407 research outputs found

    Genetic landscape of autism spectrum disorder in Vietnamese children

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    Autism spectrum disorder (ASD) is a complex disorder with an unclear aetiology and an estimated global prevalence of 1%. However, studies of ASD in the Vietnamese population are limited. Here, we first conducted whole exome sequencing (WES) of 100 children with ASD and their unaffected parents. Our stringent analysis pipeline was able to detect 18 unique variants (8 de novo and 10 ×-linked, all validated), including 12 newly discovered variants. Interestingly, a notable number of X-linked variants were detected (56%), and all of them were found in affected males but not in affected females. We uncovered 17 genes from our ASD cohort in which CHD8, DYRK1A, GRIN2B, SCN2A, OFD1 and MDB5 have been previously identified as ASD risk genes, suggesting the universal aetiology of ASD for these genes. In addition, we identified six genes that have not been previously reported in any autism database: CHM, ENPP1, IGF1, LAS1L, SYP and TBX22. Gene ontology and phenotype-genotype analysis suggested that variants in IGF1, SYP and LAS1L could plausibly confer risk for ASD. Taken together, this study adds to the genetic heterogeneity of ASD and is the first report elucidating the genetic landscape of ASD in Vietnamese children

    Precipitation of PEG/Carboxyl-modified gold nanoparticles with magnesium pyrophosphate : a new platform for real-time monitoring of loop-mediated isothermal amplification

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    2016-2017 > Academic research: refereed > Publication in refereed journal201804_a bcmaVersion of RecordRGCOthersRGC: 501413Others: PGMS Project IDs: P0009500 and P0009150Publishe

    Detecting the Effects of Changes on the Compliance of Cross-organizational Business Processes

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    An emerging challenge for collaborating business partners is to properly define and evolve their cross-organizational processes with respect to imposed global compliance rules. Since compliance verification is known to be very costly, reducing the number of compliance rules to be rechecked in the context of process changes will be crucial. Opposed to intra-organizational processes, however, change effects cannot be easily assessed in such distributed scenarios, where partners only provide restricted public views and assertions on their private processes. Even if local process changes are invisible to partners, they might affect the compliance of the cross-organizational process with the mentioned rules. This paper provides an approach for ensuring compliance when evolving a cross-organizational process. For this purpose, we construct qualified dependency graphs expressing relationships between process activities, process assertions, and compliance rules. Based on such graphs, we are able to determine the subset of compliance rules that might be affected by a particular change. Altogether, our approach increases the efficiency of compliance checking in cross-organizational settings

    Interestingness of traces in declarative process mining: The janus LTLPf Approach

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    Declarative process mining is the set of techniques aimed at extracting behavioural constraints from event logs. These constraints are inherently of a reactive nature, in that their activation restricts the occurrence of other activities. In this way, they are prone to the principle of ex falso quod libet: they can be satisfied even when not activated. As a consequence, constraints can be mined that are hardly interesting to users or even potentially misleading. In this paper, we build on the observation that users typically read and write temporal constraints as if-statements with an explicit indication of the activation condition. Our approach is called Janus, because it permits the specification and verification of reactive constraints that, upon activation, look forward into the future and backwards into the past of a trace. Reactive constraints are expressed using Linear-time Temporal Logic with Past on Finite Traces (LTLp f). To mine them out of event logs, we devise a time bi-directional valuation technique based on triplets of automata operating in an on-line fashion. Our solution proves efficient, being at most quadratic w.r.t. trace length, and effective in recognising interestingness of discovered constraints

    Data-Oriented Declarative Language for Optimizing Business Processes

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    There is a signifi cant number of declarative languages to describe business processes. They tend to be used when business processes need to be fl exible and adaptable, being not possible to use an imperative description. Declarative languages in business process have been traditionally used to describe the order of activities, specifi cally the order allowed or prohibited. Unfortunately, none of them is worried about a declarative description of exchanged data between the activities and how they can infl uence the model. In this paper, we analyse the data description capacity of a variety of declarative languages in business processes. Using this analysis, we have detected the necessity to include data exchanged aspects in the declarative descriptions. In order to solve the gap, we propose a Data-Oriented Optimization Declarative LanguagE, called DOODLE, which includes the process requirements referred to data description, and the possibility to include an optimization function about the process output data

    MAGE-A cancer/testis antigens inhibit MDM2 ubiquitylation function and promote increased levels of MDM4

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    Melanoma antigen A (MAGE-A) proteins comprise a structurally and biochemically similar sub-family of Cancer/Testis antigens that are expressed in many cancer types and are thought to contribute actively to malignancy. MAGE-A proteins are established regulators of certain cancer-associated transcription factors, including p53, and are activators of several RING finger-dependent ubiquitin E3 ligases. Here, we show that MAGE-A2 associates with MDM2, a ubiquitin E3 ligase that mediates ubiquitylation of more than 20 substrates including mainly p53, MDM2 itself, and MDM4, a potent p53 inhibitor and MDM2 partner that is structurally related to MDM2. We find that MAGE-A2 interacts with MDM2 via the N-terminal p53-binding pocket and the RING finger domain of MDM2 that is required for homo/hetero-dimerization and for E2 ligase interaction. Consistent with these data, we show that MAGE-A2 is a potent inhibitor of the E3 ubiquitin ligase activity of MDM2, yet it does not have any significant effect on p53 turnover mediated by MDM2. Strikingly, however, increased MAGE-A2 expression leads to reduced ubiquitylation and increased levels of MDM4. Similarly, silencing of endogenous MAGE-A expression diminishes MDM4 levels in a manner that can be rescued by the proteasomal inhibitor, bortezomid, and permits increased MDM2/MDM4 association. These data suggest that MAGE-A proteins can: (i) uncouple the ubiquitin ligase and degradation functions of MDM2; (ii) act as potent inhibitors of E3 ligase function; and (iii) regulate the turnover of MDM4. We also find an association between the presence of MAGE-A and increased MDM4 levels in primary breast cancer, suggesting that MAGE-A-dependent control of MDM4 levels has relevance to cancer clinically

    Inequalities and Agencies in Workplace Learning Experiences: International Student Perspectives

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    The final publication is available at Springer via http://dx.doi.org/10.1007/s12186-016-9167-2National systems of vocational education and training around the globe are facing reform driven by quality, international mobility, and equity. Evidence suggests that there are qualitatively distinctive challenges in providing and sustaining workplace learning experiences to international students. However, despite growing conceptual and empirical work, there is little evidence of the experiences of these students undertaking workplace learning opportunities as part of vocational education courses. This paper draws on a four-year study funded by the Australian Research Council that involved 105 in depth interviews with international students undertaking work integrated learning placements as part of vocational education courses in Australia. The results indicate that international students can experience different forms of discrimination and deskilling, and that these were legitimised by students in relation to their understanding of themselves as being an ‘international student’ (with fewer rights). However, the results also demonstrated the ways in which international students exercised their agency towards navigating or even disrupting these circumstances, which often included developing their social and cultural capital. This study, therefore, calls for more proactively inclusive induction and support practices that promote reciprocal understandings and navigational capacities for all involved in the provision of work integrated learning. This, it is argued, would not only expand and enrich the learning opportunities for international students, their tutors, employers, and employees involved in the provision of workplace learning opportunities, but it could also be a catalyst to promote greater mutual appreciation of diversity in the workplace
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