Genetic diversity of red-fleshed apples (Malus)

Anthocyanins are flavonoid pigments imparting red, blue, or purple pigmentation to fruits, flowers and foliage. These compounds are powerful antioxidants in vitro, and are widely believed to contribute to human health. The fruit of the domestic apple (Malus x domestica) is a popular and important source of nutrients, and is considered one of the top ‘functional foods’—those foods that have inherent health-promoting benefits beyond basic nutritional value. The pigmentation of typical red apple fruits results from accumulation of anthocyanin in the skin. However, numerous genotypes of Malus are known that synthesize anthocyanin in additional fruit tissues including the core and cortex (flesh). Red-fleshed apple genotypes are an attractive starting point for development of novel varieties for consumption and nutraceutical use through traditional breeding and biotechnology. However, cultivar development is limited by lack of characterization of the diversity of genetic backgrounds showing this trait. We identified and cataloged red-fleshed apple genotypes from four Malus diversity collections representing over 3,000 accessions including domestic cultivars, wild species, and named hybrids. We found a striking range of flesh color intensity and pattern among accessions, including those carrying the MYB10 R 6 allele conferring ectopic expression of a key transcriptional regulator of anthocyanin biosynthesis. Although MYB10 R 6 was strongly associated with red-fleshed fruit among genotypes, this allele was neither sufficient nor required for this trait in all genotypes. Nearly all red-fleshed accessions tested could be traced back to ‘Niedzwetzkyana’, a presumed natural form of M. sieversii native to central Asia.

Pathogenic LRRK2 mutations do not alter gene expression in cell model systems or human brain tissue

Point mutations in LRRK2 cause autosomal dominant Parkinson's disease. Despite extensive efforts to determine the mechanism of cell death in patients with LRRK2 mutations, the aetiology of LRRK2 PD is not well understood. To examine possible alterations in gene expression linked to the presence of LRRK2 mutations, we carried out a case versus control analysis of global gene expression in three systems: fibroblasts isolated from LRRK2 mutation carriers and healthy, non-mutation carrying controls; brain tissue from G2019S mutation carriers and controls; and HEK293 inducible LRRK2 wild type and mutant cell lines. No significant alteration in gene expression was found in these systems following correction for multiple testing. These data suggest that any alterations in basal gene expression in fibroblasts or cell lines containing mutations in LRRK2 are likely to be quantitatively small. This work suggests that LRRK2 is unlikely to play a direct role in modulation of gene expression, although it remains possible that this protein can influence mRNA expression under pathogenic cicumstances.

Adsorption of organic molecules at the TiO2(110) surface: the effect of van der Waals interactions

Understanding the interaction of organic molecules with TiO2 surfaces is important for a wide range of technological applications. While density functional theory (DFT) calculations can provide valuable insight about these interactions, traditional DFT approaches with local exchange-correlation functionals suffer from a poor description of non-bonding van der Waals (vdW) interactions. We examine here the contribution of vdW forces to the interaction of small organic molecules (methane, methanol, formic acid and glycine) with the TiO2 (110) surface, based on DFT calculations with the optB88-vdW functional. The adsorption geometries and energies at different configurations were also obtained in the standard generalized gradient approximation (GGA-PBE) for comparison. We find that the optB88-vdW consistently gives shorter surface adsorbate-to-surface distances and slightly stronger interactions than PBE for the weak (physisorbed) modes of adsorption. In the case of strongly adsorbed (chemisorbed) molecules both functionals give similar results for the adsorption geometries, and also similar values of the relative energies between different chemisorption modes for each molecule. In particular both functionals predict that dissociative adsorption is more favourable than molecular adsorption for methanol, formic acid and glycine, in general agreement with experiment. The dissociation energies obtained from both functionals are also very similar, indicating that vdW interactions do not affect the thermodynamics of surface deprotonation. However, the optB88-vdW always predicts stronger adsorption than PBE. The comparison of the methanol adsorption energies with values obtained from a Redhead analysis of temperature programmed desorption data suggests that optB88-vdW significantly overestimates the adsorption strength, although we warn about the uncertainties involved in such comparisons.

Standardized evaluation of algorithms for computer-aided diagnosis of dementia based on structural MRI: The CADDementia challenge

Algorithms for computer-aided diagnosis of dementia based on structural MRI have demonstrated high performance in the literature, but are difficult to compare as different data sets and methodology were used for evaluation. In addition, it is unclear how the algorithms would perform on previously unseen data, and thus, how they would perform in clinical practice when there is no real opportunity to adapt the algorithm to the data at hand. To address these comparability, generalizability and clinical applicability issues, we organized a grand challenge that aimed to objectively compare algorithms based on a clinically representative multi-center data set. Using clinical practice as the starting point, the goal was to reproduce the clinical diagnosis. Therefore, we evaluated algorithms for multi-class classification of three diagnostic groups: patients with probable Alzheimer's disease, patients with mild cognitive impairment and healthy controls. The diagnosis based on clinical criteria was used as reference standard, as it was the best available reference despite its known limitations. For evaluation, a previously unseen test set was used consisting of 354 T1-weighted MRI scans with the diagnoses blinded. Fifteen research teams participated with a total of 29 algorithms. The algorithms were trained on a small training set (n = 30) and optionally on data from other sources (e.g., the Alzheimer's Disease Neuroimaging Initiative, the Australian Imaging Biomarkers and Lifestyle flagship study of aging). The best performing algorithm yielded an accuracy of 63.0% and an area under the receiver-operating-characteristic curve (AUC) of 78.8%. In general, the best performances were achieved using feature extraction based on voxel-based morphometry or a combination of features that included volume, cortical thickness, shape and intensity. The challenge is open for new submissions via the web-based framework: http://caddementia.grand-challenge.org.

A proof of van Aubel's theorem using orthogonal vectors

We show how two linearly independent vectors can be used to construct two orthogonal vectors of equal magnitude in a simple way. The proof that the constructed vectors are orthogonal and of equal magnitude is a good exercise for students studying properties of scalar and vector triple products. We then show how this result can be used to prove van Aubel's theorem that relates the two line segments joining the centres of squares on opposite sides of a plane quadrilateral.

Identifying behavioural predictors of small power electricity consumption in office buildings

It is widely accepted that there is a gap between design energy and real world operational energy consumption. The behaviour of occupants is often cited as an important factor influencing building energy performance. However, its consideration, both during design and operation, is overly simplistic, often assuming a direct link between attitudes and behaviour. Alternative models of decision making from psychology highlight a range of additional influential factors and emphasise that occupants do not always act in a rational manner. Developing a better understanding of occupant decision making could help inform office energy conservation campaigns as well as models of behaviour employed during the design process. This paper assesses the contribution of various behavioural constructs on small power consumption in offices. The method is based upon the Theory of Planned Behaviour (TPB) which assumes that intention is driven by three factors: attitude, subjective norms, and perceived behavioural control, but we also consider a fourth construct: habit measured through the Self- Report Habit Index (SRHI). A questionnaire was issued to 81 participants in two UK offices. Questionnaire results for each behavioural construct were correlated against each participant’s individual workstation electricity consumption. The intentional processes proposed by TPB could not account for the observed differences in occupants’ interactions with small power appliances. Instead, occupants were interacting with small power “automatically”, with habit accounting for 11% of the variation in workstation energy consumption. The implications for occupant behaviour models and employee engagement campaigns are discussed.

Queering Philip Roth: homosocial discourse in 'An actor’s life for me', 'Letting go', 'Sabbath’s theater' and the 'American trilogy'

Much has been written on Roth’s representation of masculinity, but this critical discourse has tended to be situated within a heteronormative frame of reference, perhaps because of Roth’s popular reputation as an aggressively heterosexual, libidinous, masculinist, in some versions sexist or even misogynist author. In this essay I argue that Roth’s representation of male sexuality is more complex, ambiguous, and ambivalent than has been generally recognized. Tracing a strong thread of what I call homosocial discourse running through Roth’s oeuvre, I suggest that the series of intimate relationships with other men that many of Roth’s protagonists form are conspicuously couched in this discourse and that a recognition of this ought to reconfigure our sense of the sexual politics of Roth’s career, demonstrating in particular that masculinity in his work is too fluid and dynamic to be accommodated by the conventional binaries of heterosexual and homosexual, feminized Jew and hyper-masculine Gentile, the “ordinary sexual man” and the transgressively desiring male subject.

A systematic method of parameterisation estimation using data assimilation

In numerical weather prediction, parameterisations are used to simulate missing physics in the model. These can be due to a lack of scientific understanding or a lack of computing power available to address all the known physical processes. Parameterisations are sources of large uncertainty in a model as parameter values used in these parameterisations cannot be measured directly and hence are often not well known; and the parameterisations themselves are also approximations of the processes present in the true atmosphere. Whilst there are many efficient and effective methods for combined state/parameter estimation in data assimilation (DA), such as state augmentation, these are not effective at estimating the structure of parameterisations. A new method of parameterisation estimation is proposed that uses sequential DA methods to estimate errors in the numerical models at each space-time point for each model equation. These errors are then fitted to pre-determined functional forms of missing physics or parameterisations that are based upon prior information. We applied the method to a one-dimensional advection model with additive model error, and it is shown that the method can accurately estimate parameterisations, with consistent error estimates. Furthermore, it is shown how the method depends on the quality of the DA results. The results indicate that this new method is a powerful tool in systematic model improvement.

What controls the vertical distribution of aerosol? Relationships between process sensitivity in HadGEM3–UKCA and inter-model variation from AeroCom Phase II

The vertical profile of aerosol is important for its radiative effects, but weakly constrained by observations on the global scale, and highly variable among different models. To investigate the controlling factors in one particular model, we investigate the effects of individual processes in HadGEM3–UKCA and compare the resulting diversity of aerosol vertical profiles with the inter-model diversity from the AeroCom Phase II control experiment. In this way we show that (in this model at least) the vertical profile is controlled by a relatively small number of processes, although these vary among aerosol components and particle sizes. We also show that sufficiently coarse variations in these processes can produce a similar diversity to that among different models in terms of the global-mean profile and, to a lesser extent, the zonal-mean vertical position. However, there are features of certain models' profiles that cannot be reproduced, suggesting the influence of further structural differences between models. In HadGEM3–UKCA, convective transport is found to be very important in controlling the vertical profile of all aerosol components by mass. In-cloud scavenging is very important for all except mineral dust. Growth by condensation is important for sulfate and carbonaceous aerosol (along with aqueous oxidation for the former and ageing by soluble material for the latter). The vertical extent of biomass-burning emissions into the free troposphere is also important for the profile of carbonaceous aerosol. Boundary-layer mixing plays a dominant role for sea salt and mineral dust, which are emitted only from the surface. Dry deposition and below-cloud scavenging are important for the profile of mineral dust only. In this model, the microphysical processes of nucleation, condensation and coagulation dominate the vertical profile of the smallest particles by number (e.g. total CN  >  3 nm), while the profiles of larger particles (e.g. CN  >  100 nm) are controlled by the same processes as the component mass profiles, plus the size distribution of primary emissions. We also show that the processes that affect the AOD-normalised radiative forcing in the model are predominantly those that affect the vertical mass distribution, in particular convective transport, in-cloud scavenging, aqueous oxidation, ageing and the vertical extent of biomass-burning emissions.