Design, synthesis and biological evaluation of edaravone derivatives bearing theN-benzyl pyridinium moiety as multifunctional anti-Alzheimer’s agents

A series of multi-target directed edaravone derivatives bearingN-benzyl pyridinium moieties weredesigned and synthesised. Edaravone is a potent antioxidant with significant neuroprotective effects andN-benzyl pyridinium has previously exhibited positive results as part of a dual-site binding, peripheralanionic site (PAS) and catalytic anionic site (CAS), acetylcholinesterase (AChE) inhibitor. The designed edar-avone-N-benzyl pyridinium hybrid compounds were docked within the AChE active site. The results indi-cated interactions with conserved amino acids (Trp279 in PAS and Trp84 in CAS), suggesting good dual-site inhibitory activity. Significantin vitroAChE inhibitory activities were observed for selected compounds(IC50:1.2–4.6mM) with limited butyrylcholinesterase inhibitory activity (IC50’s>160mM), indicating excellentselectivity towards AChE (SI: 46–>278). The compounds also showed considerable antioxidant ability,similar to edaravone.In silicostudies indicated that these compounds should cross the blood–brain bar-rier, making them promising lead molecules in the development of anti-Alzheimer’s agents

The EcoThermo project: key and innovative aspects

In this paper we present the most innovative aspects of the EC-FP7 EcoThermo project. The main aim of the project consists on innovating the technique of heat cost allocation in buildings with a centralized heating system, overcoming the heat cost allocator drawbacks for reliability, measurement reproducibility and traceability and contexts of applications. Given the complexity of the project, we will focus on its main aspects, such as the use of a virtual sensor to estimate the radiators heating power, the design of electronic valves fitted out with an energy harvesting system and the original wireless communication protocol

Design, synthesis and biological evaluation of edaravone derivatives bearing the N-benzyl pyridinium moiety as multifunctional anti-Alzheimer’s agents

A series of multi-target directed edaravone derivatives bearing N-benzyl pyridinium moieties were designed and synthesised. Edaravone is a potent antioxidant with significant neuroprotective effects and N-benzyl pyridinium has previously exhibited positive results as part of a dual-site binding, peripheral anionic site (PAS) and catalytic anionic site (CAS), acetylcholinesterase (AChE) inhibitor. The designed edaravone-N-benzyl pyridinium hybrid compounds were docked within the AChE active site. The results indicated interactions with conserved amino acids (Trp279 in PAS and Trp84 in CAS), suggesting good dual-site inhibitory activity. Significant in vitro AChE inhibitory activities were observed for selected compounds (IC50: 1.2–4.6 µM) with limited butyrylcholinesterase inhibitory activity (IC50’s >160 µM), indicating excellent selectivity towards AChE (SI: 46–>278). The compounds also showed considerable antioxidant ability, similar to edaravone

Design, synthesis, and evaluation of 3,7-substituted coumarin derivatives as multifunctional Alzheimer’s disease agents

Multitarget directed ligands (MTDLs) are emerging as promising treatment options for Alzheimer’s disease (AD). Coumarin derivatives serve as a good starting point for designing MTDLs due to their inherent inhibition of monoamine oxidase (MAO) and cholinesterase enzymes, which are complicit in AD’s complex pathophysiology. A preliminary series of 3,7-substituted coumarin derivatives were synthesised and evaluated for enzyme inhibitory activity, cytotoxicity as well as neuroprotective ability. The results indicated that the compounds are weak cholinesterase inhibitors with five compounds demonstrating relatively potent inhibition and selectivity towards MAO-B with IC50 values between 0.014 and 0.498 hx00B5;mM. Significant neuroprotective effects towards MPPþ-compromised SH-SY5Y neuroblastoma cells were also observed, with no inherent cytotoxicity at 10 mM for all compounds. The overall results demonstrated that substitution of the phenylethyloxy moiety at the 7-position imparted superior general activity to the derivatives, with the propargylamine substitution at the 3-position, in particular, displaying the best MAO-B selectivity and neuroprotection

Implementation of the safe system approach in South Africa : overview of the Limpopo road safety programme

Papers presented virtually at the 41st International Southern African Transport Conference on 10-13 July 2044In line with the Sustainable Development Goals 2030 road safety has been prioritized as a key public health priority. Aligned with South African national development goals (NDP 2030) and the fact that the South Africa Government recognizes road safety and the consequences of the road safety scourge as public health and socio-economic development challenge across South Africa, and across communities. In 2018 a South African mining community and health assessment determined that road safety needs to be a key health and safety priority. In support a baseline Limpopo Province road safety analysis conducted in 2021 indicted the need to cater for the most vulnerable in society (and with that broader than the usual vulnerable road user, but also aimed at socioeconomic vulnerability) which puts road safety in the mainstream of development activities and the road safety agenda will need to aspire to achieving more. In response to address the road safety problems in the province, a targeted programme was developed. The Limpopo Road Safety Programme is premised on the Safe Systems Approach which at the heart of both the First and the Second United Nations Decade of Action and Global Road Safety Plans, as well as the National Road Safety Strategy 2030. The Limpopo Road Safety Programme aim to implement road safety actions and interventions in a targeted manner. The Limpopo Road Safety programme is a three-year initiative developed and implemented by the Impact Catalyst and is set to through public and private partnerships support communities in reducing the number of deaths and injuries from road traffic accidents (Sustainable Development Goal 3.6). This commitment is deliberately ambitious and aligned to improve people’s lives. The programme is rooted in successful public and private partnerships and the coordination of targeted interventions and actions aimed at reducing the carnage on Limpopo roads. This research paper provides an overview of the the Limpopo Road Safety programme which through the execution of thirteen targeted Safe System projects aims to improve road safety in the Limpopo Province by strengthening the various pillars of the Safe System Approach in support of road safety improvements

Novel Bone-Targeting Agent for Enhanced Delivery of Vancomycin to Bone

We examined the pharmacokinetic properties of vancomycin conjugated to a bone-targeting agent (BT) with high affinity for hydroxyapatite after systemic intravenous administration. The results confirm enhanced persistence of BT-vancomycin in plasma and enhanced accumulation in bone relative to vancomycin. This suggests that BT-vancomycin may be a potential carrier for the systemic targeted delivery of vancomycin in the treatment of bone infections, potentially reducing the reliance on surgical debridement to achieve the desired therapeutic outcome

Making connections: technological interventions to support students in using, and tutors in creating, assessment feedback

This paper explores the potential of technology to enhance the assessment and feedback process for both staff and students. The ‘Making Connections’ project aimed to better understand the connections that students make between the feedback that they receive and future assignments, and explored whether technology can help them in this activity. The project interviewed 10 tutors and 20 students, using a semi-structured approach. Data were analysed using a thematic approach, and the findings have identified a number of areas in which improvements could be made to the assessment and feedback process through the use of technology. The findings of the study cover each stage of the assessment process from the perspective of both staff and students. The findings are discussed in the context of current literature, and special attention is given to projects from the UK higher education sector intended to address the same issues. Keywords: feed-forward; assessment; practices; technology; technology-enhanced learnin

Hydrogen Epoch of Reionization Array (HERA)

The Hydrogen Epoch of Reionization Array (HERA) is a staged experiment to measure 21 cm emission from the primordial intergalactic medium (IGM) throughout cosmic reionization ($z=6-12$), and to explore earlier epochs of our Cosmic Dawn ($z\sim30$). During these epochs, early stars and black holes heated and ionized the IGM, introducing fluctuations in 21 cm emission. HERA is designed to characterize the evolution of the 21 cm power spectrum to constrain the timing and morphology of reionization, the properties of the first galaxies, the evolution of large-scale structure, and the early sources of heating. The full HERA instrument will be a 350-element interferometer in South Africa consisting of 14-m parabolic dishes observing from 50 to 250 MHz. Currently, 19 dishes have been deployed on site and the next 18 are under construction. HERA has been designated as an SKA Precursor instrument. In this paper, we summarize HERA's scientific context and provide forecasts for its key science results. After reviewing the current state of the art in foreground mitigation, we use the delay-spectrum technique to motivate high-level performance requirements for the HERA instrument. Next, we present the HERA instrument design, along with the subsystem specifications that ensure that HERA meets its performance requirements. Finally, we summarize the schedule and status of the project. We conclude by suggesting that, given the realities of foreground contamination, current-generation 21 cm instruments are approaching their sensitivity limits. HERA is designed to bring both the sensitivity and the precision to deliver its primary science on the basis of proven foreground filtering techniques, while developing new subtraction techniques to unlock new capabilities. The result will be a major step toward realizing the widely recognized scientific potential of 21 cm cosmology.Comment: 26 pages, 24 figures, 2 table

The UK Public's interests, needs and concerns around food: UK main report

This qualitative and quantitative research explored UK consumer views and priorities in relation to our responsibilities around food hygiene and safety, but also around wider interests the public see critical in shaping their food choices and lives including: health and nutrition environment and ethics price quality and convenience consumer versus business power potential food futures The top priorities for consumers, and where they would like action taken on their behalf, are around ensuring: hygiene and safety standards are maintained or strengthened equitable access to safe, healthy, affordable food easy informed decision making trustworthy food information In the context of the UK, they would like to ensure farmers and UK agriculture are protected and that locally produced food is accessible. In the wider context of the system, consumers would like action on animal welfare and waste (food and packaging), and in the long term a steer towards fair, ethical and sustainable food systems