From marine ecology to crime analysis: improving the detection of serial sexual offences using a taxonomic similarity measure

Jaccard has been the choice similarity metric in ecology and forensic psychology for comparison of sites or offences, by species or behaviour. This paper applies a more powerful hierarchical measure - taxonomic similarity (s), recently developed in marine ecology - to the task of behaviourally linking serial crime. Forensic case linkage attempts to identify behaviourally similar offences committed by the same unknown perpetrator (called linked offences). s considers progressively higher-level taxa, such that two sites show some similarity even without shared species. We apply this index by analysing 55 specific offence behaviours classified hierarchically. The behaviours are taken from 16 sexual offences by seven juveniles where each offender committed two or more offences. We demonstrate that both Jaccard and s show linked offences to be significantly more similar than unlinked offences. With up to 20% of the specific behaviours removed in simulations, s is equally or more effective at distinguishing linked offences than where Jaccard uses a full data set. Moreover, s retains significant difference between linked and unlinked pairs, with up to 50% of the specific behaviours removed. As police decision-making often depends upon incomplete data, s has clear advantages and its application may extend to other crime types. Copyright © 2007 John Wiley & Sons, Ltd.

Affect networks:a structural analysis of the relationship between work ties and job-related affect

The relationship between organizational networks and employees' affect was examined in 2 organizations. In Study 1, social network analysis of work ties and job-related affect for 259 employees showed that affect converged within work interaction groups. Similarity of affect between employees depended on the presence of work ties and structural equivalence. Affect was also related to the size and density of employees' work networks. Study 2 used a 10-week diary study of 31 employees to examine a merger of 2 organizational divisions and found that negative changes in employees' affect were related to having fewer cross-divisional ties and to experiencing greater reductions in network density. The findings suggest that affect permeates through and is shaped by organizational networks.

Similarity between class A and class B G-protein-coupled receptors exemplified through calcitonin gene-related peptide receptor modelling and mutagenesis studies

Modelling class B G-protein-coupled receptors (GPCRs) using class A GPCR structural templates is difficult due to lack of homology. The plant GPCR, GCR1, has homology to both class A and class B GPCRs. We have used this to generate a class A-class B alignment, and by incorporating maximum lagged correlation of entropy and hydrophobicity into a consensus score, we have been able to align receptor transmembrane regions. We have applied this analysis to generate active and inactive homology models of the class B calcitonin gene-related peptide (CGRP) receptor, and have supported it with site-directed mutagenesis data using 122 CGRP receptor residues and 144 published mutagenesis results on other class B GPCRs. The variation of sequence variability with structure, the analysis of polarity violations, the alignment of group-conserved residues and the mutagenesis results at 27 key positions were particularly informative in distinguishing between the proposed and plausible alternative alignments. Furthermore, we have been able to associate the key molecular features of the class B GPCR signalling machinery with their class A counterparts for the first time. These include the [K/R]KLH motif in intracellular loop 1, [I/L]xxxL and KxxK at the intracellular end of TM5 and TM6, the NPXXY/VAVLY motif on TM7 and small group-conserved residues in TM1, TM2, TM3 and TM7. The equivalent of the class A DRY motif is proposed to involve Arg(2.39), His(2.43) and Glu(3.46), which makes a polar lock with T(6.37). These alignments and models provide useful tools for understanding class B GPCR function.

Structural funds and the knowledge-based economy:a regional case-study (1999-2009)

The research presented in this thesis investigates the nature of the relationship between the development of the Knowledge-Based Economy (KBE) and Structural Funds (SF) in European regions. A particular focus is placed on the West Midlands (UK) and Silesia (Poland). The time-frame taken into account in this research is the years 1999 to 2009. This is methodologically addressed by firstly establishing a new way of calculating the General Index of the KBE for all of the EU regions; secondly, applying a number of statistical methods to measure the influence of the Funds on the changes in the regional KBE over time; and finally, by conducting a series of semi-structured stakeholder interviews in the two key case study regions: the West Midlands and Silesia. The three main findings of the thesis are: first, over the examined time-frame, the values of the KBE General Index increased in over 66% of the EU regions; furthermore, the number of the “new” EU regions in which the KBE increased over time is far higher than in the “old” EU. Second, any impact of Structural Funds on the regional KBE occurs only in the minority of the European regions and any form of functional dependency between the two can be observed only in 30% of the regions. Third, although the pattern of development of the regional KBE and the correlation coefficients differ in the cases of Silesia and the West Midlands, the analysis of variance carried out yields identical results for both regions. Furthermore, the qualitative analysis’ results show similarities in the approach towards the Structural Funds in the two key case-study regions.

Formalization of Structural Constraints of Relationships in Model „Entity-Relationship”

The basic conceptions of the model „entity-relationship” as entities, relationships, structural constraints of the relationships (index cardinality, participation degree, and structural constraints of kind (min, max)) are considered and formalized in terms of relations theory. For the binary relations two operators (min and max) are introduced; structural constraints are determined in terms of the operators; the main theorem about compatibility of these operators’ values on the source relation and inversion to it is given here.

Regrouping metric-space search index for search engine size adaptation

This work contributes to the development of search engines that self-adapt their size in response to fluctuations in workload. Deploying a search engine in an Infrastructure as a Service (IaaS) cloud facilitates allocating or deallocating computational resources to or from the engine. In this paper, we focus on the problem of regrouping the metric-space search index when the number of virtual machines used to run the search engine is modified to reflect changes in workload. We propose an algorithm for incrementally adjusting the index to fit the varying number of virtual machines. We tested its performance using a custom-build prototype search engine deployed in the Amazon EC2 cloud, while calibrating the results to compensate for the performance fluctuations of the platform. Our experiments show that, when compared with computing the index from scratch, the incremental algorithm speeds up the index computation 2–10 times while maintaining a similar search performance.

Biochemical and Structural Studies on PrfA, the Transcriptional Regulator of Virulence in Listeria monocytogenes

Abstract

Listeria monocytogenes is a gram-positive soil saprophytic bacterium that is capable of causing fatal infection in humans. The main virulence regulator PrfA, a member of the Crp/FNR family of transcriptional regulators, activates the expression of essential proteins required for host cell invasion and cell-to-cell spread. The mechanism of PrfA activation and the identity of its small molecule coactivator have remained a mystery for more than 20 years, but it is hypothesized that PrfA shares mechanistic similarity to the E. coli cAMP binding protein, Crp. Crp activates gene expression by binding cAMP, increasing the DNA binding affinity of the protein and causing a significant DNA bend that facilitates RNA polymerase binding and downstream gene activation. Our data suggests PrfA activates virulence protein expression through a mechanism distinct from the canonical Crp activation mechanism that involves a combination of cysteine residue reduction and glutathione (GSH) binding.

Listeria lacking glutathione synthase (ΔgshF) is avirulent in mice; however virulence is rescued when the bacterium expresses the constitutively active PrfA mutant G145S. Interestingly, Listeria expressing a PrfA mutant in which its four cysteines are mutated to alanine (Quad PrfA), demonstrate a 30-fold decrease in virulence. The Quad and ΔgshF double mutant strains are avirulent. DNA-binding affinity, measured through fluorescence polarization assays, indicate reduction of the cysteine side chains is sufficient to allow PrfA to binds its physiological promoters Phly and PactA with low nanomolar affinity. Oxidized PrfA binds the promoters poorly.

Unexpectedly, Quad also binds promoter DNA with nanomolar affinity, suggesting that the cysteines play a role in transcription efficiency in addition to DNA binding. Both PrfA and Quad bind GSH at physiologically relevant and comparable affinities, however GSH did not affect DNA binding in either case. Thermal denaturation assays suggest that Quad and wild-type PrfA differ structurally upon binding GSH, which supports the in vivo difference in infection between the regulator and its mutant.

Structures of PrfA in complex with cognate DNA, determined through X-ray crystallography, further support the disparity between PrfA and Crp activation mechanisms as two structures of reduced PrfA bound to Phly (PrfA-Phly30 and PrfA-Phly24) suggest the DNA adopts a less bent DNA conformation when compared to Crp-cAMP- DNA. The structure of Quad-Phly30 confirms the DNA-binding data as the protein-DNA complex adopts the same overall conformation as PrfA-Phly.

From these results, we hypothesize a two-step activation mechanism wherein PrfA, oxidized upon cell entry and unable to bind DNA, is reduced upon its intracellular release and binds DNA, causing a slight bend in the promoter and small increase in transcription of PrfA-regulated genes. The structures of PrfA-Phly30 and PrfA-Phly24 likely visualize this intermediate complex. Increasing concentrations of GSH shift the protein to a (PrfA-GSH)-DNA complex which is fully active transcriptionally and is hypothesized to resemble closely the transcriptionally active structure of the cAMP-(Crp)-DNA complex. Thermal denaturation results suggest Quad PrfA is deficient in this second step, which explains the decrease in virulence and implicates the cysteine residues as critical for transcription efficiency. Further structural and biochemical studies are on-going to clarify this mechanism of activation.

Building an index of well-being for children living in Ireland: conceptual, measurement and policy considerations

This study conceptualised and measured children’s well-being in Ireland and considered how such conceptualisations and approaches to the measurement of well-being might inform social policy for children and families living in Ireland. This research explored what is meant by children’s well-being and how it can be conceptualised and measured so as to reflect the multi-dimensionality of the concept. The study developed an index of well-being that was both theoretically and methodologically robust and could be meaningfully used to inform social policy developments for children and their families. For the first time, an index of well-being for children was developed using an explicitly articulated unifying theory of children’s well-being. Moreover, for the first time an index of wellbeing was developed for 13-year old children living in Ireland using data from Wave 2 of the national longitudinal study of children. The Structural Model of Child Well-being (SMCW), the theoretical framework that underpins the development of this study’s index, offers a comprehensive understanding of well-being. The SMCW builds on, and integrates, a range of already-established theories concerning children’s development, their agency, rights and capabilities into a unifying theory that explains well-being in its entirety. This conceptualisation of well-being moves beyond the narrow focus on child development adopted in some recent studies of children’s well-being and which perpetuate individualised and self-responsibilising conceptualisations of well-being. This study found that the SMCW can be meaningfully applied, both theoretically and operationally, to the construction of an index of well-being for children. While it was not the purpose of this study to validate the SMCW, in the process of developing the index, I concluded that there was a theoretical ‘fit’ between the conceptual orientation of the SMCW and the wider children’s well-being literature. The ‘nested’ structure of the SMCW facilitated the identification of domains, sub-domains and indicators of well-being reflecting typical conventions of index construction. The findings from the resulting index, in both its categorical and continuous forms, demonstrated how a comprehensive theory of well-being can be used to illustrate how children are faring and which children are experiencing poorer or better well-being. Furthermore, this study demonstrated how the SMCW and the resultant index can be meaningfully used to support the implementation and review of the national policy framework for children and young people in Ireland.

Structural and Functional Characterization of the Human Tribbles Homologue 2 Pseudokinase

The Tribbles Homologues are a family of three eukaryotic pseudokinases (Trb1, Trb2, Trb3) that act as allosteric inhibitors and regulatory scaffold sites in pathways governing adipogenesis, cell proliferation and insulin signaling. The Tribbles Homologues have the same overall tertiary structure of the eukaryotic protein kinase domain, but lack multiple residues necessary to catalysis in the nucleotide-binding P-loop and the Mg2+-coordinating DFG motif. Trb1 has been shown conclusively to be incapable of binding ATP, whereas a recent study presents evidence that Trb2 autophosphorylates independently of Mg2+ in vitro. This finding is surprising given the high degree of sequence similarity between the two proteins (71%), and suggests unique nucleotide binding and phosphotransfer mechanisms. The goal of this project was to investigate whether Trb2 possesses kinase activity or not and determine its structural basis. A method for the high-yield recombinant expression and purification of stable Trb2 was developed. Trb2 nucleotide binding and autophosphorylation could not be detected across multiple experimental approaches, including thermal shift assays, MANT-ATP fluorescence, radiolabeled phosphate incorporation, and nonspecific ATPase activity assays. Further characterization also revealed that Trb2 forms homomultimers with possible functional consequences, and extensive crystallization screening has yielded multiple promising conditions that could produce diffraction-quality crystals with further optimization. This project explores the difficulties in functionally characterizing putatively active pseudokinases, and proposes a structural basis for the conserved pseudokinase features of the Tribbles homologues.

Systematic review of Late Jurassic sauropods from the Museu Geológico collections (Lisboa, Portugal)

The Museu Geológico collections house some of the first sauropod references of the Lusitanian Basin Upper Jurassic record, including the Lourinhasaurus alenquerensis and Lusotitan atalaiensis lectotypes, previously considered as new species of the Apatosaurus and Brachiosaurus genera, respectively. Several fragmentary specimens have been classical referred to those taxa, but the most part of these systematic attributions are not supported herein, excluding a caudal vertebra from Maceira (MG 8804) considered as cf. Lusotitan atalaiensis. From the material housed in the Museu Geológico were identified basal eusauropods (indeterminate eusauropods and turiasaurs) and neosauropods (indeterminate neosauropods, diplodods and camarasaurids and basal titanosauriforms). Middle caudal vertebrae with lateral fossae, ventral hollow border by pronounced ventrolateral crests and quadrangular cross-section suggest for the presence of diplodocine diplodocids in north area of the Lusitanian Basin Central Sector during the Late Jurassic. A humerus collected from Praia dos Frades (MG 4976) is attributed to cf. Duriatitan humerocristatus suggesting the presence of shared sauropod forms between the Portugal and United Kingdom during the Late Jurassic. Duriatitan is an indeterminate member of Eusauropoda and the discovery of new material in both territories is necessary to confirm this systematic approach. The studied material is in according with the previous recorded paleobiodiversity for the sauropod clade during the Portuguese Late Jurassic, which includes basal eusauropods (including turiasaurs), diplodocids and macronarians (including camarasaurids and basal titanosauriforms).

Structural and Functional Lung Impairment in Adult Survivors of Bronchopulmonary Dysplasia

RATIONALE: As more preterm infants recover from severe bronchopulmonary dysplasia (BPD), it is critical to understand the clinical consequences of this condition on the lung health of adult survivors.

OBJECTIVES: To assess structural and functional lung parameters in young adult BPD survivors and preterm and term controls Methods: Young adult survivors of BPD (mean age 24) underwent spirometry, lung volumes, transfer factor, lung clearance index and fractional exhaled nitric oxide measurements together with high-resolution chest tomographic (CT) imaging and cardiopulmonary exercise testing.

MEASUREMENTS AND MAIN RESULTS: 25 adult BPD survivors, (mean ± SD gestational age 26.8 ± 2.3 weeks; birth weight 866 ± 255 g), 24 adult prematurely born non-BPD controls (gestational age 30.6 ± 1.9 weeks; birth weight 1234 ± 207 g) and 25 adult term birth control subjects (gestational age 38.5 ± 0.9 weeks; and birth weight 3569 ± 2979 g) were studied. BPD subjects were more likely to be wakened by cough (OR 9.7, 95% CI: 1.8 to 52.6), p<0.01), wheeze and breathlessness (OR 12.2, 95%CI: 1.3 to 112), p<0.05) than term controls after adjusting for sex and current smoking. Preterm subjects had greater airways obstruction than term subjects. BPD subjects had significantly lower values for FEV1 and FEF25-75 (% predicted and z scores) than term controls (both p<0.001). Although non-BPD subjects also had lower spirometric values than term controls, none of the differences reached statistical significance. More BPD subjects (25%) had fixed airflow obstruction than non-BPD (12.5%) and term (0%) subjects (p=0.004). Both BPD and non-BPD subjects had significantly greater impairment in gas transfer (KCO % predicted) than term subjects (both p<0.05). Eighteen (37%) preterm participants were classified as small for gestational age (birth weight < 10th percentile for gestational age). These subjects had significantly greater impairment in FEV1 (% predicted and z scores) than those born appropriate for gestational age. BPD survivors had significantly more severe radiographic structural lung impairment than non-BPD subjects. Both preterm groups had impaired exercise capacity compared to term controls. There was a trend for greater limitation and leg discomfort in BPD survivors.

CONCLUSIONS: Adult preterm birth survivors, especially those who developed BPD, continue to experience respiratory symptoms and exhibit clinically important levels of pulmonary impairment.

Similarity between the in vitro activity and toxicity of two different fungizone™ / lipofundin™ admixtures

Amphotericin B (AmB), an antifungal agent that presents a broad spectrum of activity, remains the gold standard in the antifungal therapy. However, sometimes the high level of toxicity forbids its clinical use. The aim of this work was to evaluate and compare the efficacy and toxicity in vitro of Fungizon™ (AmB-D) and two new different AmB formulations. Methods: three products were studied: Fungizon™, and two Fungizon™ /Lipofundin™ admixtures, which were diluted through two methods: in the first one, Fungizon™ was previously diluted with water for injection and then, in Lipofundin™ (AmB-DAL); the second method consisted of a primary dilution of AmB-D as a powder in the referred emulsion (AmB-DL). For the in vitro assay, two cell models were used: Red Blood Cells (RBC) from human donors and Candida tropicallis (Ct). The in vitro evaluation (K+ leakage, hemoglobin leakage and cell survival rate-CSR) was performed at four AmB concentrations (from 50 to 0.05mg.L-1). Results: The results showed that the action of AmB was not only concentration dependent, but also cellular type and vehicle kind dependent. At AmB concentrations of 50 mg.L-1, although the hemoglobin leakage for AmB-D was almost complete (99.51), for AmB-DAL and AmB-DL this value tended to zero. The p = 0.000 showed that AmB-D was significantly more hemolytic. Conclusion: The Fungizon™- Lipofundin™ admixtures seem to be the more valuable AmB carrier systems due to their best therapeutic index presented

A cross-sectional study assessing the association between online ratings and structural and quality of care measures : results from two German physician rating websites

BACKGROUND: Even though physician rating websites (PRWs) have been gaining in importance in both practice and research, little evidence is available on the association of patients' online ratings with the quality of care of physicians. It thus remains unclear whether patients should rely on these ratings when selecting a physician. The objective of this study was to measure the association between online ratings and structural and quality of care measures for 65 physician practices from the German Integrated Health Care Network "Quality and Efficiency" (QuE). METHODS: Online reviews from two German PRWs were included which covered a three-year period (2011 to 2013) and included 1179 and 991 ratings, respectively. Information for 65 QuE practices was obtained for the year 2012 and included 21 measures related to structural information (N = 6), process quality (N = 10), intermediate outcomes (N = 2), patient satisfaction (N = 1), and costs (N = 2). The Spearman rank coefficient of correlation was applied to measure the association between ratings and practice-related information. RESULTS: Patient satisfaction results from offline surveys and the patients per doctor ratio in a practice were shown to be significantly associated with online ratings on both PRWs. For one PRW, additional significant associations could be shown between online ratings and cost-related measures for medication, preventative examinations, and one diabetes type 2-related intermediate outcome measure. There again, results from the second PRW showed significant associations with the age of the physicians and the number of patients per practice, four process-related quality measures for diabetes type 2 and asthma, and one cost-related measure for medication. CONCLUSIONS: Several significant associations were found which varied between the PRWs. Patients interested in the satisfaction of other patients with a physician might select a physician on the basis of online ratings. Even though our results indicate associations with some diabetes and asthma measures, but not with coronary heart disease measures, there is still insufficient evidence to draw strong conclusions. The limited number of practices in our study may have weakened our findings.

On the effect of word frequency on distributional similarity

The dependency of word similarity in vector space models on the frequency of words has been noted in a few studies, but has received very little attention. We study the influence of word frequency in a set of 10 000 randomly selected word pairs for a number of different combinations of feature weighting schemes and similarity measures. We find that the similarity of word pairs for all methods, except for the one using singular value decomposition to reduce the dimensionality of the feature space, is determined to a large extent by the frequency of the words. In a binary classification task of pairs of synonyms and unrelated words we find that for all similarity measures the results can be improved when we correct for the frequency bias.

Physical and chemical kinetics of structural build-up of cement suspensions

Abstract : The structural build-up of fresh cement-based materials has a great impact on their structural performance after casting. Accordingly, the mixture design should be tailored to adapt the kinetics of build-up given the application on hand. The rate of structural build-up of cement-based suspensions at rest is a complex phenomenon affected by both physical and chemical structuration processes. The structuration kinetics are strongly dependent on the mixture’s composition, testing parameters, as well as the shear history. Accurate measurements of build-up rely on the efficiency of the applied pre-shear regime to achieve an initial well-dispersed state as well as the applied stress during the liquid-solid transition. Studying the physical and chemical mechanisms of build-up of cement suspensions at rest can enhance the fundamental understanding of this phenomenon. This can, therefore, allow a better control of the rheological and time-dependent properties of cement-based materials. The research focused on the use of dynamic rheology in investigating the kinetics of structural build-up of fresh cement pastes. The research program was conducted in three different phases. The first phase was devoted to evaluating the dispersing efficiency of various disruptive shear techniques. The investigated shearing profiles included rotational, oscillatory, and combination of both. The initial and final states of suspension’s structure, before and after disruption, were determined by applying a small-amplitude oscillatory shear (SAOS). The difference between the viscoelastic values before and after disruption was used to express the degree of dispersion. An efficient technique to disperse concentrated cement suspensions was developed. The second phase aimed to establish a rheometric approach to dissociate and monitor the individual physical and chemical mechanisms of build-up of cement paste. In this regard, the non-destructive dynamic rheometry was used to investigate the evolutions of both storage modulus and phase angle of inert calcium carbonate and cement suspensions. Two independent build-up indices were proposed. The structural build-up of various cement suspensions made with different cement contents, silica fume replacement percentages, and high-range water reducer dosages was evaluated using the proposed indices. These indices were then compared to the well-known thixotropic index (Athix.). Furthermore, the proposed indices were correlated to the decay in lateral pressure determined for various cement pastes cast in a pressure column. The proposed pre-shearing protocol and build-up indices (phases 1 and 2) were then used to investigate the effect of mixture’s parameters on the kinetics of structural build-up in phase 3. The investigated mixture’s parameters included cement content and fineness, alkali sulfate content, and temperature of cement suspension. Zeta potential, calorimetric, spectrometric measurements were performed to explore the corresponding microstructural changes in cement suspensions, such as inter-particle cohesion, rate of Brownian flocculation, and nucleation rate. A model linking the build-up indices and the microstructural characteristics was developed to predict the build-up behaviour of cement-based suspensions The obtained results showed that oscillatory shear may have a greater effect on dispersing concentrated cement suspension than the rotational shear. Furthermore, the increase in induced shear strain was found to enhance the breakdown of suspension’s structure until a critical point, after which thickening effects dominate. An effective dispersing method is then proposed. This consists of applying a rotational shear around the transitional value between the linear and non-linear variations of the apparent viscosity with shear rate, followed by an oscillatory shear at the crossover shear strain and high angular frequency of 100 rad/s. Investigating the evolutions of viscoelastic properties of inert calcite-based and cement suspensions and allowed establishing two independent build-up indices. The first one (the percolation time) can represent the rest time needed to form the elastic network. On the other hand, the second one (rigidification rate) can describe the increase in stress-bearing capacity of formed network due to cement hydration. In addition, results showed that combining the percolation time and the rigidification rate can provide deeper insight into the structuration process of cement suspensions. Furthermore, these indices were found to be well-correlated to the decay in the lateral pressure of cement suspensions. The variations of proposed build-up indices with mixture’s parameters showed that the percolation time is most likely controlled by the frequency of Brownian collisions, distance between dispersed particles, and intensity of cohesion between cement particles. On the other hand, a higher rigidification rate can be secured by increasing the number of contact points per unit volume of paste, nucleation rate of cement hydrates, and intensity of inter-particle cohesion.