Grounding oriented design

University of Technology, Sydney. Faculty of Information Technology.The symbol grounding problem[67] is a longstanding, poorly understood issue that has interested philosophers, computer scientists, and cognitive scientists alike. The grounding problem, in its various guises, refers to the task of creating meaningful representations for artificial agents. After more than 15 years of widespread debate and circular introspection of the so-called symbol grounding problem we seem none-the-wiser as to what constitutes being meaningful, and indeed grounded, for an agent[l28]. We argue, in the context of practical robotics, a grounded agent possesses a representation which faithfully reflects pertinent aspects of the world. In contrast, an ungrounded agent could be, for example, delusional or suffering from hallucinations ("false positives"), overly concerned with irrelevant things (e.g. the frame problem[93]), or incapable of reliably perceiving, recognising or anticipating relevant things in a timely manner ("false negatives"). While most grounding research concerns how to develop agents which can autonomously develop their own representations (i.e. autonomous grounding), the fact all robotic systems are grounded through human design on a case-by-case, ad-hoc bass has been overlooked. This thesis presents Grounding Oriented Design - a methodology for designing and grounding the "minds" of robotic agents. Grounding Oriented Design (or, alternatively Go-Design) is a vital first step towards the development of autonomous grounding capabilities through improved understanding of the processes by which human designers ground robot minds. Grounding Oriented Design offers guidelines and processes for iteratively decomposing a robot control problem into a set of collaborating skills, together with a notation for representing and documenting skill designs. Grounding Oriented Design consists of two main phases: basic-design which involves constructing a skill-architecture, and a detailed-design in which a skill-architecture is used to design the agent's representation and decision-making processes. A groundedness framework[l43] is used for describing and assessing the groundedness of either the complete system or of individual skills. Examples of the methodology's use and benefits are provided, while suggestions for future work are discussed

Recombination events among virulence genes in malaria parasites are associated with G-quadruplex-forming DNA motifs

Background Malaria parasites of the genus Plasmodium possess large hyper-variable families of antigen-encoding genes. These are often variantly-expressed and are major virulence factors for immune evasion and the maintenance of chronic infections. Recombination and diversification of these gene families occurs readily, and may be promoted by G-quadruplex (G4) DNA motifs within and close to the variant genes. G4s have been shown to cause replication fork stalling, DNA breakage and recombination in model systems, but these motifs remain largely unstudied in Plasmodium. Results We examined the nature and distribution of putative G4-forming sequences in multiple Plasmodium genomes, finding that their co-distribution with variant gene families is conserved across different Plasmodium species that have different types of variant gene families. In P. falciparum, where a large set of recombination events that occurred over time in cultured parasites has been mapped, we found a strong spatial association between these recombination events and putative G4-forming sequences. Finally, we searched Plasmodium genomes for the three classes of helicase that can unwind G4s: Plasmodium spp. have no identifiable homologue of the highly efficient G4 helicase PIF1, but they do encode two putative RecQ helicases and one homologue of the RAD3-family helicase FANCJ. Conclusions Our analyses, conducted at the whole-genome level in multiple species of Plasmodium, support the concept that G4s are likely to be involved in recombination and diversification of antigen-encoding gene families in this important protozoan pathogen

Measuring maternal mortality : an overview of opportunities and options for developing countries

Background:There is currently an unprecedented expressed need and demand for estimates of maternal mortality in developing countries. This has been stimulated in part by the creation of a Millennium Development Goal that will be judged partly on the basis of reductions in maternal mortality by 2015. Methods: Since the launch of the Safe Motherhood Initiative in 1987, new opportunities for data capture have arisen and new methods have been developed, tested and used. This paper provides a pragmatic overview of these methods and the optimal measurement strategies for different developing country contexts. Results: There are significant recent advances in the measurement of maternal mortality, yet also room for further improvement, particularly in assessing the magnitude and direction of biases and their implications for different data uses. Some of the innovations in measurement provide efficient mechanisms for gathering the requisite primary data at a reasonably low cost. No method, however, has zero costs. Investment is needed in measurement strategies for maternal mortality suited to the needs and resources of a country, and which also strengthen the technical capacity to generate and use credible estimates. Conclusion: Ownership of information is necessary for it to be acted upon: what you count is what you do. Difficulties with measurement must not be allowed to discourage efforts to reduce maternal mortality. Countries must be encouraged and enabled to count maternal deaths and act.WJG is funded partially by the University of Aberdeen. OMRC is partially funded by the London School of Hygiene and Tropical Medicine. CS and SA are partially funded by Johns Hopkins University. CAZ is funded by the Health Metrics Network at the World Health Organization. WJG, OMRC, CS and SA are also partially supported through an international research program, Immpact, funded by the Bill & Melinda Gates Foundation, the Department for International Development, the European Commission and USAID

Stabilising touch interactions in cockpits, aerospace, and vibrating environments

© Springer International Publishing AG, part of Springer Nature 2018. Incorporating touch screen interaction into cockpit flight systems is increasingly gaining traction given its several potential advantages to design as well as usability to pilots. However, perturbations to the user input are prevalent in such environments due to vibrations, turbulence and high accelerations. This poses particular challenges for interacting with displays in the cockpit, for example, accidental activation during turbulence or high levels of distraction from the primary task of airplane control to accomplish selection tasks. On the other hand, predictive displays have emerged as a solution to minimize the effort as well as cognitive, visual and physical workload associated with using in-vehicle displays under perturbations, induced by road and driving conditions. This technology employs gesture tracking in 3D and potentially eye-gaze as well as other sensory data to substantially facilitate the acquisition (pointing and selection) of an interface component by predicting the item the user intents to select on the display, early in the movements towards the screen. A key aspect is utilising principled Bayesian modelling to incorporate and treat the present perturbation, thus, it is a software-based solution that showed promising results when applied to automotive applications. This paper explores the potential of applying this technology to applications in aerospace and vibrating environments in general and presents design recommendations for such an approach to enhance interactions accuracy as well as safety

The ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin motifs) family

The ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin motifs) enzymes are secreted, multi-domain matrix-associated zinc metalloendopeptidases that have diverse roles in tissue morphogenesis and patho-physiological remodeling, in inflammation and in vascular biology. The human family includes 19 members that can be sub-grouped on the basis of their known substrates, namely the aggrecanases or proteoglycanases (ADAMTS1, 4, 5, 8, 9, 15 and 20), the procollagen N-propeptidases (ADAMTS2, 3 and 14), the cartilage oligomeric matrix protein-cleaving enzymes (ADAMTS7 and 12), the von-Willebrand Factor proteinase (ADAMTS13) and a group of orphan enzymes (ADAMTS6, 10, 16, 17, 18 and 19). Control of the structure and function of the extracellular matrix (ECM) is a central theme of the biology of the ADAMTS, as exemplified by the actions of the procollagen-N-propeptidases in collagen fibril assembly and of the aggrecanases in the cleavage or modification of ECM proteoglycans. Defects in certain family members give rise to inherited genetic disorders, while the aberrant expression or function of others is associated with arthritis, cancer and cardiovascular disease. In particular, ADAMTS4 and 5 have emerged as therapeutic targets in arthritis. Multiple ADAMTSs from different sub-groupings exert either positive or negative effects on tumorigenesis and metastasis, with both metalloproteinase-dependent and -independent actions known to occur. The basic ADAMTS structure comprises a metalloproteinase catalytic domain and a carboxy-terminal ancillary domain, the latter determining substrate specificity and the localization of the protease and its interaction partners; ancillary domains probably also have independent biological functions. Focusing primarily on the aggrecanases and proteoglycanases, this review provides a perspective on the evolution of the ADAMTS family, their links with developmental and disease mechanisms, and key questions for the future

The MRN complex is transcriptionally regulated by MYCN during neural cell proliferation to control replication stress

The MRE11/RAD50/NBS1 (MRN) complex is a major sensor of DNA double strand breaks, whose role in controlling faithful DNA replication and preventing replication stress is also emerging. Inactivation of the MRN complex invariably leads to developmental and/or degenerative neuronal defects, the pathogenesis of which still remains poorly understood. In particular, NBS1 gene mutations are associated with microcephaly and strongly impaired cerebellar development, both in humans and in the mouse model. These phenotypes strikingly overlap those induced by inactivation of MYCN, an essential promoter of the expansion of neuronal stem and progenitor cells, suggesting that MYCN and the MRN complex might be connected on a unique pathway essential for the safe expansion of neuronal cells. Here, we show that MYCN transcriptionally controls the expression of each component of the MRN complex. By genetic and pharmacological inhibition of the MRN complex in a MYCN overexpression model and in the more physiological context of the Hedgehog-dependent expansion of primary cerebellar granule progenitor cells, we also show that the MRN complex is required for MYCN-dependent proliferation. Indeed, its inhibition resulted in DNA damage, activation of a DNA damage response, and cell death in a MYCN- and replication-dependent manner. Our data indicate the MRN complex is essential to restrain MYCN-induced replication stress during neural cell proliferation and support the hypothesis that replication-born DNA damage is responsible for the neuronal defects associated with MRN dysfunctions.Cell Death and Differentiation advance online publication, 12 June 2015; doi:10.1038/cdd.2015.81

Effects of carrying a pregnancy and of method of delivery on urinary incontinence: a prospective cohort study

BACKGROUND: This study was carried out to identify risk factors associated with urinary incontinence in women three months after giving birth. METHODS: Urinary incontinence before and during pregnancy was assessed at study enrolment early in the third trimester. Incontinence was re-assessed three months postpartum. Logistic regression analysis was used to assess the role of maternal and obstetric factors in causing postpartum urinary incontinence. This prospective cohort study in 949 pregnant women in Quebec, Canada was nested within a randomised controlled trial of prenatal perineal massage. RESULTS: Postpartum urinary incontinence was increased with prepregnancy incontinence (adjusted odds ratio [adj0R] 6.44, 95% CI 4.15, 9.98), incontinence beginning during pregnancy (adjOR 1.93, 95% CI 1.32, 2.83), and higher prepregnancy body mass index (adjOR 1.07/unit of BMI, 95% CI 1.03,1.11). Caesarean section was highly protective (adjOR 0.27, 95% CI 0.14, 0.50). While there was a trend towards increasing incontinence with forceps delivery (adjOR 1.73, 95% CI 0.96, 3.13) this was not statistically significant. The weight of the baby, episiotomy, the length of the second stage of labour, and epidural analgesia were not predictive of urinary incontinence. Nor was prenatal perineal massage, the randomised controlled trial intervention. When the analysis was limited to women having their first vaginal birth, the same risk factors were important, with similar adjusted odds ratios. CONCLUSIONS: Urinary incontinence during pregnancy is extremely common, affecting over half of pregnant women. Urinary incontinence beginning during pregnancy roughly doubles the likelihood of urinary incontinence at 3 months postpartum, regardless whether delivery is vaginal or by Caesarean section

Outcome and human epidermal growth factor receptor (HER) 1–4 status in invasive breast carcinomas with proliferation indices evaluated by bromodeoxyuridine labelling

BACKGROUND: We have shown previously that whereas overexpression of human epidermal growth factor receptor (HER)1, HER2 and HER3 is associated with poor prognosis in breast cancer, HER4 is associated with a good prognosis. Cell proliferation is a key component of aggressive cancers and is driven by growth factors. In this study, bromodeoxyuridine (BrdU)-derived proliferation indices are correlated with clinical outcome and HER1–4 status for further clarification of the differing roles for the HER family at a biological level. METHODS: Seventy-eight invasive breast cancers had BrdU labelling in vivo to determine the BrdU labelling index (BLI) and the potential tumour doubling time (T(pot)). Long-term clinical follow-up was available for these patients. We used immunohistochemistry to establish the HER1–4 status in 55 patients from the BrdU cohort. RESULTS: We demonstrate a significant correlation between high BLI values and breast cancer-specific death (P = 0.0174). Low T(pot )times were also significantly correlated with breast cancer-specific death (P = 0.0258). However, BLI did not independently predict survival in Cox's multiple regression analysis when combined with other prognostic factors such as size, grade and nodal status. Tumours found to be positive for HER1, HER2 or HER3 had significantly (P = 0.041) higher labelling indices, with HER1 also showing significantly higher indices when considered independently (P = 0.024). Conversely, HER4 positivity was significantly correlated (P = 0.013) with low BLI values, in line with previous data associating this receptor with good prognosis tumours. CONCLUSIONS: These results support the hypothesis that HER1–3 are associated with driving tumour proliferation, whereas HER4 is involved in a non-proliferative or even protective role

Comparison of embedded and added motor imagery training in patients after stroke: Study protocol of a randomised controlled pilot trial using a mixed methods approach

Copyright @ 2009 Schuster et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: Two different approaches have been adopted when applying motor imagery (MI) to stroke patients. MI can be conducted either added to conventional physiotherapy or integrated within therapy sessions. The proposed study aims to compare the efficacy of embedded MI to an added MI intervention. Evidence from pilot studies reported in the literature suggests that both approaches can improve performance of a complex motor skill involving whole body movements, however, it remains to be demonstrated, which is the more effective one.Methods/Design: A single blinded, randomised controlled trial (RCT) with a pre-post intervention design will be carried out. The study design includes two experimental groups and a control group (CG). Both experimental groups (EG1, EG2) will receive physical practice of a clinical relevant motor task ('Going down, laying on the floor, and getting up again') over a two week intervention period: EG1 with embedded MI training, EG2 with MI training added after physiotherapy. The CG will receive standard physiotherapy intervention and an additional control intervention not related to MI.The primary study outcome is the time difference to perform the task from pre to post-intervention. Secondary outcomes include level of help needed, stages of motor task completion, degree of motor impairment, balance ability, fear of falling measure, motivation score, and motor imagery ability score. Four data collection points are proposed: twice during baseline phase, once following the intervention period, and once after a two week follow up. A nested qualitative part should add an important insight into patients' experience and attitudes towards MI. Semi-structured interviews of six to ten patients, who participate in the RCT, will be conducted to investigate patients' previous experience with MI and their expectations towards the MI intervention in the study. Patients will be interviewed prior and after the intervention period.Discussion: Results will determine whether embedded MI is superior to added MI. Findings of the semi-structured interviews will help to integrate patient's expectations of MI interventions in the design of research studies to improve practical applicability using MI as an adjunct therapy technique

Seeing the woods for the trees: the problem of information inefficiency and information overload on operator performance

One of the recurring questions in designing dynamic control environments is whether providing more information leads to better operational decisions. The idea of having every piece of information is increasingly tempting (and in safety critical domains often mandatory) but has become a potential obstacle for designers and operators. The present research study examined this challenge of appropriate information design and usability within a railway control setting. A laboratory study was conducted to investigate the presentation of different levels of information (taken from data processing framework, Dadashi et al., 2014) and the association with, and potential prediction of, the performance of a human operator when completing a cognitively demanding problem solving scenario within railways. Results indicated that presenting users only with information corresponding to their cognitive task, and in the absence of other, non task-relevant information, improves the performance of their problem solving/alarm handling. Knowing the key features of interest to various agents (machine or human) and using the data processing framework to guide the optimal level of information required by each of these agents could potentially lead to safer and more usable designs