The crystal structure of HIV-1 Nef protein bound to the Fyn kinase SH3 domain suggests a role for this complex in altered T cell receptor signaling

BACKGROUND: Human immunodeficiency virus (HIV) Nef protein accelerates virulent progression of acquired immunodeficiency syndrome (AIDS) by its interaction with specific cellular proteins involved in signal transduction and host cell activation. Nef has been shown to bind specifically to a subset of the Src family of kinases. The structures of free Nef and Nef bound to Src homology region 3 (SH3) domain are important for the elucidation of how the affinity and specificity for the Src kinase family SH3 domains are achieved, and also for the development of potential drugs and vaccines against AIDS. RESULTS: We have determined the crystal structures of the conserved core of HIV-1 Nef protein alone and in complex with the wild-type SH3 domain of the p59fyn protein tyrosine kinase (Fyn), at 3.0 A resolution. Comparison of the bound and unbound Nef structures revealed that a proline-rich motif (Pro-x-x-Pro), which is implicated in SH3 binding, is partially disordered in the absence of the binding partner; this motif only fully adopts a left-handed polyproline type II helix conformation upon complex formation with the Fyn SH3 domain. In addition, the structures show how an arginine residue (Arg77) of Nef interacts with Asp 100 of the so-called RT loop within the Fyn SH3 domain, and triggers a hydrogen-bond rearrangement which allows the loop to adapt to complement the Nef surface. The Arg96 residue of the Fyn SH3 domain is specifically accommodated in the same hydrophobic pocket of Nef as the isoleucine residue of a previously described Fyn SH3 (Arg96-->lle) mutant that binds to Nef with higher affinity than the wild type. CONCLUSIONS: The three-dimensional structures support evidence that the Nef-Fyn complex forms in vivo and may have a crucial role in the T cell perturbating action of Nef by altering T cell receptor signaling. The structures of bound and unbound Nef reveal that the multivalency of SH3 binding may be achieved by a ligand induced flexibility in the RT loop. The structures suggest possible targets for the design of inhibitors which specifically block Nef-SH3 interactions.     

Effect of beam voltage on the properties of aluminium nitride prepared by ion beam assisted deposition

The effects of nitrogen-beam voltage on the structure, stress, energy band gap and hardness of AIN thin films deposited on Si (111), Si (100) and sapphire (0001) by ion beam assisted deposition (IBAD) are reported. As the nitrogen-beam voltage was increased from 50 to 200 V, the stress and disorder in the AIN films increased as determined by X-ray diffraction, FTIR and Raman spectroscopy. The preferred orientation of the film's c-axis changed from completely normal to the film at 100 V, to a mixture of normal and in the plane of the film at 200 V. For AIN films deposited under the same conditions, the films were more highly oriented on sapphire (0001) than in Si (111). The hardness of the films increased from 18.2 to 23.7 GPa with the nitrogen-beam voltage, and possible reasons for this change in hardness are considered.     

Virtual Teams: Guide to Successful Implementation

The successful initiation and execution of a virtual team is gaining increasing attention in the design and construction community. From opportunities to integrate international and multidisciplinary teams to the opportunity to leverage the best resources in an organization on a given project, virtual teams can transform the concept of project planning and execution. However, potential barriers exist in several areas to the successful implementation of virtual teams. The needs of increased management emphasis, social and cultural understanding, and emphasis on common goals are only a few of the nontechnical factors that can turn successful virtual teaming into virtual frustration. When combined with traditional technical challenges including compatibility of systems, security, and the selection of appropriate technologies, the line between leveraging virtual technologies for enhanced solutions and introducing additional complications into the project process is one that can be easily crossed. This paper presents the findings of research that addresses the opportunities and potential barriers to successful virtual teams in the engineering, procurement, and construction industry. Combining results from current research, industry practices, and early results from nonconstruction industries, the research findings provide an initial path to successful virtual team implementation.     

Phase-change thermal energy storage using spherical capsules: performance of a test plant

The aim of this paper is the study of an industrial process of energy storage usable for air conditioning or refrigeration, investigating a test plant which is a tank with a reduced size, filled with randomly dispersed commercial nodules, placed in a refrigeration loop. The nodules are spherical capsules in which phase change materials (PCM) are encapsulated. This test plant permits the study at length of the behaviour of the tank with, in particular, the charge mode taking into account the undercooling and the discharge mode. A simulation program that considers aspects of both the surrounding heat transfer fluid and the phase-change material packed inside the nodules is developed here in the cases of the charge and the discharge processes. The simulation results are then compared with experimental observations.     

Epilepsy, cysticercosis and neurocysticercosis in Benin

Retroperitoneal extravasation is an extremely uncommon complication of duodenal ulcer perforation. The preoperative diagnosis is difficult and may even by missed at operation. There were 25 cases reported in the literature. Only one patient was correctly diagnosed preoperatively and only seven patients survived. We describe the first case of retroperitoneal extravasation from perforated duodenal ulcer presenting as scrotal sepsis.     

Comparison of a contactor catalytic membrane reactor with a conventional reactor: example of wet air oxidation

A wet air oxidation reaction was carried out in a gas/liquid catalytic membrane reactor of the contactor type. The oxidation of formic acid was used as a model reaction. The mesoporous top-layer of a ceramic tubular membrane was used as catalyst (Pt) support, and was placed at the interface of the gas (air) and liquid (HCOOH solution) phases.

A similar reaction was carried out in a conventional batch reactor, using a steering rate high enough to avoid gas-diffusion limitations, and exactly identical conditions than for the CMR (amount of catalyst, pressure, etc.). At room temperature, the CMR showed an initial activity three to six times higher than the conventional reactor. This activity increase was attributed to an easier oxygen access to the catalytic sites. Nevertheless, the catalytic membrane gradually deactivated after a few hours of operation. Different deactivation mechanisms are presented.     

Redox and pH Dual Responsive Polymer Based Nanoparticles for In Vivo Drug Delivery

Responsive nanomaterials have emerged as promising candidates as drug delivery vehicles in order to address biomedical diseases such as cancer. In this work, polymer‐based responsive nanoparticles prepared by a supramolecular approach are loaded with doxorubicin (DOX) for the cancer therapy. The nanoparticles contain disulfide bonds within the polymer network, allowing the release of the DOX payload in a reducing environment within the endoplasm of cancer cells. In addition, the loaded drug can also be released under acidic environment. In vitro anticancer studies using redox and pH dual responsive nanoparticles show excellent performance in inducing cell death and apoptosis. Zebrafish larvae treated with DOX‐loaded nanoparticles exhibit an improved viability as compared with the cases treated with free DOX by the end of a 3 d treatment. Confocal imaging is utilized to provide the daily assessment of tumor size on zebrafish larva models treated with DOX‐loaded nanoparticles, presenting sustainable reduction of tumor. This work demonstrates the development of functional nanoparticles with dual responsive properties for both in vitro and in vivo drug delivery in the cancer therapy.     

Preserving correctness during business process model configuration

A configurable process model captures a family of related process models in a single artifact. Such models are intended to be configured to fit the requirements of specific organizations or projects, leading to individualized process models that are subsequently used for domain analysis or solution design. This article proposes a formal foundation for individualizing configurable process models incrementally, while preserving correctness, both with respect to syntax and behavioral semantics. Specifically, assuming the configurable process model is behaviorally sound, the individualized process models are guaranteed to be sound. The theory is first developed in the context of Petri nets and then extended to a process modeling notation widely used in practice, namely Event-driven Process Chains.     

APROMORE: An advanced process model repository

Business process models are becoming available in large numbers due to their widespread use in many industrial applications such as enterprise and quality engineering projects. On the one hand, this raises a challenge as to their proper management: how can it be ensured that the proper process model is always available to the interested stakeholder? On the other hand, the richness of a large set of process models also offers opportunities, for example with respect to the re-use of existing model parts for new models. This paper describes the functionality and architecture of an advanced process model repository, named APROMORE. This tool brings together a rich set of features for the analysis, management and usage of large sets of process models, drawing from state-of-the art research in the field of process modeling. A prototype of the platform is presented in this paper, demonstrating its feasibility, as well as an outlook on the further development of APROMORE.     

Configurable multi-perspective business process models

A configurable process model provides a consolidated view of a family of business processes. It promotes the reuse of proven practices by providing analysts with a generic modeling artifact from which to derive individual process models. Unfortunately, the scope of existing notations for configurable process modeling is restricted, thus hindering their applicability. Specifically, these notations focus on capturing tasks and control-flow dependencies, neglecting equally important ingredients of business processes such as data and resources. This research fills this gap by proposing a configurable process modeling notation incorporating features for capturing resources, data and physical objects involved in the performance of tasks. The proposal has been implemented in a toolset that assists analysts during the configuration phase and guarantees the correctness of the resulting process models. The approach has been validated by means of a case study from the film industry.