Cellular uptake and imaging studies of gadolinium-loaded single-walled carbon nanotubes

postprintThe 18th Joint Annual Meeting of ISMRM-ESMRMB, Stockholm, Sweden, 1-7 May 2010

The two PPX-GppA homologues from Mycobacterium tuberculosis have distinct biochemical activities

Inorganic polyphosphate (poly-P), guanosine pentaphosphate (pppGpp) and guanosine tetraphosphate (ppGpp) are ubiquitous in bacteria. These molecules play a variety of important physiological roles associated with stress resistance, persistence, and virulence. In the bacterial pathogen Mycobacterium tuberculosis, the identities of the proteins responsible for the metabolism of polyphosphate and (p)ppGpp remain to be fully established. M. tuberculosis encodes two PPX-GppA homologues, Rv0496 (MTB-PPX1) and Rv1026, which share significant sequence similarity with bacterial exopolyphosphatase (PPX) and guanosine pentaphosphate 5′-phosphohydrolase (GPP) proteins. Here we delineate the respective biochemical activities of the Rv0496 and Rv1026 proteins and benchmark these against the activities of the PPX and GPP proteins from Escherichia coli. We demonstrate that Rv0496 functions as an exopolyphosphatase, showing a distinct preference for relatively short-chain poly-P substrates. In contrast, Rv1026 has no detectable exopolyphosphatase activities. Analogous to the E. coli PPX and GPP enzymes, the exopolyphosphatase activities of Rv0496 are inhibited by pppGpp and, to a lesser extent, by ppGpp alarmones, which are produced during the bacterial stringent response. However, neither Rv0496 nor Rv1026 have the ability to hydrolyze pppGpp to ppGpp; a reaction catalyzed by E. coli PPX and GPP. Both the Rv0496 and Rv1026 proteins have modest ATPase and to a lesser extent ADPase activities. pppGpp alarmones inhibit the ATPase activities of Rv1026 and, to a lesser extent, the ATPase activities of Rv0496. We conclude that PPX-GppA family proteins may not possess all the catalytic activities implied by their name and may play distinct biochemical roles involved in polyphosphate and (p)ppGpp metabolic pathways. © 2012 2012 Choi et al.published_or_final_versio

Efficient RFID Tag Placement Framework for In Building Navigation System for the Blind

To date, there are increasing buildings with complex design, multi-storey and with large-scaled area. The complicated building layout could lead to certain level of difficulties for the blind or the visually impaired people in path identification in an unfamiliar surrounding such as in a new shopping complex. Radio Frequency Identification (RFID) technology appeared as an effective solution to provide location-based information to the visually impaired or blind people in indoor environment.However, RFID tags placement which can provide high positional accuracy will become an issue in effective deployment of large-scaled RFID network in a large building. This can be a very time consuming process and it is too costly to estimate the required number of RFID tags manually. In addition, the vendors do not have a standard framework or guideline in determining the tag placement process optimally. Without knowing the meaning of tag placement which provides useful location information and effective detection for the visually impaired or blind person could cause inaccurately aiding them in navigation in a large-scaled building. Therefore, a framework with automatic suggestion of intelligent optimization for RFID tags placement in a large building will be proposed in order to effectively implement RFID based navigation network for the building in terms of cost effectiveness. This framework will become the guideline to create a friendly environment for visually impaired person enabling them to enjoy high mobility in any multi-storey or large building

Heritage branding orientation: The case of Ach. Brito and the dynamics between corporate and product heritage brands

The notion of heritage branding orientation is introduced and explicated. Heritage branding orientation is designated as embracing both product and corporate brands and differs from corporate heritage brand orientation which has an explicit corporate focus. Empirical insights are drawn from an in-depth and longitudinal case study of Ach. Brito, a celebrated Portuguese manufacturer of soaps and toiletries. This study shows how, by the pursuance of a strategy derived from a heritage branding orientation Ach. Brito – after a prolonged period of decline – achieved a dramatic strategic turnaround. The findings reveal how institutional heritage can be a strategic resource via its adoption and activation at both the product and corporate levels. Moreover, the study showed how the bi-lateral interplay between product and corporate brand levels can be mutually reinforcing. In instrumental terms, the study shows how heritage can be activated and articulated in different ways. For instance, it can re-position both product and/or corporate brands; it can be meaningfully informed by product brand heritage and shape corporate heritage; and can be of strategic importance to both medium-sized and small enterprises

Optimal search strategies for identifying sound clinical prediction studies in EMBASE

BACKGROUND: Clinical prediction guides assist clinicians by pointing to specific elements of the patient's clinical presentation that should be considered when forming a diagnosis, prognosis or judgment regarding treatment outcome. The numbers of validated clinical prediction guides are growing in the medical literature, but their retrieval from large biomedical databases remains problematic and this presents a barrier to their uptake in medical practice. We undertook the systematic development of search strategies ("hedges") for retrieval of empirically tested clinical prediction guides from EMBASE. METHODS: An analytic survey was conducted, testing the retrieval performance of search strategies run in EMBASE against the gold standard of hand searching, using a sample of all 27,769 articles identified in 55 journals for the 2000 publishing year. All articles were categorized as original studies, review articles, general papers, or case reports. The original and review articles were then tagged as 'pass' or 'fail' for methodologic rigor in the areas of clinical prediction guides and other clinical topics. Search terms that depicted clinical prediction guides were selected from a pool of index terms and text words gathered in house and through request to clinicians, librarians and professional searchers. A total of 36,232 search strategies composed of single and multiple term phrases were trialed for retrieval of clinical prediction studies. The sensitivity, specificity, precision, and accuracy of search strategies were calculated to identify which were the best. RESULTS: 163 clinical prediction studies were identified, of which 69 (42.3%) passed criteria for scientific merit. A 3-term strategy optimized sensitivity at 91.3% and specificity at 90.2%. Higher sensitivity (97.1%) was reached with a different 3-term strategy, but with a 16% drop in specificity. The best measure of specificity (98.8%) was found in a 2-term strategy, but with a considerable fall in sensitivity to 60.9%. All single term strategies performed less well than 2- and 3-term strategies. CONCLUSION: The retrieval of sound clinical prediction studies from EMBASE is supported by several search strategies

The Role of Intrapreneurship for Sustainable Innovation through Process Innovation in Small and Medium-sized Enterprises: A Conceptual Framework

A focus on innovation alone is not sufficient for sustainability in the current hostile business environment. Environment awareness and social impact as well as economic place demands on firms to contribute to sustainable development. As such, there is increased interest in sustainable innovation. On the other sides, intrapreneurship spirit of internal initiative of a firm as firm-specific capabilities is proposed to facilitate this. In the manufacturing firms, process is considered as critical and source to be innovative. Hence, process innovation is utilized to translate intrapreneurship capability for sustainable innovation. To face new circumstances in the business environment for the sustainability of SMEs, the role of intrapreneurship in transforming process innovation under existing technology for sustainable innovation achievement is another interesting view to be explored. This paper discusses the role of intrapreneurship in attaining sustainable innovation through process innovation in SMEs and develop it into an integrated framework. The framework shows that the elements of proactiveness, risk taking and autonomy in intrapreneurship provides a leverage for sustainable economic, environmental and social innovation. The study further suggests empirical investigation in the firms for future research. Keywords: Sustainable innovation; Intrapreneurship; Process innovation JEL Classification: Q5

The Dawn of Open Access to Phylogenetic Data

The scientific enterprise depends critically on the preservation of and open access to published data. This basic tenet applies acutely to phylogenies (estimates of evolutionary relationships among species). Increasingly, phylogenies are estimated from increasingly large, genome-scale datasets using increasingly complex statistical methods that require increasing levels of expertise and computational investment. Moreover, the resulting phylogenetic data provide an explicit historical perspective that critically informs research in a vast and growing number of scientific disciplines. One such use is the study of changes in rates of lineage diversification (speciation - extinction) through time. As part of a meta-analysis in this area, we sought to collect phylogenetic data (comprising nucleotide sequence alignment and tree files) from 217 studies published in 46 journals over a 13-year period. We document our attempts to procure those data (from online archives and by direct request to corresponding authors), and report results of analyses (using Bayesian logistic regression) to assess the impact of various factors on the success of our efforts. Overall, complete phylogenetic data for ~60% of these studies are effectively lost to science. Our study indicates that phylogenetic data are more likely to be deposited in online archives and/or shared upon request when: (1) the publishing journal has a strong data-sharing policy; (2) the publishing journal has a higher impact factor, and; (3) the data are requested from faculty rather than students. Although the situation appears dire, our analyses suggest that it is far from hopeless: recent initiatives by the scientific community -- including policy changes by journals and funding agencies -- are improving the state of affairs

Kajian keratan rentas mengenai pengetahuan, sikap dan amalan terhadap pencegahan demam denggi di Kampung Belawai, Sarikei dari 20 Jun hingga 5 Ogos 2000

A cross-sectional study was carried out in Kampung Belawai, Sarikei to assess the knowledge, attitude and practice of the villagers towards the prevention of Dengue Fever. The study was conducted from 20 July 2000 to 5 August 2000 by fourth year medical students from Faculty of Medicine and Health Sciences, Universiti Malaysia Sarawak (UNIMAS). A total of 232 respondents were selected based on systematic random sampling method and were interviewed by using a set of pre-tested questionnaire. A presumptive survey on Aedes larvae infestation rate was also carried out together with the interview. The majority of the respondents were female (61.3%). The results showed that the mean score for knowledge, attitude and practice of the general population was 53.5%, 69.7% and 45.7%, respectively. There was also significant association between knowledge, attitude and practice with sociodemographic factors such as age, education level and the household income. The Aedes larvae survey showed that the Breteau Index was 54.7, House Index was 33.6 and Container Index was found to be 14.4%. Pottery was the commonest container found to be infested with Aedes larvae. After the survey, an intervention program by the theme of `Hapuskan Denggi, Bekrwai Boleh! ' was carried out on 22nd and 23`d July 2000 at Kampung Belawai to raise the knowledge, attitude and practice of dengue prevention among the target population. The intervention program was also aimed to reduce the Aedes larvae infestation rate. It is recommended that continuous health education in small groups to be implemented among the target population to improve their knowledge, attitude and practice towards the prevention of Dengue Fever

Understanding Student Teachers’ Behavioural Intention to Use Technology

This study sets out to validate and test the Technology Acceptance Model (TAM) in the context of Malaysian student teachers' integration of their technology in teaching and learning. To establish factorial validity, data collected from 302 respondents were tested against the TAM using confirmatory factor analysis (CFA), and structural equation modelling (SEM) was used for model comparison and hypotheses testing. The goodness-of-fit test of the analysis shows partial support of the applicability of the TAM in a Malaysian context. Overall, the TAM accounted for 37.3% of the variance in intention to use technology among student teachers and of the five hypotheses formulated, four are supported. Perceived usefulness is a significant influence on attitude towards computer use and behavioural intention. Perceived ease of use significantly influences perceived usefulness, and finally, behavioural intention is found to be influenced by attitude towards computer use. The findings of this research contribute to the literature by validating the TAM in the Malaysian context and provide several prominent implications for the research and practice of technology integration development

Structure-guided design of purine-based probes for selective Nek2 inhibition

Nek2 (NIMA-related kinase 2) is a cell cycle-dependent serine/threonine protein kinase that regulates centrosome separation at the onset of mitosis. Overexpression of Nek2 is common in human cancers and suppression can restrict tumor cell growth and promote apoptosis. Nek2 inhibition with small molecules, therefore, offers the prospect of a new therapy for cancer. To achieve this goal, a better understanding of the requirements for selective-inhibition of Nek2 is required. 6-Alkoxypurines were identified as ATP-competitive inhibitors of Nek2 and CDK2. Comparison with CDK2-inhibitor structures indicated that judicious modification of the 6-alkoxy and 2-arylamino substituents could achieve discrimination between Nek2 and CDK2. In this study, a library of 6-cyclohexylmethoxy-2-arylaminopurines bearing carboxamide, sulfonamide and urea substituents on the 2-arylamino ring was synthesized. Few of these compounds were selective for Nek2 over CDK2, with the best result being obtained for 3-((6-(cyclohexylmethoxy)-9H-purin-2-yl)amino)-N,N-dimethylbenzamide (CDK2 IC50 = 7.0 μM; Nek2 IC50 = 0.62 μM) with >10-fold selectivity. Deletion of the 6-substituent abrogated activity against both Nek2 and CDK2. Nine compounds containing an (E)-dialkylaminovinyl substituent at C-6, all showed selectivity for Nek2, e.g. (E)-6-(2-(azepan-1-yl)vinyl)-N-phenyl-9H-purin-2-amine (CDK2 IC50 = 2.70 μM; Nek2 IC50 = 0.27 μM). Structural biology of selected compounds enabled a partial rationalization of the observed structure activity relationships and mechanism of Nek2 activation. This showed that carboxamide 11 is the first reported inhibitor of Nek2 in the DFG-in conformation