994 resultados para Ear Homology Domain


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Bordetella pertussis, the whooping cough pathogen, secretes several virulence factors among which adenylate cyclase toxin (ACT) is essential for establishment of the disease in the respiratory tract. ACT weakens host defenses by suppressing important bactericidal activities of the phagocytic cells. Up to now, it was believed that cell intoxication by ACT was a consequence of the accumulation of abnormally high levels of cAMP, generated exclusively beneath the host plasma membrane by the toxin N-terminal catalytic adenylate cyclase (AC) domain, upon its direct translocation across the lipid bilayer. Here we show that host calpain, a calcium-dependent Cys-protease, is activated into the phagocytes by a toxin-triggered calcium rise, resulting in the proteolytic cleavage of the toxin N-terminal domain that releases a catalytically active "soluble AC''. The calpain-mediated ACT processing allows trafficking of the "soluble AC'' domain into subcellular organella. At least two strategic advantages arise from this singular toxin cleavage, enhancing the specificity of action, and simultaneously preventing an indiscriminate activation of cAMP effectors throughout the cell. The present study provides novel insights into the toxin mechanism of action, as the calpain-mediated toxin processing would confer ACT the capacity for a space- and time-coordinated production of different cAMP "pools'', which would play different roles in the cell pathophysiology.

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Enhancing the handover process in broadband wireless communication deployment has traditionally motivated many research initiatives. In a high-speed railway domain, the challenge is even greater. Owing to the long distances covered, the mobile node gets involved in a compulsory sequence of handover processes. Consequently, poor performance during the execution of these handover processes significantly degrades the global end-to-end performance. This article proposes a new handover strategy for the railway domain: the RMPA handover, a Reliable Mobility Pattern Aware IEEE 802.16 handover strategy "customized" for a high-speed mobility scenario. The stringent high mobility feature is balanced with three other positive features in a high-speed context: mobility pattern awareness, different sources for location discovery techniques, and a previously known traffic data profile. To the best of the authors' knowledge, there is no IEEE 802.16 handover scheme that simultaneously covers the optimization of the handover process itself and the efficient timing of the handover process. Our strategy covers both areas of research while providing a cost-effective and standards-based solution. To schedule the handover process efficiently, the RMPA strategy makes use of a context aware handover policy; that is, a handover policy based on the mobile node mobility pattern, the time required to perform the handover, the neighboring network conditions, the data traffic profile, the received power signal, and current location and speed information of the train. Our proposal merges all these variables in a cross layer interaction in the handover policy engine. It also enhances the handover process itself by establishing the values for the set of handover configuration parameters and mechanisms of the handover process. RMPA is a cost-effective strategy because compatibility with standards-based equipment is guaranteed. The major contributions of the RMPA handover are in areas that have been left open to the handover designer's discretion. Our simulation analysis validates the RMPA handover decision rules and design choices. Our results supporting a high-demand video application in the uplink stream show a significant improvement in the end-to-end quality of service parameters, including end-to-end delay (22%) and jitter (80%), when compared with a policy based on signal-to-noise-ratio information.

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JEMS 2012 - Joint European Magnetic Symposia edited by Tiberto, P; Affronte, M; Casoli, F; Fernandez, CD; Gubbiotti, G; Marquina, C; Pratt, F; Solzi, M; Tacchi, S; Vavassori, P. 6th Joint European Magnetic Symposia (JEMS) Parma, ITALY SEP 09-14, 2012

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We studied the effect of magnetoelastic anisotropy on domain wall (DW) dynamics and remagnetization process of magnetically bistable Fe-Co-rich microwires with metallic nucleus diameters (from 1.4 to 22 mu m). We manipulated the magnetoelastic anisotropy applying the tensile stresses and changing the magnetostriction constant and strength of the internal stresses. Microwires of the same composition of metallic nucleus but with different geometries exhibit different magnetic field dependence of DW velocity with different slopes. Application of stresses resulted in decrease of the DW velocity, v, and DW mobility, S. Quite fast DW propagation (v until 2,500 m/s at H about 30 A/m) has been observed in low magnetostrictive magnetically bistable Co56Fe8Ni10Si10B16 microwires. Consequently, we observed certain correlation between the magnetoelastic energy and DW dynamics in microwires: decreasing the magnetoelastic energy, K (me), DW velocity increases.

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EMM-FM2011 – First Euro Mediterranean Meeting on Functionalized Materials, edited by Cheikhrouhou, A. 1st Euro Mediterranean Meeting on Functionalized Materials (EMM-FM). Sousse, TUNISIA . Sep. 06-10, 2011

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This is an Author's Accepted Manuscript of an article published in “Emergence: Complexity and Organization”, 15 (2), pp. 14-22 (2013), copyright Taylor & Francis.

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Linker histone H1 plays an important role in chromatin folding. Phosphorylation by cyclin-dependent kinases is the main post-translational modification of histone H1. We studied the effects of phosphorylation on the secondary structure of the DNA-bound H1 carboxy-terminal domain (CTD), which contains most of the phosphorylation sites of the molecule. The effects of phosphorylation on the secondary structure of the DNA-bound CTD were site-specific and depended on the number of phosphate groups. Full phosphorylation significantly increased the proportion of -structure and decreased that of -helix. Partial phosphorylation increased the amount of undefined structure and decreased that of -helix without a significant increase in -structure. Phosphorylation had a moderate effect on the affinity of the CTD for the DNA, which was proportional to the number of phosphate groups. Partial phosphorylation drastically reduced the aggregation of DNA fragments by the CTD, but full phosphorylation restored to a large extent the aggregation capacity of the unphosphorylated domain. These results support the involvement of H1 hyperphosphorylation in metaphase chromatin condensation and of H1 partial phosphorylation in interphase chromatin relaxation. More generally, our results suggest that the effects of phosphorylation are mediated by specific structural changes and are not simply a consequence of the net charge.

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Background: The presence of EGFR kinase domain mutations in a subset of NSCLC patients correlates with the response to treatment with the EGFR tyrosine kinase inhibitors gefitinib and erlotinib. Although most EGFR mutations detected are short deletions in exon 19 or the L858R point mutation in exon 21, more than 75 different EGFR kinase domain residues have been reported to be altered in NSCLC patients. The phenotypical consequences of different EGFR mutations may vary dramatically, but the majority of uncommon EGFR mutations have never been functionally evaluated. Results: We demonstrate that the relative kinase activity and erlotinib sensitivity of different EGFR mutants can be readily evaluated using transfection of an YFP-tagged fragment of the EGFR intracellular domain (YFP-EGFR-ICD), followed by immunofluorescence microscopy analysis. Using this assay, we show that the exon 20 insertions Ins770SVD and Ins774HV confer increased kinase activity, but no erlotinib sensitivity. We also show that, in contrast to the common L858R mutation, the uncommon exon 21 point mutations P848L and A859T appear to behave like functionally silent polymorphisms. Conclusion: The ability to rapidly obtain functional information on EGFR variants of unknown relevance using the YFP-EGFR-ICD assay might prove important in the future for the management of NSCLC patients bearing uncommon EGFR mutations. In addition, our assay may be used to determine the response of resistant EGFR mutants to novel second-generation TKIs.

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The molecular mechanics property is the foundation of many characters of proteins. Based on intramolecular hydrophobic force network, the representative family character underlying a protein’s mechanics property is described by a simple two-letter scheme. The tendency of a sequence to become a member of a protein family is scored according to this mathematical representation. Remote homologs of the WW-domain family could be easily designed using such a mechanistic signature of protein homology. Experimental validation showed that nearly all artificial homologs have the representative folding and bioactivity of their assigned family. Since the molecular mechanics property is the only consideration in this study, the results indicate its possible role in the generation of new members of a protein family during evolution.

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For a long time, the Tanzanian Fisheries Department has managed Tanzanian fisheries without incorporating other stakeholders within its management framework. On lake Victoria, the persistent use of illegal fishing gear and declining catches have led the government to realize that this system of fisheries management may no longer be viable, and have sought to incorporate fishing communities into the management structure. Through the creation of beach management units (BMUs), the Fisheries Departments have sought to persuade fishing communities to implement and enforce Tanzania's fishing regulations and to monitor the fishery. In this paper we explore a recently gathered data set that yields information on, amongst others, how Tanzanian fishing communities perceive the state of their resource base, how they view their relationship with the Fisheries Department, the efficacy of fishing regulations and other variables. We draw on a series of criteria developed by Ostron (1990) for institutional 'robustness' to explore various areas of institutional development on Lake Victoria, and to try and anticipate how the BMUs will fare. We argue there are many socio-political and economic factors that will determine how communities will receive and perceive their responsibilities towards government-imposed administrative structures at the local level, these will become 'socialized' such that they will vary from place to place. While this may bode well for problems of heterogeneity, it does not necessarily mean that fisheries management objective on Lake Victoria will be met

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The pressures placed on the natural, environmental, economic, and cultural sectors from continued growth, population shifts, weather and climate, and environmental quality are increasing exponentially in the southeastern U.S. region. Our growing understanding of the relationship of humans with the marine environment is leading us to explore new ecosystem-based approaches to coastal management, marine resources planning, and coastal adaptation that engages multiple state jurisdictions. The urgency of the situation calls for coordinated regional actions by the states, in conjunction with supporting partners and leveraging a diversity of resources, to address critical issues in sustaining our coastal and ocean ecosystems and enhancing the quality of life of our citizens. The South Atlantic Alliance (www.southatlanticalliance.org) was formally established on October 19, 2009 to “implement science-based policies and solutions that enhance and protect the value of coastal and ocean resources of the southeastern United States which support the region's culture and economy now and for future generations.” The Alliance, which includes North Carolina, South Carolina, Georgia, and Florida, will provide a regional mechanism for collaborating, coordinating, and sharing information in support of resource sustainability; improved regional alignment; cooperative planning and leveraging of resources; integrated research, observations, and mapping; increased awareness of the challenges facing the South Atlantic region; and inclusiveness and integration at all levels. Although I am preparing and presenting this overview of the South Atlantic Alliance and its current status, there are a host of representatives from agencies within the four states, universities, NGOs, and ongoing southeastern regional ocean and coastal programs that are contributing significant time, expertise, and energy to the success of the Alliance; information presented herein and to be presented in my oral presentation was generated by the collaborative efforts of these professionals. I also wish to acknowledge the wisdom and foresight of the Governors of the four states in establishing this exciting regional ocean partnership. (PDF contains 4 pages)

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To resolve the diffraction problems of the pulsed wave field directly in the temporal domain, we extend the Rayleigh diffraction integrals to the temporal domain and then discuss the approximation condition of this diffraction formula. (C) 1997 Optical Society of America.