The “Always Best Packet Switching” architecture for SIP-based mobile multimedia services

This paper presents a distributed architecture for the provision of seamless and responsive mobile multimedia services. This architecture allows its user applications to use concurrently all the wireless network interface cards (NICs) a mobile terminal is equipped with. In particular, as mobile multimedia services are usually implemented using the UDP protocol, our architecture enables the transmission of each UDP datagram through the “most suitable” (e.g. most responsive, least loaded) NIC among those available at the time a datagram is transmitted. We term this operating mode of our architecture Always Best Packet Switching (ABPS). ABPS enables the use of policies for load balancing and recovery purposes. In essence, the architecture we propose consists of the following two principal components: (i) a fixed proxy server, which acts as a relay for the mobile node and enables communications from/to this node regardless of possible firewalls and NAT systems, and (ii) a proxy client running in the mobile node responsible for maintaining a multi-path tunnel, constructed out of all the node's NICs, with the above mentioned fixed proxy server. We show how the architecture supports multimedia applications based on the SIP and RTP/RTCP protocols, and avoids the typical delays introduced by the two way message/response handshake of the SIP signaling protocol. Experimental results originated from the implementation of a VoIP application on top of the architecture we propose show the effectiveness of our approach.     

Using UML/MARTE to support performance tuning and stress testing in real-time systems

Real-time embedded systems (RTESs) operating in safety-critical domains have to satisfy strict performance requirements in terms of task deadlines, response time, and CPU usage. Two of the main factors affecting the satisfaction of these requirements are the configuration parameters regulating how the system interacts with hardware devices, and the external events triggering the system tasks. In particular, it is necessary to carefully tune the parameters in order to ensure a satisfactory trade-off between responsiveness and usage of computational resources, and also to stress test the system with worst-case inputs likely to violate the requirements. Performance tuning and stress testing are usually manual, time-consuming, and error-prone processes, because the system parameters and input values range in a large domain, and their impact over performance is hard to predict without executing the system. In this paper, we provide an approach, based on UML/MARTE, to support the generation of system configurations predicted to achieve a satisfactory trade-off between response time and CPU usage, and stress test cases that push the system tasks to violate their deadlines. First, we devise a conceptual model that specifies the abstractions required for analyzing task deadlines, response time, and CPU usage, and provide a mapping between these abstractions and UML/MARTE. Then, we prune the UML/MARTE metamodel to only contain a purpose-specific subset of entities needed to support performance tuning and stress testing. The pruned version is a supertype of UML/MARTE, which ensures that all instances of the pruned metamodel are also instances of UML/MARTE. Finally, we cast the generation of configurations and stress test cases as two constrained optimization problems (COPs) over our conceptual model. The input data for these COPs in automatically generated via a model-to-text (M2T) transformation from models specified in the pruned UML/MARTE metamodel to the Optimization Programming Language. We validate our approach in a safety-critical RTES from the maritime and energy domain, showing that (1) our conceptual model can be applied in an industrial setting with reasonable effort, and (2) the optimization problems effectively identify configurations predicted to minimize response time and CPU usage, and stress test cases that maximize deadline misses. Based on our experience, we highlight challenges and potential issues to be aware of when using UML/MARTE to support performance tuning and stress testing in an industrial context.     

Kinetostatic modeling of the clearance‐affected prismatic pair

The presence of clearance in the kinematic pairs of mechanisms has a strong influence on the mechanism performances. Where positioning tasks are concerned, clearance can be considered as one of the most relevant error sources, since it affects both accuracy and repeatability. The development of predictive models then becomes relevant, suitable for assessing in advance the influence of clearance and for correcting unacceptable effects. Several deterministic techniques assessing the accuracy of clearance‐affected mechanisms have been proposed in the literature; these techniques require the development of kinetostatic models for clearance‐affected pairs. This paper presents a modeling for clearance‐affected prismatic pairs. Such a model determines the three‐dimensional displacement between the pairing elements in the prismatic pair, and relates it to the load acting on the pair. Since the displacement depends strongly on the actual pair design, the model is described in detail for a particular pair geometry; in principle, however, this approach could be used for any geometry. The proposed model may be implemented in kinematic, kinetostatic, or dynamic analyses as well, with the purpose of computing the influence of clearance on the position and orientation error of any link of a mechanism. © 2005 Wiley Periodicals, Inc.     

Open-loop groundwater heat pumps development for large buildings: A case study

A study of the feasibility of providing the heating and cooling needs of the new, large commercial building near Turin, Italy, by means of an open-loop indirect groundwater heat pump (GWHP) system is described. A finite element subsurface flow and transport simulator (FEFLOW) was used to investigate possible configurations of extraction and injection wells for five different scenarios. Modelling results confirmed the hydrogeological capacity of the site to provide the necessary amount of groundwater and associated energy with limited environmental impact. Injection of warmer (or cooler) water in the aquifer creates a thermal plume whose dimensions and geometry depend on the properties of the subsurface formations, particularly their thermal dispersivity values. The study suggests that there are several possible well configurations that could support the GWHP system without adversely affecting the aquifer.     

Overcoming Multidrug Resistance (MDR): Design,Biological Evaluation and Molecular Modelling Studies of 2,4-Substituted Quinazoline Derivatives

Some 2,4-disubstituted quinazolines were synthesized and studied as multidrug resistance (MDR) reversers. The new derivatives carried the quinazoline-4-amine scaffold found in modulators of the ABC transporters involved in MDR, as the TKIs gefitinib and erlotinib. Their behaviour on the three ABC transporters, P-gp, MRP1 and BCRP, was investigated. Almost all compounds inhibited the P-gp activity in MDCK-MDR1 cells overexpressing P-gp, showing EC₅₀ values in the nanomolar range ( 1 d , 1 e , 2 a , 2 c , 2 e ). Some compounds were active also towards MRP1 and/or BCRP. Docking results obtained by in silico studies on the P-gp crystal structure highlighted common features for the most potent compounds. The P-gp selective compound 1 e was able to increase the doxorubicin uptake in HT29/DX cells and to restore its antineoplastic activity in resistant cancer cells in the same extent of sensitive cells. Compound 2 a displayed a dual inhibitory effect showing good activities towards both P-gp and BCRP.     

Genomic Analysis Made It Possible to Identify Gene-Driver Alterations Covering the Time Window between Diagnosis of Neuroblastoma 4S and the Progression to Stage 4

Neuroblastoma (NB) is a tumor of the developing sympathetic nervous system. Despite recent advances in understanding the complexity of NB, the mechanisms that determine its regression or progression are still largely unknown. Stage 4S NB is characterized by a favorable course of disease and often by spontaneous regression, while progression to true stage 4 is a very rare event. Here, we focused on genomic analysis of an NB case that progressed from stage 4S to stage 4 with a very poor outcome. Array-comparative genomic hybridization (a-CGH) on tumor-tissue DNA, and whole-exome sequencing (WES) on exosomes DNA derived from plasma collected at the onset and at the tumor progression, pointed out relevant genetic changes that can explain this clinical worsening. The combination of a-CGH and WES data allowed for the identification iof somatic copy number aberrations and single-nucleotide variants in genes known to be responsible for aggressive NB. KLRB1, MAPK3 and FANCA genes, which were lost at the time of progression, were studied for their possible role in this event by analyzing in silico the impact of their expression on the outcome of 786 NB patients.     

The ATP-binding site of protein kinase CK2 holds a positive electrostatic area and conserved water molecules

CK2 is a highly pleiotropic Ser/Thr protein kinase that is able to promote cell survival and enhance the tumour phenotype under specific circumstances. We have determined the crystal structure of three new complexes with tetrabromobenzimidazole derivatives that display K(i) values between 0.15 and 0.30 microM. A comparative analysis of these data with those of four other inhibitors of the same family revealed the presence of some highly conserved water molecules in the ATP-binding site. These waters reside near Lys68, in an area with a positive electrostatic potential that is able to attract and orient negatively charged ligands. The presence of this positive region and two unique bulky residues that are typical of CK2, Ile66 and Ile174, play a critical role in determining the ligand orientation and binding selectivity.