‘Patches of the endless forest’: monuments, landscape and remote perception in the Early Neolithic of southern Britain

Archaeologists have long noted that Early Neolithic long barrows tend to occupy topographic settings that afford distant views over the landscape, conversely making them conspicuous from particular areas. When Early Neolithic causewayed enclosures were eventually recognized in the 1920s, similar expectations were mapped onto them. From the 1970s, archaeologists increasingly interpreted the visual ‘orientation’ of a particular monument as an indicator of its associated territory. More recently, GIS-based viewshed analysis has facilitated demonstrations of the areas with which specific monuments were potentially intervisible. But this technical advance has impeded more sensitive thinking about the circumstances surrounding acts of vision, often by implying that views were fixed in space and time. This thesis starts from the premise that there is much more to be said about how contemporary lifeways afforded opportunities for remote perception; about the character and extent of Neolithic forest and clearings; and about how circumstances changed through time. In so doing, it offers a more nuanced, holistic and dynamic exploration of remote visual perception. I argue that perceptions of monuments were intimately linked to short-range transhumance – the practice of distancing livestock from crops throughout the summer in forest clearings, with access to water to support dairy production. In largely forested landscapes, monuments would only become visible on the final approach, though heralded by distinctive sounds and smells. Corridors of lower vegetation along watercourses, which herders would probably follow, might afford occasional glimpses of the clearing (as distinct from the monument), represented in upland settings by a 'notch' on the skyline. Over time, grazing would increase the size of clearings, affording more distant reciprocal views. In low-lying regions, watercourses themselves provided summer grazing and boat travel might afford remote views. In short, though monuments were visually linked to specific communities, these links operated in more varied and complex ways than usually acknowledged, and changed through time

Genome-Wide Association and Genomic Selection for Resistance to Amoebic Gill Disease in Atlantic Salmon

Abstract Amoebic gill disease (AGD) is one of the largest threats to salmon aquaculture, causing serious economic and animal welfare burden. Treatments can be expensive and environmentally damaging, hence the need for alternative strategies. Breeding for disease resistance can contribute to prevention and control of AGD, providing long-term cumulative benefits in selected stocks. The use of genomic selection can expedite selection for disease resistance due to improved accuracy compared to pedigree-based approaches. The aim of this work was to quantify and characterize genetic variation in AGD resistance in salmon, the genetic architecture of the trait, and the potential of genomic selection to contribute to disease control. An AGD challenge was performed in ∼1,500 Atlantic salmon, using gill damage and amoebic load as indicator traits for host resistance. Both traits are heritable (h2 ∼0.25-0.30) and show high positive correlation, indicating they may be good measurements of host resistance to AGD. While the genetic architecture of resistance appeared to be largely polygenic in nature, two regions on chromosome 18 showed suggestive association with both AGD resistance traits. Using a cross-validation approach, genomic prediction accuracy was up to 18% higher than that obtained using pedigree, and a reduction in marker density to ∼2,000 SNPs was sufficient to obtain accuracies similar to those obtained using the whole dataset. This study indicates that resistance to AGD is a suitable trait for genomic selection, and the addition of this trait to Atlantic salmon breeding programs can lead to more resistant stocks.</jats:p

Crystal structure of a mixed solvated form of amoxapine acetate

The mixed solvated salt 4-(2-chloro­dibenzo[b,f][1,4]oxazepin-11-yl)piperazin-1-ium acetate-acetic acid-cyclo­hexane (2/2/1), C17H17ClN3O+·C2H3O2-·C2H4O2·0.5C6H12, crystallizes with one mol­ecule of protonated amoxapine (AXPN), an acetate anion and a mol­ecule of acetic acid together with half a mol­ecule of cyclo­hexane. In the centrosymmetric crystal, both enanti­omers of the protonated AXPN mol­ecule stack alternatively along [001]. Acetate anions connect the AXPN cations through N-H...O hydrogen bonding in the [010] direction, creating a sheet lying parallel to (100). The acetic acid mol­ecules are linked to the acetate anions via O-H...O hydrogen bonds within the sheets. Within the sheets there are also a number of C-H...O hydrogen bonds present. The cyclo­hexane solvent mol­ecules occupy the space between the sheets

From discovery to scale-up: alpha-lipoic acid : nicotinamide co-crystals in a continuous oscillatory baffled crystalliser

The crystalline nutritional supplement alpha-lipoic acid degrades rapidly on exposure to temperatures above its melting point 65 degrees C and to light. A small-scale experimental co-crystal screen has produced three novel co-crystals of alpha-lipoic acid that each display enhanced thermal stability and differences in aqueous solubilities compared to alpha-lipoic acid. In each case, the initial screening procedure produced tens of milligrams of material enabling initial identification, characterisation and crystal structure determination. The structure of the alpha-lipoic acid : nicotinamide co-crystal was determined by single crystal X-ray diffraction and used for subsequent phase identification. Scale-up of the co-crystallisation process of alpha-lipoic acid with nicotinamide was then investigated in a continuous oscillatory baffled crystalliser. Over 1 kg of solid co-crystals was produced using a continuous crystallisation process in a continuous oscillatory baffled crystalliser at a throughput of 350 g h-1 yielding a purity of 99% demonstrating this as an effective route to rapid scale-up of a novel co-crystal system

From discovery to scale-up: alpha-lipoic acid : nicotinamide co-crystals in a continuous oscillatory baffled crystalliser

The crystalline nutritional supplement alpha-lipoic acid degrades rapidly on exposure to temperatures above its melting point 65 degrees C and to light. A small-scale experimental co-crystal screen has produced three novel co-crystals of alpha-lipoic acid that each display enhanced thermal stability and differences in aqueous solubilities compared to alpha-lipoic acid. In each case, the initial screening procedure produced tens of milligrams of material enabling initial identification, characterisation and crystal structure determination. The structure of the alpha-lipoic acid : nicotinamide co-crystal was determined by single crystal X-ray diffraction and used for subsequent phase identification. Scale-up of the co-crystallisation process of alpha-lipoic acid with nicotinamide was then investigated in a continuous oscillatory baffled crystalliser. Over 1 kg of solid co-crystals was produced using a continuous crystallisation process in a continuous oscillatory baffled crystalliser at a throughput of 350 g h-1 yielding a purity of 99% demonstrating this as an effective route to rapid scale-up of a novel co-crystal system

Rapid continuous antisolvent crystallization of multi-component systems

This paper describes the application of a novel antisolvent crystallization approach to rapid production of tunable solid solutions of hydrophobic amino acids, comprising L-leucine, L-isoleucine and L-valine. The antisolvent approach provides an alternative to other crystallization routes, e.g., ball-milling, liquid-assisted grinding and slurry methods, to achieve required multi-component solid phases. We report new crystal structures of L-leucine:L-isoleucine and L-leucine:L-valine, and confirm a recent report on a new form of L-isoleucine:L-valine. We used these multi-component complexes as a test set of materials to demonstrate translation of small scale batch antisolvent crystallization to a continuous production process

Impact of paracetamol impurities on face properties : investigating the surface of single crystals using TOF-SIMS

Understanding the mechanism of interaction between pharmaceutical molecules (APIs) and impurities on crystal surfaces is a key concept in understanding purification and for the design of pharmaceutical crystallization processes. Several techniques may be used to study crystal surface properties, such as scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS), which provide detailed imaging and elemental surface characterization. Time of flight secondary ion mass spectrometry (TOF-SIMS) is valuable in determining molecular identity and distribution. By combining TOF-SIMS, SEM, and optical (OM) and Raman microscopies, we can evaluate the usefulness of TOF-SIMS as a surface characterization technique for pharmaceutical crystals. 4-Nitrophenol has been selected as an impurity that can be incorporated during crystallization of acetaminophen (paracetamol). This study explores the distribution of impurity and its concentration on the different crystal faces of samples obtained by crystallization over a range of impurity loadings and supersaturation conditions. Raman maps of paracetamol single crystal faces were analyzed using the characteristic Raman peak intensity of 4-nitrophenol to identify regions where it accumulated; Raman maps of three single crystals produced in the presence of 4-nitrophenol using different crystallization procedures highlight how it can be difficult to detect very low concentrations of similar chemical species. In contrast, the 4-nitrophenol monoisotopic mass obtained via TOF-SIMS was shown to be detectable in all the three single crystals produced. This indicates that TOF-SIMS can be a valuable technique for single crystal impurity distribution mapping even when the impurity concentration is very low

Genome wide association and genomic prediction for growth traits in juvenile farmed Atlantic salmon using a high density SNP array

Background The genetic architecture of complex traits in farmed animal populations is of interest from a scientific and practical perspective. The use of genetic markers to predict the genetic merit (breeding values) of individuals is commonplace in modern farm animal breeding schemes. Recently, high density SNP arrays have become available for Atlantic salmon, which facilitates genomic prediction and association studies using genome-wide markers and economically important traits. The aims of this study were (i) to use a high density SNP array to investigate the genetic architecture of weight and length in juvenile Atlantic salmon; (ii) to assess the utility of genomic prediction for these traits, including testing different marker densities; (iii) to identify potential candidate genes underpinning variation in early growth. Results A pedigreed population of farmed Atlantic salmon (n = 622) were measured for weight and length traits at one year of age, and genotyped for 111,908 segregating SNP markers using a high density SNP array. The heritability of both traits was estimated using pedigree and genomic relationship matrices, and was comparable at around 0.5 and 0.6 respectively. The results of the GWA analysis pointed to a polygenic genetic architecture, with no SNPs surpassing the genome-wide significance threshold, and one SNP associated with length at the chromosome-wide level. SNPs surpassing an arbitrary threshold of significance (P &#60; 0.005, ~ top 0.5 % of markers) were aligned to an Atlantic salmon reference transcriptome, identifying 109 SNPs in transcribed regions that were annotated by alignment to human, mouse and zebrafish protein databases. Prediction of breeding values was more accurate when applying genomic (GBLUP) than pedigree (PBLUP) relationship matrices (accuracy ~ 0.7 and 0.58 respectively) and 5,000 SNPs were sufficient for obtaining this accuracy increase over PBLUP in this specific population. Conclusions The high density SNP array can effectively capture the additive genetic variation in complex traits. However, the traits of weight and length both appear to be very polygenic with only one SNP surpassing the chromosome-wide threshold. Genomic prediction using the array is effective, leading to an improvement in accuracy compared to pedigree methods, and this improvement can be achieved with only a small subset of the markers in this population. The results have practical relevance for genomic selection in salmon and may also provide insight into variation in the identified genes underpinning body growth and development in salmonid species

A rational single particle design approach using an acoustic levitation system and X-ray tomography

The understanding and optimisation of particle morphologies is a common objective for particle engineering approaches either to improve material-handling in the manufacturing process or to influence Critical Quality Attributes (CQAs) linked to product performance. This study demonstrates the rational development of pharmaceutical formulations by conducting single particle experiments to investigate the range of achievable particle attributes across a pragmatic design space. An acoustic levitator was employed to provide a container-less particle design environment for single droplet drying experiments with starting droplet volumes between 10 ul – 80 ul. The temperature and humidity was controlled by an enclosure. The system gave access to characterise the particle formation and subsequent drying process using thermal and high speed imaging techniques. The dried particles were subject to visual and quantitative analysis using nano-focused x-ray tomography to allow a three-dimensional structural description. Extracted morphological descriptors of each particle have been related to solid phase nucleation and growth kinetics. Special emphasis of this study is the evaluation of the solid phase porosity, structural thickness and crystallinity influenced by the solidification from solution and with an impact on key particle performance attributes such as mechanical stability, manufacturability, solubility and solid state stability. Formulations of an active pharmaceutical ingredient with polymeric excipients have been developed to address challenges of a highly crystalline solid with large elongated primary particles. The formulated particles exhibited significantly improved structural modifications leading to an increased mechanical stability, (partially) suppressed crystallinity and tailored dissolution rates. The overall observed diversity of particle properties obtained from single droplet experiments for changing compound systems expressed the importance of an in-depth characterisation of the solidification process prior to process implementation. In summary this study combined the capabilities of an acoustic levitation system and a nano-focused x-ray tomograph to provide a platform to investigate the particle formation and allows a morphological characterisation on a single droplet scale. A comprehensive study enables the development of a mechanistic understanding for a rational particle design approach of novel compound systems targeting critical particle properties influencing particle performance. The fundamental knowledge gained from this method can then be transferred to develop a design space for process applications involving particle formation and drying such as spray drying

6-Methyl-1,3,5-triazine-2,4-diamine butane-1,4-diol monosolvate

The title co-crystal, C4H7N5·C4H10O2, crystallizes with one molecule of 6-methyl-1,3,5-triazine-2,4-diamine (DMT) and one molecule of butane-1,4-diol in the asymmetric unit. The DMT molecules form ribbons involving centrosymmetric R22(8) dimer motifs between DMT molecules along the c-axis direction. These ribbons are further hydrogen bonded to each other through butane-1,4-diol, forming sheets parallel to (121)