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.     

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.     

Questionnaire-based variability modeling for system configuration

Variability management is a recurrent issue in systems engineering. It arises for example in enterprise systems, where modules are configured and composed to meet the requirements of individual customers based on modifications to a reference model. It also manifests itself in the context of software product families, where variants of a system are built from a common code base. This paper proposes an approach to capture system variability based on questionnaire models that include order dependencies and domain constraints. The paper presents analysis techniques to detect circular dependencies and contradictory constraints in questionnaire models, as well as techniques to incrementally prevent invalid configurations by restricting the space of allowed answers to a question based on previous answers. The approach has been implemented as a toolset and has been used in practice to capture configurable process models for film post-production.

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.     

Joint stiffness identification of six-revolute industrial serial robots

Although robots tend to be as competitive as CNC machines for some operations, they are not yet widely used for machining operations. This may be due to the lack of certain technical information that is required for satisfactory machining operation. For instance, it is very difficult to get information about the stiffness of industrial robots from robot manufacturers. As a consequence, this paper introduces a robust and fast procedure that can be used to identify the joint stiffness values of any six-revolute serial robot. This procedure aims to evaluate joint stiffness values considering both translational and rotational displacements of the robot end-effector for a given applied wrench (force and torque). In this paper, the links of the robot are assumed to be much stiffer than its actuated joints. The robustness of the identification method and the sensitivity of the results to measurement errors and the number of experimental tests are also analyzed. Finally, the actual Cartesian stiffness matrix of the robot is obtained from the joint stiffness values and can be used for motion planning and to optimize machining operations.     

Influences of haptic communication on a shared manual task

With the advent of new haptic feedback devices, researchers are giving serious consideration to the incorporation of haptic communication in collaborative virtual environments. For instance, haptic interactions based tools can be used for medical and related education whereby students can train in minimal invasive surgery using virtual reality before approaching human subjects. To design virtual environments that support haptic communication, a deeper understanding of humans′ haptic interactions is required. In this paper, human′s haptic collaboration is investigated. A collaborative virtual environment was designed to support performing a shared manual task. To evaluate this system, 60 medical students participated to an experimental study. Participants were asked to perform in dyads a needle insertion task after a training period. Results show that compared to conventional training methods, a visual-haptic training improves user′s collaborative performance. In addition, we found that haptic interaction influences the partners′ verbal communication when sharing haptic information. This indicates that the haptic communication training changes the nature of the users′ mental representations. Finally, we found that haptic interactions increased the sense of copresence in the virtual environment: haptic communication facilitates users′ collaboration in a shared manual task within a shared virtual environment. Design implications for including haptic communication in virtual environments are outlined.     

A flexible,object-centric approach for business process modelling

Mainstream business process modelling techniques often promote a design paradigm wherein the activities that may be performed within a case, together with their usual execution order, form the backbone on top of which other aspects are anchored. This Fordist paradigm, while effective in standardised and production-oriented domains, breaks when confronted with processes in which case-by-case variations and exceptions are the norm. We contend that the effective design of flexible processes calls for a substantially different modelling paradigm. Motivated by requirements from the human services domain, we explore the hypothesis that a framework consisting of a small set of coordination concepts, combined with established object-oriented modelling principles, provides a suitable foundation for designing highly flexible processes. Several human service delivery processes have been designed using this framework, and the resulting models have been used to realise a system to support these processes in a pilot environment.