. The ability of some biostimulant products such as Ascophyllum nodosum extracts (ANE) to enhance the tolerance of crops to drought stress has been observed by growers. The objective of this study was to investigate if different commercial ANE biostimulants provided the same tolerance to tomato plants (cv. Moneymaker) subjected to a defined drought period. A compositional characterisation of the key macromolecules of ANEs was performed. In addition, the role of ANE biostimulants in inducing changes of chlorophyll and osmolytes levels, MDA production, dehydrin isoform pattern and dehydrin gene expression levels was assessed. The three ANE biostimulants evaluated were found to provide different levels of tolerance to drought stressed tomato plants. The level of drought tolerance provided was related to changes in the concentration of osmolytes and expression of tas14 dehydrin gene. Taken together, our results highlight that despite the fact all ANE biostimulants were manufactured from the same raw material, their ability to maintain crop productivity during and after drought stress was not the same.

Advanced diagnostics are enabling cancer treatments to become increasingly tailored to the individual through developments in immunotherapies and targeted therapies. However, long turnaround times and high costs of molecular testing hinder the widespread implementation of targeted cancer treatments. Meanwhile, gold-standard histopathological assessment carried out by a trained pathologist is widely regarded as routine and mandatory in most cancers. Recently, methods have been developed to mine hidden information from histopathological slides using deep learning applied to scanned and digitized slides; deep learning comprises a collection of computational methods which learn patterns in data in order to make predictions. Such methods have been reported to be successful in a variety of cancers for predicting the presence of biomarkers such as driver mutations, tumour mutational burden, and microsatellite instability. This information could prove valuable to pathologists and oncologists in clinical decision making for cancer treatment and triage for in-depth sequencing. In addition to identifying molecular features, deep learning has been applied to predict prognosis and treatment response in certain cancers. Despite reported successes, many challenges remain before the clinical implementation of such diagnostic strategies in the clinical setting is possible. This review aims to outline recent developments in the field of deep learning for predicting molecular genetics from histopathological slides, as well as to highlight limitations and pitfalls of working with histopathology slides in deep learning.

The use of biostimulants to enhance crop productivity is beginning to be adopted into mainstream agricultural practice. There is an emerging consensus on the critical role that low-cost and scalable chitosan oligosaccharide production systems can play in meeting the demands of this “greener” approach in agriculture. The objective of our research was to produce chitosan oligosaccharides (CHOS) mixtures that can work as plant biostimulants using cost effective enzymes. Commercial chitosans with a consistent formulation and available in bulk were used in the study. Chitosans were characterized in terms of degree of N-acetylation (pH-metric titration) and molecular weight (Ubbelohde viscometer). The yield of the CHOS were determined along with their physicochemical characteristics. The biological activity of the different CHOS mixtures were evaluated for efficacy against a fungal pathogen (F. oxysporum) in the susceptible tomato cultivar ‘Moneymaker’. The performance of some CHOS resulted in significant enhancements in a number of plant health indicators such as increased biomass, disease control and induction of ISR markers. Finally, the optimal CHOS preparation in terms of plant bioactivity was scaled up and validated by a preliminary field trial with the industrial tomato cultivar ‘H9661’. The effectiveness of this treatment on crop productivity was consistent with the results observed in the lab and similar to other commercial plant biostimulants.

Deep learning has become a key workload in the data centre and edge leading to an arms race for compute dominance in this space. FPGAs have shown they can compete by combining deterministic low-latency with high throughput and flexibility. In particular, due to FPGAs' bit-level programmability, FPGAs can efficiently implement arbitrary precisions and numeric data types which is critical to fast evolving fields like deep learning. In this work, we explore minifloat (floating point representations with non-standard exponent and mantissa sizes) implementations on the FPGA, and show how we use a block floating point implementation that shares the exponent across many numbers to reduce the required logic to perform floating point operations. We will show that using this technique we can significantly improve the performance of the FPGA with no impact to accuracy. Using this approach, we show how we can reduce logic utilization by 3x, and memory bandwidth and capacity required by more than 40%.

Overlays have shown significant promise for field-programmable gate-arrays (FPGAs) as they allow for fast development cycles and remove many of the challenges of the traditional FPGA hardware design flow. However, this often comes with a significant performance burden resulting in very little adoption of overlays for practical applications. In this paper, we tailor an overlay to a specific application domain, and we show how we maintain its full programmability without paying for the performance overhead traditionally associated with overlays. Specifically, we introduce an overlay targeted for deep neural network inference with only ~1% overhead to support the control and reprogramming logic using a lightweight very-long instruction word (VLIW) network. Additionally, we implement a sophisticated domain specific graph compiler that compiles deep learning languages such as Caffe or Tensorflow to easily target our overlay. We show how our graph compiler performs architecture-driven software optimizations to significantly boost performance of both convolutional and recurrent neural networks (CNNs/RNNs) - we demonstrate a 3x improvement on ResNet-101 and a 12x improvement for long short-term memory (LSTM) cells, compared to naive implementations. Finally, we describe how we can tailor our hardware overlay, and use our graph compiler to achieve ~900 fps on GoogLeNet on an Intel Arria 10 1150 - the fastest ever reported on comparable FPGAs., Comment: Accepted in the International Conference on Field-Programmable Logic and Applications (FPL 2018)

After decades of research, High-Level Synthesis has finally caught on as a mainstream design technique for FPGAs. However, achieving performance results that are comparable to designing at a hardware description level still remains a challenge. In this talk, we illustrate how we achieve world class performance results on HPC applications by using OpenCL. Specifically, we show how we achieve 1Tflop of performance on a matrix multiply and over 1.3Tflops on a CNN application, run on Intel's 20nm Arria 10 FPGA device. By leveraging specific coding styles, we show how you can achieve peak performance on the FPGA without having to resort to tedious hardware design languages. Finally, we will describe spatial coding techniques that lead to efficient structures, such as systolic-arrays, to ensure that the FPGA runs efficiently.

Convolutional neural nets (CNNs) have become a practical means to perform vision tasks, particularly in the area of image classification. FPGAs are well known to be able to perform convolutions efficiently, however, most recent efforts to run CNNs on FPGAs have shown limited advantages over other devices such as GPUs. Previous approaches on FPGAs have often been memory bound due to the limited external memory bandwidth on the FPGA device. We show a novel architecture written in OpenCL(TM), which we refer to as a Deep Learning Accelerator (DLA), that maximizes data reuse and minimizes external memory bandwidth. Furthermore, we show how we can use the Winograd transform to significantly boost the performance of the FPGA. As a result, when running our DLA on Intel's Arria 10 device we can achieve a performance of 1020 img/s, or 23 img/s/W when running the AlexNet CNN benchmark. This comes to 1382 GFLOPs and is 10x faster with 8.4x more GFLOPS and 5.8x better efficiency than the state-of-the-art on FPGAs. Additionally, 23 img/s/W is competitive against the best publicly known implementation of AlexNet on nVidia's TitanX GPU.

Traditional estimation techniques significantly under-call the true monetary value of the resource on which mine plans and operations base their business. At the Olympic Dam, this is worth billions of dollars. Realising this value requires mine planning engineers to be supplied with an accurate recoverable resource model that correctly estimates the tonnes and grade for a specified support and timescale, at the time of mining.

The work investigates the application of ultrasound for improved extraction of bioactive compounds namely total phenolics, fucose, and uronic acid from brown seaweed (Ascophyllum nodosum). Key process parameters of ultrasonic intensity (UI), extraction time, and solvent type were investigated to optimize extraction yields. The maximum yields on dry basis (db) of total phenolics, fucose, and uronic acid were 82.70 mg GAE/gdb, 135.76 mg/gdb, and 197.19 mg/gdb, respectively. Maximum bioactive yields were obtained using 0.03 M HCl as solvent at an UI of 75.78 W cm−2. Extraction kinetics over a 22 hour period were successfully modelled using Peleg’s model. This extraction kinetic study demonstrates that ultrasound pretreatment can significantly enhance extraction of bioactives from brown seaweed.

Biostimulants for crop management are gaining increased attention with continued demand for increased crop yields. Seaweed extracts represent one category of biostimulant, with Ascophyllum nodosum extracts (ANE) widely used for yield and quality enhancement. This study investigated how the composition of two ANE biostimulants (ANE A and ANE B) affects plant mRNA transcriptomes, using the model plant Arabidopsis thaliana. Using Affymetrix Ath1 microarrays, significant heterogeneity was detected between the ANE biostimulants in terms of their impacts on the mRNA transcriptome of A. thaliana plants, which accumulated significantly more biomass than untreated controls. Genes dysregulated by the ANE biostimulants are associated with a wide array of predicted biological processes, molecular functions, and subcellular distributions. ANE A dysregulated 4.47% of the transcriptome, whereas ANE B dysregulated 0.87%. The compositions of both ANEs were significantly different, with a 4-fold difference in polyphenol levels, the largest observed. The standardization of the composition of ANE biostimulants represents a challenge for providing consistent effects on plant gene expression and biostimulation.

Beta-galactosidase is an enzyme administered as a digestive supplement to treat lactose intolerance, a genetic condition prevalent in most world regions. The gene encoding an acid-stable beta-galactosidase potentially suited for use as a digestive supplement was cloned from Aspergillus niger van Tiegh, sequenced and expressed in Pichia pastoris. The purified recombinant protein exhibited kinetic properties similar to those of the native enzyme and thus was also competitively inhibited by its product, galactose, at application-relevant concentrations. In order to alleviate this product inhibition, a model of the enzyme structure was generated based on a Penicillium sp. beta-galactosidase crystal structure with bound beta-galactose. This led to targeted mutagenesis of an Asp(258)-Ser-Tyr-Pro-Leu-Gly-Phe amino acid motif in the A. niger van Tiegh enzyme and isolation from the resultant library of a mutant beta-galactosidase enzyme with reduced sensitivity to inhibition by galactose (K (i) of 6.46 mM galactose, compared with 0.76 mM for the wildtype recombinant enzyme). The mutated enzyme also exhibited an increased K (m) (3.76 mM compared to 2.21 mM) and reduced V (max) (110.8 micromol min(-1) mg(-1) compared to 172.6 micromol min(-1) mg(-1)) relative to the wild-type enzyme, however, and its stability under simulated fasting gastric conditions was significantly reduced. The study nevertheless demonstrates the potential to rationally engineer the A. niger van Tiegh enzyme to relieve product inhibition and create mutants with improved, application-relevant kinetic properties for treatment of lactose intolerance.

Extracellular beta-galactosidase produced by a strain of Aspergillus niger van Tiegh was purified to homogeneity using a combination of gel filtration, ion-exchange, chromatofocusing, and hydrophobic interaction chromatographies. The enzyme displayed a temperature optimum of 65 degrees C and a low pH optimum of between 2.0 and 4.0. The monomeric glycosylated enzyme displayed a molecular mass of 129 kDa and an isoelectric point of 4.7. Protein database similarity searching using mass spectrometry-derived sequence data indicate that the enzyme shares homology with a previously sequenced A. niger beta-galactosidase. Unlike currently commercialised products, the enzyme displayed a high level of stability when exposed to simulated gastric conditions in vitro, retaining 68+/-2% of original activity levels. This acid-stable, acid-active beta-galactosidase was formulated, along with a neutral beta-galactosidase from Kluyveromyces marxianus DSM5418, in a novel two-segment capsule system designed to ensure delivery of enzymes of appropriate physicochemical properties to both stomach and small intestine. When subjected to simulated full digestive tract conditions, the twin lactase-containing capsule hydrolyzed, per unit activity, some 3.5-fold more lactose than did the commercial supplemental enzyme. The acid-stable, acid-active enzyme, along with the novel two-segment delivery system, may prove beneficial in the more effective treatment of lactose intolerance.

Functional-based screening of crude beta-galactosidase activities from 42 yeast strains resulted in the selection of a single enzyme of potential interest as a digestive supplement. beta-Galactosidase produced by Kluyveromyces marxianus DSM5418 was purified to homogeneity by a combination of gel filtration, ion-exchange, and hydroxylapatite chromatographies. The denatured (123 kDa) and native molecular masses (251 kDa) suggest that the enzyme is a homodimer. The optimum pH and temperature of the purified enzyme were 6.8 and 37 degrees C, respectively. The unpurified beta-galactosidase in particular displayed a high level of stability when exposed to simulated intestinal conditions in vitro for 4 h. Matrix-assisted laser desorption ionization mass sectrometry analysis revealed that the enzyme's trypsin-generated peptide mass fingerprint shares several peptide fragment hits with beta-galactosidases from Kluyveromyces lactis. This confirms the enzyme's identity and indicates that significant sequence homology exists between these enzymes.

The search for new antioxidants of natural origin derived from plants and seaweeds is still very important at present. In our study, the acetone extract of A. nodosum was investigated for its potential use as a natural antioxidant, natural feed additive with antibacterial activity and as a tyrosinase inhibitor. This study could be useful in the context of improved utilization of the A. nodosum extract in the food and cosmetics industry, being not only economically advantageous but also environmentally friendly. Extracts showed antioxidant activity with application of different methodologies: 1,1-diphenyl-2-picrilhydracil DPPH· radicals scavenging (39 %, 4 mg of freeze-dried sample), β-carotene-linoleic acid antioxidant assay (11 %, 4 mg of freeze-dried sample), O2· radicals scavenging activity (IC50 0.43 mg mL−1), OH· radicals scavenging activity (IC50 1.55 mg mL−1), and iron chelation ability (IC50 0.56 mg mL−1). The extract showed considerable antibacterial activity being more effective against gram-positive bacteria (Micrococcus luteus, Staphylococcus aureus) than against gram-negative bacteria (Escherichia coli, Enterococcus aerogenes). Results of tyrosinase assay for the acetone extract of Ascophyllum nodosum presented 65.6 % inhibition of tyrosinase activity at the IC50 value of 0.1 mg mL−1. The outcomes of our study support potential utilization of this brown seaweed as a source of natural antioxidants. Antioxidant activity of the studied seaweed can be apparently explained by the free radicals scavenging activity, particularly related to the mechanisms of O 2 − · radicals scavenging activity, OH· radicals inactivation, and iron chelation ability.

The increasing concerns launched by debates about climate changes added to the uncontrolled growth of world population have opened a market to natural inputs for a more sustainable agriculture. Taking those concerns together, it is very important to think in advance in terms of finding solutions to increase the food production, with improved quality and in a supposed changing environment. Natural substances such as seaweed biostimulants are coming up as inputs for crops yield and abiotic stress tolerance enhancement with increasing use in agriculture. In this scene, it is important to understand effects and mode of action of these substances on plant physiology to permit the development of consistent products and guarantee the delivery of solutions to growers that assist them in solving their needs. Therefore, this research was carried out aiming to understand the role of agrochemicals (classical plant growth regulators and seaweed biostimulants) on root development and hormonal relations of tomato \'Micro-Tom\' and Arabidopsis under water deficit conditions. Ascophyllum nodosum extracts (ANE) ability to stimulate endogenous hormonal responses in conditions of drought and osmotic stress was tested. We carried out experiments with two plant models: one is classically used in plant science studies and the other, a crop-like plant model whose scientific findings can be applied for several crops. We used tomato hormonal mutants and reporter lines grown in conditions of drought stress to study the effects of plant growth regulators and seaweed extracts on root growth and hormonal responses, respectively. Additionally, we tested in vitro the effects of these substances on root growth of Arabidopsis seedlings under osmotic stress conditions. The root development of tomato and Arabidopsis was negatively affected by the presence of water deficit caused by drought and osmotic stress, respectively. Gibberellins biosynthesis inhibitors only affected the root growth of gibberellin-deficient mutant (gib-3). Extracts of the same seaweed presented different effects on root growth of Arabidopsis seedlings and hormonal responsiveness in roots of tomato, possibly due to variability in their compositions. ANE A and B show opposite effects on root growth. ANE A promotes root growth, whereas ANE B shows inhibitory effects. These substances seem to have little influence on auxin responses in roots, however, they alter the balance between abscisic acid and ethylene under drought conditions. The standardization of the composition of seaweed extracts complemented with studies on their physiological and molecular effects in crops is crucial for the establishment of these agricultural inputs as one of the solutions for current and future requirements of food production. As crescentes preocupações oriundas a partir dos atuais debates sobre mudanças climáticas somadas ao descontrolado crescimento da população mundial têm dado espaço para o uso de insumos agrícolas naturais, objetivando sustentabilidade na agricultura. Diante de tais preocupações, é importante pensar antecipadamente e encontrar maneiras de aumentar a produção e a qualidade de alimentos, em um ambiente de supostas mudanças climáticas. Substâncias naturais, como bioestimulantes à base de alga, estão ganhando relevância como melhoradores da produtividade e tolerância a estresses abióticos com crescentes usos na agricultura. Diante desse cenário, é importante compreender os efeitos e modos de ação dessas substâncias na fisiologia das plantas para permitir o desenvolvimento de produtos consistentes e garantir aos produtores soluções que atendam às suas necessidades. Portanto, este estudo foi realizado com o objetivo de entender o papel de agroquímicos (reguladores vegetais clássicos e biostimulantes à base da alga) sobre o desenvolvimento radicular e relações hormonais do tomateiro \'Micro-Tom\' e Arabidopsis sob condições de estresse hídrico. Foi testada a habilidade de extratos Ascophyllum nodosum (ANE) em estimular respostas hormonais em condições de seca e estresse osmótico. Foram realizados experimentos com duas plantas-modelo: Arabidopsis que é largamente utilizada em estudos científicos de plantas e o tomateiro \'Micro-Tom\', uma planta-modelo mais adequada para estudos aplicados à agricultura sob condições tropicais. Foram utilizados mutantes hormonais e linhas-repórter de tomate cultivadas em condições de seca para o estudo dos efeitos dos reguladores vegetias e extratos de alga no crescimento radicular e respostas hormonais, respectivamente. Além disso, foram testados in vitro os efeitos dessas substâncias no crescimento radicular de plântulas de Arabidopsis em condições de estresse osmótico. O desenvolvimento radicular do tomateiro e Arabidopsis foi negativamente afetado pela ocorrência do déficit hídrico causado por seca e estresse osmótico, respectivamente. Inibidores de giberelinas afetaram apenas o crescimento radicular do mutante com baixo nível endógeno giberelinas (gib-3). Extratos da mesma espécie de alga apresentaram diferentes efeitos no crescimento radicular de plântulas de Arabidopsis e resposta hormonal em raízes de tomateiro. ANE A e B aprensenta efeitos opostos no desenvolvimento de raízes. ANE A promove o crescimento radicular enquanto ANE A inibe. ANEs pouco influenciam as respostas auxínicas, contudo, essas substâncias alteram o balanço entre entre ácido abscísico e etileno sob condições de estresse hídrico por seca. A padronização da composição de extratos de alga somada aos estudos sobre os seus efeitos fisiológicos e moleculares em culturas é crucial para o estabelecimento desses insumos agrícolas como uma das soluções para as necessidades atuais e futuras da produção de alimentos.