• BMB Reports
• /
• 제51권8호
• /
• pp.371-372
• /
• 2018

Cardiovascular disease such as atherosclerosis is caused by imbalanced lipid metabolism and represents a leading cause of death worldwide. Epidemiological studies show that patients with systemic autoimmune diseases exhibit a higher incidence of atherosclerosis. Conversely, hyperlipidemia has been known to accelerate the incidence of autoimmune diseases in humans and in animal models. However, there is a considerable gap in our understanding of how atherosclerosis impacts the development of the autoimmunity in humans, and vice versa. The atherosclerosis-related autoimmune diseases include psoriasis, rheumatoid arthritis, systemic lupus erythematosus (SLE) and diabetes mellitus. By using animal models of atherosclerosis and SLE, we have recently demonstrated that hyperlipidemia significantly accelerates the development of autoantibodies, by inducing autoimmune follicular helper T ($T_{FH}$) cells. Mechanistic studies have identified that hyperlipidemia induces IL-27 production in a TLR4-dependent manner, likely via downregulating LXR expression in dendritic cells. In this case, mice lacking IL-27 do not develop enhanced antibody responses. Thus it is noted that these findings propose a mechanistic insight responsible for the tight association between cardiovascular diseases and SLE in humans.

• Nuclear Engineering and Technology
• /
• 제41권7호
• /
• pp.953-968
• /
• 2009

It is important to accurately predict the temperature and density distributions in large stratified enclosures both for design optimization and accident analysis. Current reactor system analysis codes only provide lumped-volume based models that can give very approximate results. Previous scaling analysis has shown that stratified mixing processes in large stably stratified enclosures can be described using one-dimensional differential equations, with the vertical transport by jets modeled using integral techniques. This allows very large reductions in computational effort compared to three-dimensional CFD simulation. The BMIX++ (Berkeley mechanistic MIXing code in C++) code was developed to implement such ideas. This paper summarizes major models for the BMIX++ code, presents the two-plume mixing experiment simulation as one validation example, and describes the codes' application to the liquid salt buffer pool system in the AHTR (Advanced High Temperature Reactor) design. Three design options have been simulated and they exhibit significantly different stratification patterns. One of design options shows the mildest thermal stratification and is identified as the best design option. This application shows that the BMIX++ code has capability to provide the reactor designers with insights to understand complex mixing behavior with mechanistic methods. Similar analysis is possible for liquid-metal cooled reactors.

• Journal of Korean Neurosurgical Society
• /
• 제62권3호
• /
• pp.272-287
• /
• 2019

The mechanistic target of rapamycin (mTOR) pathway coordinates the metabolic activity of eukaryotic cells through environmental signals, including nutrients, energy, growth factors, and oxygen. In the nervous system, the mTOR pathway regulates fundamental biological processes associated with neural development and neurodegeneration. Intriguingly, genes that constitute the mTOR pathway have been found to be germline and somatic mutation from patients with various epileptic disorders. Hyperactivation of the mTOR pathway due to said mutations has garnered increasing attention as culprits of these conditions : somatic mutations, in particular, in epileptic foci have recently been identified as a major genetic cause of intractable focal epilepsy, such as focal cortical dysplasia. Meanwhile, epilepsy models with aberrant activation of the mTOR pathway have helped elucidate the role of the mTOR pathway in epileptogenesis, and evidence from epilepsy models of human mutations recapitulating the features of epileptic patients has indicated that mTOR inhibitors may be of use in treating epilepsy associated with mutations in mTOR pathway genes. Here, we review recent advances in the molecular and genetic understanding of mTOR signaling in epileptic disorders. In particular, we focus on the development of and limitations to therapies targeting the mTOR pathway to treat epileptic seizures. We also discuss future perspectives on mTOR inhibition therapies and special diagnostic methods for intractable epilepsies caused by brain somatic mutations.

• 한국물환경학회지
• /
• 제36권6호
• /
• pp.621-635
• /
• 2020

Water quality models are scientific tools that simulate and interpret the relationship between physical, chemical and biological reactions to external pollutant loads in water systems. They are actively used as a key technology in environmental water management. With recent advances in computational power, water quality modeling technology has evolved into a coupled three-dimensional modeling of hydrodynamics, water quality, and ecological inputs. However, there is uncertainty in the simulated results due to the increasing model complexity, knowledge gaps in simulating complex aquatic ecosystem, and the distrust of stakeholders due to nontransparent modeling processes. These issues have become difficult obstacles for the practical use of water quality models in the water management decision process. The objectives of this paper were to review the theoretical background, needs, and development status of water quality modeling technology. Additionally, we present the potential future directions of water quality modeling technology as a scientific tool for national environmental water management. The main development directions can be summarized as follows: quantification of parameter sensitivities and model uncertainty, acquisition and use of high frequency and high resolution data based on IoT sensor technology, conjunctive use of mechanistic models and data-driven models, and securing transparency in the water quality modeling process. These advances in the field of water quality modeling warrant joint research with modeling experts, statisticians, and ecologists, combined with active communication between policy makers and stakeholders.

• BMB Reports
• /
• 제52권1호
• /
• pp.70-85
• /
• 2019

Reduction of insulin/insulin-like growth factor 1 (IGF1) signaling (IIS) extends the lifespan of various species. So far, several longevity mouse models have been developed containing mutations related to growth signaling deficiency by targeting growth hormone (GH), IGF1, IGF1 receptor, insulin receptor, and insulin receptor substrate. In addition, p70 ribosomal protein S6 kinase 1 (S6K1) knockout leads to lifespan extension. S6K1 encodes an important kinase in the regulation of cell growth. S6K1 is regulated by mechanistic target of rapamycin (mTOR) complex 1. The v-myc myelocytomatosis viral oncogene homolog (MYC)-deficient mice also exhibits a longevity phenotype. The gene expression profiles of these mice models have been measured to identify their longevity mechanisms. Here, we summarize our knowledge of long-lived mouse models related to growth and discuss phenotypic characteristics, including organ-specific gene expression patterns.

• BMB Reports
• /
• 제56권1호
• /
• pp.43-48
• /
• 2023

Pre-clinical models are critical in gaining mechanistic and biological insights into disease progression. Recently, patient-derived organoid models have been developed to facilitate our understanding of disease development and to improve the discovery of therapeutic options by faithfully recapitulating in vivo tissues or organs. As technological developments of organoid models are rapidly growing, computational methods are gaining attention in organoid researchers to improve the ability to systematically analyze experimental results. In this review, we summarize the recent advances in organoid models to recapitulate human diseases and computational advancements to analyze experimental results from organoids.

• Korean Membrane Journal
• /
• 제7권1호
• /
• pp.1-18
• /
• 2005

The permeate flux decline due to membrane fouling can be addressed using a variety of theoretical stand-points. Judicious selection of an appropriate theory is a key toward successful prediction of the permeate flux. The essential criterion f3r such a decision appears to be a detailed characterization of the feed solution and membrane properties. Modem theories are capable of accurately predicting several properties of colloidal systems that are important in membrane separation processes from fundamental information pertaining to the particle size, charge, and solution ionic strength. Based on such information, it is relatively straight-forward to determine the properties of the concentrated colloidal dispersion in a polarized layer or the cake layer properties. Incorporation of such information in the framework of the standard theories of membrane filtration, namely, the convective diffusion equation coupled with an appropriate permeate transport model, can lead to reasonably accurate prediction of the permeate flux due to colloidal fouling. The schematic of the essential approach has been delineated in Figure 5. The modern approaches based on appropriate cell models appear to predict the permeate flux behavior in crossflow membrane filtration processes quite accurately without invoking novel theoretical descriptions of particle back transport mechanisms or depending on adjust-able parameters. Such agreements have been observed for a wide range of particle size ranging from small proteins like BSA (diameter ${\~}$6 nm) to latex suspensions (diameter ${\~}1\;{\mu}m$). There we, however, several areas that need further exploration. Some of these include: 1) A clear mechanistic description of the cake formation mechanisms that clearly identifies the disorder to order transition point in different colloidal systems. 2) Determining the structure of a cake layer based on the interparticle and hydrodynamic interactions instead of assuming a fixed geometrical structure on the basis of cell models. 3) Performing well controlled experiments where the cake deposition mechanism can be observed for small colloidal particles (< $1\;{\mu}m$). 4) A clear mechanistic description of the critical operating conditions (for instance, critical pressure) which can minimize the propensity of colloidal membrane fluting. 5) Developing theoretical approaches to account for polydisperse systems that can render the models capable of handing realistic feed solutions typically encountered in diverse applications of membrane filtration.

• BMB Reports
• /
• 제56권12호
• /
• pp.625-632
• /
• 2023

Nonsense-mediated mRNA decay (NMD) is both a quality control mechanism and a gene regulation pathway. It has been studied for more than 30 years, with an accumulation of many mechanistic details that have often led to debate and hence to different models of NMD activation, particularly in higher eukaryotes. Two models seem to be opposed, since the first requires intervention of the exon junction complex (EJC) to recruit NMD factors downstream of the premature termination codon (PTC), whereas the second involves an EJC-independent mechanism in which NMD factors concentrate in the 3'UTR to initiate NMD in the presence of a PTC. In this review we describe both models, giving recent molecular details and providing experimental arguments supporting one or the other model. In the end it is certainly possible to imagine that these two mechanisms co-exist, rather than viewing them as mutually exclusive.

• 대한기계학회:학술대회논문집
• /
• 대한기계학회 2007년도 춘계학술대회A
• /
• pp.1522-1525
• /
• 2007

Circular milling operations are used to enlarge die and cylinder bores, and machine airframe pockets. In this case, cutting force varies as cutting tool position relative to workpiece. This paper presents a mechanistic model of geometric uncut chip thickness by predicting time varying cutter-part intersection as the cutter travels along the circular path. Compared with experimental results, the suggested cutting force model shows a good agreement.

• Journal of Biosystems Engineering
• /
• 제37권4호
• /
• pp.258-264
• /
• 2012

Purpose: This review aims at introducing 3 modeling approaches classified into 3 categories based on the purpose (estimation or prediction), structure (linear or non-linear) and phase (steady-state or dynamic-state); 1) statistical approaches, 2) kinetic modeling and 3) mechanistic modeling. We hope that this review can be a useful guide in the model-based approach of calcium metabolism as well as illustrates an application of engineering tools in studying biosystems. Background: The meaning of biosystems has been expanded, including agricultural/food system as well as biological systems like genes, cells and metabolisms. This expansion has required a useful tool for assessing the biosystems and modeling has arisen as a method that satisfies the current inquiry. To suit for the flow of the era, examining the system which is a little bit far from the traditional biosystems may be interesting issue, which can enlarge our insights and provide new ideas for prospective biosystem-researches. Herein, calcium metabolic models reviewed as an example of application of modeling approaches into the biosystems. Review: Calcium is an essential nutrient widely involved in animal and human metabolism including bone mineralization and signaling pathways. For this reason, the calcium metabolic system has been studied in various research fields of academia and industries. To study calcium metabolism, model-based system analyses have been utilized according to the purpose, subject characteristics, metabolic sites of interest, and experimental design. Either individual metabolic pathways or a whole homeostasis has been modeled in a number of studies.