643 resultados para Reveal
Resumo:
The objective of this paper is to develop insights into firms’ strategic capability development processes within product innovation projects. In particular, the research aims at investigating the interactions among product innovation, knowledge processes, and capability development within firms. Building on qualitative data from the auto-industry, our analysis reveals that across four product innovation projects, the case company developed architectural knowledge and capability. Findings reveal that, along with changes at each level of product architecture, “design knowledge” and “design capability” have been developed at the same level of product architecture, leading to capability development at that level. Furthermore, findings suggest that such capability transformation resulting from knowledge and capability creation over the course of case projects leads to modularization of product architecture. Overall, the research contributes to identifying and emphasizing the role of micro processes in capability development and renewal, which in turn enhances our understanding of strategic capability development processes.
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A promising approach to the persistent problem of workplace sexual harassment (SH) is encouraging interventions by bystanders. Adopting a typology developed by Bowes-Sperry and O'Leary-Kelly that considers the level of immediacy and involvement of bystander interventions, this study explored 74 detailed descriptions of SH events that occurred in Australian workplaces. The findings reveal that despite the hidden nature of SH, there is significant involvement of actors who are not direct targets but their actions are frequently delayed, temporary or ineffective. The study makes two contributions to the study and practice of HRM. First, it provides important evidence of the different ways that bystanders respond to SH in real workplaces and the relative likelihood of these actions. Second, the study points to relevant contextual features evident in the scenarios described which determine if and how bystanders intervene. We discuss the utility of the bystander framework for future research and practice, including the development of bystander interventions as a potentially innovative response to the persistent and damaging problem of workplace SH.
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The Ugly Australian Underground documents the music, songwriting, aesthetics and struggles of fifty of Australia’s most innovative and significant bands and artists currently at the creative peak of their careers. The book provides a rare insight into the critically heralded cult music scene in Australia. The author, Jimi Kritzler, is both a journalist and a musician, and is personally connected to the musicians he interviews through his involvement in this music subculture. The interviews are extremely personal and reveal much more than any interview granted to street press or blogs. They deal with not only the music and songwriting processes of each band, but in some circumstances their struggles with drugs, involvement in crime and the death of band members.
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For design-build (DB) projects, owners normally use lump sum and Guaranteed Maximum Price (GMP) as the major contract payment provisions. However, there was a lack of empirical studies to compare the project performance within different contract types and investigate how different project characteristics affect the owners’ selection of contract arrangement. Project information from Design-build Institute of America (DBIA) database was collected to reveal the statistical relationship between different project characteristics and contract types and to compare project performance between lump sum and GMP contract. The results show that lump sum is still the most frequently used contract method for DB projects, especially in the public sector. However, projects using GMP contract are more likely to have less schedule delay and cost overrun as compared to those with lump sum contract. The chi-square tests of cross tabulations reveal that project type, owner type, and procurement method affect the selection of contract types significantly. Civil infrastructure rather than industrial engineering project tends to use lump sum more frequently; and qualification-oriented contractor selection process resorts to GMP more often compared with cost-oriented process. The findings of this research contribute to the current body of knowledge concerning the effect of associated project characteristics on contract type selection. Overall, the results of this study provide empirical evidence from real DB projects that can be used by owners to select appropriate contract types and eventually improve future project performance.
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Over the past decades, universities have increasingly become involved in entrepreneurial activities. Despite efforts to embrace their ‘third mission’, universities still demonstrate great heterogeneity in terms of their involvement in academic entrepreneurship. This papers adopts an institutional perspective to understand how organizational characteristics affect research scientists’ entrepreneurial intentions. Specifically, we study the impact of university culture and climate on entrepreneurial intentions, including intentions to spin off a company, to engage in patenting or licensing and to interact with industry through contract research or consulting. Using a sample of 437 research scientists from Swedish and German universities, our results reveal that the extent to which universities articulate entrepreneurship as a fundamental element of their mission fosters research scientists’ intentions to engage in spin-off creation and intellectual property rights, but not industry-science interaction. Furthermore, the presence of university role models positively affects research scientists’ propensity to engage in entrepreneurial activities, both directly and indirectly through entrepreneurial self-efficacy. Finally, research scientists working at universities which explicitly reward people for ‘third mission’ related output show higher levels of spin-off and patenting or licensing intentions. This study has implications for both academics and practitioners, including university managers and policy makers.
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Canonical single-stranded DNA-binding proteins (SSBs) from the oligosaccharide/oligonucleotide-binding (OB) domain family are present in all known organisms and are critical for DNA replication, recombination and repair. The SSB from the hyperthermophilic crenarchaeote Sulfolobus solfataricus (SsoSSB) has a ‘simple’ domain organization consisting of a single DNA-binding OB fold coupled to a flexible C-terminal tail, in contrast with other SSBs in this family that incorporate up to four OB domains. Despite the large differences in the domain organization within the SSB family, the structure of the OB domain is remarkably similar all cellular life forms. However, there are significant differences in the molecular mechanism of ssDNA binding. We have determined the structure of the SsoSSB OB domain bound to ssDNA by NMR spectroscopy. We reveal that ssDNA recognition is modulated by base-stacking of three key aromatic residues, in contrast with the OB domains of human RPA and the recently discovered human homologue of SsoSSB, hSSB1. We also demonstrate that SsoSSB binds ssDNA with a footprint of five bases and with a defined binding polarity. These data elucidate the structural basis of DNA binding and shed light on the molecular mechanism by which these ‘simple’ SSBs interact with ssDNA.
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The aim of this thesis is to examine how risk tolerance and risk perception, two important but often misunderstood constructs, jointly influence client investment decisions in a financial advice context. By distinguishing the roles of these two risk constructs in client decision-making, in this thesis a new direction in studying financial/investment risks is provided while practice and regulation in the financial services industry is potentially informed. Based on the literature relating to risks and individual decision-making, a theoretical framework is developed and relevant hypotheses are tested in two studies with financial adviser clients in Australia. Results reveal that financial risk tolerance influences asset allocation both directly and indirectly through risk perception. The intervening role of risk perception suggests that risk tolerance affects how clients perceive the riskiness of an investment product which influences client decision-making.
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The scale of environmental problems in China is clearly evident. This paper analyses foreign direct investment (FDI) in China with a finite mixture model, also known as latent class model to understand the relationship between FDI and several pollutions. This is used to regresses FDI as function covariates including pollutants. The results reveal that FDI is affected by pollutants. There are cases reducing pollution deters foreign investment in China.
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Background The EphB4 receptor tyrosine kinase is overexpressed in many cancers including prostate cancer. The molecular mechanisms by which this ephrin receptor influences cancer progression are complex as there are tumor-promoting ligand-independent mechanisms in place as well as ligand-dependent tumor suppressive pathways. Methods We employed transient knockdown of EPHB4 in prostate cancer cells, coupled with gene microarray analysis, to identify genes that were regulated by EPHB4 and may represent linked tumor-promoting factors. We validated target genes using qRT-PCR and employed functional assays to determine their role in prostate cancer migration and invasion. Results We discovered that over 500 genes were deregulated upon EPHB4 siRNA knockdown, with integrin β8 (ITGB8) being the top hit (29-fold down-regulated compared to negative non-silencing siRNA). Gene ontology analysis found that the process of cell adhesion was highly deregulated and two other integrin genes, ITGA3 and ITGA10, were also differentially expressed. In parallel, we also discovered that over-expression of EPHB4 led to a concomitant increase in ITGB8 expression. In silico analysis of a prostate cancer progression microarray publically available in the Oncomine database showed that both EPHB4 and ITGB8 are highly expressed in prostatic intraepithelial neoplasia, the precursor to prostate cancer. Knockdown of ITGB8 in PC-3 and 22Rv1 prostate cancer cells in vitro resulted in significant reduction of cell migration and invasion. Conclusions These results reveal that EphB4 regulates integrin β8 expression and that integrin β8 plays a hitherto unrecognized role in the motility of prostate cancer cells and thus targeting integrin β8 may be a new treatment strategy for prostate cancer.
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A lack of access to primary care services, decreasing numbers of general practitioners (GPs) and free of charge visits have been cited as factors contributing to the rising demand on emergency departments. This study aims to investigate the sources of patients' referrals to emergency departments and track changes in the source of referral over a six-year period in Queensland. Data from Queensland Emergency Departments Information Systems were analyzed based on records from 21 hospitals for the periods 2003–04 to 2008–09. The emergency department data were compared with publicly available data on GPs services and patients attendance rates. In Queensland, the majority of patients are self-referred and a 6.6% growth between 2003–04 and 2008–09 (84.4% to 90% respectively) has been observed. The number of referrals made by GPs, hospitals and community services decreased by 29.4%, 40%, 42% respectively during the six-year period. The full-time workload equivalent GPs per 100,000 people increased by 4.5% and the number of GP attendances measured per capita rose by 4% (4.25 to 4.42). An examination of changes in the triage category of self-referred patients revealed an increase in triage category 1-3 by 60%, 36.2%, and 14.4% respectively. The number of self-referred patients in triage categories 4–5 decreased by 10.5% and 21.9% respectively. The results of this analysis reveal that although the number of services provided by GPs increased, the amount of referrals decreased, and the proportion of self-referred patients to emergency departments rose during the six-year period. In addition, a growth in urgent triage categories (1–3) has been observed, with a decline in the number of non-urgent categories (4–5) among patients who came directly to emergency departments. Understanding the reasons behind this situation is crucial for appropriate demand management. Possible explanations will be sought and presented based on patients' responses to an emergency department users' questionnaire.
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The study is the first to analyze genetic and environmental factors that affect brain fiber architecture and its genetic linkage with cognitive function. We assessed white matter integrity voxelwise using diffusion tensor imaging at high magnetic field (4 Tesla), in 92 identical and fraternal twins. White matter integrity, quantified using fractional anisotropy (FA), was used to fit structural equation models (SEM) at each point in the brain, generating three-dimensional maps of heritability. We visualized the anatomical profile of correlations between white matter integrity and full-scale, verbal, and performance intelligence quotients (FIQ, VIQ, and PIQ). White matter integrity (FA) was under strong genetic control and was highly heritable in bilateral frontal (a 2 = 0.55, p = 0.04, left; a 2 = 0.74, p = 0.006, right), bilateral parietal (a 2 = 0.85, p < 0.001, left; a 2 = 0.84, p < 0.001, right), and left occipital (a 2 = 0.76, p = 0.003) lobes, and was correlated with FIQ and PIQ in the cingulum, optic radiations, superior fronto- occipital fasciculus, internal capsule, callosal isthmus, and the corona radiata (p = 0.04 for FIQ and p = 0.01 for PIQ, corrected for multiple comparisons). In a cross-trait mapping approach, common genetic factors mediated the correlation between IQ and white matter integrity, suggesting a common physiological mechanism for both, and common genetic determination. These genetic brain maps reveal heritable aspects of white matter integrity and should expedite the discovery of single-nucleotide polymorphisms affecting fiber connectivity and cognition.
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Control of iron homeostasis is essential for healthy central nervous system function: iron deficiency is associated with cognitive impairment, yet iron overload is thought to promote neurodegenerative diseases. Specific genetic markers have been previously identified that influence levels of transferrin, the protein that transports iron throughout the body, in the blood and brain. Here, we discovered that transferrin levels are related to detectable differences in the macro- and microstructure of the living brain. We collected brain MRI scans from 615 healthy young adult twins and siblings, of whom 574 were also scanned with diffusion tensor imaging at 4 Tesla. Fiber integrity was assessed by using the diffusion tensor imaging-based measure of fractional anisotropy. In bivariate genetic models based on monozygotic and dizygotic twins, we discovered that partially overlapping additive genetic factors influenced transferrin levels and brain microstructure. We also examined common variants in genes associated with transferrin levels, TF and HFE, and found that a commonly carried polymorphism (H63D at rs1799945) in the hemochromatotic HFE gene was associated with white matter fiber integrity. This gene has a well documented association with iron overload. Our statistical maps reveal previously unknown influences of the same gene on brain microstructure and transferrin levels. This discovery may shed light on the neural mechanisms by which iron affects cognition, neurodevelopment, and neurodegeneration.
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We used diffusion tensor magnetic resonance imaging (DTI) to reveal the extent of genetic effects on brain fiber microstructure, based on tensor-derived measures, in 22 pairs of monozygotic (MZ) twins and 23 pairs of dizygotic (DZ) twins (90 scans). After Log-Euclidean denoising to remove rank-deficient tensors, DTI volumes were fluidly registered by high-dimensional mapping of co-registered MP-RAGE scans to a geometrically-centered mean neuroanatomical template. After tensor reorientation using the strain of the 3D fluid transformation, we computed two widely used scalar measures of fiber integrity: fractional anisotropy (FA), and geodesic anisotropy (GA), which measures the geodesic distance between tensors in the symmetric positive-definite tensor manifold. Spatial maps of intraclass correlations (r) between MZ and DZ twins were compared to compute maps of Falconer's heritability statistics, i.e. the proportion of population variance explainable by genetic differences among individuals. Cumulative distribution plots (CDF) of effect sizes showed that the manifold measure, GA, comparably the Euclidean measure, FA, in detecting genetic correlations. While maps were relatively noisy, the CDFs showed promise for detecting genetic influences on brain fiber integrity as the current sample expands.
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Identifying genetic variants influencing human brain structures may reveal new biological mechanisms underlying cognition and neuropsychiatric illness. The volume of the hippocampus is a biomarker of incipient Alzheimer's disease and is reduced in schizophrenia, major depression and mesial temporal lobe epilepsy. Whereas many brain imaging phenotypes are highly heritable, identifying and replicating genetic influences has been difficult, as small effects and the high costs of magnetic resonance imaging (MRI) have led to underpowered studies. Here we report genome-wide association meta-analyses and replication for mean bilateral hippocampal, total brain and intracranial volumes from a large multinational consortium. The intergenic variant rs7294919 was associated with hippocampal volume (12q24.22; N = 21,151; P = 6.70 × 10 -16) and the expression levels of the positional candidate gene TESC in brain tissue. Additionally, rs10784502, located within HMGA2, was associated with intracranial volume (12q14.3; N = 15,782; P = 1.12 × 10 -12). We also identified a suggestive association with total brain volume at rs10494373 within DDR2 (1q23.3; N = 6,500; P = 5.81 × 10 -7).
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This paper describes algorithms that can identify patterns of brain structure and function associated with Alzheimer's disease, schizophrenia, normal aging, and abnormal brain development based on imaging data collected in large human populations. Extraordinary information can be discovered with these techniques: dynamic brain maps reveal how the brain grows in childhood, how it changes in disease, and how it responds to medication. Genetic brain maps can reveal genetic influences on brain structure, shedding light on the nature-nurture debate, and the mechanisms underlying inherited neurobehavioral disorders. Recently, we created time-lapse movies of brain structure for a variety of diseases. These identify complex, shifting patterns of brain structural deficits, revealing where, and at what rate, the path of brain deterioration in illness deviates from normal. Statistical criteria can then identify situations in which these changes are abnormally accelerated, or when medication or other interventions slow them. In this paper, we focus on describing our approaches to map structural changes in the cortex. These methods have already been used to reveal the profile of brain anomalies in studies of dementia, epilepsy, depression, childhood- and adult-onset schizophrenia, bipolar disorder, attention-deficit/hyperactivity disorder, fetal alcohol syndrome, Tourette syndrome, Williams syndrome, and in methamphetamine abusers. Specifically, we describe an image analysis pipeline known as cortical pattern matching that helps compare and pool cortical data over time and across subjects. Statistics are then defined to identify brain structural differences between groups, including localized alterations in cortical thickness, gray matter density (GMD), and asymmetries in cortical organization. Subtle features, not seen in individual brain scans, often emerge when population-based brain data are averaged in this way. Illustrative examples are presented to show the profound effects of development and various diseases on the human cortex. Dynamically spreading waves of gray matter loss are tracked in dementia and schizophrenia, and these sequences are related to normally occurring changes in healthy subjects of various ages.