Studying the evolution of software through software clustering and concept analysis

This thesis describes an investigation into the use of software clustering and concept analysis techniques for studying the evolution of software. These techniques produce representations of software systems by clustering similar entities in the system together. The software engineering community has used these techniques for a number of different reasons but this is the first study to investigate their uses for evolution. The representations produced by software clustering and concept analysis techniques can be used to trace changes to a software system over a number of different versions of the system. This information can be used by system maintainers to identify worrying evolutionary trends or assess a proposed change by comparing it to the effects of an earlier, similar change. The work described here attempts to establish whether the use of software clustering and concept analysis techniques for studying the evolution of software is worth pursuing. Four techniques, chosen based on an extensive literature survey of the field, have been used to create representations of versions of a test software system. These representations have been examined to assess whether any observations about the evolution of the system can be drawn from them. The results are positive and it is thought that evolution of software systems could be studied by using these techniques

Identification of b-catenin and other RNAs in developing thalamic axons

This thesis provides evidence for the presence of multiple RNAs in the axons and growth cones of developing thalamic cells, particularly the mRNA for the cell adhesion and Wnt-signalling-related molecule b-catenin. After many decades of effort, mRNAs have been shown to be present in the axons of many different systems in recent years. Furthermore, these mRNAs have been shown to be locally translated at the growth cone, and this local translation is required for axons to turn in response to multiple guidance cues. As studies accumulate, it is becoming clear that different axonal systems contain different complements of mRNAs and have different requirements for local translation. One axonal system which has not been investigated to date is the thalamocortical tract. The nuclei of the thalamus are connected to the areas of the cortex via bundles of axons which travel from the thalamus to the cortex via the ventral telencephalon during embyronic development. These axons make a number of turns and are guided by many cues and other axonal tracts before innervating their cortical target. In this thesis, a quantitative real-time polymerase chain reaction (qRT-PCR) approach is developed to isolate multiple mRNAs from developing thalamic axons in vitro, including b-catenin mRNA, b-actin mRNA, 18S ribosomal RNA and ten other mRNAs. The method used should be suitable for use with other axonal systems and also for testing the effect of guidance cues on mRNA expression in axons. The qRT-PCR results for b-catenin, b-actin and 18S have been validated using in situ hybridisation. Analysis of in situ hybridisation results indicates that b-catenin and 18S, but not b-actin, are upregulated in the growth cone compared to the axon. As b-catenin has been shown to be involved in axon guidance via Slit and ephrin guidance cues in other axonal systems, and these guidance cues act upon thalamocortical axons, the identification of b-catenin mRNA in thalamic axons is an important step towards a full understanding of the thalamocortical system. The results presented here indicate that local protein synthesis is likely to occur in thalamic axons as it does in other axonal systems, and that local translation is likely to be important for thalamic axonal responses to guidance cues and other axonal tracts

The Far-Ultraviolet Spectrum and Short Timescale Variability of AM Herculis from Observations with the Hopkins Ultraviolet Telescope

Using the Hopkins Ultraviolet Telescope (HUT), we have obtained 850-1850 angstrom spectra of the magnetic cataclysmic variable star AM Her in the high state. These observations provide high time resolution spectra of AM Her in the FUV and sample much of the orbital period of the system. The spectra are not well-modelled in terms of simple white dwarf (WD) atmospheres, especially at wavelengths shortward of Lyman alpha. The continuum flux changes by a factor of 2 near the Lyman limit as a function of orbital phase; the peak fluxes are observed near magnetic phase 0.6 when the accreting pole of the WD is most clearly visible. The spectrum of the hotspot can be modelled in terms of a 100 000 K WD atmosphere covering 2% of the WD surface. The high time resolution of the HUT data allows an analysis of the short term variability and shows the UV luminosity to change by as much as 50% on timescales as short as 10 s. This rapid variability is shown to be inconsistent with the clumpy accretion model proposed to account for the soft X-ray excess in polars. We see an increase in narrow line emission during these flares when the heated face of the secondary is in view. The He II narrow line flux is partially eclipsed at secondary conjunction, implying that the inclination of the system is greater than 45 degrees. We also present results from models of the heated face of the secondary. These models show that reprocessing on the face of the secondary star of X-ray/EUV emission from the accretion region near the WD can account for the intensities and kinematics of most of the narrow line components observed.Comment: 19 pp., 12 fig., 3 tbl. To appear in The Astrophysical Journal. Also available at http://greeley.pha.jhu.edu/papers/amherpp.ps.g

Polarisation in spin-echo experiments: Multi-point and lock-in measurements.

Spin-echo instruments are typically used to measure diffusive processes and the dynamics and motion in samples on ps and ns time scales. A key aspect of the spin-echo technique is to determine the polarisation of a particle beam. We present two methods for measuring the spin polarisation in spin-echo experiments. The current method in use is based on taking a number of discrete readings. The implementation of a new method involves continuously rotating the spin and measuring its polarisation after being scattered from the sample. A control system running on a microcontroller is used to perform the spin rotation and to calculate the polarisation of the scattered beam based on a lock-in amplifier. First experimental tests of the method on a helium spin-echo spectrometer show that it is clearly working and that it has advantages over the discrete approach, i.e., it can track changes of the beam properties throughout the experiment. Moreover, we show that real-time numerical simulations can perfectly describe a complex experiment and can be easily used to develop improved experimental methods prior to a first hardware implementation

Associations of vitamin D pathway genes with circulating 25-hydroxyvitamin-D, 1,25-dihydroxyvitamin-D, and prostate cancer:a nested case-control study

Vitamin D pathway single nucleotide polymorphisms (SNPs) are potentially useful proxies for investigating whether circulating vitamin D metabolites [total 25-hydroxyvitamin-D, 25(OH)D; 1,25-dihydroxyvitamin, 1,25(OH)2D] are causally related to prostate cancer. We investigated associations of sixteen SNPs across seven genes with prostate-specific antigen-detected prostate cancer

Chromosomal assembly of the nuclear genome of the endosymbiontbearing trypanosomatid Angomonas deanei

Abstract Angomonas deaneiA. deane

Does Bone Resorption Stimulate Periosteal Expansion? A Cross-Sectional Analysis of b-C-telopeptides of Type I Collagen ( CTX),Genetic Markers of the RANKL Pathway, and Periosteal Circumference as Measured by

Peer reviewe

A genome-wide association study identifies protein quantitative trait loci (pQTLs)

There is considerable evidence that human genetic variation influences gene expression. Genome-wide studies have revealed that mRNA levels are associated with genetic variation in or close to the gene coding for those mRNA transcripts - cis effects, and elsewhere in the genome - trans effects. The role of genetic variation in determining protein levels has not been systematically assessed. Using a genome-wide association approach we show that common genetic variation influences levels of clinically relevant proteins in human serum and plasma. We evaluated the role of 496,032 polymorphisms on levels of 42 proteins measured in 1200 fasting individuals from the population based InCHIANTI study. Proteins included insulin, several interleukins, adipokines, chemokines, and liver function markers that are implicated in many common diseases including metabolic, inflammatory, and infectious conditions. We identified eight Cis effects, including variants in or near the IL6R (p = 1.8×10 -57), CCL4L1 (p = 3.9×10-21), IL18 (p = 6.8×10-13), LPA (p = 4.4×10-10), GGT1 (p = 1.5×10-7), SHBG (p = 3.1×10-7), CRP (p = 6.4×10-6) and IL1RN (p = 7.3×10-6) genes, all associated with their respective protein products with effect sizes ranging from 0.19 to 0.69 standard deviations per allele. Mechanisms implicated include altered rates of cleavage of bound to unbound soluble receptor (IL6R), altered secretion rates of different sized proteins (LPA), variation in gene copy number (CCL4L1) and altered transcription (GGT1). We identified one novel trans effect that was an association between ABO blood group and tumour necrosis factor alpha (TNF-alpha) levels (p = 6.8×10-40), but this finding was not present when TNF-alpha was measured using a different assay , or in a second study, suggesting an assay-specific association. Our results show that protein levels share some of the features of the genetics of gene expression. These include the presence of strong genetic effects in cis locations. The identification of protein quantitative trait loci (pQTLs) may be a powerful complementary method of improving our understanding of disease pathways. © 2008 Melzer et al

Impact of vaccination on the association of COVID-19 with cardiovascular diseases:An OpenSAFELY cohort study

Infection with SARS-CoV-2 is associated with an increased risk of arterial and venous thrombotic events, but the implications of vaccination for this increased risk are uncertain. With the approval of NHS England, we quantified associations between COVID-19 diagnosis and cardiovascular diseases in different vaccination and variant eras using linked electronic health records for ~40% of the English population. We defined a 'pre-vaccination' cohort (18,210,937 people) in the wild-type/Alpha variant eras (January 2020-June 2021), and 'vaccinated' and 'unvaccinated' cohorts (13,572,399 and 3,161,485 people respectively) in the Delta variant era (June-December 2021). We showed that the incidence of each arterial thrombotic, venous thrombotic and other cardiovascular outcomes was substantially elevated during weeks 1-4 after COVID-19, compared with before or without COVID-19, but less markedly elevated in time periods beyond week 4. Hazard ratios were higher after hospitalised than non-hospitalised COVID-19 and higher in the pre-vaccination and unvaccinated cohorts than the vaccinated cohort. COVID-19 vaccination reduces the risk of cardiovascular events after COVID-19 infection. People who had COVID-19 before or without being vaccinated are at higher risk of cardiovascular events for at least two years.</p

The effects of height and BMI on prostate cancer incidence and mortality:a Mendelian randomization study in 20,848 cases and 20,214 controls from the PRACTICAL consortium

Background\ud \ud Epidemiological studies suggest a potential role for obesity and determinants of adult stature in prostate cancer risk and mortality, but the relationships described in the literature are complex. To address uncertainty over the causal nature of previous observational findings, we investigated associations of height- and adiposity-related genetic variants with prostate cancer risk and mortality.\ud \ud Methods\ud \ud We conducted a case–control study based on 20,848 prostate cancers and 20,214 controls of European ancestry from 22 studies in the PRACTICAL consortium. We constructed genetic risk scores that summed each man’s number of height and BMI increasing alleles across multiple single nucleotide polymorphisms robustly associated with each phenotype from published genome-wide association studies.\ud \ud Results\ud \ud The genetic risk scores explained 6.31 and 1.46 % of the variability in height and BMI, respectively. There was only weak evidence that genetic variants previously associated with increased BMI were associated with a lower prostate cancer risk (odds ratio per standard deviation increase in BMI genetic score 0.98; 95 % CI 0.96, 1.00; p = 0.07). Genetic variants associated with increased height were not associated with prostate cancer incidence (OR 0.99; 95 % CI 0.97, 1.01; p = 0.23), but were associated with an increase (OR 1.13; 95 % CI 1.08, 1.20) in prostate cancer mortality among low-grade disease (p heterogeneity, low vs. high grade <0.001). Genetic variants associated with increased BMI were associated with an increase (OR 1.08; 95 % CI 1.03, 1.14) in all-cause mortality among men with low-grade disease (p heterogeneity = 0.03).\ud \ud Conclusions\ud \ud We found little evidence of a substantial effect of genetically elevated height or BMI on prostate cancer risk, suggesting that previously reported observational associations may reflect common environmental determinants of height or BMI and prostate cancer risk. Genetically elevated height and BMI were associated with increased mortality (prostate cancer-specific and all-cause, respectively) in men with low-grade disease, a potentially informative but novel finding that requires replication