Neurodevelopmental animal models of schizophrenia: Effects on prepulse inhibition

Epidemiological studies have shown increased incidence of schizophrenia in patients subjected to different forms of pre- or perinatal stress. However, as the onset of schizophrenic illness does not usually occur until adolescence or early adulthood, it is not yet fully understood how disruption of early brain development may ultimately lead to malfunction years later. In order to elucidate a possible role for neurodevelopmental factors in the pathogenesis of schizophrenia and to highlight potential new treatments, animal models are needed. Prepulse inhibition (PPI) is a model of sensorimotor gating mechanisms in the brain. It is disrupted in schizophrenia patients and the disruption can be reversed with atypical antipsychotics. It has been widely used in animal studies to explore central mechanisms possibly involved in schizophrenia. There has been a recent surge of behavioural and neurochemical animal studies on neurodevelopmental models, particularly on the effects of postweaning isolation, maternal separation and neonatal lesions of the hippocampus. In these models, long lasting alterations in behaviour and/or molecular changes in specific brain regions are observed, comparable to those seen in schizophrenia. The aim of this article is to critically review the available literature on such neurodevelopmental animal models with special focus on the effects on PPI and brain regions that are putatively involved in regulation of PPI.

The development of virtual leaf surface models for interactive agrichemical spray applications

This project constructed virtual plant leaf surfaces from digitised data sets for use in droplet spray models. Digitisation techniques for obtaining data sets for cotton, chenopodium and wheat leaves are discussed and novel algorithms for the reconstruction of the leaves from these three plant species are developed. The reconstructed leaf surfaces are included into agricultural droplet spray models to investigate the effect of the nozzle and spray formulation combination on the proportion of spray retained by the plant. A numerical study of the post-impaction motion of large droplets that have formed on the leaf surface is also considered.

Scoping study into wound management nurse practitioner models of practice

Objectives The primary objective of this research was to investigate wound management nurse practitioner (WMNP) models of service for the purposes of identifying parameters of practice and how patient outcomes are measured. Methods A scoping study was conducted with all authorised WMNPs in Australia from October to December 2012 using survey methodology. A questionnaire was developed to obtain data on the role and practice parameters of authorised WMNPs in Australia. The tool comprised seven sections and included a total of 59 questions. The questionnaire was distributed to all members of the WMNP Online Peer Review Group, to which it was anticipated the majority of WMNPs belonged. Results Twenty-one WMNPs responded (response rate 87%), with the results based on a subset of respondents who stated that, at the time of the questionnaire, they were employed as a WMNP, therefore yielding a response rate of 71% (n≤15). Most respondents (93%; n≤14) were employed in the public sector, with an average of 64 occasions of service per month. The typical length of a new case consultation was 60min, with 32min for follow ups. The most frequently performed activity was wound photography (83%; n≤12), patient, family or carer education (75%; n≤12), Doppler ankle-brachial pressure index assessment (58%; n≤12), conservative sharp wound debridement (58%; n≤12) and counselling (50%; n≤12). The most routinely prescribed medications were local anaesthetics (25%; n≤12) and oral antibiotics (25%; n≤12). Data were routinely collected by 91% of respondents on service-related and wound-related parameters to monitor patient outcomes, to justify and improve health services provided. Conclusion This study yielded important baseline information on this professional group, including data on patient problems managed, the types of interventions implemented, the resources used to accomplish outcomes and how outcomes are measured.

Effect of constitutive material models on seismic response of two-story reinforced concrete frame

This paper focuses on the finite element (FE) response sensitivity and reliability analyses considering smooth constitutive material models. A reinforced concrete frame is modeled for FE sensitivity analysis followed by direct differentiation method under both static and dynamic load cases. Later, the reliability analysis is performed to predict the seismic behavior of the frame. Displacement sensitivity discontinuities are observed along the pseudo-time axis using non-smooth concrete and reinforcing steel model under quasi-static loading. However, the smooth materials show continuity in response sensitivity at elastic to plastic transition points. The normalized sensitivity results are also used to measure the relative importance of the material parameters on the structural responses. In FE reliability analysis, the influence of smoothness behavior of reinforcing steel is carefully noticed. More efficient and reasonable reliability estimation can be achieved by using smooth material model compare with bilinear material constitutive model.

Murine, but not human, ephrin-B2 can be efficiently cleaved by the serine protease kallikrein-4: Implications for xenograft models of human prostate cancer

Background Ephrin-B2 is the sole physiologically-relevant ligand of the receptor tyrosine kinase EphB4, which is over-expressed in many epithelial cancers, including 66% of prostate cancers, and contributes to cancer cell survival, invasion and migration. Crucially, however, the cancer-promoting EphB4 signalling pathways are independent of interaction with its ligand ephrin-B2, as activation of ligand-dependent signalling causes tumour suppression. Ephrin-B2, however, is often found on the surface of endothelial cells of the tumour vasculature, where it can regulate angiogenesis to support tumour growth. Proteolytic cleavage of endothelial cell ephrin-B2 has previously been suggested as one mechanism whereby the interaction between tumour cell-expressed EphB4 and endothelial cell ephrin-B2 is regulated to support both cancer promotion and angiogenesis. Methods An in silico approach was used to search accessible surfaces of 3D protein models for cleavage sites for the key prostate cancer serine protease, KLK4, and this identified murine ephrin-B2 as a potential KLK4 substrate. Mouse ephrin-B2 was then confirmed as a KLK4 substrate by in vitro incubation of recombinant mouse ephrin-B2 with active recombinant human KLK4. Cleavage products were visualised by SDS-PAGE, silver staining and Western blot and confirmed by N-terminal sequencing. Results At low molar ratios, KLK4 cleaved murine ephrin-B2 but other prostate-specific KLK family members (KLK2 and KLK3/PSA) were less efficient, suggesting cleavage was KLK4-selective. The primary KLK4 cleavage site in murine ephrin-B2 was verified and shown to correspond to one of the in silico predicted sites between extracellular domain residues arginine 178 and asparagine 179. Surprisingly, the highly homologous human ephrin-B2 was poorly cleaved by KLK4 at these low molar ratios, likely due to the 3 amino acid differences at this primary cleavage site. Conclusion These data suggest that in in vivo mouse xenograft models, endogenous mouse ephrin-B2, but not human tumour ephrin-B2, may be a downstream target of cancer cell secreted human KLK4. This is a critical consideration when interpreting data from murine explants of human EphB4+/KLK4+ cancer cells, such as prostate cancer cells, where differential effects may be seen in mouse models as opposed to human clinical situations.

Extending building information models to construction specifications

This project examined the role that written specifications play in the building procurement process and the relationship that specifications should have with respect to the use of BIM within the construction industry. A three-part approach was developed to integrate specifications, product libraries and BIM. Typically handled by different disciplines within project teams, these provide the basis for a holistic approach to the development of building descriptions through the design process and into construction.

Some major problems with existing models and terminology associated with kimberlite pipes from a volcanological perspective, and some suggestions

Five significant problems hinder advances in understanding of the volcanology of kimberlites: (1) kimberlite geology is very model driven; (2) a highly genetic terminology drives deposit or facies interpretation; (3) the effects of alteration on preserved depositional textures have been grossly underestimated; (4) the level of understanding of the physical process significance of preserved textures is limited; and, (5) some inferred processes and deposits are not based on actual, modern volcanological processes. These issues need to be addressed in order to advance understanding of kimberlite volcanological pipe forming processes and deposits. The traditional, steep-sided southern African pipe model (Class I) consists of a steep tapering pipe with a deep root zone, a middle diatreme zone and an upper crater zone (if preserved). Each zone is thought to be dominated by distinctive facies, respectively: hypabyssal kimberlite (HK, descriptively called here massive coherent porphyritic kimberlite), tuffisitic kimberlite breccia (TKB, descriptively here called massive, poorly sorted lapilli tuff) and crater zone facies, which include variably bedded pyroclastic kimberlite and resedimented and reworked volcaniclastic kimberlite (RVK). Porphyritic coherent kimberlite may, however, also be emplaced at different levels in the pipe, as later stage intrusions, as well as dykes in the surrounding country rock. The relationship between HK and TKB is not always clear. Sub-terranean fluidisation as an emplacement process is a largely unsubstantiated hypothesis; modern in-vent volcanological processes should initially be considered to explain observed deposits. Crater zone volcaniclastic deposits can occur within the diatreme zone of some pipes, indicating that the pipe was largely empty at the end of the eruption, and subsequently began to fill-in largely through resedimentation and sourcing of pyroclastic deposits from nearby vents. Classes II and III Canadian kimberlite models have a more factual, descriptive basis, but are still inadequately documented given the recency of their discovery. The diversity amongst kimberlite bodies suggests that a three-model classification is an over-simplification. Every kimberlite is altered to varying degrees, which is an intrinsic consequence of the ultrabasic composition of kimberlite and the in-vent context; few preserve original textures. The effects of syn- to post-emplacement alteration on original textures have not been adequately considered to date, and should be back-stripped to identify original textural elements and configurations. Applying sedimentological textural configurations as a guide to emplacement processes would be useful. The traditional terminology has many connotations about spatial position in pipe and of process. Perhaps the traditional terminology can be retained in the industrial situation as a general lithofacies-mining terminological scheme because it is so entrenched. However, for research purposes a more descriptive lithofacies terminology should be adopted to facilitate detailed understanding of deposit characteristics, important variations in these, and the process origins. For example every deposit of TKB is different in componentry, texture, or depositional structure. However, because so many deposits in many different pipes are called TKB, there is an implication that they are all similar and that similar processes were involved, which is far from clear.

Middle managers' uncertainty management during organizational change

Purpose This study aims to identify factors that facilitate or inhibit middle managers' experience of uncertainty management during organizational change. Design/methodology/approach The approach is qualitative and involved interviews with 40 middle managers from a range of organizations. Findings Analysis revealed that at the pre‐implementation stage, uncertainty focused on the strategic concept of the change, whereas at implementation, uncertainty related to the appropriate procedures to implement. Middle managers’ uncertainty management was found to be important in assisting their employees in the change transition. The factors identified as being either facilitators or barriers to uncertainty management focused on themes related to the design of change, communication with both senior management and their own staff, support from senior management, role conflict, and peer interaction. A model was created to link facilitators and barriers with uncertainty to guide future research. Research limitations/implications Implications for organizational change research along with practical implications are discussed. Originality/value This study provides insight into the positive contributions middle managers can make during change, along with suggesting what factors are facilitators or barriers to this positive role.

A longitudinal study of employee adaptation to organizational change: The role of change-related information and change-related self-efficacy

This study examined the role of information, efficacy, and 3 stressors in predicting adjustment to organizational change. Participants were 589 government employees undergoing an 18-month process of regionalization. To examine if the predictor variables had long-term effects on adjustment, the authors assessed psychological well-being, client engagement, and job satisfaction again at a 2-year follow-up. At Time 1, there was evidence to suggest that information was indirectly related to psychological well-being, client engagement, and job satisfaction, via its positive relationship to efficacy. There also was evidence to suggest that efficacy was related to reduced stress appraisals, thereby heightening client engagement. Last, there was consistent support for the stress-buffering role of Time 1 self-efficacy in the prediction of Time 2 job satisfaction.

Linking business goals to process models in semantic business process modeling

Broad knowledge is required when a business process is modeled by a business analyst. We argue that existing Business Process Management methodologies do not consider business goals at the appropriate level. In this paper we present an approach to integrate business goals and business process models. We design a Business Goal Ontology for modeling business goals. Furthermore, we devise a modeling pattern for linking the goals to process models and show how the ontology can be used in query answering. In this way, we integrate the intentional perspective into our business process ontology framework, enriching the process description and enabling new types of business process analysis. © 2008 IEEE.

Cross database training of audio-visual hidden Markov models for phone recognition

Speech recognition can be improved by using visual information in the form of lip movements of the speaker in addition to audio information. To date, state-of-the-art techniques for audio-visual speech recognition continue to use audio and visual data of the same database for training their models. In this paper, we present a new approach to make use of one modality of an external dataset in addition to a given audio-visual dataset. By so doing, it is possible to create more powerful models from other extensive audio-only databases and adapt them on our comparatively smaller multi-stream databases. Results show that the presented approach outperforms the widely adopted synchronous hidden Markov models (HMM) trained jointly on audio and visual data of a given audio-visual database for phone recognition by 29% relative. It also outperforms the external audio models trained on extensive external audio datasets and also internal audio models by 5.5% and 46% relative respectively. We also show that the proposed approach is beneficial in noisy environments where the audio source is affected by the environmental noise.

A Web-based system enabling the integration, analysis, and 3D sub-surface visualization of groundwater monitoring data and geological models

The 3D Water Chemistry Atlas is an intuitive, open source, Web-based system that enables the three-dimensional (3D) sub-surface visualization of ground water monitoring data, overlaid on the local geological model (formation and aquifer strata). This paper firstly describes the results of evaluating existing virtual globe technologies, which led to the decision to use the Cesium open source WebGL Virtual Globe and Map Engine as the underlying platform. Next it describes the backend database and search, filtering, browse and analysis tools that were developed to enable users to interactively explore the groundwater monitoring data and interpret it spatially and temporally relative to the local geological formations and aquifers via the Cesium interface. The result is an integrated 3D visualization system that enables environmental managers and regulators to assess groundwater conditions, identify inconsistencies in the data, manage impacts and risks and make more informed decisions about coal seam gas extraction, waste water extraction, and water reuse.

A longitudinal investigation of coping processes during a merger: Implications for job satisfaction and organizational identification

This study tested the utility of a stress and coping model of employee adjustment to a merger. Two hundred and twenty employees completed both questionnaires (Time 1: 3 months after merger implementation; Time 2: 2 years later). Structural equation modeling analyses revealed that positive event characteristics predicted greater appraisals of self-efficacy and less stress at Time 1. Self-efficacy, in turn, predicted greater use of problem-focused coping at Time 2, whereas stress predicted a greater use of problem-focused and avoidance coping. Finally, problem-focused coping predicted higher levels of job satisfaction and identification with the merged organization (Time 2), whereas avoidance coping predicted lower identification.

The importance of connexin hemichannels during chondroprogenitor cell differentiation in hydrogel versus microtissue culture models

Appropriate selection of scaffold architecture is a key challenge in cartilage tissue engineering. Gap junction-mediated intercellular contacts play important roles in precartilage condensation of mesenchymal cells. However, scaffold architecture could potentially restrict cell-cell communication and differentiation. This is particularly important when choosing the appropriate culture platform as well as scaffold-based strategy for clinical translation, that is, hydrogel or microtissues, for investigating differentiation of chondroprogenitor cells in cartilage tissue engineering. We, therefore, studied the influence of gap junction-mediated cell-cell communication on chondrogenesis of bone marrow-derived mesenchymal stromal cells (BM-MSCs) and articular chondrocytes. Expanded human chondrocytes and BM-MSCs were either (re-) differentiated in micromass cell pellets or encapsulated as isolated cells in alginate hydrogels. Samples were treated with and without the gap junction inhibitor 18-α glycyrrhetinic acid (18αGCA). DNA and glycosaminoglycan (GAG) content and gene expression levels (collagen I/II/X, aggrecan, and connexin 43) were quantified at various time points. Protein localization was determined using immunofluorescence, and adenosine-5'-triphosphate (ATP) was measured in conditioned media. While GAG/DNA was higher in alginate compared with pellets for chondrocytes, there were no differences in chondrogenic gene expression between culture models. Gap junction blocking reduced collagen II and extracellular ATP in all chondrocyte cultures and in BM-MSC hydrogels. However, differentiation capacity was not abolished completely by 18αGCA. Connexin 43 levels were high throughout chondrocyte cultures and peaked only later during BM-MSC differentiation, consistent with the delayed response of BM-MSCs to 18αGCA. Alginate hydrogels and microtissues are equally suited culture platforms for the chondrogenic (re-)differentiation of expanded human articular chondrocytes and BM-MSCs. Therefore, reducing direct cell-cell contacts does not affect in vitro chondrogenesis. However, blocking gap junctions compromises cell differentiation, pointing to a prominent role for hemichannel function in this process. Therefore, scaffold design strategies that promote an increasing distance between single chondroprogenitor cells do not restrict their differentiation potential in tissue-engineered constructs.