β-N-methylamino-L-alanine Enhances Neurotoxicity Through Multiple Mechanisms

The idea that the environmental toxin β-N-methylamino-l-alanine (BMAA) is involved in neurodegenerative diseases on Guam has risen and fallen over the years. The theory has gained greater interest with recent reports that BMAA is biomagnified, is widely distributed around the planet, and is present in the brains of Alzheimer\u27s patients in Canada. We provide two important new findings. First, we show that BMAA at concentrations as low as 10 μM can potentiate neuronal injury induced by other insults. This is the first evidence that BMAA at concentrations below the mM range can enhance death of cortical neurons and illustrates potential synergistic effects of environmental toxins with underlying neurological conditions. Second, we show that the mechanism of BMAA toxicity is threefold: it is an agonist for NMDA and mGluR5 receptors, and induces oxidative stress. The results provide further support for the hypothesis that BMAA plays a role in neurodegenerative diseases

Inclusion of chemical effect in a fully coupled THM finite element code

Bentonite-rich clays can be used as a buffer / backfill material in deep geological repositories for nuclear waste. The prediction of the long-term performance of a buffer / backfill in such a complex environment, where the temperature, humidity and chemistry of water change, requires a fully thermo-hydro-mechanical-chemical (THMC) coupled numerical code. This paper presents a simple extension of a THM coupled finite element code to include chemical effects. After deriving the governing salt mass balance equation and discussing its implementation into the code, the paper verifies the extended framework against an analytical solution for 1D salt transport. In addition, the article presents a validation example in which the code replicates experimental data. The numerical results obtained from the extended THMC coupled finite element code encourage further investigation of the chemical effects on the mechanical and thermal behaviour of the material, which would serve the ultimate goal of achieving a safer design of the nuclear waste storage facility.Postprint (published version

Neural network fault diagnosis of a trolling motor based on feature reduction techniques for an unmanned surface vehicle

This article presents a novel approach to the diagnosis of unbalanced faults in a trolling motor under stationary operating conditions. The trolling motor being typically of that used as the propulsion system for an unmanned surface vehicle, the diagnosis approach is based on the use of discrete wavelet transforms as a feature extraction tool and a time-delayed neural network for fault classification. The time-delayed neural network classifies between healthy and faulty conditions of the trolling motor by analysing the stator current and vibration. To overcome feature redundancy, which affects diagnosis accuracy, several feature reduction methods have been tested, and the orthogonal fuzzy neighbourhood discriminant analysis approach is found to be the most effective method. Four faulty conditions were analysed under laboratory conditions, where one of the blades causing damage to the trolling motor is cut into 10%, 25%, half and then into full to simulate the effects of propeller blades being damaged partly or fully. The results obtained from the real-time simulation demonstrate the effectiveness and reliability of the proposed methodology in classifying the different faults faster and accurately

Identification of key thermal couplings affecting the bentonite behaviour in a deep geological nuclear waste repository

Deep geological nuclear waste repositories use the multi-layer Engineered Barrier System (EBS) to isolate nuclear waste from the environment. The key component of the barrier is densely compacted bentonite, closely resembling claystone. Therefore, to ensure safety, we need a numerical model for the bentonite and the barrier that predicts EBS behaviour during transient thermal, hydraulic, mechanical and chemical conditions. The paper identifies key mechanisms and processes affecting the bentonite in the barrier due to temperature changes (thermal couplings) based on advanced fully-coupled Finite Element Method simulations. The paper investigates 1) non-isothermal infiltration experiment on FEBEX bentonite (Villar and Gomez-Espina, 2009) and, 2) Centro de Investigaciones Energeticas Medioambientales y Tecnologicas (Ciemat) test (Martin et al., 2006), presenting 10 simulation configurations that are set up by inactivating one thermal coupling/variable at a time. The difference between these simulations and the baseline model results, examined in terms of the net mean stress (swelling pressure), suction and fluid flow, give insights into the significance of investigated coupling. Results suggest that thermal couplings related to vapour density, viscosity, water retention curve, and molecular diffusivity are among the most influential. The study additionally highlights the importance of water transport as liquid and gas, and water evaporation and condensation

Implementation and validation of pressure-dependent gas permeability model for bentonite in FEM code Thebes

In an Engineered Barrier System of a nuclear waste repository, gas migrates through: a) diffusion/advection of dissolved gases, b) two-phase continuum flow, c) dilatant pathway flow and d) single-phase gas flow through macro-fractures in the soil. The gas production rate and the corresponding gas pressure accumulation affect the clay material behaviour and its properties such as air entry value. For the safe design of the EBS system, computational models need to account for the identified transport mechanisms. This study presents an enhancement in the finite element code Thebes [1, 2] that replicates the observed increase in permeability at higher gas pressures, e.g. due to pore dilatancy and gas fracture as proposed by Xu et al. [3]. The formulation links permeability to gas pressure and threshold/critical pressure. For model validation, the study utilizes a gas injection experiment carried out in IfG (Institute for Rock Mechanics, Germany) on Opalinus Clay [4]. The results show a good fit against the measurements while giving insight into gas flow through clays

A Robust Bearing Fault Detection and Diagnosis Technique for Brushless DC Motors Under Non-stationary Operating Conditions

Rolling element bearing defects are among the main reasons for the breakdown of electrical machines, and therefore, early diagnosis of these is necessary to avoid more catastrophic failure consequences. This paper presents a novel approach for identifying rolling element bearing defects in brushless DC motors under non-stationary operating conditions. Stator current and lateral vibration measurements are selected as fault indicators to extract meaningful features, using a discrete wavelet transform. These features are further reduced via the application of orthogonal fuzzy neighbourhood discriminative analysis. A recurrent neural network is then used to detect and classify the presence of bearing faults. The proposed system is implemented and tested in simulation on data collected from an experimental setup, to verify its effectiveness and reliability in accurately detecting and classifying the various faults

A constitutive framework for the chemo-mechanical behaviour of unsaturated non-expansive clays

Both osmotic and matric suction changes have a significant influence on the mechanical behaviour of clays. Despite the different types of interactions at the microstructural level, both suctions havea relevant effect on the fabric of non-expansive clays. Starting from experimental observations at the laboratory scale, it is possible to identify some common features characterizing the mechanical response of non-expansive clays to salinity and degree of saturation changes. This paper presents an elastoplasticframework to reproduce the behaviour of unsaturated clayey soils upon changes in the salt concentration of the pore fluid. In particular, it presents a strategy to include osmotic suction induced by pore fluid salinity in BBM-like models [1]. The model was implemented in the Thebes code and it was calibrated on experimental data performed on Boom clay [2] and remoulded loess [3]

Isochondodendrine and 2[prime or minute]-norcocsuline: additional alkaloids from Triclisia subcordata induce cytotoxicity and apoptosis in ovarian cancer cell lines

Triclisia subcordata Oliv (Menispermeaceae) is used in herbal medicine for the treatment of cancer and other diseases in Africa. This study aims to isolate minor alkaloids present in this plant and assay their cytotoxic activities. Isochondodendrine and 2[prime or minute]-norcocsuline as two minor alkaloids together with the abundant cycleanine were isolated and identified by mass spectrometry and NMR spectroscopy. Both isochondodendrine and 2[prime or minute]-norcocsuline exhibited in vitro cytotoxicity in four ovarian cancer cell lines (A2780, IGROV-1, OVCAR-8, and OVCAR-4) with IC50 ranges of 3.5-17 [small mu ]M and 0.8-6.2 [small mu ]M respectively. These alkaloids showed mostly slightly weaker potencies when tested using normal human ovarian epithelial cells, IC50 = 10.5 +/- 1.2 [small mu ]M and 8.0 +/- 0.2 [small mu ]M for isochondodendrine and 2[prime or minute]-norcocsuline, respectively. The alkaloids induced apoptosis in ovarian cancer cells because they activated caspases 3/7, induced cleavage of PARP, increased the subG1 population in cell cycle analysis and increased Annexin V/propidium iodide staining. These observations suggest that isochondodendrine and 2[prime or minute]-norcocsuline contributing to the cytotoxic activity of T. subcordata may be suitable starting points for the future development of novel therapeutics to treat ovarian cancer

Pancreas preserving distal duodenectomy: a versatile operation for a range of infra-papillary pathologies

AIM To investigate the range of pathologies treated by pancreas preserving distal duodenectomy (PPDD) and present the outcome of follow-up. METHODS Neoplastic lesions of the duodenum are treated conventionally by pancreaticoduodenectomy. Lesions distal to the major papilla may be suitable for a pancreas-preserving distal duodenectomy, potentially reducing morbidity and mortality. We present our experience with this procedure. Selective intraoperative duodenoscopy assessed the relationship of the papilla to the lesion. After duodenal mobilisation and confirmation of the site of the lesion, the duodenum was transected distal to the papilla and beyond the duodenojejunal flexure and a side-to-side duodenojejunal anastomosis was formed. Patients were identified from a prospectively maintained database and outcomes determined from digital health records with a dataset including demographics, co-morbidities, mode of presentation, preoperative imaging and assessment, nutritional support needs, technical operative details, blood transfusion requirements, length of stay, pathology including lymph node yield and lymph node involvement, length of follow-up, complications and outcomes. Related published literature was also reviewed. RESULTS Twenty-four patients had surgery with the intent of performing PPDD from 2003 to 2016. Nineteen underwent PPDD successfully. Two patients planned for PPDD proceeded to formal pancreaticoduodenectomy (PD) while three had unresectable disease. Median post-operative follow-up was 32 mo. Pathologies resected included duodenal adenocarcinoma (n = 6), adenomas (n = 5), gastrointestinal stromal tumours (n = 4) and lipoma, bleeding duodenal diverticulum, locally advanced colonic adenocarcinoma and extrinsic compression (n = 1 each). Median postoperative length of stay (LOS) was 8 d and morbidity was low [pain and nausea/vomiting (n = 2), anastomotic stricture (n = 1), pneumonia (n = 1), and overwhelming postsplenectomy sepsis (n = 1, asplenic patient)]. PPDD was associated with a significantly shorter LOS than a contemporaneous PD series [PPDD 8 (6-14) d vs PD 11 (10-16) d, median (IQR), P = 0.026]. The 30-d mortality was zero and 16 of 19 patients are alive to date. One patient died of recurrent duodenal adenocarcinoma 18 mo postoperatively and two died of unrelated disease (at 2 mo and at 8 years respectively). CONCLUSION PPDD is a versatile operation that can provide definitive treatment for a range of duodenal pathologies including adenocarcinoma