Microfluidic devices for terahertz spectroscopy of biomolecules

We demonstrate microfluidic devices for terahertz spectroscopy of biomolecules in aqueous solutions. The devices are fabricated out of a plastic material that is both mechanically rigid and optically transparent with near-zero dispersion in the terahertz frequency range. Using a low-power terahertz time-domain spectrometer, we experimentally measure the absorption spectra of the vibrational modes of bovine serum albumin from 0.5–2.5 THz and find good agreement with previously reported data obtained using large-volume solutions and a high-power free-electron laser. Our results demonstrate the feasibility of performing high sensitivity terahertz spectroscopy of biomolecules in aqueous solutions with detectable molecular quantities as small as 10 picomoles using microfluidic devices

Fantasies of subjugation: a discourse theoretical account of British policy on the European Union

The decision by the UK government to hold a referendum on Britain’s membership of the European Union (EU) marks an important development in policy towards the EU. Policy changes of this kind must be understood in the historical and political context in which they occur. This includes the framing of the policy issues within public discourse. In the UK, policies are formed in a discursive environment which is overwhelmingly hostile towards the EU. Debates are structured by a predominantly Euroskeptic discourse which emphasizes the UK’s separation and heterogeneity from the rest of the EU. Drawing on the logics of critical explanation, this article examines the structure and affective power of Euroskeptic discourses which dictate the terms of the EU debate. It presents a case study of the recent EU treaty revision process, culminating in the Treaty of Lisbon. In so doing, it enables a deeper understanding of recent policy developments

The Regulatory Landscape of a Core Maize Domestication Module Controlling Bud Dormancy and Growth Repression

Many domesticated crop plants have been bred for increased apical dominance, displaying greatly reduced axillary branching compared to their wild ancestors. In maize, this was achieved through selection for a gain-of-function allele of the TCP transcription factor teosinte branched1 (tb1). The mechanism for how a dominant Tb1 allele increased apical dominance, is unknown. Through ChIP seq, RNA seq, hormone and sugar measurements on 1 mm axillary bud tissue, we identify the genetic pathways putatively regulated by TB1. These include pathways regulating phytohormones such as gibberellins, abscisic acid and jasmonic acid, but surprisingly, not auxin. In addition, metabolites involved in sugar sensing such as trehalose 6-phosphate were increased. This suggests that TB1 induces bud suppression through the production of inhibitory phytohormones and by reducing sugar levels and energy balance. Interestingly, TB1 also putatively targets several other domestication loci, including teosinte glume architecture1, prol1.1/grassy tillers1, as well as itself. This places tb1 on top of the domestication hierarchy, demonstrating its critical importance during the domestication of maize from teosinte

What guidance are researchers given on how to present network meta-analyses to end-users such as policymakers and clinicians? A systematic review

© 2014 Sullivan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Introduction: Network meta-analyses (NMAs) are complex methodological approaches that may be challenging for non-technical end-users, such as policymakers and clinicians, to understand. Consideration should be given to identifying optimal approaches to presenting NMAs that help clarify analyses. It is unclear what guidance researchers currently have on how to present and tailor NMAs to different end-users. Methods: A systematic review of NMA guidelines was conducted to identify guidance on how to present NMAs. Electronic databases and supplementary sources were searched for NMA guidelines. Presentation format details related to sample formats, target audiences, data sources, analysis methods and results were extracted and frequencies tabulated. Guideline quality was assessed following criteria developed for clinical practice guidelines. Results: Seven guidelines were included. Current guidelines focus on how to conduct NMAs but provide limited guidance to researchers on how to best present analyses to different end-users. None of the guidelines provided reporting templates. Few guidelines provided advice on tailoring presentations to different end-users, such as policymakers. Available guidance on presentation formats focused on evidence networks, characteristics of individual trials, comparisons between direct and indirect estimates and assumptions of heterogeneity and/or inconsistency. Some guidelines also provided examples of figures and tables that could be used to present information. Conclusions: Limited guidance exists for researchers on how best to present NMAs in an accessible format, especially for non-technical end-users such as policymakers and clinicians. NMA guidelines may require further integration with end-users' needs, when NMAs are used to support healthcare policy and practice decisions. Developing presentation formats that enhance understanding and accessibility of NMAs could also enhance the transparency and legitimacy of decisions informed by NMAs.The Canadian Institute of Health Research (CIHR) Drug Safety and Effectiveness Network (Funding reference number – 116573)

TWEAK-FN14 signaling induces lysosomal degradation of a cIAP1–TRAF2 complex to sensitize tumor cells to TNFα

Synthetic inhibitor of apoptosis (IAP) antagonists induce degradation of IAP proteins such as cellular IAP1 (cIAP1), activate nuclear factor κB (NF-κB) signaling, and sensitize cells to tumor necrosis factor α (TNFα). The physiological relevance of these discoveries to cIAP1 function remains undetermined. We show that upon ligand binding, the TNF superfamily receptor FN14 recruits a cIAP1–Tnf receptor-associated factor 2 (TRAF2) complex. Unlike IAP antagonists that cause rapid proteasomal degradation of cIAP1, signaling by FN14 promotes the lysosomal degradation of cIAP1–TRAF2 in a cIAP1-dependent manner. TNF-like weak inducer of apoptosis (TWEAK)/FN14 signaling nevertheless promotes the same noncanonical NF-κB signaling elicited by IAP antagonists and, in sensitive cells, the same autocrine TNFα-induced death occurs. TWEAK-induced loss of the cIAP1–TRAF2 complex sensitizes immortalized and minimally passaged tumor cells to TNFα-induced death, whereas primary cells remain resistant. Conversely, cIAP1–TRAF2 complex overexpression limits FN14 signaling and protects tumor cells from TWEAK-induced TNFα sensitization. Lysosomal degradation of cIAP1–TRAF2 by TWEAK/FN14 therefore critically alters the balance of life/death signals emanating from TNF-R1 in immortalized cells

Beliefs about the Minds of Others Influence How We Process Sensory Information

Attending where others gaze is one of the most fundamental mechanisms of social cognition. The present study is the first to examine the impact of the attribution of mind to others on gaze-guided attentional orienting and its ERP correlates. Using a paradigm in which attention was guided to a location by the gaze of a centrally presented face, we manipulated participants' beliefs about the gazer: gaze behavior was believed to result either from operations of a mind or from a machine. In Experiment 1, beliefs were manipulated by cue identity (human or robot), while in Experiment 2, cue identity (robot) remained identical across conditions and beliefs were manipulated solely via instruction, which was irrelevant to the task. ERP results and behavior showed that participants' attention was guided by gaze only when gaze was believed to be controlled by a human. Specifically, the P1 was more enhanced for validly, relative to invalidly, cued targets only when participants believed the gaze behavior was the result of a mind, rather than of a machine. This shows that sensory gain control can be influenced by higher-order (task-irrelevant) beliefs about the observed scene. We propose a new interdisciplinary model of social attention, which integrates ideas from cognitive and social neuroscience, as well as philosophy in order to provide a framework for understanding a crucial aspect of how humans' beliefs about the observed scene influence sensory processing

Integrated information increases with fitness in the evolution of animats

One of the hallmarks of biological organisms is their ability to integrate disparate information sources to optimize their behavior in complex environments. How this capability can be quantified and related to the functional complexity of an organism remains a challenging problem, in particular since organismal functional complexity is not well-defined. We present here several candidate measures that quantify information and integration, and study their dependence on fitness as an artificial agent ("animat") evolves over thousands of generations to solve a navigation task in a simple, simulated environment. We compare the ability of these measures to predict high fitness with more conventional information-theoretic processing measures. As the animat adapts by increasing its "fit" to the world, information integration and processing increase commensurately along the evolutionary line of descent. We suggest that the correlation of fitness with information integration and with processing measures implies that high fitness requires both information processing as well as integration, but that information integration may be a better measure when the task requires memory. A correlation of measures of information integration (but also information processing) and fitness strongly suggests that these measures reflect the functional complexity of the animat, and that such measures can be used to quantify functional complexity even in the absence of fitness data.Comment: 27 pages, 8 figures, one supplementary figure. Three supplementary video files available on request. Version commensurate with published text in PLoS Comput. Bio

Towards a Mathematical Theory of Cortical Micro-circuits

The theoretical setting of hierarchical Bayesian inference is gaining acceptance as a framework for understanding cortical computation. In this paper, we describe how Bayesian belief propagation in a spatio-temporal hierarchical model, called Hierarchical Temporal Memory (HTM), can lead to a mathematical model for cortical circuits. An HTM node is abstracted using a coincidence detector and a mixture of Markov chains. Bayesian belief propagation equations for such an HTM node define a set of functional constraints for a neuronal implementation. Anatomical data provide a contrasting set of organizational constraints. The combination of these two constraints suggests a theoretically derived interpretation for many anatomical and physiological features and predicts several others. We describe the pattern recognition capabilities of HTM networks and demonstrate the application of the derived circuits for modeling the subjective contour effect. We also discuss how the theory and the circuit can be extended to explain cortical features that are not explained by the current model and describe testable predictions that can be derived from the model