The Pro-Inflammatory Deletion Allele of the NF-κB1 Polymorphism Is Characterized by a Depletion of Subunit p50 in Sepsis

The functionally important NF-κB1 promoter polymorphism (−94ins/delATTG) significantly shapes inflammation and impacts the outcome of sepsis. However, exploratory studies elucidating the molecular link of this genotype-dependent pattern are lacking. Accordingly, we analyzed lipopolysaccharide-stimulated peripheral blood mononuclear cells from both healthy volunteers (n = 20) and septic patients (n = 10). All individuals were genotyped for the −94ins/delATTG NF-κB1 promoter polymorphism. We found a diminished nuclear activity of the NF-κB subunit p50 in ID/DD genotypes after 48 h of lipopolysaccharide stimulation compared to II genotypes (p = 0.025). This was associated with higher TNF-α (p = 0.005) and interleukin 6 concentrations (p = 0.014) and an increased production of mitochondrial radical oxygen species in ID/DD genotypes (p = 0.001). Although ID/DD genotypes showed enhanced activation of mitochondrial biogenesis, they still had a significantly diminished cellular ATP content (p = 0.046) and lower mtDNA copy numbers (p = 0.010) compared to II genotypes. Strikingly, these findings were mirrored in peripheral blood mononuclear cells taken from septic patients. Our results emphasize the crucial aspect of considering NF-κB subunits in sepsis. We showed here that the deletion allele of the NF-κB1 (−94ins/delATTG) polymorphism was associated with the lower nuclear activity of subunit p50, which, in turn, was associated with aggravated inflammation and mitochondrial dysfunction.     

Algorithmic probabilistic game semantics

We present a detailed account of a translation from probabilistic call-by-value programs with procedures to Rabin’s probabilistic automata. The translation is fully abstract in that programs exhibit the same computational behaviour if and only if the corresponding automata are language-equivalent. Since probabilistic language equivalence is decidable, we can apply the translation to analyse the behaviour of probabilistic programs and protocols. We illustrate our approach on a number of case studies.     

Designing on-site: Facilitating participatory contextual architecture with mobile phones

Some movements within modern architecture particularly emphasise the importance of matching buildings to their surroundings. However, practicing such “contextual architecture” is highly challenging and typically not something the future inhabitants of a building are well equipped for participating in. This paper explores the potentials of using mobile phone technology for facilitating such client participation in the parts of an architecture process that take place on the building site. For this we introduce ArchiLens, a mobile system for interactive on-site 3D visualisation of houses, and findings from a field study with 40 participants in the process of building or modifying their home. The study showed that using the system helped evoke people’s imagination of the look and feel of their future house, and envision it in context. This enabled them to participate more closely in the design process on-site by iteratively reviewing design alternatives and exploring, for example, other placements and materials.     

Where does model-driven engineering help? Experiences from three industrial cases

There have been few experience reports from industry on how Model-Driven Engineering (MDE) is applied and what the benefits are. This paper summarizes the experiences of three large industrial participants in a European research project with the objective of developing techniques and tools for applying MDE on the development of large and complex software systems. The participants had varying degrees of previous experience with MDE. They found MDE to be particularly useful for providing abstractions of complex systems at multiple levels or from different viewpoints, for the development of domain-specific models that facilitate communication with non-technical experts, for the purposes of simulation and testing, and for the consumption of models for analysis, such as performance-related decision support and system design improvements. From the industrial perspective, a methodology is considered to be useful and cost-efficient if it is possible to reuse solutions in multiple projects or products. However, developing reusable solutions required extra effort and sometimes had a negative impact on the performance of tools. While the companies identified several benefits of MDE, merging different tools with one another in a seamless development environment required several transformations, which increased the required implementation effort and complexity. Additionally, user-friendliness of tools and the provision of features for managing models of complex systems were identified as crucial for a wider industrial adoption of MDE.     

Transient Friction in Pressurized Pipes. I: Investigation of Zielke’s Model

This paper investigates the well-known model for unsteady friction developed by Zielke in 1968. The model is based on weights of past local bulk accelerations and is analytically correct for laminar flow, but computationally demanding. Different models have been proposed using dynamic properties, typically based on instantaneous accelerations (IAB) that are more rapid in computational schemes. Unfortunately, they are not as accurate as Zielke’s model and fail to model certain types of transients. This paper points out that the water hammer transient is dominated by a periodicity varying along the pipe. Because of this, the unsteady friction calculated by the Zielke model is distributed nonuniformly along the pipe, and changes in the pipe length change the local unsteady friction. This phenomenon may explain why IAB models using calibrated coefficients to match experimental results have a large span in value for the reported coefficients. This paper will hopefully contribute to further work to find highly accurate and rapid models. The subject deserves to be brought up for discussion as a part of a total understanding of the problem.     

Transient Friction in Pressurized Pipes. II: Two-Coefficient Instantaneous Acceleration–Based Model

The goal in the field of modeling of hydraulic transients is a comprehensive model for pipe networks that is computationally fast and accurate. The fastest models are the one-dimensional (1D) models that use instantaneous acceleration–based (IAB) properties, but unfortunately these models are not as accurate as the more demanding 1D convolution-based (CB) models or quasi two-dimensional models. Focusing on a single pipe, this paper investigates the fundamental behavior of the much more accurate 1D CB model to find two coefficients for use with the two-coefficient formulation of the much-used modified IAB (MIAB) model for complete closing of a downstream valve. Two coefficients are found based on the weighting function used in the CB model, and these coefficients vary along the pipe length. Simulations are compared with two experimental results from tests performed at University of Adelaide in Australia in 1995. The experimental results are for different initial Reynolds numbers of approximately 2,000 and 5,800. The results show very good agreement between simulations and experiments. The improvement of the MIAB model is not general, and for the time being, only complete closure of a downstream valve in a single pipeline at low Reynolds numbers has been investigated.     

Overview of the MPEG Reconfigurable Video Coding Framework

Video coding technology in the last 20 years has evolved producing a variety of different and complex algorithms and coding standards. So far the specification of such standards, and of the algorithms that build them, has been done case by case providing monolithic textual and reference software specifications in different forms and programming languages. However, very little attention has been given to provide a specification formalism that explicitly presents common components between standards, and the incremental modifications of such monolithic standards. The MPEG Reconfigurable Video Coding (RVC) framework is a new ISO standard currently under its final stage of standardization, aiming at providing video codec specifications at the level of library components instead of monolithic algorithms. The new concept is to be able to specify a decoder of an existing standard or a completely new configuration that may better satisfy application-specific constraints by selecting standard components from a library of standard coding algorithms. The possibility of dynamic configuration and reconfiguration of codecs also requires new methodologies and new tools for describing the new bitstream syntaxes and the parsers of such new codecs. The RVC framework is based on the usage of a new actor/ dataflow oriented language called CAL for the specification of the standard library and instantiation of the RVC decoder model. This language has been specifically designed for modeling complex signal processing systems. CAL dataflow models expose the intrinsic concurrency of the algorithms by employing the notions of actor programming and dataflow. The paper gives an overview of the concepts and technologies building the standard RVC framework and the non standard tools supporting the RVC model from the instantiation and simulation of the CAL model to software and/or hardware code synthesis.