Discrete element modelling of high aspect ratio sphero-cylinder particle packing

This paper presents Discrete Element Model simulations of packing of rigid sphero-cylinders. The method has been used before but this study considers higher aspect ratios, up to 30. This posed some modelling challenges in terms of stability which were overcome by imposing limits on the particle motion. The results show very good agreement with experimental data in the literature and more detailed in-house experiments for packing volume fraction. Model results on particle orientation are also shown. The model has the potential for predicting packing of fibrous particles and fibre bundles relevant to the preparation of preforms for the production of polymer and metallic matrix composites. Future model developments will include adding flexibility by connecting sphero-cylinders as subelements to describe a particle

The impact of immobilisation and inflammation on the regulation of muscle mass and insulin resistance: different routes to similar end points

Loss of muscle mass and insulin sensitivity are common phenotypic traits of immobilisation and increased inflammatory burden. The suppression of muscle protein synthesis is the primary driver of muscle mass loss in human immobilisation, and includes blunting of post‐prandial increases in muscle protein synthesis. However, the mechanistic drivers of this suppression are unresolved. Immobilisation also induces limb insulin resistance in humans, which appears to be attributable to the reduction in muscle contraction per se. Again mechanistic insight is missing however, such that we do not know how muscle senses its “inactivity status” or whether the proposed drivers of muscle insulin resistance are simply arising as a consequence of immobilisation. An heightened inflammatory state is associated with major and rapid changes in muscle protein turnover and mass, and dampened insulin‐stimulated glucose disposal and oxidation in both rodents and humans. A limited amount of research has attempted to elucidate molecular regulators of muscle mass loss and insulin resistance during increased inflammatory burden, but rarely concurrently. Nevertheless, there is evidence that Akt (protein kinase B) signalling and FOXO transcription factors form part of a common signalling pathway in this scenario, such that molecular cross‐talk between atrophy and insulin signalling during heightened inflammation is believed to be possible (Fig. 1). To conclude, whilst muscle mass loss and insulin resistance are common end‐points of immobilisation and increased inflammatory burden, a lack of understanding of the mechanisms responsible for these traits exists such that a substantial gap in understanding of the pathophysiology in humans endures

The Regulatory Roles of PPARs in Skeletal Muscle Fuel Metabolism and Inflammation: Impact of PPAR Agonism on Muscle in Chronic Disease, Contraction and Sepsis

The peroxisome proliferator-activated receptor (PPAR) family of transcription factors has been demonstrated to play critical roles in regulating fuel selection, energy expenditure and inflammation in skeletal muscle and other tissues. Activation of PPARs, through endogenous fatty acids and fatty acid metabolites or synthetic compounds, has been demonstrated to have lipid-lowering and anti-diabetic actions. This review will aim to provide a comprehensive overview of the functions of PPARs in energy homeostasis, with a focus on the impacts of PPAR agonism on muscle metabolism and function. The dysregulation of energy homeostasis in skeletal muscle is a frequent underlying characteristic of inflammation-related conditions such as sepsis. However, the potential benefits of PPAR agonism on skeletal muscle protein and fuel metabolism under these conditions remains under-investigated and is an area of research opportunity. Thus, the effects of PPARγ agonism on muscle inflammation and protein and carbohydrate metabolism will be highlighted, particularly with its potential relevance in sepsis-related metabolic dysfunction. The impact of PPARδ agonism on muscle mitochondrial function, substrate metabolism and contractile function will also be described

Discrete element modelling of flexible fibre packing

This paper presents Discrete Element Model simulations of packing of non-cohesive flexible fibres in a cylindrical vessel. No interstitial fluid effects are modelled. Each fibre-particle is modelled as a series of connected sphero-cylinders. In an initial study each particle is modelled a single rigid sphero-cylinder; the method has been used before but this study considers higher aspect ratios up to 30. This posed some modelling challenges in terms of stability which were overcome by imposing limits on the particle angular velocity. The results show very good agreement with experimental data in the literature and more detailed in-house experiments for packing volume fraction. Model results on particle orientation are also shown. The model is developed to include flexibility by connecting sphero-cylinders as sub-elements to describe a particle. Some basic tests are shown for the joint model that connects the sub-elements. The simulation results show similar trends to the rigid particle results with increased packing fraction. The effects of number of sub-elements, joint properties and contact friction are examined. The model has the potential for predicting packing of fibrous particles and fibre bundles relevant to the preparation of preforms for the production of discontinuously-reinforced polymer, ceramic and metallic matrix composites

MultiFusion: Fusing Pre-Trained Models for Multi-Lingual, Multi-Modal Image Generation

The recent popularity of text-to-image diffusion models (DM) can largely be attributed to the intuitive interface they provide to users. The intended generation can be expressed in natural language, with the model producing faithful interpretations of text prompts. However, expressing complex or nuanced ideas in text alone can be difficult. To ease image generation, we propose MultiFusion that allows one to express complex and nuanced concepts with arbitrarily interleaved inputs of multiple modalities and languages. MutliFusion leverages pre-trained models and aligns them for integration into a cohesive system, thereby avoiding the need for extensive training from scratch. Our experimental results demonstrate the efficient transfer of capabilities from individual modules to the downstream model. Specifically, the fusion of all independent components allows the image generation module to utilize multilingual, interleaved multimodal inputs despite being trained solely on monomodal data in a single language

Flame spheroidisation of dense and porous Ca2Fe2O5 microspheres

Compositionally uniform magnetic Ca2Fe2O5 (srebrodolskite) microspheres created via a rapid, single-stage flame spheroidisation (FS) process using magnetite and carbonate based porogen (1:1 Fe3O4:CaCO3) feedstock powders, are described. Two types of Ca2Fe2O5 microsphere are produced: dense (35 - 80 µm), and porous (125 - 180 µm). Scanning electron microscopy (SEM) based techniques are used to image and quantify these. Complementary high-temperature X-ray diffraction (HT-XRD) measurements and thermogravimetric analysis (TGA) provide insights into the initial process of porogen feedstock decomposition, prior to the coalescence of molten droplets and spheroidisation, driven by surface tension. Evolution of CO2 gas (from porogen decomposition) is attributed to the development of interconnected porosity within the porous microspheres. This occurs during Ca2Fe2O5 rapid cooling and solidification. The facile FS-processing route provides a method for the rapid production of both dense and porous magnetic microspheres, with high levels of compositional uniformity and excellent opportunity for size control. The controllability of these factors make the FS production method useful for a range of healthcare, energy and environmental remediation applications

Human adaptation to immobilization: Novel insights of impacts on glucose disposal and fuel utilization

Background: Bed rest (BR) reduces whole-body insulin-stimulated glucose disposal (GD) and alters muscle fuel metabolism, but little is known about metabolic adaptation from acute to chronic BR nor the mechanisms involved, particularly when volunteers are maintained in energy balance. Methods: Healthy males (n=10, 24.0±1.3years), maintained in energy balance, underwent 3-day BR (acute BR). A second cohort matched for sex and body mass index (n=20, 34.2±1.8years) underwent 56-day BR (chronic BR). A hyperinsulinaemic euglycaemic clamp (60mU/m2/min) was performed to determine rates of whole-body insulin-stimulated GD before and after BR (normalized to lean body mass). Indirect calorimetry was performed before and during steady state of each clamp to calculate rates of whole-body fuel oxidation. Muscle biopsies were taken to determine muscle glycogen, metabolite and intramyocellular lipid (IMCL) contents, and the expression of 191 mRNA targets before and after BR. Two-way repeated measures analysis of variance was used to detect differences in endpoint measures. Results: Acute BR reduced insulin-mediated GD (Pre 11.5±0.7 vs. Post 9.3±0.6mg/kg/min, P<0.001), which was unchanged in magnitude following chronic BR (Pre 10.2±0.4 vs. Post 7.9±0.3mg/kg/min, P<0.05). This reduction in GD was paralleled by the elimination of the 35% increase in insulin-stimulated muscle glycogen storage following both acute and chronic BR. Acute BR had no impact on insulin-stimulated carbohydrate (CHO; Pre 3.69±0.39 vs. Post 4.34±0.22mg/kg/min) and lipid (Pre 1.13±0.14 vs. Post 0.59±0.11mg/kg/min) oxidation, but chronic BR reduced CHO oxidation (Pre 3.34±0.18 vs. Post 2.72±0.13mg/kg/min, P<0.05) and blunted the magnitude of insulin-mediated inhibition of lipid oxidation (Pre 0.60±0.07 vs. Post 0.85±0.06mg/kg/min, P<0.05). Neither acute nor chronic BR increased muscle IMCL content. Plentiful mRNA abundance changes were detected following acute BR, which waned following chronic BR and reflected changes in fuel oxidation and muscle glycogen storage at this time point. Conclusions: Acute BR suppressed insulin-stimulated GD and storage, but the extent of this suppression increased no further in chronic BR. However, insulin-mediated inhibition of fat oxidation after chronic BR was less than acute BR and was accompanied by blunted CHO oxidation. The juxtaposition of these responses shows that the regulation of GD and storage can be dissociated from substrate oxidation. Additionally, the shift in substrate oxidation after chronic BR was not explained by IMCL accumulation but reflected by muscle mRNA and pyruvate dehydrogenase kinase 4 protein abundance changes, pointing to lack of muscle contraction per se as the primary signal for muscle adaptation

Peroxisome proliferator-activated receptor γ agonism attenuates endotoxaemia-induced muscle protein loss and lactate accumulation in rats

The peroxisome proliferator-activated receptor γ (PPARγ) agonist rosiglitazone (Rosi) appears to provide protection against organ dysfunction during endotoxaemia. We examined the potential benefits of Rosi on skeletal muscle protein maintenance and carbohydrate metabolism during lipopolysaccharide (LPS)-induced endotoxaemia. Sprague-Dawley rats were fed either standard chow (control) or standard chow containing Rosi (8.5±0.1 mg.kg-1.day-1) for two weeks before and during 24 h continuous intravenous infusion of LPS (15 μg.kg-1.h-1) or saline. Rosi blunted LPS-induced increases in muscle tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) mRNA by 70% (P<0.05) and 64% (P<0.01), respectively. Furthermore, Rosi suppressed the LPS-induced reduction in phosphorylated AKT and phosphorylated Forkhead box O (FOXO) 1 protein, as well as the upregulation of muscle RING finger 1 (MuRF1; P<0.01) mRNA, and the LPS-induced increase in 20S proteasome activity (P<0.05). Accordingly, LPS reduced the muscle protein:DNA ratio (~30%, P<0.001), which Rosi offset. Increased muscle pyruvate dehydrogenase kinase 4 (PDK4) mRNA (P<0.001) and muscle lactate accumulation (P<0.001) during endotoxaemia were suppressed by Rosi. Thus, pre-treatment with Rosi reduced muscle cytokine accumulation and blunted muscle protein loss and lactate accumulation during endotoxaemia, and at least in part by reducing activation of molecular events known to increase muscle protein breakdown and mitochondrial pyruvate use

Expression of pH-Sensitive TRPC4 in Common Skin Tumors

TRPCs (transient receptor potential classical or cation channels) play a crucial role in tumor biology, especially in the Ca2+ homeostasis in cancer cells. TRPC4 is a pH-sensitive member of this family of proteins. As solid tumors exhibit an inversed pH-gradient with lowered extracellular and increased intracellular pH, both contributing to tumor progression, TRPC4 might be a signaling molecule in the altered tumor microenvironment. This is the first study to investigate the expression profiles of TRPC4 in common skin cancers such as basal cell carcinoma (BCC), squamous cell carcinoma (SCC), malignant melanoma (MM) and nevus cell nevi (NCN). We found that all SCCs, NCNs, and MMs show positive TRPC4-expression, while BCCs do only in about half of the analyzed samples. These data render TRPC4 an immunohistochemical marker to distinguish SCC and BCC, and this also gives rise to future studies investigating the role of TRPC4 in tumor progression, and especially metastasis as BCCs very rarely spread and are mostly negative for TRPC4