A Connectionist Approach to Embodied Conceptual Metaphor

A growing body of data has been gathered in support of the view that the mind is embodied and that cognition is grounded in sensory-motor processes. Some researchers have gone so far as to claim that this paradigm poses a serious challenge to central tenets of cognitive science, including the widely held view that the mind can be analyzed in terms of abstract computational principles. On the other hand, computational approaches to the study of mind have led to the development of specific models that help researchers understand complex cognitive processes at a level of detail that theories of embodied cognition (EC) have sometimes lacked. Here we make the case that connectionist architectures in particular can illuminate many surprising results from the EC literature. These models can learn the statistical structure in their environments, providing an ideal framework for understanding how simple sensory-motor mechanisms could give rise to higher-level cognitive behavior over the course of learning. Crucially, they form overlapping, distributed representations, which have exactly the properties required by many embodied accounts of cognition. We illustrate this idea by extending an existing connectionist model of semantic cognition in order to simulate findings from the embodied conceptual metaphor literature. Specifically, we explore how the abstract domain of time may be structured by concrete experience with space (including experience with culturally specific spatial and linguistic cues). We suggest that both EC researchers and connectionist modelers can benefit from an integrated approach to understanding these models and the empirical findings they seek to explain

An Emergent Approach to Analogical Inference

In recent years, a growing number of researchers have proposed that analogy is a core component of human cognition. According to the dominant theoretical viewpoint, analogical reasoning requires a specific suite of cognitive machinery, including explicitly coded symbolic representations and a mapping or binding mechanism that operates over these representations. Here we offer an alternative approach: we find that analogical inference can emerge naturally and spontaneously from a relatively simple, error-driven learning mechanism without the need to posit any additional analogy-specific machinery. The results also parallel findings from the developmental literature on analogy, demonstrating a shift from an initial reliance on surface feature similarity to the use of relational similarity later in training. Variants of the model allow us to consider and rule out alternative accounts of its performance. We conclude by discussing how these findings can potentially refine our understanding of the processes that are required to perform analogical inference

The Neuroscience Information Framework: A Data and Knowledge Environment for Neuroscience

With support from the Institutes and Centers forming the NIH Blueprint for Neuroscience Research, we have designed and implemented a new initiative for integrating access to and use of Web-based neuroscience resources: the Neuroscience Information Framework. The Framework arises from the expressed need of the neuroscience community for neuroinformatic tools and resources to aid scientific inquiry, builds upon prior development of neuroinformatics by the Human Brain Project and others, and directly derives from the Society for Neuroscience’s Neuroscience Database Gateway. Partnered with the Society, its Neuroinformatics Committee, and volunteer consultant-collaborators, our multi-site consortium has developed: (1) a comprehensive, dynamic, inventory of Web-accessible neuroscience resources, (2) an extended and integrated terminology describing resources and contents, and (3) a framework accepting and aiding concept-based queries. Evolving instantiations of the Framework may be viewed at http://nif.nih.gov, http://neurogateway.org, and other sites as they come on line

Population genetics of trypanosoma brucei rhodesiense: clonality and diversity within and between foci

African trypanosomes are unusual among pathogenic protozoa in that they can undergo their complete morphological life cycle in the tsetse fly vector with mating as a non-obligatory part of this development. Trypanosoma brucei rhodesiense, which infects humans and livestock in East and Southern Africa, has classically been described as a host-range variant of the non-human infective Trypanosoma brucei that occurs as stable clonal lineages. We have examined T. b. rhodesiense populations from East (Uganda) and Southern (Malawi) Africa using a panel of microsatellite markers, incorporating both spatial and temporal analyses. Our data demonstrate that Ugandan T. b. rhodesiense existed as clonal populations, with a small number of highly related genotypes and substantial linkage disequilibrium between pairs of loci. However, these populations were not stable as the dominant genotypes changed and the genetic diversity also reduced over time. Thus these populations do not conform to one of the criteria for strict clonality, namely stability of predominant genotypes over time, and our results show that, in a period in the mid 1990s, the previously predominant genotypes were not detected but were replaced by a novel clonal population with limited genetic relationship to the original population present between 1970 and 1990. In contrast, the Malawi T. b. rhodesiense population demonstrated significantly greater diversity and evidence for frequent genetic exchange. Therefore, the population genetics of T. b. rhodesiense is more complex than previously described. This has important implications for the spread of the single copy T. b. rhodesiense gene that allows human infectivity, and therefore the epidemiology of the human disease, as well as suggesting that these parasites represent an important organism to study the influence of optional recombination upon population genetic dynamics

Pyrimidine biosynthesis is not an essential function for trypanosoma brucei bloodstream forms

<p>Background: African trypanosomes are capable of both pyrimidine biosynthesis and salvage of preformed pyrimidines from the host, but it is unknown whether either process is essential to the parasite.</p> <p>Methodology/Principal Findings: Pyrimidine requirements for growth were investigated using strictly pyrimidine-free media, with or without single added pyrimidine sources. Growth rates of wild-type bloodstream form Trypanosoma brucei brucei were unchanged in pyrimidine-free medium. The essentiality of the de novo pyrimidine biosynthesis pathway was studied by knocking out the PYR6-5 locus that produces a fusion product of orotate phosphoribosyltransferase (OPRT) and Orotidine Monophosphate Decarboxylase (OMPDCase). The pyrimidine auxotroph was dependent on a suitable extracellular pyrimidine source. Pyrimidine starvation was rapidly lethal and non-reversible, causing incomplete DNA content in new cells. The phenotype could be rescued by addition of uracil; supplementation with uridine, 2′deoxyuridine, and cytidine allowed a diminished growth rate and density. PYR6-5−/− trypanosomes were more sensitive to pyrimidine antimetabolites and displayed increased uracil transport rates and uridine phosphorylase activity. Pyrimidine auxotrophs were able to infect mice although the infection developed much more slowly than infection with the parental, prototrophic trypanosome line.</p> <p>Conclusions/Significance: Pyrimidine salvage was not an essential function for bloodstream T. b. brucei. However, trypanosomes lacking de novo pyrimidine biosynthesis are completely dependent on an extracellular pyrimidine source, strongly preferring uracil, and display reduced infectivity. As T. brucei are able to salvage sufficient pyrimidines from the host environment, the pyrimidine biosynthesis pathway is not a viable drug target, although any interruption of pyrimidine supply was lethal.</p&gt

Genome3D: integrating a collaborative data pipeline to expand the depth and breadth of consensus protein structure annotation.

Genome3D (https://www.genome3d.eu) is a freely available resource that provides consensus structural annotations for representative protein sequences taken from a selection of model organisms. Since the last NAR update in 2015, the method of data submission has been overhauled, with annotations now being 'pushed' to the database via an API. As a result, contributing groups are now able to manage their own structural annotations, making the resource more flexible and maintainable. The new submission protocol brings a number of additional benefits including: providing instant validation of data and avoiding the requirement to synchronise releases between resources. It also makes it possible to implement the submission of these structural annotations as an automated part of existing internal workflows. In turn, these improvements facilitate Genome3D being opened up to new prediction algorithms and groups. For the latest release of Genome3D (v2.1), the underlying dataset of sequences used as prediction targets has been updated using the latest reference proteomes available in UniProtKB. A number of new reference proteomes have also been added of particular interest to the wider scientific community: cow, pig, wheat and mycobacterium tuberculosis. These additions, along with improvements to the underlying predictions from contributing resources, has ensured that the number of annotations in Genome3D has nearly doubled since the last NAR update article. The new API has also been used to facilitate the dissemination of Genome3D data into InterPro, thereby widening the visibility of both the annotation data and annotation algorithms

Herschel-HIFI detections of hydrides towards AFGL 2591 (Envelope emission versus tenuous cloud absorption)

The Heterodyne Instrument for the Far Infrared (HIFI) onboard the Herschel Space Observatory allows the first observations of light diatomic molecules at high spectral resolution and in multiple transitions. Here, we report deep integrations using HIFI in different lines of hydrides towards the high-mass star forming region AFGL 2591. Detected are CH, CH+, NH, OH+, H2O+, while NH+ and SH+ have not been detected. All molecules except for CH and CH+ are seen in absorption with low excitation temperatures and at velocities different from the systemic velocity of the protostellar envelope. Surprisingly, the CH(JF,P = 3/2_2,- - 1/2_1,+) and CH+(J = 1 - 0, J = 2 - 1) lines are detected in emission at the systemic velocity. We can assign the absorption features to a foreground cloud and an outflow lobe, while the CH and CH+ emission stems from the envelope. The observed abundance and excitation of CH and CH+ can be explained in the scenario of FUV irradiated outflow walls, where a cavity etched out by the outflow allows protostellar FUV photons to irradiate and heat the envelope at larger distances driving the chemical reactions that produce these molecules.Comment: Accepted for publication in Astronomy and Astrophysics (HIFI first results issue

Effects of beta-alanine supplementation on brain homocarnosine/carnosine signal and cognitive function: an exploratory study

Objectives: Two independent studies were conducted to examine the effects of 28 d of beta-alanine supplementation at 6.4 g d-1 on brain homocarnosine/carnosine signal in omnivores and vegetarians (Study 1) and on cognitive function before and after exercise in trained cyclists (Study 2). Methods: In Study 1, seven healthy vegetarians (3 women and 4 men) and seven age- and sex-matched omnivores undertook a brain 1H-MRS exam at baseline and after beta-alanine supplementation. In study 2, nineteen trained male cyclists completed four 20-Km cycling time trials (two pre supplementation and two post supplementation), with a battery of cognitive function tests (Stroop test, Sternberg paradigm, Rapid Visual Information Processing task) being performed before and after exercise on each occasion. Results: In Study 1, there were no within-group effects of beta-alanine supplementation on brain homocarnosine/carnosine signal in either vegetarians (p = 0.99) or omnivores (p = 0.27); nor was there any effect when data from both groups were pooled (p = 0.19). Similarly, there was no group by time interaction for brain homocarnosine/carnosine signal (p = 0.27). In study 2, exercise improved cognitive function across all tests (P0.05) of beta-alanine supplementation on response times or accuracy for the Stroop test, Sternberg paradigm or RVIP task at rest or after exercise. Conclusion: 28 d of beta-alanine supplementation at 6.4g d-1 appeared not to influence brain homocarnosine/ carnosine signal in either omnivores or vegetarians; nor did it influence cognitive function before or after exercise in trained cyclists

Block of C/EBPα function by phosphorylation in acute myeloid leukemia with FLT3 activating mutations

Mutations constitutively activating FLT3 kinase are detected in ∼30% of acute myelogenous leukemia (AML) patients and affect downstream pathways such as extracellular signal–regulated kinase (ERK)1/2. We found that activation of FLT3 in human AML inhibits CCAAT/enhancer binding protein α (C/EBPα) function by ERK1/2-mediated phosphorylation, which may explain the differentiation block of leukemic blasts. In MV4;11 cells, pharmacological inhibition of either FLT3 or MEK1 leads to granulocytic differentiation. Differentiation of MV4;11 cells was also observed when C/EBPα mutated at serine 21 to alanine (S21A) was stably expressed. In contrast, there was no effect when serine 21 was mutated to aspartate (S21D), which mimics phosphorylation of C/EBPα. Thus, our results suggest that therapies targeting the MEK/ERK cascade or development of protein therapies based on transduction of constitutively active C/EBPα may prove effective in treatment of FLT3 mutant leukemias resistant to the FLT3 inhibitor therapies

Extended supersymmetric sigma models in AdS_4 from projective superspace

There exist two superspace approaches to describe N=2 supersymmetric nonlinear sigma models in four-dimensional anti-de Sitter (AdS_4) space: (i) in terms of N=1 AdS chiral superfields, as developed in arXiv:1105.3111 and arXiv:1108.5290; and (ii) in terms of N=2 polar supermultiplets using the AdS projective-superspace techniques developed in arXiv:0807.3368. The virtue of the approach (i) is that it makes manifest the geometric properties of the N=2 supersymmetric sigma-models in AdS_4. The target space must be a non-compact hyperkahler manifold endowed with a Killing vector field which generates an SO(2) group of rotations on the two-sphere of complex structures. The power of the approach (ii) is that it allows us, in principle, to generate hyperkahler metrics as well as to address the problem of deformations of such metrics. Here we show how to relate the formulation (ii) to (i) by integrating out an infinite number of N=1 AdS auxiliary superfields and performing a superfield duality transformation. We also develop a novel description of the most general N=2 supersymmetric nonlinear sigma-model in AdS_4 in terms of chiral superfields on three-dimensional N=2 flat superspace without central charge. This superspace naturally originates from a conformally flat realization for the four-dimensional N=2 AdS superspace that makes use of Poincare coordinates for AdS_4. This novel formulation allows us to uncover several interesting geometric results.Comment: 88 pages; v3: typos corrected, version published in JHE