Scanning Electrochemical Microscopy of DNA Monolayers Modified with Nile Blue

Scanning electrochemical microscopy (SECM) is used to probe long-range charge transport (CT) through DNA monolayers containing the redox-active Nile Blue (NB) intercalator covalently affixed at a specific location in the DNA film. At substrate potentials negative of the formal potential of covalently attached NB, the electrocatalytic reduction of Fe(CN)63− generated at the SECM tip is observed only when NB is located at the DNA/solution interface; for DNA films containing NB in close proximity to the DNA/electrode interface, the electrocatalytic effect is absent. This behavior is consistent with both rapid DNA-mediated CT between the NB intercalator and the gold electrode as well as a rate-limiting electron transfer between NB and the solution phase Fe(CN)63−. The DNA-mediated nature of the catalytic cycle is confirmed through sequence-specific and localized detection of attomoles of TATA-binding protein, a transcription factor that severely distorts DNA upon binding. Importantly, the strategy outlined here is general and allows for the local investigation of the surface characteristics of DNA monolayers both in the absence and in the presence of DNA binding proteins. These experiments highlight the utility of DNA-modified electrodes as versatile platforms for SECM detection schemes that take advantage of CT mediated by the DNA base pair stack

An improved direct colorimetric method for the quantitative analysis of urinary hippuric acid as an index of toluene exposure

An improved direct colorimetric method for determining the concentration of urinary hippuric acid as an index of toluene exposure was described. One tenth ml of urine was diluted with 0.4 ml 0.01 M phosphate buffer H 6.9 and mixed with 0.5 ml pyridine. The mixture was layered on 0.2 ml benzenesulfonyl chloride. The reaction was started by mixing for one min with a mechanical shaker. The colored solution was allowed to stand for 30 min, diluted with 5 ml ethanol, and absorbance measured at 410 nm within 30 min after the dilution. The coefficient of variation of this method was 6% and the recovery 103% when urine contains about 0.2-0.5 mg hippuric acid per ml of urine. The concentration was linear up to 2.0 mg per ml hippuric acid in a specimen.</p

Learning the preferences of physicians for the organization of result lists of medical evidence articles

Objectives Despite many clinical decision support systems (CDSSs) being rated as highly usable, CDSSs have not been widely adopted in clinical practice. We posit that there are factors aside from usability that impact adoption of CDSSs; in particular we are interested in the role played by MDs intrinsic motivation to use computer-based support. Our research aim is to investigate the relationship between usability and intrinsic motivation in order to learn about adoption of CDSS in clinical practice. Methods Following the evaluation of a CDSS, 19 MDs completed a 2 part questionnaire about their intrinsic motivation to use computer-based support in general and the usability of the evaluated CDSS. Results The analysis of MDs motivation to use computer-based support demonstrated that MDs are comfortable using computer-based support and in general find using it quite easy (a motivation rating of 0.66 on a (0, 1) scale was computed). However MDs also reported a perceived lack of competence associated with a lack of prior experience using technology in practice, which results in pressure and tension. The considered CDSS scored highly on all usability dimensions and a usability rating of 0.74 was recorded. The examination of the relationship between motivation and usability suggested that users who were motivated to use computer-based support experienced better usability than those who reported low levels of motivation. Conclusions Our small case study suggests that an important factor supplementing the usability of CDSSs is intrinsic motivation to use computer-based support in general. We posit that the lack of such a measure thus far in CDSS evaluation may to some extent explain seeming MD satisfaction with CDSSs on one hand, but their limited adoption on the other. We recommend that clinical managers responsible for deploying CDSS should invest in training MDs to use technology underlying computer-based support applications instead of focusing only on the features of the specific CDSS to be deployed

Neurologically motivated coupling functions in models of motor coordination

This is the final version. Available from the Society for Industrial and Applied Mathematics via the DOI in this recordWe present an analysis of two Haken–Kelso–Bunz (HKB) oscillators coupled by a neurologically motivated function. We study the effect of time delay and weighted self-feedback and mutual feedback on the synchronization behavior of the model. We focus on identifying parameter regimes supporting experimentally observed decrease in oscillation amplitude and loss of anti-phase stability that has inspired the development of the HKB model. We show that a combination of cross-talk and nonlinearity in the coupling, along with physiologically relevant time delay, is able to quantitatively account for both drop in oscillation amplitude and loss of anti-phase stability in a frequency dependent manner. Furthermore, we demonstrate that the transition between discrete and rhythmic movements could be captured by this model. To this end, we carry out theoretical and numerical analysis of the emergence of in-phase and anti-phase oscillations.Engineering and Physical Science Research Council (EPSRC

Diversification rates and phenotypic evolution in venomous snakes (Elapidae)

Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited.The relationship between rates of diversification and of body size change (a common proxy for phenotypic evolution) was investigated across Elapidae, the largest radiation of highly venomous snakes. Time-calibrated phylogenetic trees for 175 species of elapids (more than 50% of known taxa) were constructed using seven mitochondrial and nuclear genes. Analyses using these trees revealed no evidence for a link between speciation rates and changes in body size. Two clades (Hydrophis, Micrurus) show anomalously high rates of diversification within Elapidae, yet exhibit rates of body size evolution almost identical to the general elapid ‘background’ rate. Although correlations between speciation rates and rates of body size change exist in certain groups (e.g. ray-finned fishes, passerine birds), the two processes appear to be uncoupled in elapid snakes. There is also no detectable shift in diversification dynamics associated with the colonization of Australasia, which is surprising given that elapids appear to be the first clade of venomous snakes to reach the continent

Robust spike timing in an excitable cell with delayed feedback

This is the author accepted manuscript. The final version is available from the Royal Society via the DOI in this recordData and materials availability: Data and computer code related to the mathematical model and dynamic clamp experiments can be downloaded from the GitHub repository https://github.com/SlowinskiPiotr/MorrisLecarDDEThe initiation and regeneration of pulsatile activity is a ubiquitous feature observed in excitable systems with delayed feedback. Here, we demonstrate this phenomenon in a real biological cell. We establish a critical role of the delay resulting from the finite propagation speed of electrical impulses on the emergence of persistent multiple-spike patterns. We predict the co-existence of a number of such patterns in a mathematical model and use a biological cell subject to dynamic clamp to confirm our predictions in a living mammalian system. Given the general nature of our mathematical model and experimental system, we believe that our results capture key hallmarks of physiological excitability that are fundamental to information processing.Medical Research Council (MRC)Wellcome TrustEngineering and Physical Sciences Research Council (EPSRC)Technical University of Munich – Institute for Advanced StudyRoyal Societ

A feasibility study using movement and perspective-taking as a diagnostic aid for psychosis

This is the final version.STUDY SUMMARY Study Title: A feasibility study using movement and perspective-taking as a diagnostic aid for psychosis. Internal ref. no. (or short title): Movement and perspective-taking as a diagnostic aid for psychosis. Study Design: Feasibility study. Study Participants: People accepted for an assessment for psychosis or risk of developing psychosis and people with first episode psychosis or being at risk of developing psychosis. Planned Size of Sample (if applicable): 100 service users and 50 controls. Follow up duration (if applicable): N/A. Planned Study Period: 1/3/18 - 31/8/18. Research Question/Aim(s): 1/ We want to investigate accuracy of classifiers based on movement and coordination during an interaction with a computer avatar in people who are considered at risk of psychosis or who have a newly diagnosed psychotic disorder, compared to healthy controls and those who do not have psychosis or a future risk of psychosis. 2/ We want to investigate feasibility of this diagnostic procedure in a clinical setting and gather opinions about the task and the interface from the service users and clinicians

Artificial Intelligence and Intellectual Property Law - Position Statement of the Max Planck Institute for Innovation and Competition of 9 April 2021 on the Current Debate

This Position Statement presents a broad overview of issues arising at the intersection of AI and IP law based on the work of the Max Planck Institute for Innovation and Competition research group on Regulation of the Digital Economy. While the analysis is approached mainly from a perspective de lege lata, it also identifies questions which require further reflection de lege ferenda supported by in-depth interdisciplinary research. The scope is confined to substantive European IP law, in particular, as regards copyright, patents, designs, databases and trade secrets. Specific AI-related issues are mapped out around the core questions of IP law, namely, the eligibility for protection under the respective IP regimes, allocation of rights and the scope of protection. The structure of the analysis reflects three key components of AI: inputs required for the development of AI systems, AI as a process and the output of AI applications. Overall, it is emphasised that, while recent legal and policy discussions have mostly focused on AI-aided and AI-generated output, a more holistic view that accounts for the role of IP law across the AI innovation cycle is indispensable