Phosphatase and tensin homologue/protein kinase B pathway linked to motor neuron survival in human superoxide dismutase 1-related amyotrophic lateral sclerosis

Gene expression profiling has been used previously with spinal cord homogenates and laser capture microdissected motor neurons to determine the mechanisms involved in neurodegeneration in amyotrophic lateral sclerosis. However, while cellular and animal model work has focused on superoxide dismutase 1-related amyotrophic lateral sclerosis, the transcriptional profile of human mutant superoxide dismutase 1 motor neurons has remained undiscovered. The aim of this study was to apply gene expression profiling to laser captured motor neurons from human superoxide dismutase 1-related amyotrophic lateral sclerosis and neurologically normal control cases, in order to determine those pathways dysregulated in human superoxide dismutase 1-related neurodegeneration and to establish potential pathways suitable for therapeutic intervention. Identified targets were then validated in cultured cell models using lentiviral vectors to manipulate the expression of key genes. Microarray analysis identified 1170 differentially expressed genes in spinal cord motor neurons from superoxide dismutase 1-related amyotrophic lateral sclerosis, compared with controls. These genes encoded for proteins in multiple functional categories, including those involved in cell survival and cell death. Further analysis determined that multiple genes involved in the phosphatidylinositol-3 kinase signalling cascade were differentially expressed in motor neurons that survived the disease process. Functional experiments in cultured cells and primary motor neurons demonstrate that manipulating this pathway by reducing the expression of a single upstream target, the negative phosphatidylinositol-3 kinase regulator phosphatase and tensin homology, promotes a marked pro-survival effect. Therefore, these data indicate that proteins in the phosphatidylinositol-3 kinase pathway could represent a target for therapeutic manipulation in motor neuron degeneration

Loss of ATF2 Function Leads to Cranial Motoneuron Degeneration during Embryonic Mouse Development

The AP-1 family transcription factor ATF2 is essential for development and tissue maintenance in mammals. In particular, ATF2 is highly expressed and activated in the brain and previous studies using mouse knockouts have confirmed its requirement in the cerebellum as well as in vestibular sense organs. Here we present the analysis of the requirement for ATF2 in CNS development in mouse embryos, specifically in the brainstem. We discovered that neuron-specific inactivation of ATF2 leads to significant loss of motoneurons of the hypoglossal, abducens and facial nuclei. While the generation of ATF2 mutant motoneurons appears normal during early development, they undergo caspase-dependent and independent cell death during later embryonic and foetal stages. The loss of these motoneurons correlates with increased levels of stress activated MAP kinases, JNK and p38, as well as aberrant accumulation of phosphorylated neurofilament proteins, NF-H and NF-M, known substrates for these kinases. This, together with other neuropathological phenotypes, including aberrant vacuolisation and lipid accumulation, indicates that deficiency in ATF2 leads to neurodegeneration of subsets of somatic and visceral motoneurons of the brainstem. It also confirms that ATF2 has a critical role in limiting the activities of stress kinases JNK and p38 which are potent inducers of cell death in the CNS

CFB cyclones at high temperature: Operational results and design assessment

Pressure drop and cut size measurements are reported for a full scale cyclone operating within a 58 MWth CFB-combustor unit at 775 degrees C. The paper reviews the vast number of equations to calculate the pressure drop and separation efficiency of cyclones, generally for operation at ambient temperature and at low C-s [< 0.5]. None of the literature correlations predicts the pressure drop with a fair accuracy within the range of experimental operating conditions. The cut size d(50) can be estimated using direct empirical methods or using the Stokes number, Stk5o. Both methods were used to compare measured and predicted values of d(50). With the exception of Muschelknautz and Krambrock, none of the equations made accurate predictions. Finally, an alternative method to determine the friction factor of the pressure drop equation (Euler number, Eu) and of the cut size is proposed. The Eu number is determined from the geometry of common cyclones, and the derived value of Stk5o defines more accurate cut sizes. The remaining discrepancy of less than 5%, when compared with the measured values, is tentatively explained in terms of a reduced cyclone diameter due to the solids layer formed near its wall. Further measurements, mostly using positron emission particle tracking, elucidate the particle motion in the cyclone and both tracking results and the influence of the particle movement on Eu and Stk(50) will be discussed in a follow-up paper. (c) 2008 Chinese Society of Particuology and Institute of Process Engineering, Chinese Academy of Sciences. Published by Elsevier B.V. All rights reserved.status: publishe

Corrosion behaviour of lean duplex stainless steel in advanced oxidation process (AOP) based wastewater treatment plants

The corrosion of lean duplex stainless steel alloys is examined when applied as a construction material in advanced oxidation processes. Both electrochemical and immersion experiments have been carried out when subjecting wastewater to ozone or Fenton oxidation. The electrochemical experiments suggest that the presence of dissolved ozone at the levels tested does not result in an increased pitting susceptibility for none of the alloys included in the research. However, the application of Fenton reagents induces pitting corrosion to the studied lean duplex alloys. The immersion experiments highlight that crevice corrosion occurs during wastewater treatment with both ozone and Fenton reagents

A critical review of ammonia recovery from anaerobic digestate of organic wastes via stripping

Anaerobic digestion is a well-established technology that valorises organic wastes to produce renewable energy as biogas. The ammonia released during this process can be inhibitory if it exceeds a threshold concentration. Additionally, ammonia is a harmful environmental pollutant and also a renewable source of energy, thus establishing a need for the recovery of ammonia. Gas-liquid stripping is one such widely researched technology to recover ammonia from wastewater. However, there have not been any reviews focusing solely on the application of stripping to recover ammonia from the anaerobic digestate of organic wastes. This study reviews the current state of research in this field, focusing on the factors affecting the ammonia recovery, stripping column designs and linking of an anaerobic digester to a stripping column. An overview of the work done on the modelling of the ammonia stripping from digestate is also included. This review offers a direction for further research in this field; i.e., experimental and modelling studies on i) the effect of digestate composition on ammonia recovery and ii) the effect of stripping gas on ammonia removal

A new methodology to efficiently test pitting corrosion: design of a 3D-printed sample holder to avoid the occurrence of crevice corrosion in chemically aggressive media

Pitting susceptibility of metals in corrosive environment is usually measured using a three-electrode set-up to conduct accelerated corrosion tests. A widely accepted methodology consists in mounting a sample in epoxy resin and connect it with a copper wire. However, in chloride-rich environments, this often results in the occurrence of crevice corrosion instead of pitting. In this study, a new 3D-printed sample holder was designed and its efficiency to study pitting corrosion of metals validated. The new method enables to study of pitting corrosion by improving edge enclosure, thus avoiding crevice corrosion. The validation is based on two case studies where stainless steel samples are polarized in (i) 500-ppm Cl− at ambient temperature and (ii) saturated Ca(OH)2 with 1-M Cl− at 60 °C. The specifically chosen grade (AISI 316 L) shows failure of the electrode clearly initiated at the epoxy sample edge in traditional tests and poor reproducibility. Results showed that the use of the 3D-printed sample holder significantly improved the reliability and efficiency of the testing method, clearly avoiding unrealistic crevice corrosion in the tested conditions. The designed sample holder therefore enables more realistic and representative pitting results in corrosion research opening the possibility of conducting far less-expensive repetitive tests

Pitting and general corrosion susceptibilities of materials for high level radioactive waste (HLW) disposal

The disposal of high-level radioactive waste (HLW) in deep stable geological formations is accepted at an international level to be the most promising option for its long-term management. The supercontainer concept is currently being considered as the Belgian reference design, wherein the waste will be stored in geological stable clay formations. The outer barrier of the supercontainer is the envelope, which should be made of a corrosion-resistant material as it will be in contact with the aggressive species leaching from the host rock (i.e., chloride) and diffusing through the cementitious barriers of the disposal system. Polarization measurements are carried out to study the pitting susceptibility and the uniform corrosion of possible candidate materials in chloride-rich concrete pore solutions, aerated by high-purity oxygen. The tests are carried out at a deep soil-representative temperature of 60 °C. All materials showed high pitting resistance in aerated concrete pore solutions and can withstand chloride concentrations up to 1 M. Regular 316L and LDX2304 stainless steel also showed good corrosion resistance and can serve as a more economical alternative. The pH of the used pore solutions did affect the measured corrosion rate irrespective of the alloying elements inside the steel grades