Mechanism of action of the nongenotoxic peroxisome proliferators: role of the peroxisome proliferator-activator receptor alpha

Peroxisome proliferators are a diverse group of chemicals that include several therapeutically used drugs (e.g., hypolipidemic agents), plasticizers and organic solvents used in the chemical industry, herbicides, and naturally occurring hormones. As the name implies, peroxisome proliferators cause an increase in the number and size of peroxisomes in the liver, kidney, and heart tissue of susceptible species, such as rats and mice. Long-term administration of peroxisome proliferators can cause liver cancer in these animals, a response that has been the central issue of research on peroxisome proliferators for many years. Peroxisome proliferators are representative of the class of nongenotoxic carcinogens that cause cancer through mechanisms that do not involve direct DNA damage. The fact that humans are frequently exposed to these agents makes them of particular concern to government regulatory agencies responsible for assuring human safety. Whether frequent exposure to peroxisome proliferators represents a hazard to humans is unknown; however, increased cancer risk has not been shown to be associated with long-term therapeutic administration of the hypolipidemic drugs gemfibrozil, fenofibrate, and clofibrate. To make sound judgments regarding the safety of peroxisome proliferators, the validity of extrapolating results from rodent bioassays to humans must be based on the agents' mechanism of action and species differences in biologic activity and carcinogenicity. The peroxisome proliferator-activated receptor alpha (PPARalpha), a member of the nuclear receptor superfamily, has been found to mediate the activity of peroxisome proliferators in mice. Gene-knockout mice lacking PPARalpha are refractory to peroxisome proliferation and peroxisome proliferator-induced changes in gene expression. Furthermore, PPARalpha-null mice are resistant to hepatocarcinogenesis when fed a diet containing a potent nongenotoxic carcinogen WY-14,643. Recent studies have revealed that humans have considerably lower levels of PPARalpha in liver than rodents, and this difference may, in part, explain the species differences in the carcinogenic response to peroxisome proliferators.     

Multiple cerebellar infarction due to vertebral artery obstruction and bulbar symptoms associated with vertical subluxation and atlanto-occipital subluxation in ankylosing spondylitis

Ankylosing spondylitis (AS) results in disease-specific inflammation at the site of ligamentous insertion into the bone. Atlantoaxial joint subluxation and vertical subluxation of the axis may occur as a consequence of instability resulting from the inflammatory process. Spontaneous anterior atlantoaxial subluxation is a well recognized complication in about 2% of patients with AS, and presents with or without signs of spinal cord compression. Vertical subluxation may follow anterior or posterior subluxation. It was noted in 3-8% of patients with rheumatoid arthritis, but is an exceedingly rare complication of AS. Moreover, it has never been reported that multiple cerebellar infarction and bulbar symptoms developed spontaneously due to atlanto-occipital subluxation and vertical subluxation in a patient with a long [corrected] history of AS. We describe a man with AS who developed multiple cerebellar infarction due to vertebral artery obstruction and bulbar symptoms associated with atlanto-occipital subluxation and vertical subluxation.     

Robust multidisciplinary UAS design optimisation

There are many applications in aeronautical/aerospace engineering where some values of the design parameters/states cannot be provided or determined accurately. These values can be related to the geometry (wingspan, length, angles) and or to operational flight conditions that vary due to the presence of uncertainty parameters (Mach, angle of attack, air density and temperature, etc.). These uncertainty design parameters cannot be ignored in engineering design and must be taken into the optimisation task to produce more realistic and reliable solutions. In this paper, a robust/uncertainty design method with statistical constraints is introduced to produce a set of reliable solutions which have high performance and low sensitivity. Robust design concept coupled with Multi-Objective Evolutionary Algorithms (MOEAs) is defined by applying two statistical sampling formulas; mean and variance/standard deviation associated with the optimisation fitness/objective functions. The methodology is based on a canonical evolution strategy and incorporates the concepts of hierarchical topology, parallel computing and asynchronous evaluation. It is implemented for two practical Unmanned Aerial System (UAS) design problems; the first case considers robust multi-objective (single-disciplinary: aerodynamics) design optimisation and the second considers a robust multidisciplinary (aero-structures) design optimisation. Numerical results show that the solutions obtained by the robust design method with statistical constraints have a more reliable performance and sensitivity in both aerodynamics and structures when compared to the baseline design.     

Indoor atmospheric corrosion in Cuba. A report about indoor localized corrosion

Indoor weight loss of steel, chloride, sulphur compounds and dust deposition rate were determined in six storehouses having different characteristics. Relative humidity and temperature were determined in three storehouses. A model for indoor corrosion of steel depending on time of exposure and deposition of dust, sulphur compounds and chlorides is proposed. Dust deposition plays an important role indoors. The position of the sample has also a significant influence on corrosion. Indoor corrosion aggressivity in Cuban storehouses ranges in classification IC3 and IC4 according to the new ISO proposal of indoor aggressivity.A report about the presence of localized corrosion indoors (filiform like) using a special designed sample is made.     

Analysis of chill-cast NiAl intermetallic compound with copper additions

This study carried out a characterization of chill-cast NiAl alloys with copper additions, which were added to NiAl, such that the resulting alloy composition occurred in the β-field of the ternary NiAlCu phase diagram. The alloys were vacuum induction melted and casted in copper chill molds to produce ingots 0.002 m thick, 0.020 m wide, and 0.050 m long. X-ray diffractometry (XRD) and transmission electron microscopy (TEM) performed in chill-cast ingots identified mainly the presence of the β-(Ni,Cu)Al phase. As-cast ingots showed essentially no ductility at room temperature except for the Ni₅₀Al₄₀Cu₁₀ alloy, which showed 1.79% of elongation at room temperature. Ingots with this alloy composition were then heat treated under a high-purity argon atmosphere at 550 °C (24 h) and cooled either in the furnace or in air, until room temperature was reached. β-(Ni,Cu)Al and γ′(Ni,Cu)₃Al were present in specimens cooled in the furnace and β-(Ni,Cu)Al, γ′(Ni,Cu)₃Al plus martensite-(Ni,Cu)Al were present in specimens cooled in air. Thermogravimetric analysis indicated that martensite transformation was the result of a solid-state reaction with M _s ∼ 470 and M _f ∼ 430 °C. Tensile tests performed on bulk heat-treated ingots showed room-temperature ductility between 3 and 6%, depending on the cooling media.     

Interactional Order and Constructed Ways of Seeing with Touchless Imaging Systems in Surgery

While surgical practices are increasingly reliant on a range of digital imaging technologies, the ability for clinicians to interact and manipulate these digital representations in the operating theatre using traditional touch based interaction devices is constrained by the need to maintain sterility. To overcome these concerns with sterility, a number of researchers are have been developing ways of enabling interaction in the operating theatre using touchless interaction techniques such as gesture and voice to allow clinicians control of the systems. While there have been important technical strides in the area, there has been little in the way of understanding the use of these touchless systems in practice. With this in mind we present a touchless system developed for use during vascular surgery. We deployed the system in the endovascular suite of a large hospital for use in the context of real procedures. We present findings from a study of the system in use focusing on how, with touchless interaction, the visual resources were embedded and made meaningful in the collaborative practices of surgery. In particular we discuss the importance of direct and dynamic control of the images by the clinicians in the context of talk and in the context of other artefact use as well as the work performed by members of the clinical team to make themselves sensable by the system. We discuss the broader implications of these findings for how we think about the design, evaluation and use of these systems.