Cellular immune responses in human immunodeficiency virus (HIV)-1-infected children: Is immune restoration by highly active anti-retroviral therapy comparable to non-progression?

The objective of this study was to investigate whether the restored immune functions of vertically human immunodeficiency virus (HIV)-infected children who were severely immunodeficient before the initiation of highly active anti-retroviral therapy (HAART) are comparable to those of untreated slow progressors. We therefore assessed T cell proliferation and cytokine [interferon (IFN)-γ, interleukin (IL)-5 and IL-13] secretions after mitogen, recall antigens and HIV-1-specific stimulation in 12 untreated slow progressors, 16 untreated progressors and 18 treated patients. Treated children were profoundly immunodeficient before the initiation of HAART and had long-lasting suppression of viral replication on treatment. We demonstrated that slow progressors are characterized not only by the preservation of HIV-1-specific lymphoproliferative responses but also by the fact that these responses are clearly T helper type 1 (Th1)-polarized. Children on HAART had proliferative responses to HIV-1 p24 antigen, purified protein derivative (PPD) and tetanus antigen similar to slow progressors and higher than those of progressors. However, in contrast to slow progressors, most treated children exhibited a release of Th2 cytokines accompanying the IFN-γ secretion in response to the HIV-1 p24 antigen. Moreover, despite higher proliferative responses to phytohaemagglutinin (PHA) than the two groups of untreated children, treated children had lower levels of IFN-γ secretion in response to PHA than slow progressors. These data show that in severely immunodeficient vertically HIV-infected children, a long-lasting HAART allows recovering lymphoproliferative responses similar to untreated slow progressors. However, alterations in IFN-γ secretion in response to the mitogen PHA persisted, and their cytokine release after HIV-specific stimulation was biased towards a Th2 response. © 2011 The Authors. Clinical and Experimental Immunology © 2011 British Society for Immunology.

Multilevel refinement for the vehicle routing problem

Multilevel approaches to computational problems are pervasive across many areas of applied mathematics and scientific computing. The multilevel paradigm uses recursive coarsening to create a hierarchy of approximations to the original problem, then an initial solution is found for the coarsest problem and iteratively refined and improved at each level, coarsest to finest. The solution process is aided by the global perspective (or `global view') imparted to the optimisation by the coarsening. This paper looks at their application to the Vehicle Routing Problem.

A study of modelling approaches for rail vehicle collision behaviour

A rigid wall model has been used widely in the numerical simulation of rail vehicle impacts. Finite element impact modelling of rail vehicles is generally based on a half-width and full-length or half-length structure, depending on the symmetry. The structure and components of rail vehicles are normally designed to cope with proof loading to ensure adequate ride performance. In this paper, the authors present a study of a rail vehicle with driving cab focused on improving the modelling approach and exploring the intrinsic structural weaknesses to enhance its crashworthiness. The underpinning research used finite element analysis and compared the behaviour of the rail vehicle in different impact scenarios. It was found that the simulation of a rigid wall impact can mask structural weaknesses; that even a completely symmetrical impact may lead to an asymmetrical result; that downward bending is an intrinsic weakness of conventional rail vehicles and that a rigid part of the vehicle structure, such as the body bolster, may cause uncoordinated deformation and shear fracture between the vehicle sections. These findings have significance for impact simulation, the full-scale testing of rail vehicles and rail vehicle design in general.

Multilevel refinement strategies for the capacity vehicle routing problem

We discuss the application of the multilevel (ML) refinement technique to the Vehicle Routing Problem (VRP), and compare it to its single-level (SL) counterpart. Multilevel refinement recursively coarsens to create a hierarchy of approximations to the problem and refines at each level. A SL algorithm, which uses a combination of standard VRP heuristics, is developed first to solve instances of the VRP. A ML version, which extends the global view of these heuristics, is then created, using variants of the construction and improvement heuristics at each level. Finally some multilevel enhancements are developed. Experimentation is used to find suitable parameter settings and the final version is tested on two well-known VRP benchmark suites. Results comparing both SL and ML algorithms are presented.

The application of multilevel refinement to the vehicle routing problem

We discuss the application of the multilevel (ML) refinement technique to the Vehicle Routing Problem (VRP), and compare it to its single-level (SL) counterpart. Multilevel refinement recursively coarsens to create a hierarchy of approximations to the problem and refines at each level. A SL heuristic, termed the combined node-exchange composite heuristic (CNCH), is developed first to solve instances of the VRP. A ML version (the ML-CNCH) is then created, using the construction and improvement heuristics of the CNCH at each level. Experimentation is used to find a suitable combination, which extends the global view of these heuristics. Results comparing both SL and ML are presented.

Analysis of the structural characteristics of an intermediate rail vehicle and their effect on vehicle crash performance

In the current paper, the authors present an analysis of the structural characteristics of an intermediate rail vehicle and their effects on crash performance of the vehicle. Theirs is a simulation based analysis involving four stages. First, the crashworthiness of the vehicle is assessed by simulating an impact of the vehicle with a rigid wall. Second, the structural characteristics of the vehicle are analysed based on the structural behaviour during this impact and then the structure is modified. Third, the modified vehicle is tested again in the same impact scenario with a rigid wall. Finally, the modified vehicle is subjected to a modelled head-on impact which mirrors the real-life impact interface between two intermediate vehicles in a train impact. The emphasis of the current study is on the structural characteristics of the intermediate vehicle and the differences compared to an impact of a leading vehicle. The study shows that, similar to a leading vehicle, bending, or jackknifing is a main form of failure in this conventionally designed intermediate vehicle. It has also been found that the location of the door openings creates a major difference in the behaviour of an intermediate vehicle. It causes instability of the vehicle in the door area and leads to high stresses at the joint of the end beam with the solebar and shear stresses at the joint of the inner pillar with the cantrail. Apart from this, the shapes of the vehicle ends and impact interfaces are also different and have an effect on the crash performance of the vehicles. The simulation results allow the identification of the structural characteristics and show the effectiveness of relevant modifications. The conclusions have general relevance for the crashworthiness of rail vehicle design

Counter-terrorism, anti-extremism, armed conflict and human rights: using a Russian case study

This paper critically examines Russia’s compliance with human rights obligations and the rule of law in its ‘war on terror’. It seeks to draw wider parallels with respect for human rights in the framework of the fight against ‘new global terrorism’. Threats to due process, the discriminatory application of the forces of law and order specifically against perceived “non-traditional” Muslim communities, and a ratcheting up of fear of an Islamist threat can be traced following the war in Chechnya and the handling of the Dubrovka Theatre and Beslan school sieges. To what extent are there commonalities with UK complicity in the practice of extraordinary rendition, with atrocities perpetrated in Iraq and Afghanistan, and abuses in Abu Ghraib and Guantanamo? Are the impact of these reflected in domestic security policy and British minority ethnic community relations? [From the Author]

Explicit finite volume modeling of aircraft anti-icing and de-icing

In this paper, a runback water and ice prediction model is extended to anti-icing and thermal de-icing situations. The resulting coupled equations that govern thin-film flow, ice accretion, and heat conduction in the multilayered system substrate-ice-water are solved using an explicit finite volume approach. The procedure is implemented in the three-dimensional icing code ICECREMO2, and both structured and unstructured grids can be considered. Numerical results are presented to compare the present code simulations to some data provided by other ice prediction codes and to show the capabilities of the present numerical tool.