111,229 research outputs found

    Protein flexibility is key to cisplatin crosslinking in calmodulin

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    Chemical crosslinking in combination with Fourier transform ion cyclotron resonance mass spectrometry (FTICR MS) has significant potential for studying protein structures and proteinprotein interactions. Previously, cisplatin has been shown to be a crosslinker and crosslinks multiple methionine (Met) residues in apo-calmodulin (apo-CaM). However, the inter-residue distances obtained from nuclear magnetic resonance structures are inconsistent with the measured distance constraints by crosslinking. Met residues lie too far apart to be crosslinked by cisplatin. Here, by combining FTICR MS with a novel computational flexibility analysis, the flexible nature of the CaM structure is found to be key to cisplatin crosslinking in CaM. It is found that the side chains of Met residues can be brought together by flexible motions in both apo-CaM and calcium-bound CaM (Ca4-CaM). The possibility of cisplatin crosslinking Ca4-CaM is then confirmed by MS data. Therefore, flexibility analysis as a fast and low-cost computational method can be a useful tool for predicting crosslinking pairs in protein crosslinking analysis and facilitating MS data analysis. Finally, flexibility analysis also indicates that the crosslinking of platinum to pairs of Met residues will effectively close the nonpolar groove and thus will likely interfere with the binding of CaM to its protein targets, as was proved by comparing assays for cisplatin-modified/unmodified CaM binding to melittin. Collectively, these results suggest that cisplatin crosslinking of apo-CaM or Ca4-CaM can inhibit the ability of CaM to recognize its target proteins, which may have important implications for understanding the mechanism of tumor resistance to platinum anticancer drugs

    Toward a model of computational attention based on expressive behavior: applications to cultural heritage scenarios

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    Our project goals consisted in the development of attention-based analysis of human expressive behavior and the implementation of real-time algorithm in EyesWeb XMI in order to improve naturalness of human-computer interaction and context-based monitoring of human behavior. To this aim, perceptual-model that mimic human attentional processes was developed for expressivity analysis and modeled by entropy. Museum scenarios were selected as an ecological test-bed to elaborate three experiments that focus on visitor profiling and visitors flow regulation

    Construction of Latent Descriptor Space and Inference Model of Hand-Object Interactions

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    Appearance-based generic object recognition is a challenging problem because all possible appearances of objects cannot be registered, especially as new objects are produced every day. Function of objects, however, has a comparatively small number of prototypes. Therefore, function-based classification of new objects could be a valuable tool for generic object recognition. Object functions are closely related to hand-object interactions during handling of a functional object; i.e., how the hand approaches the object, which parts of the object and contact the hand, and the shape of the hand during interaction. Hand-object interactions are helpful for modeling object functions. However, it is difficult to assign discrete labels to interactions because an object shape and grasping hand-postures intrinsically have continuous variations. To describe these interactions, we propose the interaction descriptor space which is acquired from unlabeled appearances of human hand-object interactions. By using interaction descriptors, we can numerically describe the relation between an object's appearance and its possible interaction with the hand. The model infers the quantitative state of the interaction from the object image alone. It also identifies the parts of objects designed for hand interactions such as grips and handles. We demonstrate that the proposed method can unsupervisedly generate interaction descriptors that make clusters corresponding to interaction types. And also we demonstrate that the model can infer possible hand-object interactions

    Putting culture under the spotlight reveals universal information use for face recognition

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    Background: Eye movement strategies employed by humans to identify conspecifics are not universal. Westerners predominantly fixate the eyes during face recognition, whereas Easterners more the nose region, yet recognition accuracy is comparable. However, natural fixations do not unequivocally represent information extraction. So the question of whether humans universally use identical facial information to recognize faces remains unresolved. Methodology/Principal Findings: We monitored eye movements during face recognition of Western Caucasian (WC) and East Asian (EA) observers with a novel technique in face recognition that parametrically restricts information outside central vision. We used ‘Spotlights’ with Gaussian apertures of 2°, 5° or 8° dynamically centered on observers’ fixations. Strikingly, in constrained Spotlight conditions (2°, 5°) observers of both cultures actively fixated the same facial information: the eyes and mouth. When information from both eyes and mouth was simultaneously available when fixating the nose (8°), as expected EA observers shifted their fixations towards this region. Conclusions/Significance: Social experience and cultural factors shape the strategies used to extract information from faces, but these results suggest that external forces do not modulate information use. Human beings rely on identical facial information to recognize conspecifics, a universal law that might be dictated by the evolutionary constraints of nature and not nurture

    Generating collaborative systems for digital libraries: A model-driven approach

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    This is an open access article shared under a Creative Commons Attribution 3.0 Licence (http://creativecommons.org/licenses/by/3.0/). Copyright @ 2010 The Authors.The design and development of a digital library involves different stakeholders, such as: information architects, librarians, and domain experts, who need to agree on a common language to describe, discuss, and negotiate the services the library has to offer. To this end, high-level, language-neutral models have to be devised. Metamodeling techniques favor the definition of domainspecific visual languages through which stakeholders can share their views and directly manipulate representations of the domain entities. This paper describes CRADLE (Cooperative-Relational Approach to Digital Library Environments), a metamodel-based framework and visual language for the definition of notions and services related to the development of digital libraries. A collection of tools allows the automatic generation of several services, defined with the CRADLE visual language, and of the graphical user interfaces providing access to them for the final user. The effectiveness of the approach is illustrated by presenting digital libraries generated with CRADLE, while the CRADLE environment has been evaluated by using the cognitive dimensions framework

    Unveiling the multimedia unconscious: implicit cognitive processes and multimedia content analysis

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    One of the main findings of cognitive sciences is that automatic processes of which we are unaware shape, to a significant extent, our perception of the environment. The phenomenon applies not only to the real world, but also to multimedia data we consume every day. Whenever we look at pictures, watch a video or listen to audio recordings, our conscious attention efforts focus on the observable content, but our cognition spontaneously perceives intentions, beliefs, values, attitudes and other constructs that, while being outside of our conscious awareness, still shape our reactions and behavior. So far, multimedia technologies have neglected such a phenomenon to a large extent. This paper argues that taking into account cognitive effects is possible and it can also improve multimedia approaches. As a supporting proof-of-concept, the paper shows not only that there are visual patterns correlated with the personality traits of 300 Flickr users to a statistically significant extent, but also that the personality traits (both self-assessed and attributed by others) of those users can be inferred from the images these latter post as "favourite"

    Dynamic control of selectivity in the ubiquitination pathway revealed by an ASP to GLU substitution in an intra-molecular salt-bridge network

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    Ubiquitination relies on a subtle balance between selectivity and promiscuity achieved through specific interactions between ubiquitin-conjugating enzymes (E2s) and ubiquitin ligases (E3s). Here, we report how a single aspartic to glutamic acid substitution acts as a dynamic switch to tip the selectivity balance of human E2s for interaction toward E3 RING-finger domains. By combining molecular dynamic simulations, experimental yeast-two-hybrid screen of E2-E3 (RING) interactions and mutagenesis, we reveal how the dynamics of an internal salt-bridge network at the rim of the E2-E3 interaction surface controls the balance between an “open”, binding competent, and a “closed”, binding incompetent state. The molecular dynamic simulations shed light on the fine mechanism of this molecular switch and allowed us to identify its components, namely an aspartate/glutamate pair, a lysine acting as the central switch and a remote aspartate. Perturbations of single residues in this network, both inside and outside the interaction surface, are sufficient to switch the global E2 interaction selectivity as demonstrated experimentally. Taken together, our results indicate a new mechanism to control E2-E3 interaction selectivity at an atomic level, highlighting how minimal changes in amino acid side-chain affecting the dynamics of intramolecular salt-bridges can be crucial for protein-protein interactions. These findings indicate that the widely accepted sequence-structure-function paradigm should be extended to sequence-structure-dynamics-function relationship and open new possibilities for control and fine-tuning of protein interaction selectivity
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