The respiratory chain inhibitor rotenone affects peroxisomal dynamics via its microtubule-destabilizing activity

This is the author accepted manuscript. The final version is available from Springer Verlag via the DOI in this record.Peroxisomes and mitochondria in mammalian cells are closely linked subcellular organelles, which maintain a redox-sensitive relationship. Their interplay and role in ROS signalling is supposed to impact on age-related and degenerative disorders. Whereas the generation of peroxisome-derived oxidative stress can affect mitochondrial morphology and function, little is known about the impact of mitochondria-derived oxidative stress on peroxisomes. Here, we investigated the effect of the mitochondrial complex I inhibitor rotenone on peroxisomal and mitochondrial membrane dynamics. We show that rotenone treatment of COS-7 cells alters peroxisome morphology and distribution. However, this effect is related to its microtubule-destabilising activity rather than to the generation of oxidative stress. Rotenone also induced alterations in mitochondrial morphology, which – in contrast to its effect on peroxisomes - were dependent on the generation of ROS but independent of its microtubule-active properties. The importance of our findings for the peroxisome-mitochondria redox relationship and the interpretation of in cellulo and in vivo studies with rotenone, which is widely used to study Parkinson’s disease, are discussed.We would like to acknowledge the support of T. A. Schrader, N. A. Bonekamp and J. Jordan (University of Castilla-La Mancha, Albacete, Spain). This work was supported by the Biotechnology and Biological Sciences Research Council (BB/K006231/1, BB/N01541X/1 to M.S.), the Portuguese Foundation for Science and Technology and FEDER/COMPETE (SFRH/BPD/37725/2007 to M.G.L), the University of Aveiro, PT and CLES, University of Exeter, UK. M.S. is supported by a Marie Curie Initial Training Network (ITN) action PerFuMe (316723)

Multi-purpose high shear melt conditioning technology for effective melt quality and for recycling of Al-alloy scrap

Melt quality is crucial for both continuous and shape casting of light alloys and in order toimprove it, removal of excessive inclusions, accumulated impurities and unwanted gases becomes necessary. To address this problem, a new multi-purpose high shear liquid metal treatment technology, based on intensive melt shearing by a rotor/stator unit, has been developed. The device ensures achieving uniform temperature and chemical composition and an efficient dispersion of gas and solid phases in the melt with minimal disturbance of melt surface, and can be used, among other things, for de-gassing and deironing of Al-alloy melts. Efficient degassing is achieved by dispersing each argon bubble into many small ones, which significantly increases the overall surface area of the bubbles and the time they remain in the melt capturing hydrogen before reaching the surface. This allows using much lower inert gas flow and mixing times than conventional rotary degassing. When applied to Al-alloy scrap, with accumulated iron, the high shear melt treatment speeds up the nucleation and growth of primary Fe-rich intermetallic particles, allowing a faster removal rate. Therefore it reduces processing times, increasing recycling productivity, and facilitates full metal circulation of secondary Al-alloys.EPSRC Future Lime Hub (UK) under grant number EP/N007638/1; European commission Seventh Framework (FP7) under grant number 603577

Improved Defect Control and Mechanical Property Variation in High-Pressure Die Casting of A380 Alloy by High Shear Melt Conditioning

EPSRC UK in the EPSRC Centre for Innovative Manufacturing in Liquid Metal Engineering (The EPSRC Centre—LiME)

In-situ microstructural control of A6082 alloy to modify second phase particles by melt conditioned direct chill (MC-DC) casting process - A novel approach

© 2021 The Authors. Controlling the formation of noncompact second phase particles during direct chill (DC) casting of aluminium alloys with grain refiner addition remains challenging, as it results in energy intensive homogenisation and deformation problems. In this work, we employed a novel strategy in the DC casting of A6082 alloy to produce billets with a fine-scale dispersion of second phase particles. The strategy involves maintaining 2–7 °C above alloy liquidus as a thermal condition in the sump by in-situ melt conditioning (MC) using a rotor-stator high-shear device operated at a critical rotation speed. As a result, in-situ control of solidification behaviour is achieved to precisely tailor the as-cast microstructure. The billet grain refinement is attained by MC-DC casting without the deliberate addition of chemical grain refiners. The microstructure of the MC-DC cast billet at the critical rotation speed showed a fine-scale dendritic structure with refined secondary dendrite arm spacing (SDAS). The solidification front proceeded with a shallow sump and a corresponding shorter solidification time, higher cooling rate, higher temperature gradient, and smooth solidification rate profile. The ideal fine-scale dendrites with low SDAS divided the remaining eutectic liquid into fine-scale and isolated liquid pockets, resulting in fine-scale, compact morphology, and uniform distribution of second phase particles in the as-cast microstructure. The MC-DC casting process showed the ability to increase the cast house production rate by increasing the casting speed without bleeding the billet. The present approach could be beneficial for eliminating or reducing the homogenisation practice and may also introduce significant flexibility in using recycled Al alloys in the industry.Engineering and Physical Sciences Research Council (EPSRC) of the UK and Constellium (UK) STEP Al prosperity partnership grant (EP/S036296/1)

Melt conditioned direct chill (MC-DC) casting of AA-6111 aluminium alloy formulated from incinerator bottom ash (IBA)

© 2019 by the authors. The melt conditioned direct chill (MC-DC) casting process has been used for the production of billets of AA-6111 alloy formulated from recycled aluminium derived from incinerator bottom ash (IBA). The billets were homogenised and then extruded into planks. Optical metallography of the MC-DC billets showed equiaxed refined grains in comparison to DC and grain refined (DC-GR) billets formulated from the same scrap source. Microstructure evaluation for the extruded planks showed a less extensive peripheral coarse grain (PCG) for the MC-DC sampleInnovate UK. Financial support from the ‘Recycling of Aluminium through Innovative Technology’ (REALITY) Project No. 102797 led by Jaguar Land Rover (JLR)

De-Ironing of Aluminium Alloy Melts by High Shear Melt Conditioning Technology: An Overview

Data Availability Statement: The data presented in this manuscript is available on request from the corresponding author.Copyright: © 2022 by the authors. The main problem of recycling aluminium scrap is the gradual accumulation of impurities, especially iron, which tend to form undesired intermetallic compounds that affect the integrity and the mechanical performance of the castings. In this paper, we aim to provide an overview on the topic of iron removal from aluminium melts through primary intermetallic precipitation and the progress made during the LiME Hub project to understand the process and to develop a more efficient procedure. We cover both thermodynamic analysis and experimental validation. We found that high shear melt conditioning technology enhances the typically slow nucleation and growth of the dense primary intermetallics, speeding up their sedimentation and allowing a faster removal of Fe from the melt by simple gravity sedimentation. It also promotes the formation of smaller and more compact Fe-rich intermetallics, allowing an increased volume fraction recovery and mitigating their effect of being present in the final castings. The technology is not limited to batch processing, with a 90% efficiency, but can also be applied to continuous melt treatment of aluminium scrap, with currently 60% efficiency, and could be combined with other solid–liquid separation techniques to increase the purification efficiency even more.EPSRC (UK) under grant number EP/N007638/1; European Commission under Grant No. 603577; Innovate UK under Project No.102797

In-vitro model systems to study Hepatitis C Virus

Hepatitis C virus (HCV) is a major cause of chronic liver diseases including steatosis, cirrhosis and hepatocellular carcinoma. Currently, there is no vaccine available for prevention of HCV infection due to high degree of strain variation. The current treatment of care, Pegylated interferon α in combination with ribavirin is costly, has significant side effects and fails to cure about half of all infections. The development of in-vitro models such as HCV infection system, HCV sub-genomic replicon, HCV producing pseudoparticles (HCVpp) and infectious HCV virion provide an important tool to develop new antiviral drugs of different targets against HCV. These models also play an important role to study virus lifecycle such as virus entry, endocytosis, replication, release and HCV induced pathogenesis. This review summarizes the most important in-vitro models currently used to study future HCV research as well as drug design

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns

Motivational determinants among physicians in Lahore, Pakistan

Introduction: Human resource crises in developing countries have been identified as a critical aspect of poor quality and low accessibility in health care. Worker motivation is an important facet of this issue. Specifically, motivation among physicians, who are an important bridge between health systems and patients, should be considered. This study aimed to identify the determinants of job motivation among physicians, a neglected perspective, especially in developing countries. Methods: A stratified random sample of 360 physicians was selected from public primary, public secondary and public and private tertiary health facilities in the Lahore district, Pakistan. Pretested, semi-structured, self-administered questionnaires were used. For the descriptive part of this study, physicians were asked to report their 5 most important work motivators and demotivators within the context of their current jobs and in general. Responses were coded according to emergent themes and frequencies calculated. Of the 30 factors identified, 10 were classified as intrinsic, 16 as organizational and 4 as socio-cultural. Results: Intrinsic and socio-cultural factors like serving people, respect and career growth were important motivators. Conversely, demotivators across setups were mostly organizational, especially in current jobs. Among these, less pay was reported the most frequently. Fewer opportunities for higher qualifications was a demotivator among primary and secondary physicians. Less personal safety and poor working conditions were important in the public sector, particularly among female physicians. Among private tertiary physicians financial incentives other than pay and good working conditions were motivators in current jobs. Socio-cultural and intrinsic factors like less personal and social time and the inability to financially support oneself and family were more important among male physicians. Conclusion: Motivational determinants differed across different levels of care, sectors and genders. Nonetheless, the important motivators across setups in this study were mostly intrinsic and socio-cultural, which are difficult to affect while the demotivators were largely organizational. Many can be addressed even at the facility level such as less personal safety and poor working conditions. Thus, in resource limited settings a good strategic starting point could be small scale changes that may markedly improve physicians' motivation and subsequently the quality of health care