Some issues in the 'archaeology' of software evolution

During a software project's lifetime, the software goes through many changes, as components are added, removed and modified to fix bugs and add new features. This paper is intended as a lightweight introduction to some of the issues arising from an `archaeological' investigation of software evolution. We use our own work to look at some of the challenges faced, techniques used, findings obtained, and lessons learnt when measuring and visualising the historical changes that happen during the evolution of software

Fishing Top Predators Indirectly Affects Condition and Reproduction in a Reef-fish Community

To examine the indirect effects of fishing on energy allocation in non-target prey species, condition and reproductive potential were measured for five representative species (two-spot red snapper Lutjanus bohar, arc-eye hawkfish Paracirrhites arcatus, blackbar devil Plectroglyphidodon dickii, bicolour chromis Chromis margaritifer and whitecheek surgeonfish Acanthurus nigricans) from three reef-fish communities with different levels of fishing and predator abundance in the northern Line Islands, central Pacific Ocean. Predator abundance differed by five to seven-fold among islands, and despite no clear differences in prey abundance, differences in prey condition and reproductive potential among islands were found. Body condition (mean body mass adjusted for length) was consistently lower at sites with higher predator abundance for three of the four prey species. Mean liver mass (adjusted for total body mass), an indicator of energy reserves, was also lower at sites with higher predator abundance for three of the prey species and the predator. Trends in reproductive potential were less clear. Mean gonad mass (adjusted for total body mass) was high where predator abundance was high for only one of the three species in which it was measured. Evidence of consistently low prey body condition and energy reserves in a diverse suite of species at reefs with high predator abundance suggests that fishing may indirectly affect non-target prey-fish populations through changes in predation and predation risk

Synthesis of a protected keto-lysidine analogue via improved preparation of arabino-isocytosine nucleosides

Anhydrouridines react with aliphatic amines to give N-alkyl isocytosines, but reported procedures often demand very long reaction times and can be low yielding, with narrow scope. A modified procedure for such reactions has been developed, using microwave irradiation, significantly reducing reaction time and allowing facile access to a diverse range of novel nucleosides on the gram scale. The method has been used to prepare a precursor to a novel analogue of lysidine, a naturally occurring iminonucleoside found in (t)RNA

BioMiCo:A supervised Bayesian model for inference of microbial community structure

Here, we describe a novel hierarchical model for Bayesian inference of microbial communities (BioMiCo). The model takes abundance data derived from environmental DNA, and models the composition of each sample by a two-level hierarchy of mixture distributions constrained by Dirichlet priors. BioMiCo is supervised, using known features for samples and appropriate prior constraints to overcome the challenges posed by many variables, sparse data, and large numbers of rare species. The model is trained on a portion of the data, where it learns how assemblages of species are mixed to form communities and how assemblages are related to the known features of each sample. Training yields a model that can predict the features of new samples. We used BioMiCo to build models for three serially sampled datasets and tested their predictive accuracy across different time points. The first model was trained to predict both body site (hand, mouth, and gut) and individual human host. It was able to reliably distinguish these features across different time points. The second was trained on vaginal microbiomes to predict both the Nugent score and individual human host. We found that women having normal and elevated Nugent scores had distinct microbiome structures that persisted over time, with additional structure within women having elevated scores. The third was trained for the purpose of assessing seasonal transitions in a coastal bacterial community. Application of this model to a high-resolution time series permitted us to track the rate and time of community succession and accurately predict known ecosystem-level events

Hormonal modulation of breast cancer gene expression: implications for intrinsic subtyping in premenopausal women

Clinics are increasingly adopting gene-expression profiling to diagnose breast cancer subtype, providing an intrinsic, molecular portrait of the tumor. For example, the PAM50- based Prosigna test quantifies expression of 50 key genes to classify breast cancer subtype, and this method of classification has been demonstrated to be superior over traditional immunohistochemical methods that detect proteins, to predict risk of disease recurrence. However, these tests were largely developed and validated using breast cancer samples from postmenopausal women. Thus, the accuracy of such tests has not been explored in the context of the hormonal fluctuations in estrogen and progesterone that occur during the menstrual cycle in premenopausal women. Concordance between traditional methods of subtyping and the new tests in premenopausal women is likely to depend on the stage of the menstrual cycle at which the tissue sample is taken and the relative effect of hormones on expression of genes versus proteins. The lack of knowledge around the effect of fluctuating estrogen and progesterone on gene expression in breast cancer patients raises serious concerns for intrinsic subtyping in premenopausal women, which comprise about 25% of breast cancer diagnoses. Further research on the impact of the menstrual cycle on intrinsic breast cancer profiling is required if premenopausal women are to benefit from the new technology of intrinsic subtyping.Sarah M. Bernhardt, Pallave Dasari, David Walsh, Amanda R. Townsend, Timothy J. Price, and Wendy V. Ingma

High Pressure Processing of Dairy Foods

End of Project ReportThe term High Pressure Processing (HPP) is used to describe the technology whereby products are exposed to very high pressures in the region of 50 - 800 MPa (500 - 8000 Atmospheres). The potential application of HPP in the food industry has gained popularity in recent years, due to developments in the construction of HPP equipment which makes the technology more affordable. Applying HPP to food products results in modifications to interactions between individual components, rates of enzymatic reactions and inactivation of micro-organisms. The first commercial HPP products appeared on the market in 1991 in Japan, where HPP is now being used commercially for products such as jams, sauces, fruit juices, rice cakes and desserts. The pioneering research into the application of HPP to milk dates back to the end of the 19th century. Application of HPP to milk has been shown to modify its gel forming characteristics as well as reducing its microbial load. HPP offers the potential to induce similar effects to those generated by heat on milk protein. Recent reports have also indicated that HPP could accelerate the ripening of cheese. Much of the Irish cheese industry is based on the production of Cheddar cheese, the ripening time for which can vary from 4 - 12 months or more, depending on grade. A substantial portion of the cost associated with Cheddar manufacture is therefore attributed to storage under controlled conditions during ripening. Thus, any technology which may accelerate the ripening of Cheddar cheese while maintaining a balanced flavour and texture is of major economic significance. While food safety is a dominant concern, consumers are increasingly demanding foods that maintain their natural appearance and flavour, while free of chemical preservatives. HPP offers the food industry the possibility of achieving these twin goals as this technology can lead to reduced microbial loads without detrimentally effecting the nutritional or sensory qualities of the product. The development of food ingredients with novel functional properties offers the dairy industry an opportunity to revitalise existing markets and develop new ones. HPP can lead to modifications in the structure of milk components, in particular protein, which may provide interesting possibilities for the development of high value nutritional and functional ingredients. Hence these projects set out to investigate the potential of HPP in the dairy industry and to identify products and processes to which it could be applied.Department of Agriculture, Food and the Marin

Individual responses to topical ibuprofen gel or capsaicin cream for painful knee osteoarthritis: a series of n-of-1 trials

OBJECTIVES: To determine individual responses to ibuprofen gel or capsaicin cream for painful, radiographic knee OA using a series of n-of-1 trials. METHODS: Twenty-two participants were allocated 5% ibuprofen gel (A) and 0.025% capsaicin cream (B) in random sequence (AB or BA). Patients underwent up to 3 treatment cycles, each comprising one treatment for 4 weeks, an individualized washout period (maximum 4 weeks), then the other treatment for 4 weeks. Differential (ibuprofen or capsaicin) response was defined when change-from-baseline pain intensity scores (0-10 NRS) differed by ≥1 between treatments in ≥2 cycles within a participant. RESULTS: A total of 104 treatment periods were aggregated. Mean pain reduction was 1.2 (95% CI: 0.5, 1.8) on ibuprofen and 1.6 (95% CI: 0.9, 2.4) on capsaicin (P = 0.221). Of 22 participants, 4 (18%) had a greater response to ibuprofen, 9 (41%) to capsaicin, 4 (18%) had similar responses, and 5 (23%) were undetermined. CONCLUSION: Irrespective of equal efficacy overall, 59% of people displayed a greater response to one treatment over the other. Patients who do not benefit from one type of topical treatment should be offered to try another, which may be more effective. N-of-1 trials are useful to identify individual response to treatment. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov, NCT03146689

Demonstration of the donor characteristics of Si and O defects in GaN using hybrid QM/MM

Using hybrid quantum mechanical/molecular mechanical (QM/MM) embedded cluster calculations, we investigate the stabilization of silicon and oxygen dopants in GaN. Formation energies of Si on a Ga site and O on an N site are calculated at two levels of theory using conventional thermochemical and kinetic exchange and correlation density functionals (B97‐2 and BB1k). We confirm the shallow donor nature of these substitutional defects. We find that the 0/1+ transition levels for both Si and O species lie well above the bottom of the conduction band, in agreement with previous supercell‐based simulations. The origin of this artifact is discussed in the context of relevant experimental results and we show how correct in‐gap shallow levels can be ascertained in good agreement with experiment. This is the peer reviewed version of the following article: Demonstration of the donor characteristics of Si and O defects in GaN using hybrid QM/MM, which has been published in final form at https://onlinelibrary.wiley.com/doi/abs/10.1002/pssa.201600445. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Version

High-contrast imaging constraints on gas giant planet formation - The Herbig Ae/Be star opportunity

Planet formation studies are often focused on solar-type stars, implicitly considering our Sun as reference point. This approach overlooks, however, that Herbig Ae/Be stars are in some sense much better targets to study planet formation processes empirically, with their disks generally being larger, brighter and simply easier to observe across a large wavelength range. In addition, massive gas giant planets have been found on wide orbits around early type stars, triggering the question if these objects did indeed form there and, if so, by what process. In the following I briefly review what we currently know about the occurrence rate of planets around intermediate mass stars, before discussing recent results from Herbig Ae/Be stars in the context of planet formation. The main emphasis is put on spatially resolved polarized light images of potentially planet forming disks and how these images - in combination with other data - can be used to empirically constrain (parts of) the planet formation process. Of particular interest are two objects, HD100546 and HD169142, where, in addition to intriguing morphological structures in the disks, direct observational evidence for (very) young planets has been reported. I conclude with an outlook, what further progress we can expect in the very near future with the next generation of high-contrast imagers at 8-m class telescopes and their synergies with ALMA.Comment: Accepted by Astrophysics and Space Science as invited short review in special issue about Herbig Ae/Be stars; 12 pages incl. 5 figures, 2 tables and reference