Identification of joint parameters using FRF based decoupling

Structural and mechanical systems are assembled from smaller components using mechanical joints. The mechanical properties of the joints must be modeled in order to perform subsequent design and analysis of the structure or mechanical system. This study provides an analytical method of determining the parameters that describe the behavior of the joints using frequency response function (FRF) data that is measured at joint nodes. The variation in FRFs is derived by utilizing the consistent response conditions at the same joint nodes of the assembly system and the portioned subsystems. The variation reflects the mechanical properties of the joint and is utilized to extract the joint parameters. The validity of the proposed method is illustrated in two numerical applications

Mesenchymal Stem Cell-Derived Extracellular Vesicle Therapy for Stroke: Challenges and Progress

Stroke is the leading cause of physical disability among adults. Stem cells such as mesenchymal stem cells (MSCs) secrete a variety of bioactive substances, including trophic factors and extracellular vesicles (EVs), into the injured brain, which may be associated with enhanced neurogenesis, angiogenesis, and neuroprotection. EVs are circular membrane fragments (30 nm−1 μm) that are shed from the cell surface and harbor proteins, microRNAs, etc. Since 2013 when it was first reported that intravenous application of MSC-derived EVs in a stroke rat model improved neurological outcomes and increased angiogenesis and neurogenesis, many preclinical studies have shown that stem cell-derived EVs can be used in stroke therapy, as an alternative approach to stem cell infusion. Although scientific research regarding MSC-derived EV therapeutics is still at an early stage, research is rapidly increasing and is demonstrating a promising approach for patients with severe stroke. MSC therapies have already been tested in preclinical studies and clinical trials, and EV-mediated therapy has unique advantages over cell therapies in stroke patients, in terms of biodistribution (overcoming the first pass effect and crossing the blood-brain-barrier), cell-free paradigm (avoidance of cell-related problems such as tumor formation and infarcts caused by vascular occlusion), whilst offering an off-the-shelf approach for acute ischemic stroke. Recently, advances have been made in the understanding of the function and biogenesis of EVs and EVs therapeutics for various diseases. This review presents the most recent advances in MSC-derived EV therapy for stroke, focusing on the application of this strategy for stroke patients

Mesenchymal Stem Cell-Extracellular Vesicle Therapy for Stroke: Scalable Production and Imaging Biomarker Studies

A major clinical hurdle to translate MSC-derived extracellular vesicles (EVs) is the lack of a method to scale-up the production of EVs with customized therapeutic properties. In this study, we tested whether EV production by a scalable 3D-bioprocessing method is feasible and improves neuroplasticity in animal models of stroke using MRI study. MSCs were cultured in a 3D-spheroid using a micro-patterned well. The EVs were isolated with filter and tangential flow filtration and characterized using electron microscopy, nanoparticle tracking analysis, and small RNA sequencing. Compared to conventional 2D culture, the production-reproduction of EVs (the number/size of particles and EV purity) obtained from 3D platform were more consistent among different lots from the same donor and among different donors. Several microRNAs with molecular functions associated with neurogenesis were upregulated in EVs obtained from 3D platform. EVs induced both neurogenesis and neuritogenesis via microRNAs (especially, miR-27a-3p and miR-132-3p)-mediated actions. EV therapy improved functional recovery on behavioral tests and reduced infarct volume on MRI in stroke models. The dose of MSC-EVs of 1/30 cell dose had similar therapeutic effects. In addition, the EV group had better anatomical and functional connectivity on diffusion tensor imaging and resting-state functional MRI in a mouse stroke model. This study shows that clinical-scale MSC-EV therapeutics are feasible, cost-effective, and improve functional recovery following experimental stroke, with a likely contribution from enhanced neurogenesis and neuroplasticity

Upper Gastrointestinal Tract Foreign Bodies

Foreign body ingestion, a common emergency encountered in clinical practice, is a potentially serious condition. Most foreign bodies in the gastrointestinal tract pass spontaneously. However, objects that are relatively long or large may lodge in the upper gastrointestinal tract, potentially causing perforation, bleeding, and obstruction. This literature review summarizes the natural history and clinical aspects of these types of foreign bodies in adults as well as the various methods for their removal. Endoscopic removal is a relatively safe and effective procedure for removing these types of foreign bodies. The development of endoscopic techniques and devices has resulted in their widespread use, with good results, as the primary treatment

The ancient phosphatidylinositol 3-kinase signaling system is a master regulator of energy and carbon metabolism in algae

Algae undergo a complete metabolic transformation under stress by arresting cell growth, inducing autophagy and hyperaccumulating biofuel precursors such as triacylglycerols and starch. However, the regulatory mechanisms behind this stress-induced transformation are still unclear. Here, we use biochemical, mutational, and “omics” approaches to demonstrate that PI3K signaling mediates the homeostasis of energy molecules and influences carbon metabolism in algae. In Chlamydomonas reinhardtii, the inhibition and knockdown (KD) of algal class III PI3K led to significantly decreased cell growth, altered cell morphology, and higher lipid and starch contents. Lipid profiling of wild-type and PI3K KD lines showed significantly reduced membrane lipid breakdown under nitrogen starvation (-N) in the KD. RNA-seq and network analyses showed that under -N conditions, the KD line carried out lipogenesis rather than lipid hydrolysis by initiating de novo fatty acid biosynthesis, which was supported by tricarboxylic acid cycle down-regulation and via acetyl-CoA synthesis from glycolysis. Remarkably, autophagic responses did not have primacy over inositide signaling in algae, unlike in mammals and vascular plants. The mutant displayed a fundamental shift in intracellular energy flux, analogous to that in tumor cells. The high free fatty acid levels and reduced mitochondrial ATP generation led to decreased cell viability. These results indicate that the PI3K signal transduction pathway is the metabolic gatekeeper restraining biofuel yields, thus maintaining fitness and viability under stress in algae. This study demonstrates the existence of homeostasis between starch and lipid synthesis controlled by lipid signaling in algae and expands our understanding of such processes, with biotechnological and evolutionary implications.Ministry of Science, ICT and Future Planning 2015M3A6A2065697Ministry of Oceans and Fisheries 2015018