66 research outputs found

    Computation with Polynomial Equations and Inequalities arising in Combinatorial Optimization

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    The purpose of this note is to survey a methodology to solve systems of polynomial equations and inequalities. The techniques we discuss use the algebra of multivariate polynomials with coefficients over a field to create large-scale linear algebra or semidefinite programming relaxations of many kinds of feasibility or optimization questions. We are particularly interested in problems arising in combinatorial optimization.Comment: 28 pages, survey pape

    Extended RDF: Computability and Complexity Issues

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    ERDF stable model semantics is a recently proposed semantics for ERDF ontologies and a faithful extension of RDFS semantics on RDF graphs. In this paper, we elaborate on the computability and complexity issues of the ERDF stable model semantics. Based on the undecidability result of ERDF stable model semantics, decidability under this semantics cannot be achieved, unless ERDF ontologies of restricted syntax are considered. Therefore, we propose a slightly modified semantics for ERDF ontologies, called ERDF #n- stable model semantics. We show that entailment under this semantics is, in general, decidable and also extends RDFS entailment. Equivalence statements between the two semantics are provided. Additionally, we provide algorithms that compute the ERDF #n-stable models of syntax-restricted and general ERDF ontologies. Further, we provide complexity results for the ERDF #nstable model semantics on syntax-restricted and general ERDF ontologies. Finally, we provide complexity results for the ERDF stable model semantics on syntax-restricted ERDF ontologies

    The significance of tumour microarchitectural features in breast cancer prognosis: a digital image analysis

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    BACKGROUND: As only a minor portion of the information present in histological sections is accessible by eye, recognition and quantification of complex patterns and relationships among constituents relies on digital image analysis. In this study, our working hypothesis was that, with the application of digital image analysis technology, visually unquantifiable breast cancer microarchitectural features can be rigorously assessed and tested as prognostic parameters for invasive breast carcinoma of no special type. METHODS: Digital image analysis was performed using public domain software (ImageJ) on tissue microarrays from a cohort of 696 patients, and validated with a commercial platform (Visiopharm). Quantified features included elements defining tumour microarchitecture, with emphasis on the extent of tumour-stroma interface. The differential prognostic impact of tumour nest microarchitecture in the four immunohistochemical surrogates for molecular classification was analysed. Prognostic parameters included axillary lymph node status, breast cancer-specific survival, and time to distant metastasis. Associations of each feature with prognostic parameters were assessed using logistic regression and Cox proportional models adjusting for age at diagnosis, grade, and tumour size. RESULTS: An arrangement in numerous small nests was associated with axillary lymph node involvement. The association was stronger in luminal tumours (odds ratio (OR) = 1.39, p = 0.003 for a 1-SD increase in nest number, OR = 0.75, p = 0.006 for mean nest area). Nest number was also associated with survival (hazard ratio (HR) = 1.15, p = 0.027), but total nest perimeter was the parameter most significantly associated with survival in luminal tumours (HR = 1.26, p = 0.005). In the relatively small cohort of triple-negative tumours, mean circularity showed association with time to distant metastasis (HR = 1.71, p = 0.027) and survival (HR = 1.8, p = 0.02). CONCLUSIONS: We propose that tumour arrangement in few large nests indicates a decreased metastatic potential. By contrast, organisation in numerous small nests provides the tumour with increased metastatic potential to regional lymph nodes. An outstretched pattern in small nests bestows tumours with a tendency for decreased breast cancer-specific survival. Although further validation studies are required before the argument for routine quantification of microarchitectural features is established, our approach is consistent with the demand for cost-effective methods for triaging breast cancer patients that are more likely to benefit from chemotherapy

    Heart Rate during Conflicts Predicts Post-Conflict Stress-Related Behavior in Greylag Geese

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    Background: Social stressors are known to be among the most potent stressors in group-living animals. This is not only manifested in individual physiology (heart rate, glucocorticoids), but also in how individuals behave directly after a conflict. Certain ‘stress-related behaviors ’ such as autopreening, body shaking, scratching and vigilance have been suggested to indicate an individual’s emotional state. Such behaviors may also alleviate stress, but the behavioral context and physiological basis of those behaviors is still poorly understood. Methodology/Principal Findings: We recorded beat-to-beat heart rates (HR) of 22 greylag geese in response to agonistic encounters using fully implanted sensor-transmitter packages. Additionally, for 143 major events we analyzed the behavior shown by our focal animals in the first two minutes after an interaction. Our results show that the HR during encounters and characteristics of the interaction predicted the frequency and duration of behaviors shown after a conflict. Conclusions/Significance: To our knowledge this is the first study to quantify the physiological and behavioral responses to single agonistic encounters and to link this to post conflict behavior. Our results demonstrate that ‘stress-related behaviors’ are flexibly modulated by the characteristics of the preceding aggressive interaction and reflect the individual’s emotional strain, which is linked to autonomic arousal. We found no support for the stress-alleviating hypothesis, but we propose tha

    Carotenoid Distribution in Living Cells of Haematococcus pluvialis (Chlorophyceae)

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    Haematococcus pluvialis is a freshwater unicellular green microalga belonging to the class Chlorophyceae and is of commercial interest for its ability to accumulate massive amounts of the red ketocarotenoid astaxanthin (3,3′-dihydroxy-β,β-carotene-4,4′-dione). Using confocal Raman microscopy and multivariate analysis, we demonstrate the ability to spectrally resolve resonance–enhanced Raman signatures associated with astaxanthin and β-carotene along with chlorophyll fluorescence. By mathematically isolating these spectral signatures, in turn, it is possible to locate these species independent of each other in living cells of H. pluvialis in various stages of the life cycle. Chlorophyll emission was found only in the chloroplast whereas astaxanthin was identified within globular and punctate regions of the cytoplasmic space. Moreover, we found evidence for β-carotene to be co-located with both the chloroplast and astaxanthin in the cytosol. These observations imply that β-carotene is a precursor for astaxanthin and the synthesis of astaxanthin occurs outside the chloroplast. Our work demonstrates the broad utility of confocal Raman microscopy to resolve spectral signatures of highly similar chromophores in living cells

    Cervical human papillomavirus infection and squamous intraepithelial lesions in rural Gambia, West Africa: viral sequence analysis and epidemiology

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    The development of effective strategies against cervical cancer in Africa requires accurate type specific data on human papillomavirus (HPV) prevalence, including determination of DNA sequences in order to maximise local vaccine efficacy. We have investigated cervical HPV infection and squamous intraepithelial lesions (SIL) in an unselected cohort of 1061 women in a rural Gambian community. Squamous intraepithelial lesions was diagnosed using cytology and histology, HPV was typed by PCR-ELISA of DNA extracts, which were also DNA sequenced. The prevalence of cervical HPV infection was 13% and SIL were observed in 7% of subjects. Human papillomavirus-16 was most prevalent and most strongly associated with SIL. Also common were HPV-18, -33, -58 and, notably, -35. Human papillomavirus DNA sequencing revealed HPV-16 samples to be exclusively African type 1 (Af1). Subjects of the Wolof ethnic group had a lower prevalence of HPV infection while subjects aged 25–44 years had a higher prevalence of cervical precancer than older or younger subjects. This first report of HPV prevalence in an unselected, unscreened rural population confirms high rates of SIL and HPV infection in West Africa. This study has implications for the vaccination of Gambian and other African populations in the prevention of cervical cancer

    Attachment styles modulate neural markers of threat and imagery when engaging in self-criticism

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    Attachment styles hold important downstream consequences for mental health through their contribution to the emergence of self-criticism. To date, no work has extended our understanding of the influence of attachment styles on self-criticism at a neurobiological level. Herein we investigate the relationship between self-reported attachment styles and neural markers of self-criticism using fMRI. A correlation network analysis revealed lingual gyrus activation during self-criticism, a marker of visual mental imagery, correlated with amygdala activity (threat response). It also identified that secure attachment positively correlated with lingual gyrus activation, whilst avoidant attachment was negatively correlated with lingual gyrus activation. Further, at greater levels of amygdala response, more securely attached individuals showed greater lingual gyrus activation, and more avoidantly attached individuals showed less lingual gyrus activation. Our data provide the first evidence that attachment mechanisms may modulate threat responses and mental imagery when engaging in self-criticism, which have important clinical and broader social implications.Australian Postgraduate Scholarship

    Monitoring quality and coverage of harm reduction services for people who use drugs: a consensus study.

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    BACKGROUND AND AIMS: Despite advances in our knowledge of effective services for people who use drugs over the last decades globally, coverage remains poor in most countries, while quality is often unknown. This paper aims to discuss the historical development of successful epidemiological indicators and to present a framework for extending them with additional indicators of coverage and quality of harm reduction services, for monitoring and evaluation at international, national or subnational levels. The ultimate aim is to improve these services in order to reduce health and social problems among people who use drugs, such as human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infection, crime and legal problems, overdose (death) and other morbidity and mortality. METHODS AND RESULTS: The framework was developed collaboratively using consensus methods involving nominal group meetings, review of existing quality standards, repeated email commenting rounds and qualitative analysis of opinions/experiences from a broad range of professionals/experts, including members of civil society and organisations representing people who use drugs. Twelve priority candidate indicators are proposed for opioid agonist therapy (OAT), needle and syringe programmes (NSP) and generic cross-cutting aspects of harm reduction (and potentially other drug) services. Under the specific OAT indicators, priority indicators included 'coverage', 'waiting list time', 'dosage' and 'availability in prisons'. For the specific NSP indicators, the priority indicators included 'coverage', 'number of needles/syringes distributed/collected', 'provision of other drug use paraphernalia' and 'availability in prisons'. Among the generic or cross-cutting indicators the priority indicators were 'infectious diseases counselling and care', 'take away naloxone', 'information on safe use/sex' and 'condoms'. We discuss conditions for the successful development of the suggested indicators and constraints (e.g. funding, ideology). We propose conducting a pilot study to test the feasibility and applicability of the proposed indicators before their scaling up and routine implementation, to evaluate their effectiveness in comparing service coverage and quality across countries. CONCLUSIONS: The establishment of an improved set of validated and internationally agreed upon best practice indicators for monitoring harm reduction service will provide a structural basis for public health and epidemiological studies and support evidence and human rights-based health policies, services and interventions

    Interleukin 10-mediated immunosuppression by a variant CD4 T cell epitope of Plasmodium falciparum.

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    The immunodominant CD4 T cell epitope region, Th2R, of the circumsporozoite protein of Plasmodium falciparum is highly polymorphic. Such variation might be utilized by the parasite to escape from or interfere with CD4 T cell effector functions. Here, we show that costimulation with naturally occurring altered peptide ligands (APL) can induce a rapid change from IFNgamma production to the immunosuppressive mediator interleukin 10 (IL-10). This mechanism may contribute to the low levels of T cell responses observed to this pathogen in malaria-endemic areas
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