Cognition simulation and learning

The purpose of this paper is to describe new computer software that has been specifically developed to aid experiential learning in groups and with individuals. The software is designed to conduct a pseudosimula- tion involving ramifications and interaction of qualitative ideas, beliefs, attitudes, and values. It has been developed over the past four years through a continual interaction between the state of theory and software, and has been used with a variety of decision-making groups

Positivity of hexagon perturbation theory

The hexagon-form-factor program was proposed as a way to compute three- and higher-point correlation functions in $\mathcal{N}=4$ super-symmetric Yang-Mills theory and in the dual AdS$_5\times$S$^5$ superstring theory, by exploiting the integrability of the theory in the 't Hooft limit. This approach is reminiscent of the asymptotic Bethe ansatz in that it applies to a large-volume expansion. Finite-volume corrections can be incorporated through L\"uscher-like formulae, though the systematics of this expansion is largely unexplored so far. Strikingly, finite-volume corrections may feature negative powers of the 't Hooft coupling $g$ in the small-$g$ expansion, potentially leading to a breakdown of the formalism. In this work we show that the finite-volume perturbation theory for the hexagon is positive and thereby compatible with the weak-coupling expansion for arbitrary $n$-point functions.Comment: v2: misprints corrected, further details on physical magnons adde

A dyad of lymphoblastic lysosomal cysteine proteases degrades the antileukemic drug L-asparaginase

l-Asparaginase is a key therapeutic agent for treatment of childhood acute lymphoblastic leukemia (ALL). There is wide individual variation in pharmacokinetics, and little is known about its metabolism. The mechanisms of therapeutic failure with l-asparaginase remain speculative. Here, we now report that 2 lysosomal cysteine proteases present in lymphoblasts are able to degrade l-asparaginase. Cathepsin B (CTSB), which is produced constitutively by normal and leukemic cells, degraded asparaginase produced by Escherichia coli (ASNase) and Erwinia chrysanthemi. Asparaginyl endopeptidase (AEP), which is overexpressed predominantly in high-risk subsets of ALL, specifically degraded ASNase. AEP thereby destroys ASNase activity and may also potentiate antigen processing, leading to allergic reactions. Using AEP-mediated cleavage sequences, we modeled the effects of the protease on ASNase and created a number of recombinant ASNase products. The N24 residue on the flexible active loop was identified as the primary AEP cleavage site. Sole modification at this site rendered ASNase resistant to AEP cleavage and suggested a key role for the flexible active loop in determining ASNase activity. We therefore propose what we believe to be a novel mechanism of drug resistance to ASNase. Our results may help to identify alternative therapeutic strategies with the potential of further improving outcome in childhood ALL

Was the cold European winter 2009-2010 modified by anthropogenic climate change? An attribution study

An attribution study has been performed to investigate the degree to which the unusually cold European winter 2009-2010 was modified by anthropogenic climate change. Two different methods have been included for the attribution: one based on a large HadGEM3-A ensemble and one based on a statistical surrogate method. Both methods are evaluated by comparing simulated winter temperature means, trends, standard deviations, skewness, return periods, and 5 % quantiles with observations. While the surrogate method performs well, HadGEM3-A in general underestimates the trend in winter by a factor of 2/3. It has a mean cold bias dominated by the mountainous regions and also underestimates the cold 5 % quantile in many regions of Europe. Both methods show that the probability of experiencing a winter as cold as 2009-2010 has been reduced by approximately a factor of two due to anthropogenic changes. The method based on HadGEM3-A ensembles gives somewhat larger changes than the surrogate method because of differences in the definition of the unperturbed climate. The results are based on two diagnostics: the coldest day in winter and the largest continuous area with temperatures colder than twice the local standard deviation. The results are not sensitive to the choice of bias correction except in the mountainous regions. Previous results regarding the behavior of the measures of the changed probability have been extended. The counter-intuitive behavior for heavy-tailed distributions is found to hold for a range of measures and for events that become more rare in a changed climate

Impact of brain tissue filtering on neurostimulation fields: A modeling study

Electrical neurostimulation techniques, such as deep brain stimulation (DBS) and transcranial magnetic stimulation (TMS), are increasingly used in the neurosciences, e.g., for studying brain function, and for neurotherapeutics, e.g., for treating depression, epilepsy, and Parkinson's disease. The characterization of electrical properties of brain tissue has guided our fundamental understanding and application of these methods, from electrophysiologic theory to clinical dosing-metrics. Nonetheless, prior computational models have primarily relied on ex-vivo impedance measurements. We recorded the in-vivo impedances of brain tissues during neurosurgical procedures and used these results to construct MRI guided computational models of TMS and DBS neurostimulatory fields and conductance-based models of neurons exposed to stimulation. We demonstrated that tissues carry neurostimulation currents through frequency dependent resistive and capacitive properties not typically accounted for by past neurostimulation modeling work. We show that these fundamental brain tissue properties can have significant effects on the neurostimulatory-fields (capacitive and resistive current composition and spatial/temporal dynamics) and neural responses (stimulation threshold, ionic currents, and membrane dynamics). These findings highlight the importance of tissue impedance properties on neurostimulation and impact our understanding of the biological mechanisms and technological potential of neurostimulatory methods.United States. Defense Advanced Research Projects Agency (Contract W31P4Q-09-C-0117)National Institute of Neurological Disorders and Stroke (U.S.) (Award R43NS062530)National Institute of Neurological Disorders and Stroke (U.S.) (Award 1R44NS080632

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The Security imaginary: Explaining military isomorphism

This article proposes the notion of a security imaginary as a heuristic tool for exploring military isomorphism (the phenomenon that weapons and military strategies begin to look the same across the world) at a time when the US model of defence transformation is being adopted by an increasing number of countries. Built on a critical constructivist foundation, the security-imaginary approach is contrasted with rationalist and neo-institutionalist ways of explaining military diffusion and emulation. Merging cultural and constructivist themes, the article offers a ‘strong cultural’ argument to explain why a country would emulate a foreign military model and how this model is constituted in and comes to constitute a society’s security imaginary.Web of Scienc

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