Dissimilarities in alignment-free methods for phylogenetic analysis based on genomes

Whole genome sequences are generally accepted as excellent tools for studying evolutionary relationships. Due to the problems caused by the uncertainty in alignment, existing tools for phylogenetic analysis based on multiple alignments could not be directly applied to the whole-genome comparison and phylogenomic studies. There has been a growing interest in alignment-free methods for phylogenetic analysis using complete genome data. The “distances” used in these alignment-free methods are not proper distance metrics in the strict mathematical sense. In this study, we first review them in a more general frame — dissimilarity. Then we propose some new dissimilarities for phylogenetic analysis. Last three genome datasets are employed to evaluate these dissimilarities from a biological point of view.

2D hexagonal mesoporous platinum films exhibiting biaxial, in-plane pore alignment

The synthesis of 2D hexagonal mesoporous platinum films with biaxial, in-plane pore alignment is demonstrated by electrodeposition through an aligned lyotropic liquid crystal templating phase. Shear force is used to align a hexagonal lyotropic liquid crystalline templating phase of an inexpensive and a commercially available surfactant, C16EO10, at the surface of an electrode. Electrodeposition and subsequent characterisation of the films produced shows that the orientation and alignment of the phase is transferred to the deposited material. Transmission electron microscopy confirms the expected nanostructure of the films, whilst transmission and grazing incidence small angle X-ray scattering analysis confirms biaxial, in plane alignment of the pore structure. In addition further electrochemical studies in dilute sulfuric acid and methanol show that the pores are accessible to electrolyte solution as indicated by a large current flow; the modified electrode therefore has a high surface area, that catalyses methanol oxidation, and the pores have a very large aspect ratio (of theoretical maximum 2 × 105). Films with such aligned mesoporosity will advance the field of nanotechnology where the control of pore structure is paramount. The method reported is sufficiently generic to be used to control the structure and order of many materials, thus increasing the potential for the development of a wide range of novel electronic and optical devices.

A novel route for tethering graphene with iron oxide and its magnetic field alignment in polymer nanocomposites

We present a new route of tethering graphene nanoplatelets (GNPs) with Fe3O4 nanoparticles to enable their alignment in an epoxy using a weak magnetic field. The GNPs are first stabilised in water using polyvinylpyrrolidone (PVP) and Fe3O4 nanoparticles are then attached via co-precipitation. The resultant Fe3O4/PVP-GNPs nanohybrids are superparamagnetic and can be aligned in an epoxy resin, before gelation, by applying a weak magnetic field as low as 0.009 T. A theoretical model describing the alignment process is presented and used to quantify the effects of key parameters on the time needed for the alignment process. Compared to the unmodified epoxy, the resulting epoxy polymer nanocomposites containing randomly-oriented Fe3O4/PVP-GNPs nanohybrids exhibit significantly improved electrical conductivities by up to three orders of magnitude and fracture energies by up to 300%. The alignment of the Fe3O4/PVP-GNPs nanohybrids in the epoxy polymer nanocomposites transverse to the direction of crack propagation further increased the fracture energy by 50%, and the electrical conductivity by seven fold in the alignment direction, compared to the nanocomposites containing randomly-oriented nanohybrids.

Chiasmolithus species in middle Eocene and Oligocene sediments of ODP Holes 105-647A and 120-748B

In this preliminary biometric study of the calcareous nannofossil species Chiasmolithus expansus, Chiasmolithus oamaruensis, and Chiasmolithus altus from the upper middle Eocene to lower Oligocene of Sites 647 and 748, we document a complete gradation of forms among all three species. Chiasmolithus oamaruensis has significantly higher morphologic variance than the other species. The Chiasmolithus population at each site changes from C. expansus to C. oamaruensis and then to C. altus. This may not reflect a true evolutionary sequence because a major reversal in shape change of the central cross-bar structure accompanies this sequence, and because C. altus is morphologically closer to C. expansus than it is to C. oamaruensis. The change in the width of the cross-bar structure is primarily a result of changes in the alignment of the central connecting bar, rather than of changes in the cross-bar angle. At Site 748, two fluctuations in morphology produce sample populations intermediate between all three species. In addition, reported stratigraphic and paleogeographic occurrences of C. oamaruensis and C. altus show different latitudinal distributions. These morphological and distributional patterns may be explained by a continuous morphologic gradient between C. oamaruensis and C. altus, with C. oamaruensis occurring more commonly in cool-water paleoenvironments, and C. altus occurring more commonly in cold-water paleoenvironments. Thus, paleoenvironmental fluctuations at Site 748 may be the cause of the morphologic fluctuations in Chiasmolithus. This hypothesis can be tested against previously proposed evolutionary models by more detailed sampling of sections along a latitudinal transect.

Latent variable models in statistical genetics

Understanding the complexities that are involved in the genetics of multifactorial diseases is still a monumental task. In addition to environmental factors that can influence the risk of disease, there is also a number of other complicating factors. Genetic variants associated with age of disease onset may be different from those variants associated with overall risk of disease, and variants may be located in positions that are not consistent with the traditional protein coding genetic paradigm. Latent Variable Models are well suited for the analysis of genetic data. A latent variable is one that we do not directly observe, but which is believed to exist or is included for computational or analytic convenience in a model. This thesis presents a mixture of methodological developments utilising latent variables, and results from case studies in genetic epidemiology and comparative genomics. Epidemiological studies have identified a number of environmental risk factors for appendicitis, but the disease aetiology of this oft thought useless vestige remains largely a mystery. The effects of smoking on other gastrointestinal disorders are well documented, and in light of this, the thesis investigates the association between smoking and appendicitis through the use of latent variables. By utilising data from a large Australian twin study questionnaire as both cohort and case-control, evidence is found for the association between tobacco smoking and appendicitis. Twin and family studies have also found evidence for the role of heredity in the risk of appendicitis. Results from previous studies are extended here to estimate the heritability of age-at-onset and account for the eect of smoking. This thesis presents a novel approach for performing a genome-wide variance components linkage analysis on transformed residuals from a Cox regression. This method finds evidence for a dierent subset of genes responsible for variation in age at onset than those associated with overall risk of appendicitis. Motivated by increasing evidence of functional activity in regions of the genome once thought of as evolutionary graveyards, this thesis develops a generalisation to the Bayesian multiple changepoint model on aligned DNA sequences for more than two species. This sensitive technique is applied to evaluating the distributions of evolutionary rates, with the finding that they are much more complex than previously apparent. We show strong evidence for at least 9 well-resolved evolutionary rate classes in an alignment of four Drosophila species and at least 7 classes in an alignment of four mammals, including human. A pattern of enrichment and depletion of genic regions in the profiled segments suggests they are functionally significant, and most likely consist of various functional classes. Furthermore, a method of incorporating alignment characteristics representative of function such as GC content and type of mutation into the segmentation model is developed within this thesis. Evidence of fine-structured segmental variation is presented.

Contribution of cross-functional teams to the improvement in operational performance

Purpose: The purpose of this paper is to explore the role of cross-functional teams in the alignment between system effectiveness and operational effectiveness after the implementation of enterprise information systems (EIS). In addition, it aims to explore the contribution of cross-functional teams to improvement in operational performance. ---------- Design/methodology/approach: The research uses a combination of qualitative and quantitative methods, in a two-stage methodological approach, to investigate the influence of cross-functional teams on the alignment between system effectiveness and operational effectiveness and the impact of the stated alignment on the improvement in operational performance. ---------- Findings: Initial findings suggest that factors stemming from system effectiveness and the performance objectives stemming from operational effectiveness are important and significantly well correlated factors that promote the alignment between the effectiveness of technological implementation and the effectiveness of operations. In addition, confirmatory factor analysis has been used to find the structural relationships and provide explanations for the stated alignment and the contribution of cross-functional teams to the improvement in operational performance. ---------- Research limitations/implications: The principal limitation of this study is its small sample size. ---------- Practical implications: Cross-functional teams have been used by many organisations as a way of involving expertise from different functional areas in the implementation of innovative technologies. An appropriate use of the dimensions that emerged from this research, in the context of cross-functional teams, will assist organisations to properly utilise cross-functional teams with the aim of improving operational performance. ---------- Originality/value: The paper presents a new approach to measure the effectiveness of EIS implementation by adding new dimensions to measure it.

Integrating information security policy management with corporate risk management for strategic alignment

Information security policy defines the governance and implementation strategy for information security in alignment with the corporate risk policy objectives and strategies. Research has established that alignment between corporate concerns may be enhanced when strategies are developed concurrently using the same development process as an integrative relationship is established. Utilizing the corporate risk management framework for security policy management establishes such an integrative relationship between information security and corporate risk management objectives and strategies. There is however limitation in the current literature on presenting a definitive approach that fully integrates security policy management with the corporate risk management framework. This paper presents an approach that adopts a conventional corporate risk management framework for security policy development and management to achieve alignment with the corporate risk policy. A case example is examined to illustrate the alignment achieved in each process step with a security policy structure being consequently derived in the process. It is shown that information security policy management outcomes become both integral drivers and major elements of the corporate-level risk management considerations. Further study should involve assessing the impact of the use of the proposed framework in enhancing alignment as perceived in this paper.

Multiple evolutionary rate classes in animal genome evolution

The proportion of functional sequence in the human genome is currently a subject of debate. The most widely accepted figure is that approximately 5% is under purifying selection. In Drosophila, estimates are an order of magnitude higher, though this corresponds to a similar quantity of sequence. These estimates depend on the difference between the distribution of genomewide evolutionary rates and that observed in a subset of sequences presumed to be neutrally evolving. Motivated by the widening gap between these estimates and experimental evidence of genome function, especially in mammals, we developed a sensitive technique for evaluating such distributions and found that they are much more complex than previously apparent. We found strong evidence for at least nine well-resolved evolutionary rate classes in an alignment of four Drosophila species and at least seven classes in an alignment of four mammals, including human. We also identified at least three rate classes in human ancestral repeats. By positing that the largest of these ancestral repeat classes is neutrally evolving, we estimate that the proportion of nonneutrally evolving sequence is 30% of human ancestral repeats and 45% of the aligned portion of the genome. However, we also question whether any of the classes represent neutrally evolving sequences and argue that a plausible alternative is that they reflect variable structure-function constraints operating throughout the genomes of complex organisms.

Degree of value alignment : a grounded theory of rural nurse resignations

INTRODUCTION: The shortage of nurses willing to work in rural Australian healthcare settings continues to worsen. Australian rural areas have a lower retention rate of nurses than metropolitan counterparts, with more remote communities experiencing an even higher turnover of nursing staff. When retention rates are lower, patient outcomes are known to be poorer. This article reports a study that sought to explore the reasons why registered nurses resign from rural hospitals in the state of New South Wales, Australia. METHODS: Using grounded theory methods, this study explored the reasons why registered nurses resigned from New South Wales rural hospitals. Data were collected from 12 participants using semi-structured interviews; each participant was a registered nurse who had resigned from a rural hospital. Nurses who had resigned due to retirement, relocation or maternity leave were excluded. Interviews were transcribed verbatim and imported into NVivo software. The constant comparative method of data collection and analysis was followed until a core category emerged. RESULTS: Nurses resigned from rural hospitals when their personal value of how nursing should occur conflicted with the hospital's organisational values driving the practice of nursing. These conflicting values led to a change in the degree of value alignment between the nurse and hospital. The degree of value alignment occurred in three dynamic stages that nurses moved through prior to resigning. The first stage, sharing values, was a time when a nurse and a hospital shared similar values. The second stage was conceding values where, due to perceived changes in a hospital's values, a nurse felt that patient care became compromised and this led to a divergence of values. The final stage was resigning, a stage where a nurse 'gave up' as they felt that their professional integrity was severely compromised. The findings revealed that when a nurse and organisational values were not aligned, conflict was created for a nurse about how they could perform nursing that aligned with their internalised professional values and integrity. Resignation occurred when nurses were unable to realign their personal values to changed organisational values - the organisational values changed due to rural area health service restructures, centralisation of budgets and resources, cumbersome hierarchies and management structures that inhibited communication and decision making, out-dated and ineffective operating systems, insufficient and inexperienced staff, bullying, and a lack of connectedness and shared vision. CONCLUSIONS: To fully comprehend rural nurse resignations, this study identified three stages that nurses move through prior to resignation. Effective retention strategies for the nursing workforce should address contributors to a decrease in value alignment and work towards encouraging the coalescence of nurses' and hospitals' values. It is imperative that strategies enable nurses to provide high quality patient care and promote a sense of connectedness and a shared vision between nurse and hospital. Senior managers need to have clear ways to articulate and imbue organisational values and be explicit in how these values accommodate nurses' values. Ward-level nurse managers have a significant responsibility to ensure that a hospital's values (both explicit and implicit) are incorporated into ward culture.

Creating change in government to address the social determinants of health: How can efforts be improved?

Background The evidence base for the impact of social determinants of health has been strengthened considerably in the last decade. Increasingly, the public health field is using this as a foundation for arguments and actions to change government policies. The Health in All Policies (HiAP) approach, alongside recommendations from the 2010 Marmot Review into health inequalities in the UK (which we refer to as the ‘Fairness Agenda’), go beyond advocating for the redesign of individual policies, to shaping the government structures and processes that facilitate the implementation of these policies. In doing so, public health is drawing on recent trends in public policy towards ‘joined up government’, where greater integration is sought between government departments, agencies and actors outside of government. Methods In this paper we provide a meta-synthesis of the empirical public policy research into joined up government, drawing out characteristics associated with successful joined up initiatives. We use this thematic synthesis as a basis for comparing and contrasting emerging public health interventions concerned with joined-up action across government. Results We find that HiAP and the Fairness Agenda exhibit some of the characteristics associated with successful joined up initiatives, however they also utilise ‘change instruments’ that have been found to be ineffective. Moreover, we find that – like many joined up initiatives – there is room for improvement in the alignment between the goals of the interventions and their design. Conclusion Drawing on public policy studies, we recommend a number of strategies to increase the efficacy of current interventions. More broadly, we argue that up-stream interventions need to be ‘fit-for-purpose’, and cannot be easily replicated from one context to the next.

Recognition and alignment of homologous DNA sequences between minichromosomes and single-stranded DNA promoted by RecA protein

The incorporation of DNA into nucleosomes and higher-order forms of chromatin in vivo creates difficulties with respect to its accessibility for cellular functions such as transcription, replication, repair and recombination. To understand the role of chromatin structure in the process of homologous recombination, we have studied the interaction of nucleoprotein filaments, comprised of RecA protein and ssDNA, with minichromosomes. Using this paradigm, we have addressed how chromatin structure affects the search for homologous DNA sequences, and attempted to distinguish between two mutually exclusive models of DNA-DNA pairing mechanisms. Paradoxically, we found that the search for homologous sequences, as monitored by unwinding of homologous or heterologous duplex DNA, was facilitated by nucleosomes, with no discernible effect on homologous pairing. More importantly, unwinding of minichromosomes required the interaction of nucleoprotein filaments and led to the accumulation of circular duplex DNA sensitive to nuclease P1. Competition experiments indicated that chromatin templates and naked DNA served as equally efficient targets for homologous pairing. These and other findings suggest that nucleosomes do not impede but rather facilitate the search for homologous sequences and establish, in accordance with one proposed model, that unwinding of duplex DNA precedes alignment of homologous sequences at the level of chromatin. The potential application of this model to investigate the role of chromosomal proteins in the alignment of homologous sequences in the context of cellular recombination is considered.

Shear alignment of a disordered lamellar mesophase

The shear alignment of an initially disordered lamellar phase is examined using lattice Boltzmann simulations of a mesoscopic model based on a free-energy functional for the concentration modulation. For a small shear cell of width 8 lambda, the qualitative features of the alignment process are strongly dependent on the Schmidt number Sc = nu/D (ratio of kinematic viscosity and mass diffusion coefficient). Here, lambda is the wavelength of the concentration modulation. At low Schmidt number, it is found that there is a significant initial increase in the viscosity, coinciding with the alignment of layers along the extensional axis, followed by a decrease at long times due to the alignment along the flow direction. At high Schmidt number, alignment takes place due to the breakage and reformation of layers because diffusion is slow compared to shear deformation; this results in faster alignment. The system size has a strong effect on the alignment process; perfect alignment takes place for a small systems of width 8 lambda and 16 lambda, while a larger system of width 32 lambda does not align completely even at long times. In the larger system, there appears to be a dynamical steady state in which the layers are not perfectly aligned-where there is a balance between the annealing of defects due to shear and the creation due to an instability of the aligned lamellar phase under shear. We observe two types of defect creation mechanisms: the buckling instability under dilation, which was reported earlier, as well as a second mechanism due to layer compression.

Identification of Local Conformational Similarity in Structurally Variable Regions of Homologous Proteins Using Protein Blocks

Structure comparison tools can be used to align related protein structures to identify structurally conserved and variable regions and to infer functional and evolutionary relationships. While the conserved regions often superimpose well, the variable regions appear non superimposable. Differences in homologous protein structures are thought to be due to evolutionary plasticity to accommodate diverged sequences during evolution. One of the kinds of differences between 3-D structures of homologous proteins is rigid body displacement. A glaring example is not well superimposed equivalent regions of homologous proteins corresponding to a-helical conformation with different spatial orientations. In a rigid body superimposition, these regions would appear variable although they may contain local similarity. Also, due to high spatial deviation in the variable region, one-to-one correspondence at the residue level cannot be determined accurately. Another kind of difference is conformational variability and the most common example is topologically equivalent loops of two homologues but with different conformations. In the current study, we present a refined view of the ``structurally variable'' regions which may contain local similarity obscured in global alignment of homologous protein structures. As structural alphabet is able to describe local structures of proteins precisely through Protein Blocks approach, conformational similarity has been identified in a substantial number of `variable' regions in a large data set of protein structural alignments; optimal residue-residue equivalences could be achieved on the basis of Protein Blocks which led to improved local alignments. Also, through an example, we have demonstrated how the additional information on local backbone structures through protein blocks can aid in comparative modeling of a loop region. In addition, understanding on sequence-structure relationships can be enhanced through our approach. This has been illustrated through examples where the equivalent regions in homologous protein structures share sequence similarity to varied extent but do not preserve local structure.

Ramachandran analysis of conserved glycyl residues in homologous proteins of known structure

High conservation of glycyl residues in homologous proteins is fairly frequent. It is commonly understood that glycine tends to be highly conserved either because of its unique Ramachandran angles or to avoid steric clash that would arise with a larger side chain. Using a database of aligned 3D structures of homologous proteins we identified conserved Gly in 288 alignment positions from 85 families. Ninety-six of these alignment positions correspond to conserved Gly residue with (phi, ) values allowed for non-glycyl residues. Reasons for this observation were investigated by in-silico mutation of these glycyl residues to Ala. We found in 94% of the cases a short contact exists between the C atom of the introduced Ala with the atoms which are often distant in the primary structure. This suggests the lack of space even for a short side chain thereby explaining high conservation of glycyl residues even when they adopt (phi, ) values allowed for Ala. In 189 alignment positions, the conserved glycyl residues adopt (phi, ) values which are disallowed for Ala. In-silico mutation of these Gly residues to Ala almost always results in steric hindrance involving C atom of Ala as one would expect by comparing Ramachandran maps for Ala and Gly. Rare occurrence of the disallowed glycyl conformations even in ultrahigh resolution protein structures are accompanied by short contacts in the crystal structures and such disallowed conformations are not conserved in the homologues. These observations raise the doubt on the accuracy of such glycyl conformations in proteins.

Scalar dissipation rate transport in the corrugated flamelets and thin reaction zones regime for turbulent premixed flames

The characteristics of the scalar dissipation rate transport in the corrugated flamelets and the thin reaction zones regimes are studied based on two three-dimensional Direct Numerical Simulation (DNS) databases for freely propagating statistically planar turbulent premixed flames. The turbulent flame parameters are so chosen that the database which represents the corrugated flamelets regime has a global Damköhler number Da>1 whereas the database representing the thin reaction zones regime has Da <1. It is demonstrated that the terms originating from the correlation between fluctuating velocity and scalar gradient T1 shows strong Da dependence. The terms originating from dilatation T2, the scalar inner product of gradients of velocity and scalar fields T3 and the correlation between reaction rate and scalar gradients T4 and the dissipation term D2 remain important for both the flames. However, T3 dissipates scalar dissipation rate in the Da > 1 flame while it produces scalar dissipation rate in the Da < 1 flame. This difference is because of the change in the alignment between scalar and velocity gradients