Aptamer-based multiplexed proteomic technology for biomarker discovery

Interrogation of the human proteome in a highly multiplexed and efficient manner remains a coveted and challenging goal in biology. We present a new aptamer-based proteomic technology for biomarker discovery capable of simultaneously measuring thousands of proteins from small sample volumes (15 [mu]L of serum or plasma). Our current assay allows us to measure ~800 proteins with very low limits of detection (1 pM average), 7 logs of overall dynamic range, and 5% average coefficient of variation. This technology is enabled by a new generation of aptamers that contain chemically modified nucleotides, which greatly expand the physicochemical diversity of the large randomized nucleic acid libraries from which the aptamers are selected. Proteins in complex matrices such as plasma are measured with a process that transforms a signature of protein concentrations into a corresponding DNA aptamer concentration signature, which is then quantified with a DNA microarray. In essence, our assay takes advantage of the dual nature of aptamers as both folded binding entities with defined shapes and unique sequences recognizable by specific hybridization probes. To demonstrate the utility of our proteomics biomarker discovery technology, we applied it to a clinical study of chronic kidney disease (CKD). We identified two well known CKD biomarkers as well as an additional 58 potential CKD biomarkers. These results demonstrate the potential utility of our technology to discover unique protein signatures characteristic of various disease states. More generally, we describe a versatile and powerful tool that allows large-scale comparison of proteome profiles among discrete populations. This unbiased and highly multiplexed search engine will enable the discovery of novel biomarkers in a manner that is unencumbered by our incomplete knowledge of biology, thereby helping to advance the next generation of evidence-based medicine

Corpus2Wiki: A MediaWiki-based Tool for Automatically Generating Wikiditions in Digital Humanities

We describe current developments of Corpus2Wiki. Corpus2Wiki is a tool for generating so-calledWikiditions out of text corpora. It provides text analyses, annotations and their visualizations without requiring programming or advanced computer skills. By using TextImager as a back-end, Corpus2Wiki can automatically analyze input documents at different linguistic levels. Currently, it automatically annotates information regarding lemmatization, parts of speech, morphological information, named entities, geolocations and topic labels based on the Dewey Decimal Classification (DDC). Any results are stored and displayed by means of a modified and extended MediaWiki which makes it easy to further process texts and their annotations. The aim of this paper is to present the capabilities of Corpus2wiki, to point out the improvements made and to make suggestions for further development

Abdominal Pain Associated With Anorexia Nervosa and Median Arcuate Ligament Syndrome: A Rare Condition Shadowed by a Postoperative Conversion Disorder

Median arcuate ligament syndrome (MALS) is an often discounted and vexing condition that may go unnoticed in a population of patients with complex comorbid conditions or those with poor psychiatric health. We report a unique case of a patient with anorexia nervosa in whom the successful operation for MALS was briefly complicated by a postoperative conversion disorder. </jats:p

Investigating the correspondence between driver head position and glance location

The relationship between a driver's glance orientation and corresponding head rotation is highly complex due to its nonlinear dependence on the individual, task, and driving context. This paper presents expanded analytic detail and findings from an effort that explored the ability of head pose to serve as an estimator for driver gaze by connecting head rotation data with manually coded gaze region data using both a statistical analysis approach and a predictive (i.e., machine learning) approach. For the latter, classification accuracy increased as visual angles between two glance locations increased. In other words, the greater the shift in gaze, the higher the accuracy of classification. This is an intuitive but important concept that we make explicit through our analysis. The highest accuracy achieved was 83% using the method of Hidden Markov Models (HMM) for the binary gaze classification problem of (a) glances to the forward roadway versus (b) glances to the center stack. Results suggest that although there are individual differences in head-glance correspondence while driving, classifier models based on head-rotation data may be robust to these differences and therefore can serve as reasonable estimators for glance location. The results suggest that driver head pose can be used as a surrogate for eye gaze in several key conditions including the identification of high-eccentricity glances. Inexpensive driver head pose tracking may be a key element in detection systems developed to mitigate driver distraction and inattention. Keywords: Head movements, Glance classification, Head-glance correspondence, Driver distractionNew England University Transportation CenterSantos Family FoundationToyota Motor Corporation (Class Action Settlement Safety Research and Education Program

Study protocol: neonatal colonisation and infection with Ureaplasma in very immature preterm infants born <29 weeks of gestation (NEO-CONSCIOUS) – a prospective multicentre study assessing early life colonisation rates and potentially associated adverse outcomes

Preterm infants, particularly those born before 29 weeks of gestation, are at increased risk of developing bronchopulmonary dysplasia (BPD) and other complications of prematurity. Substantial evidence suggests that respiratory tract colonisation with Ureaplasma species significantly contributes to pulmonary inflammation, impaired lung function and subsequent lung disease especially in very immature infants. Moreover, Ureaplasma exposure has been implicated in the pathogenesis of other inflammation-related sequelae of prematurity. Although representing a potentially actionable risk factor for adverse short-term and long-term neonatal outcome, controversies on Ureaplasma -associated morbidity remain and recommendations for screening practices in preterm infants are missing. The NEO-CONSCIOUS (Neonatal Colonisation and Infection with Ureaplasma in very immature preterm infants born <29 weeks of gestation) study aims to assess the incidence of Ureaplasma colonisation and infection in very preterm infants at high risk of adverse outcome, the extent of potentially accompanying inflammation and the impact on short-term and long-term morbidity. Methods and analysis This is a prospective observational multicentre study being conducted in level III neonatal intensive care units in Germany and Austria. In total, 400 infants born before 29 weeks of gestation are screened for Ureaplasma colonisation immediately after birth. In addition, biomarkers of systemic inflammation are determined on day 1 and day 28. The study infants are followed up until discharge and at 2 years corrected age. The primary outcome BPD and/or death is assessed at 36 weeks postmenstrual age. Secondary outcomes include systemic inflammation, secondary infections, intraventricular haemorrhage, periventricular leukomalacia, necrotising enterocolitis, retinopathy of prematurity and neurodevelopmental outcome at 24 months corrected age. Ethics and dissemination The study has been approved by the ethics committees in Würzburg and Leipzig and the local ethics committees of all participating centres. Results will be disseminated through peer-reviewed international publications and conferences. The study is registered with the German Clinical Trials Register, ID DRKS00033001. Trial registration number German Clinical Trials Register (DRKS00033001)

Semantic Networks: Structure and Dynamics

During the last ten years several studies have appeared regarding language complexity. Research on this issue began soon after the burst of a new movement of interest and research in the study of complex networks, i.e., networks whose structure is irregular, complex and dynamically evolving in time. In the first years, network approach to language mostly focused on a very abstract and general overview of language complexity, and few of them studied how this complexity is actually embodied in humans or how it affects cognition. However research has slowly shifted from the language-oriented towards a more cognitive-oriented point of view. This review first offers a brief summary on the methodological and formal foundations of complex networks, then it attempts a general vision of research activity on language from a complex networks perspective, and specially highlights those efforts with cognitive-inspired aim

Pragmatic and promiscuous: explaining the rise of competitive political militias across Africa

Across African states, militias have become one of the main agents of political violence, accounting for a third of all recent conflict. Militia violence is attributed to cultural reactions to disorder, failing and predatory states, and local cleavages which emerge during civil wars. However, activity largely occurs in democratizing states without civil wars. This article presents a typology of militias based on their local roles and actions and an explanation for the prevalence of “competition militias.” Changes in macro politics ushered in a new era of conflict and fragmentation among political elites; militias operate as private armies for these elites. The goal of this violence is to alter the political landscape, increase power for patrons, protect supportive communities, and hinder opponents. Incentives within African democratic institutions reward the use of force by elites. As a result, African democracies, and states transitioning into democracy, are not likely to be internally peaceful. Furthermore, the dominant type of conflict across African states shifts to accommodate the goals of violent agents within modern political contexts