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The efficient preservation of protein in silage for livestock feed is dependent on the rate and extent of proteolysis. Previous research on fresh forage indicated enhanced protein stability in certain Festulolium (ryegrass × fescue hybrids) cultivars compared to ryegrass. This is the first report of an experiment to test the hypothesis that a Lolium perenne × Festuca arundinacea var glaucescens cultivar had reduced proteolysis compared to perennial ryegrass (L. perenne) during the ensiling process. Forages were harvested in May (Cut 2) and August (Cut 4), wilted for 24 h and ensiled in laboratory‐scale silos. Silage was destructively sampled at 0 h, 9 h, 24 h, 48 h, 72 h, 14 days and 90 days post‐ensiling, and dry matter (DM), pH and chemical composition were determined. At Cut 2, there was no difference in crude protein between treatments but ryegrass had higher soluble nitrogen (SN) (P < 0.001) and grass × time interactions (p = 0.03) indicated higher rates of proteolysis. By Cut 4, Festulolium had (5.5% units) higher CP than ryegrass (p < 0.001) but SN did not differ. Ammonia‐N did not differ between silages in either cut. DM differences (11.8% units) between treatments in Cut 4 (v.2.2% in Cut 2) may have masked effects on proteolysis, highlighting the importance of management on silage quality. This was despite higher WSC in ryegrass in both cuts (p < 0.001), with grass × time interactions (Cut 2; p = 0.03) showing slower WSC decline in ryegrass in Cut 4 (p < 0.001). Silage pH values did not differ between grasses in either cut, but grass × time interactions (p < 0.001) showed a slower decline in both ryegrass cuts, resulting in higher (p < 0.05) pH at 24 h and 72 h for Cuts 2 and 4, respectively. Overall, the hypothesis for an enhanced protein stability in Festulolium when ensiled as ruminant feed was evidenced by lower SN but not ammonia‐N in an early‐cut silage with a comparable DM to ryegrass. An experiment tested the hypothesis that a Festulolium had reduced proteolysis compared to perennial ryegrass when ensiled. The benefits of Festulolium silage as ruminant feed were evidenced by lower soluble nitrogen but not ammonia‐N in an early‐cut silage with a comparable DM to ryegrass. [ABSTRACT FROM AUTHOR]

The increasing frequency of droughts and floods on grasslands, due to climate change, increases the risk of soil compaction. Soil compaction affects both soil and forage productivity. Differing grasses may counteract some effects of compaction due to differences in their root architecture and ontogeny. To compare their resilience to soil compaction, three Festulolium (ryegrass and fescue species' hybrids) forage grass cultivars comprising differing root architecture and ontogeny were compared in replicated field plots, together with a ryegrass and tall fescue variety as controls. Pre‐compaction soil and forage properties were determined in spring using > four‐year‐old plots to generate baseline data. Half of each field plot was then artificially compacted using farm machinery. Forage dry matter yield (DMY) was determined over four cuts. After the final harvest, post compaction soil characteristics and root biomass (RB) were compared between grasses in the non‐compacted and compacted soils. Pre‐compaction data showed that soil under Festulolium and ryegrass had similar water infiltration rates, higher than soil under tall fescue plots. Tiller density of the Festulolium at this time was significantly higher than fescue but not the ryegrass control. Forage DMY was significantly lower (p <.001) with compacted soil at the first cut but, by the completion of the growing season, there was no effect of soil compaction on total DMY. Tall fescue had a higher total DMY than other grasses, which all produced similar annual yields. Soil bulk density and penetration resistance were higher, and grass tiller density was lower in compacted soils. Root biomass in compacted soils showed a tendency for Festulolium cv Lp × Fg to have higher RB than the ryegrass at 0–15 cm depth. Overall, findings showed alternative grass root structures provide differing resilience to machinery compaction, and root biomass production can be encouraged without negative impacts on forage productivity. [ABSTRACT FROM AUTHOR]

Motivation: Identifying phenotypes based on high-content cellular images is challenging. Conventional image analysis pipelines for phenotype identification comprise multiple independent steps, with each step requiring method customization and adjustment of multiple parameters. Results: Here, we present an approach based on a multi-scale convolutional neural network (M-CNN) that classifies, in a single cohesive step, cellular images into phenotypes by using directly and solely the images' pixel intensity values. The only parameters in the approach are the weights of the neural network, which are automatically optimized based on training images. The approach requires no a priori knowledge or manual customization, and is applicable to single- or multichannel images displaying single or multiple cells. We evaluated the classification performance of the approach on eight diverse benchmark datasets. The approach yielded overall a higher classification accuracy compared with state-of-the-art results, including those of other deep CNN architectures. In addition to using the network to simply obtain a yes-or-no prediction for a given phenotype, we use the probability outputs calculated by the network to quantitatively describe the phenotypes. This study shows that these probability values correlate with chemical treatment concentrations. This finding validates further our approach and enables chemical treatment potency estimation via CNNs. [ABSTRACT FROM AUTHOR]

High-throughput screening (HTS) is an integral part of early drug discovery. Herein, we focused on those small molecules in a screening collection that have never shown biological activity despite having been exhaustively tested in HTS assays. These compounds are referred to as 'dark chemical matter' (DCM). We quantified DCM, validated it in quality control experiments, described its physicochemical properties and mapped it into chemical space. Through analysis of prospective reporter-gene assay, gene expression and yeast chemogenomics experiments, we evaluated the potential of DCM to show biological activity in future screens. We demonstrated that, despite the apparent lack of activity, occasionally these compounds can result in potent hits with unique activity and clean safety profiles, which makes them valuable starting points for lead optimization efforts. Among the identified DCM hits was a new antifungal chemotype with strong activity against the pathogen Cryptococcus neoformans but little activity at targets relevant to human safety. [ABSTRACT FROM AUTHOR]

An experiment investigated whether the inclusion of chicory (Cichorium intybus) in swards grazed by beef steers altered their performance, carcass characteristics or parasitism when compared to steers grazing perennial ryegrass (Lolium perenne). Triplicate 2-ha plots were established with a chicory/ryegrass mix or ryegrass control. Forty-eight Belgian Blue-cross steers were used in the first grazing season and a core group (n = 36) were retained for finishing in the second grazing season. The experiment comprised of a standardisation and measurement period. During standardisation, steers grazed a ryegrass/white clover pasture as one group. Animals were allocated to treatment on the basis of liveweight, body condition and faecal egg counts (FEC) determined 7 days prior to the measurement period. The measurement period ran from 25 May until 28 September 2010 and 12 April until 11 October 2011in the first and second grazing year. Steers were weighed every 14 days at pasture or 28 days during housing. In the first grazing year, faecal samples were collected for FEC and parasite cultures. At the end of the first grazing year, individual blood samples were taken to determine O. ostertagi antibody and plasma pepsinogen levels. During winter, animals were housed as one group and fed silage. In the second grazing year, steers were slaughtered when deemed to reach fat class 3. Data on steer performance showed no differences in daily live-weight gain which averaged 1.04 kg/day. The conformation, fat grade and killing out proportion of beef steers grazing chicory/ryegrass or ryegrass were not found to differ. No differences in FEC, O. ostertagi antibody or plasma pepsinogen levels of beef steers grazing either chicory/ryegrass or ryegrass were observed. Overall, there were no detrimental effects of including chicory in swards grazed by beef cattle on their performance, carcass characteristics or helminth parasitism, when compared with steers grazing ryegrass. [ABSTRACT FROM AUTHOR]

The National HE STEM Programme has funded the production of a series of guides on transition, induction and retention of students in STEM subjects. The guides cover transition to HE, the first year experience, social engagement, curriculum development to support retention, maths support, optimising the part-time experience, and using data to understand the issues. The paper discusses why the guides were produced and how the project was managed. The literature forming the general background to the project is presented, together with the research underpinning particular guides. The paper summarises the content of each guide, and discusses the lessons learned from the project as a whole. [ABSTRACT FROM AUTHOR]

Typically, screening collections of pharmaceutical companies contain more than a million compounds today. However, for certain high-throughput screening (HTS) campaigns, constraints posed by the assay throughput and/or the reagent costs make it impractical to screen the entire deck. Therefore, it is desirable to effectively screen subsets of the collection based on a hypothesis or a diversity selection. How to select compound subsets is a subject of ongoing debate. The authors present an approach based on extended connectivity fingerprints to carry out diversity selection on a per plate basis (instead of a per compound basis). HTS data from 35 Novartis screens spanning 5 target classes were investigated to assess the performance of this approach. The analysis shows that selecting a fingerprint-diverse subset of 250K compounds, representing 20% of the screening deck, would have achieved significantly higher hit rates for 86% of the screens. This measure also outperforms the Murcko scaffold-based plate selection described previously, where only 49% of the screens showed similar improvements. Strikingly, the 2-fold improvement in average hit rates observed for 3 of 5 target classes in the data set indicates a target bias of the plate (and thus compound) selection method. Even though the diverse subset selection lacks any target hypothesis, its application shows significantly better results for some targets—namely, G-protein-coupled receptors, proteases, and protein-protein interactions—but not for kinase and pathway screens. The synthetic origin of the compounds in the diverse subset appears to influence the screening hit rates. Natural products were the most diverse compound class, with significantly higher hit rates compared to the compounds from the traditional synthetic and combinatorial libraries. These results offer empirical guidelines for plate-based diversity selection to enhance hit rates, based on target class and the library type being screened. [ABSTRACT FROM AUTHOR]

Angiogenesis is crucial for tumor growth. Angiogenesis inhibitors, such as O-(chloracetyl-carbamoyl) fumagillol (TNP-470), are thus emerging as a new class of anticancer drugs. In clinical trials, TNP-470 slowed tumor growth in patients with metastatic cancer. However, at higher doses necessary for tumor regression, many patients experienced neurotoxicity. We therefore synthesized and characterized a water-soluble conjugate of N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer, Gly-Phe-Leu-Gly linker and TNP-470. This conjugate accumulated selectively in tumor vessels because of the enhanced permeability and retention (EPR) effect. HPMA copolymer-TNP-470 substantially enhanced and prolonged the activity of TNP-470 in vivo in tumor and hepatectomy models. Polymer conjugation prevented TNP-470 from crossing the blood-brain barrier (BBB) and decreased its accumulation in normal organs, thereby avoiding drug-related toxicities. Treatment with TNP-470 caused weight loss and neurotoxic effects in mice, whereas treatment with the conjugate did not. This new approach for targeting angiogenesis inhibitors specifically to the tumor vasculature may provide a new strategy for the rational design of cancer therapies. [ABSTRACT FROM AUTHOR]

This work addresses the problem of enriching high throughput screening (HTS) data of mixtures of five compounds/well without any redundancies and where no structural information of the drug target is available. Devising a mathematical model for mixtures of compounds is extremely difficult. Instead, we employed extended-connectivity fingerprints (ECFPs), which are a new class of fingerprints for molecular characterization. We calculated the Tanimoto similarity between all the compounds which appeared in the active mixtures and ranked them in order of decreasing similarity. This methodology enriched the data in three recent in-house HTS campaigns that were conducted in five compounds/well mixtures. The top 10% most similar compounds captured between 29% and 41% of the active compounds. Although this methodology is not particularly sensitive, considering the quality of the data (ca. 80% noise presumed to be inactive) and the simplicity of the method, we find it useful. It offers a true opportunity to quickly prioritize and enrich primary screening data from mixtures of compounds and therefore reduce the time and the high costs of the secondary screening. [ABSTRACT FROM AUTHOR]

An account of group work at a day centre for elderly people which, by using Reminiscence Therapy, tapped into a time when their morale had been high; with some interesting results. [ABSTRACT FROM PUBLISHER]

An introduction is presented that discusses issue articles on topics including control engineering, international engineering students, and programme outcomes for engineering education.

An introduction is presented that discusses issue articles on topics including the use of social media for feedback in engineering courses, the enhancement of student engagement in engineering education, and the use of online testing in engineering courses.

The author introduces the updated appearance of the journal, developed by organization The Higher Education Academy, the revisions to the journal's website, located at journals.heacademy.ac.uk, and acknowledges the 23 reviewers from Great Britain and globally who contributed to the issue.