992 resultados para Target acquisition.
Resumo:
While past knowledge-based approaches to service innovation have emphasized the role of knowledge integration in the delivery of customer-focused solutions, these approaches do not adequately address the complexities inherent in knowledge acquisition and integration in project-oriented firms. Adopting a dynamic capability framework and building on knowledge-based approaches to innovation, the current study examines how the interplay of learning capabilities and knowledge integration capability impacts service innovation and sustained competitive advantage. This two-stage multi-sample study finds that entrepreneurial project-oriented service firms in their quest for competitive advantage through greater innovation invest in knowledge acquisition and integration capabilities. Implications for theory and practice are discussed and directions for future research provided.
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Objectives This study builds on research undertaken by Bernasco and Nieuwbeerta and explores the generalizability of a theoretically derived offender target selection model in three cross-national study regions. Methods Taking a discrete spatial choice approach, we estimate the impact of both environment- and offender-level factors on residential burglary placement in the Netherlands, the United Kingdom, and Australia. Combining cleared burglary data from all study regions in a single statistical model, we make statistical comparisons between environments. Results In all three study regions, the likelihood an offender selects an area for burglary is positively influenced by proximity to their home, the proportion of easily accessible targets, and the total number of targets available. Furthermore, in two of the three study regions, juvenile offenders under the legal driving age are significantly more influenced by target proximity than adult offenders. Post hoc tests indicate the magnitudes of these impacts vary significantly between study regions. Conclusions While burglary target selection strategies are consistent with opportunity-based explanations of offending, the impact of environmental context is significant. As such, the approach undertaken in combining observations from multiple study regions may aid criminology scholars in assessing the generalizability of observed findings across multiple environments.
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Despite the very substantial body of primary sources and secondary literature on Australia’s much-litigated statutory provisions proscribing misleading or deceptive conduct, the courts have provided little in the way of assistance about how to establish the knowledge base of the target audience at whom the public statement was directed. The purpose of this case note is to compare and contrast two recent decisions of the High Court of Australia that highlight the difficulties faced by applicants in attempting to establish a contravention of the relevant legislation where conduct is directed at a segment of the public or the public as a whole.
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The chlamydiae are obligate intracellular parasites that have evolved specific interactions with their various hosts and host cell types to ensure their successful survival and consequential pathogenesis. The species Chlamydia pneumoniae is ubiquitous, with serological studies showing that most humans are infected at some stage in their lifetime. While most human infections are asymptomatic, C. pneumoniae can cause more-severe respiratory disease and pneumonia and has been linked to chronic diseases such as asthma, atherosclerosis, and even Alzheimer's disease. The widely dispersed animal-adapted C. pneumoniae strains cause an equally wide range of diseases in their hosts. It is emerging that the ability of C. pneumoniae to survive inside its target cells, including evasion of the host's immune attack mechanisms, is linked to the acquisition of key metabolites. Tryptophan and arginine are key checkpoint compounds in this host-parasite battle. Interestingly, the animal strains of C. pneumoniae have a slightly larger genome, enabling them to cope better with metabolite restrictions. It therefore appears that as the evolutionarily more ancient animal strains have evolved to infect humans, they have selectively become more "susceptible" to the levels of key metabolites, such as tryptophan. While this might initially appear to be a weakness, it allows these human C. pneumoniae strains to exquisitely sense host immune attack and respond by rapidly reverting to a persistent phase. During persistence, they reduce their metabolic levels, halting progression of their developmental cycle, waiting until the hostile external conditions have passed before they reemerge.
Potential role of EPB41L3 (Protein 4.1B/Dal-1) as a target for treatment of advanced prostate cancer
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Background: Loss of erythrocyte membrane protein band 4.1-like 3 (EPB41L3; aliases: protein 4.1B, differentially expressed in adenocarcinoma of the lung-1 (Dal-1)) expression has been implicated in tumor progression. Objective: To evaluate literature describing the role of EPB41L3 in tumorigenesis and metastasis, and to consider whether targeting this gene would be useful in the treatment of prostate cancer. Methods: A literature review of studies describing EPB41L3 and its aliases was conducted. Online databases (NCBI, SwissProt) were also interrogated to collect further data. Results/conclusion: A growing body of evidence supports a role for loss of EPB41L3 in tumor progression, including in prostate cancer. Therapeutic strategies that could be harnessed to upregulate EPB41L3 gene expression in prostate cancer cells are currently being developed.
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Background: Serosorting, the practice of seeking to engage in unprotected anal intercourse with partners of the same HIV status as oneself, has been increasing among men who have sex with men. However, the effectiveness of serosorting as a strategy to reduce HIV risk is unclear, especially since it depends on the frequency of HIV testing. Methods: We estimated the relative risk of HIV acquisition associated with serosorting compared with not serosorting by using a mathematical model, informed by detailed behavioral data from a highly studied cohort of gay men. Results: We demonstrate that serosorting is unlikely to be highly beneficial in many populations of men who have sex with men, especially where the prevalence of undiagnosed HIV infections is relatively high. We find that serosorting is only beneficial in reducing the relative risk of HIV transmission if the prevalence of undiagnosed HIV infections is less than ∼20% and ∼40%, in populations of high (70%) and low (20%) treatment rates, respectively, even though treatment reduces the absolute risk of HIV transmission. Serosorting can be expected to lead to increased risk of HIV acquisition in many settings. In settings with low HIV testing rates serosorting can more than double the risk of HIV acquisition. Conclusions: Therefore caution should be taken before endorsing the practice of serosorting. It is very important to continue promotion of frequent HIV testing and condom use, particularly among people at high risk.
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Missoni is a luxury Italian knitwear brand that partnered with Target in September 2011 releasing a large, one off, mass-market collection that ranged from apparel to home wares. The collaboration received extensive media coverage and was consequently extremely sought after. The online sales site crashed within hours of opening while shelves were cleared in stores minutes after trading began. Within hours more than 40000 items from the collection were posted for sale online at greatly inflated prices. Evaluation of the case study revealed that sales of the Missoni collection increased following the collaboration and the value of the publicity generated at estimated US$100 million. The lack of available stock, despite the enormous hype created, reinforced Missoni’s luxury image. Missoni was able to gain massive awareness of the brand despite not employing any of its own communication channels in the promotion of the collaboration. However the co-branded collaboration was distinctively Missoni, potentially inciting comparison and confusion with the signature line. Nevertheless, this study shows that co-branding strategies can offer a viable opportunity for luxury brands to increase their market share, while they maintain their market position.
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Purpose: Older adults have increased visual impairment, including refractive blur from presbyopic multifocal spectacle corrections, and are less able to extract visual information from the environment to plan and execute appropriate stepping actions; these factors may collectively contribute to their higher risk of falls. The aim of this study was to examine the effect of refractive blur and target visibility on the stepping accuracy and visuomotor stepping strategies of older adults during a precision stepping task. Methods: Ten healthy, visually normal older adults (mean age 69.4 ± 5.2 years) walked up and down a 20 m indoor corridor stepping onto selected high and low-contrast targets while viewing under three visual conditions: best-corrected vision, +2.00 DS and +3.00 DS blur; the order of blur conditions was randomised between participants. Stepping accuracy and gaze behaviours were recorded using an eyetracker and a secondary hand-held camera. Results: Older adults made significantly more stepping errors with increasing levels of blur, particularly exhibiting under-stepping (stepping more posteriorly) onto the targets (p<0.05), while visuomotor stepping strategies did not significantly alter. Stepping errors were also significantly greater for the low compared to the high contrast targets and differences in visuomotor stepping strategies were found, including increased duration of gaze and increased interval between gaze onset and initiation of the leg swing when stepping onto the low contrast targets. Conclusions: These findings highlight that stepping accuracy is reduced for low visibility targets, and for high levels of refractive blur at levels typically present in multifocal spectacle corrections, despite significant changes in some of the visuomotor stepping strategies. These findings highlight the importance of maximising the contrast of objects in the environment, and may help explain why older adults wearing multifocal spectacle corrections exhibit an increased risk of falling.
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Transfer schemes are an alternative means of acquiring control of a company to making a takeover bid under the provisions in Ch 6 of the Corporations Act 2001 (Cth). The recent decision Re Kumarina Resources Ltd [2013] FCA 549 overturned long-standing practice in relation to a certain type of transfer scheme. If followed, the decision would allow a “bidder” to vote at scheme meetings where the scheme consideration for the acquisition of the target shares are shares in another company, and the scheme results in a merger. But the bidder is not allowed to vote where the scheme consideration is cash. The article points out the difficulties arising from this decision and argues that it should not be followed. In providing a “no objection” statement, the Australian Securities and Investments Commission (ASIC) has created uncertainty as to the approach it will take towards the bidders being allowed to vote at scheme meetings where the scheme consideration for the acquisition of target shares are shares in another company. The article also points out that in providing the no objection statement in Kumarina, ASIC appears to have ignored breaches of s 606(1) of the Corporations Act. There is a pressing need for ASIC to clarify its position and, in particular, whether or not it will provide a no objection statement in respect of future transfer schemes where a bidder (or its parent company) votes at the scheme meeting.
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Leucine is a key amino acid for initiating translation in muscle cells, but the dose-dependent effects of leucine on intracellular signaling are poorly characterized. This study examined the effect that increasing doses of leucine would have on changes in mechanistic target of rapamycin (mTOR)–mediated signaling, rates of protein synthesis, and cell size in C2C12 cells. We hypothesized that a leucine “threshold” exists, which represents the minimum stimulus required to initiate mTOR signaling in muscle cells. Acute exposure to 1.5, 3.2, 5.0, and 16.1 mM leucine increased phosphorylation of mTORSer2448 (~1.4-fold; P < .04), 4E-BP1 Thr37/46 (~1.9-fold; P < .001), and rpS6Ser235/6 (~2.3-fold; P < .001). However, only p70S6kThr389 exhibited a dose-dependent response to leucine with all treatments higher than control (~4-fold; P < .001) and at least 5 mM higher than the 1.5-mM concentration (1.2-fold; P < .02). Rates of protein synthesis were not altered by any treatment. Seven days of exposure to 0.5, 1.5, 5.0, and 16.5 mM leucine resulted in an increase in cell size in at least 5 mM treatments (~1.6-fold, P < .001 vs control). Our findings indicate that even at low leucine concentrations, phosphorylation of proteins regulating translation initiation signaling is enhanced. The phosphorylation of p70S6kThr389 follows a leucine dose-response relationship, although this was not reflected by the acute protein synthetic response. Nevertheless, under the conditions of the present study, it appears that leucine concentrations of at least 5 mM are necessary to enhance cell growth.
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Sortase A is a membrane enzyme responsible for the anchoring of surface-exposed proteins to the cell wall envelope of Gram-positive bacteria. As a well-studied member of the sortase subfamily catalysing the cell wall anchoring of important virulence factors to the surface of staphylococci, enterococci and streptococci, sortase A plays a critical role in Gram-positive bacterial pathogenesis. It is thus considered a promising target for the development of new anti-infective drugs that aim to interfere with important Gram-positive virulence mechanisms, such as adhesion to host tissues, evasion of host defences, and biofilm formation. The additional properties of sortase A as an enzyme that is not required for Gram-positive bacterial growth or viability and is conveniently located on the cell membrane making it more accessible to inhibitor targeting, constitute additional reasons reinforcing the view that sortase A is an ideal target for anti-virulence drug development. Many inhibitors of sortase A have been identified to date using high-throughput or in silico screening of compound libraries (synthetic or natural), and while many have proved useful tools for probing the action model of the enzyme, several are also promising candidates for the development into potent inhibitors. This review is focused on the most promising sortase A inhibitor compounds that are currently in development as leads towards a new class of anti-infective drugs that are urgently needed to help combat the alarming increase in antimicrobial resistance.
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We report that tumor cells devoid of their mitochondrial genome (mtDNA) show delayed tumor growth and that tumor formation is associated with acquisition of mtDNA from host cells. This leads to partial recovery of mitochondrial function in cells derived from primary tumors grown from cells without mtDNA and a shorter lag in tumor growth. Cell lines from circulating tumor cells showed further recovery of mitochondrial respiration and an intermediate lag to tumor growth, while cells from lung metastases exhibited full restoration of respiratory function and no lag in tumor growth. Stepwise assembly of mitochondrial respiratory supercomplexes was correlated with acquisition of respiratory function. Our findings indicate horizontal transfer of mtDNA from host cells in the tumor microenvironment to tumor cells with compromised respiratory function to re-establish respiration and tumor-initiating efficacy. These results suggest a novel pathophysiological process for overcoming mtDNA damage and support the notion of high plasticity of malignant cells.
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Background Value for money (VfM) on collaborative construction projects is dependent on the learning capabilities of the organisations and people involved. Within the context of infrastructure delivery, there is little research about the impact of organisational learning capability on project value. The literature contains a multiplicity of often un-testable definitions about organisational learning abilities. This paper defines learning capability as a dynamic capability that participant organisations purposely develop to add value to collaborative projects. The paper reports on a literature review that proposes a framework that conceptualises learning capability to explore the topic. This work is the first phase of a large-scale national survey funded by the Alliancing Association of Australasia and the Australian Research Council. Methodology Desk-top review of leading journals in the areas of strategic management, strategic alliances and construction management, as well as recent government documents and industry guidelines, was undertaken to synthesise, conceptualise and operationalise the concept of learning capability. The study primarily draws on the theoretical perspectives of the resource-based view of the firm (e.g. Barney 1991; Wernerfelt 1984), absorptive capacity (e.g. Cohen and Levinthal 1990; Zahra and George 2002); and dynamic capabilities (e.g. Helfat et al. 2007; Teece et al. 1997; Winter 2003). Content analysis of the literature was undertaken to identify key learning routines. Content analysis is a commonly used methodology in the social sciences area. It provides rich data through the systematic and objective review of literature (Krippendorff 2004). NVivo 9, a qualitative data analysis software package, was used to assist in this process. Findings and Future Research The review process resulted in a framework for the conceptualisation of learning capability that shows three phases of learning: (1) exploratory learning, (2) transformative learning and (3) exploitative learning. These phases combine both internal and external learning routines to influence project performance outcomes and thus VfM delivered under collaborative contracts. Sitting within these phases are eight categories of learning capability comprising knowledge articulation, identification, acquisition, dissemination, codification, internationalisation, transformation and application. The learning routines sitting within each category will be disaggregated in future research as the basis for measureable items in a large-scale survey study. The survey will examine the extent to which various learning routines influence project outcomes, as well as the relationships between them. This will involve identifying the routines that exist within organisations in the construction industry, their resourcing and rate of renewal, together with the extent of use and perceived value within the organisation. The target population is currently estimated to be around 1,000 professionals with experience in relational contracting in Australia. This future research will build on the learning capability framework to provide data that will assist construction organisations seeking to maximise VfM on construction projects.