Structural Components Research Articles

12347 Cholesterol Biosynthesis Inhibitor Ro 48-8071 Suppresses Growth Of Triple-negative Breast Cancer Cells By Inducing Apoptosis And Suppressing Angiogenesis

Abstract Disclosure: Y. Liang: None. S.M. Hyder: None. Triple-negative breast cancers (TNBC) lack ER, PR and Her2neu, proteins that are commonly targeted in breast cancer therapies. Women who suffer from TNBC have limited treatment options and are administered toxic chemotherapeutic agents. They have poor prognosis due to the emergence of drug-resistant cells that lead to tumor metastasis. New non-toxic therapeutic strategies to control TNBC progression, and prevent metastasis are urgently needed. Cholesterol is an essential structural and functional component of cell membranes necessary for tumor growth and progression. Therefore, inhibiting cholesterol production is an attractive therapeutic strategy since tumor cells grow rapidly, and need a greater supply of cholesterol. We targeted oxidosqualene cyclase (OSC), an enzyme that occurs downstream of HMGCoA-reductase in the cholesterol biosynthetic pathway, to disrupt tumor growth. RO 48-8071 (4′-[6-(allylmethylamino)hexyloxy]-4-bromo-2′-fluorobenzophenone fumarate) (RO), has emerged as a useful chemotherapeutic agent for treating several forms of primary tumors but its effect on TNBC is not known. Pharmacological doses of RO potently reduced the viability of both MDA-MB-231 and BT20 TNBC cells in a dose dependent manner (1-50 μM). IC50 values for loss of cell viability was approximately 10 μM for both cell lines following 48 h exposure to RO. Doses close to the IC50 for OSC (1-10 nM) also reduced cell viability following exposure of TNBC cells to RO for a week. Importantly, RO had no effect on the viability of normal human mammary cells. FACS analysis revealed that RO dose-dependently induced apoptosis of TNBC cell lines in vitro. In vivo, administration of 5-10 mg/kg RO to mice with BT-20 TNBC cell-derived xenografts (100 mm3) inhibited tumor growth with no apparent toxicity. Immunohistochemical analysis of tumor tissues at the end of treatment showed that RO increased TUNEL expression, suggesting that the in vivo effects of RO were also exerted through mechanisms affecting apoptosis. Furthermore, IHC of tumor sections showed that RO also reduced levels of the angiogenic markers VEGF and CD-31 (blood vessels) in vivo, indicating that suppression of angiogenesis is also part of the mechanism through which RO exerts its anti-tumor effects. We conclude that RO is a potent inhibitor of TNBC and that its anti-tumor effects involve mechanisms that induce apoptosis and suppress angiogenesis. Presentation: 6/2/2024

7076 Inhibiting Oxidosqualene Cyclase, an Enzyme in the Cholesterol Biosynthetic Pathway, Suppresses Lung Metastasis of Triple-negative Breast Cancer Cells

Abstract Disclosure: Y. Liang: None. S.M. Hyder: None. Triple-negative breast cancers (TNBC) lack ER, PR and Her2neu proteins that are commonly targeted in breast cancer therapies. As a consequence, women who suffer from TNBC have poor prognosis and limited treatment options, and are usually administered toxic, non-specific chemotherapeutic agents. Drug-resistance almost always occurs, leading to tumor metastasis, the main cause of patient death. New non-toxic therapeutic strategies to control metastasis of TNBC are urgently needed. Cholesterol is an essential structural and functional component of cell membranes that is necessary for the growth of both primary tumors and metastatic colonies that reside in distant organs. Therefore, inhibiting cholesterol production is an attractive therapeutic strategy. Treatment with statins, a class of cholesterol biosynthesis inhibitors that target HMGCoA-reductase, is associated with certain undesirable side effects; consequently, we targeted oxidosqualene cyclase (OSC), an enzyme that occurs downstream of HMGCoA-reductase in the cholesterol biosynthetic pathway, to disrupt tumor metastasis. Potent small molecule inhibitors of OSC have been identified. RO 48-8071 (4′-[6-(allylmethylamino)hexyloxy]-4-bromo-2′-fluorobenzophenone fumarate) (RO), has emerged as a useful chemotherapeutic agent for treating several forms of primary tumors. We developed a mouse model for studying lung metastasis using a MDA-MB-231 variant (LM2) TNBC cell line obtained from Dr. Massagué (Memorial Sloan-Kettering Cancer Center). These are aggressive cells, and injection of only 2 X 10[5] cells produces detectable lung metastatic colonies in approximately 4-6 weeks. We inoculated female nu/nu mice, 5-6 weeks old, with 2 X 10[5] MDA-MB-231/LM2 cells in 0.1 ml DMEM/F12 medium without serum via tail vein. Five days after tumor cell inoculation animals received 20 mg/kg (n=6), 40 mg/kg (n=7) RO (ip) or vehicle alone (n=7) every other day for two weeks. Animals were then sacrificed, and both lungs harvested and immediately fixed in Bouin’s fixative. Metastatic colonies on the lung surface were identified and counted under a dissecting microscope. Our study showed that RO effectively reduced lung metastasis without affecting animal weight. Compared with 56 + 7 colonies (Mean ± SEM) in controls given vehicle alone, RO significantly reduced lung metastatic colonies to 28 ± 5 in animals exposed to 20 mg/kg and 6 ± 1 in 40 mg/kg treated animals (p<0.05, ANOVA). Reduction in number of colonies in 40 mg/kg group was also significantly different from colonies counted in 20 mg/kg treated animals. Our study is the first to demonstrate that disruption of cholesterol biosynthesis in a model of human TNBC leads to reduced metastasis in lungs. Further studies will determine mechanisms through which RO suppresses TNBC metastasis to the lungs. Supported by Zalk Missouri Professor Endowment Funds. Presentation: 6/3/2024

Genome-Wide Characterization and Development of Simple Sequence Repeat Markers for Molecular Diversity Analyses in Yellowhorn (Xanthoceras sorbifolium Bunge).

Yellowhorn (Xanthoceras sorbifolium Bunge) is a valuable ornamental, medicinal, and woody oilseed species that is indigenous to China. The breeding improvement of yellowhorn has been hindered by a lack of suitable markers and sufficient information regarding the molecular diversity of this species. In this study, we conducted a comprehensive analysis of the yellowhorn genome to characterize the simple sequence repeat (SSR) loci. A total of 4,007,201 SSRs were successfully identified. Among these markers, mono-nucleotide SSRs were most abundant in the genome, while the tri-nucleotide SSRs accounted for the highest proportion in coding sequences. The GO and KEGG function enrichment analysis revealed that most SSR loci in coding sequences were associated with potential biological functions. Additionally, we used 30 pairs of primers to amplify SSR markers to gain a better understanding of the genetic variation in yellowhorn germplasms. The average values of observed heterozygosity and polymorphism information content were 0.625 and 0.517, respectively. Population structure, phylogeny and principal component analyses identified two distinct subclusters. Furthermore, yellowhorn germplasms with the same geographical distribution tended to group together. Moreover, a total of 26 yellowhorn core collections, which accounted for approximately 14.94% of the total yellowhorn germplasms, effectively represented the genetic diversity of all original germplasms. Our findings not only unveiled the genetic diversity and population structure of yellowhorn germplasms but also investigated the yellowhorn core collection, which will serve as a strong basis for yellowhorn management and genetic improvement.

Finite Element Analysis of Leaf Spring Fabricated Via Fused Deposition Modeling (FDM)

An introduction to fused deposition modeling, or 3D printing technology, will be given in this chapter. The basic idea of additive manufacturing and its underlying scientific theory will be presented at the outset of this chapter as a novel and emerging industrial technology. The parameters used to predict the melt deposition of polymers and their basic interactions with the structural component qualities will also be covered in this chapter. The chapter will provide a brief description of the quality features of FDM products concerning the process parameters. The additive manufacturing process will involve layering material to produce three-dimensional (3D) parts using a class of manufacturing technologies known as additive manufacturing (AM). This substance will include composite, metal, polymer, or concrete materials. A manufacturing process will need to have the following three main elements to be designated as an AM technique: making visual 3D models with computers and computer-aided design (CAD), utilizing a variety of CAD tools such as AutoCAD, SolidWorks, CATIA, and others. Some of these programs will be either closed- source or open-source. For additive manufacturing to be successful, an engineer or artist working with several computers will need to be proficient in using multiple operating systems. With these CAD tools and user experiences, it will be possible to produce a variety of complex 3D product models. The amount of material a 3D printer will take and the time it will require will be important factors influencing the additive manufacturing process.

The current state of Kazakhstan financial system: theoretical and practical aspects

Against the backdrop of the global challenges of the current economic situation, the financial system of the Republic of Kazakhstan is becoming an important tool for ensuring the sustainable development of the national economy, acting as a factor in stimulating its growth. This study was undertaken to analyze the state of the national financial system based on theoretical principles that determine its structure and significance in financial development. The financial system of Kazakhstan mainly solves the problem of providing the national economy with financial resources and promoting economic growth. At the same time, an analysis of the state of the financial system, based on theoretical principles regarding its significance and indicators of the country’s financial development, allows us to identify key problems and directions for its further development. In the context of ensuring economic growth, the role of the financial system is considered from the point of view of indicators characterizing the degree of its development. The study identifies structural components of the financial system that correlate with the Financial Development Index provided by the International Monetary Fund (IMF). This approach allows us to assess the current state of Kazakhstan's financial system, identify problems, and identify areas for further improvement. The study's results highlight the need to improve the efficiency of financial institutions, emphasizing the role of market mechanisms in the formation and distribution of the country's financial resources. Kazakhstan's financial system needs further reforms to achieve sustainable economic development.

A Comparison of Free and Mapped Meshes for Static Structural Analysis

Abstract This study addresses the challenge faced by Finite Element Analysts when choosing between free and mapped meshes, especially in terms of convergence stability and solution accuracy. The investigation focuses on 3D solid models under static structural loading, analyzed using Ansys® and MSC Patran®. Both free and mapped mesh types, employing equivalent 3D solid elements, are used to assess an aircraft structural component under design load conditions, with fixed boundaries. For free meshes, Tet10 elements in Patran (equivalent to Solid 72 in Ansys) are used, whereas for mapped meshes, CPENTA / CHEXA elements in Patran (equivalent to Wed6 / Hex8 in Ansys) are employed. Mesh convergence studies ensure that discretization does not affect the numerical solution. Notably, a significant stress increase is observed with successive refinement of free meshes, while mapped meshes achieve mesh independence at coarser refinement levels. Comparison of fringe plots indicates the same location for maximum deformation and equivalent stress in both free and mapped mesh models. The findings demonstrate that free meshes tend to underpredict maximum deformation and equivalent stress compared to mapped meshes, with both meshes showing deformation and stress at consistent locations. The findings underscore the importance of carefully choosing the appropriate mesh type, particularly when analyzing critical structural components, to ensure reliability and accuracy in FEA simulations.

Influence of randomly placed resonant aggregates on the attenuation properties of metaconcrete: A numerical study

Concrete is a key material for many structural components in engineering, but its acoustic performance remains under discussion. Hence, the potential of the so-called metaconcrete has gained attention in research, mainly due to its capability to control vibrations and sound transmission when resonant aggregates are embedded in the concrete. These resonant aggregates are designed to have resonant frequencies regarding frequency bands of interest, so the interaction with the incident sound waves is attenuated within those frequencies. While available research has focused on the characterization of metaconcrete with a periodic arrangement of resonant aggregates, there is a gap regarding how their random allocation affects the characterization of metaconcrete. This study focuses on the numerical analysis of metaconcrete and the influence of randomly placed resonant aggregates on its attenuation properties. The numerical approach concentrates on the aggregate's material composition, location and volume fraction within the concrete to identify configurations that exhibit great wave attenuation. The results have shown that the attenuation effect is substantially advantageous when using a multi-frequency configuration for aggregates within the metaconcrete. Additionally, the random embedding of resonant aggregates offers a practical solution for their application in concrete structures.

Development and analysis of Fe-doped ZnO nanoparticle-infused sisal fiber reinforced hybrid polymer composites for high-performance sound absorption and thermal insulation applications

In the current study, sisal fiber-reinforced hybrid composites have been developed by integrating a bidirectional mat with a blend of epoxy using Fe-doped ZnO (IDZO) nanoparticles at concentrations of 0.2, 0.4, 0.6, and 0.8 wt%. Hand-lay-up approach was used to create the composites. The composites were characterized through a comprehensive analysis of their density, water absorption, elasticity, thermogravimetric analysis, mechanical resistance, thermal conductivity, microhardness, and propagation of sound properties, including sound absorption coefficients and sound transmission class ratings. As filler loading increased, the bio-composite sample’s hardness increased under the density and void volume fraction values, with 0.8 wt% composite sample showing the superior micro-hardness. A positive correlation was observed between the ZnO nanoparticle weight percentage and thermal conductivity, with improve nanoparticle content leading to improved thermal performance. Composites containing 0.4 wt percent nanoparticles showed superior tensile strength (66.8–84.16 MPa), flexural strength (97.69–120.02 MPa) and flexural modulus (3.56–7.68 GPa). It has been observed that the weight percentage of IDZO filler greatly influences the sound absorption efficiency of the current composites. These findings highlight the promising potential of these novel biocomposites in advanced engineering applications, emphasizing their usefulness in demanding environments with biodegradability and high-performance thermal, mechanical, and acoustic properties. Based on the sound transmission class ratings, the sisal fiber biocomposites have been regarded as great adoptions for use as sound-absorbing materials such as wall partitions, doors, enclosures, and structural components, thermal insulation systems, and electrical insulation.

3D bioprinting of an intervertebral disc tissue analogue with a highly aligned annulus fibrosus via suspended layer additive manufacture.

Intervertebral disc (IVD) function is achieved through integration of its two component regions: the nucleus pulposus (NP) and the annulus fibrosus (AF). The NP is soft (0.3-5 kPa), gelatinous and populated by spherical NP cells in a polysaccharide-rich extracellular matrix (ECM). The AF is much stiffer (~100 kPa) and contains layers of elongated AF cells in an aligned, fibrous ECM. Degeneration of the disc is a common problem with age being a major risk factor. Progression of IVD degeneration leads to chronic pain and can result in permanent disability. The development of therapeutic solutions for IVD degeneration is impaired by a lack of in vitro models of the disc that are capable of replicating the fundamental structure and biology of the tissue. This study aims to investigate if a newly developed suspended hydrogel bioprinting system (termed SLAM) could be employed to fabricate IVD analogues with integrated structural and compositional features similar to native tissue. Bioprinted IVD analogues were fabricated to recapitulate structural, morphological and biological components present in the native tissue. The constructs replicated key structural components of native tissue with the presence of a central, polysaccharide-rich NP surrounded by organised, aligned collagen fibres in the AF. Cell tracking, actin and matrix staining demonstrated that embedded NP and AF cells exhibited morphologies and phenotypes analogous to what is observed in vivo with elongated, aligned AF cells and spherical NP cells that deposited HA into the surrounding environment. Critically, it was also observed that the NP and AF regions contained a defined cellular and material interface and segregated regions of the two cell types, thus mimicking the highly regulated structure of the IVD.

Macroanatomy, Histomorphometry, and Androgen Receptor Expression in the Epididymis of Kacang Goats Aged 4, 8, and 12 Months

The epididymis is a crucial component of the goat's reproductive structure. The epididymis is responsible for the transportation, concentration, and maturation of sperm. This study aimed to examine the differences in the structure of macro and microanatomy, tissue composition, and the existence of androgen receptors in the epididymis of Kacang goats aged 4, 8, and 12 months. The assessment of macroscopic organ growth was done immediately after sampling, whereas microscopic measurements were carried out following histological preparations using hematoxylin-eosin (HE) and immunohistochemical (IHC) procedures. The results on the macroscopic anatomy of the epididymis indicated a significant association between age with the width of the caput dexter and sinister and the circumference of the right cauda. However, no significant relationship was found between age with the corpus length and the left cauda's circumference. Significant variations were observed in the diameter and concentration of the agglutinated spermatozoa in the lumen during histomorphometry of the epididymis in three age groups of Kacang goats. There were no statistically significant variations in the expression of androgen receptors among the three age groups. This study showed that the correlation coefficient test reveals a positive relationship between age and the caput width and corpus length dimensions, indicating that these measurements tend to grow as age increases. On the other hand, the diameter of the agglutinated spermatozoa in the epididymal lumen exhibits significant variations between the ages of 4 months, with the ages of 8 months and 12 months, suggesting that the sperm becomes fully matured by the age of 8 months.

A hybrid construct with tailored 3D structure for directing pre-vascularization in engineered tissues

Hybrid 3D constructs combining different structural components afford unique opportunities to engineer functional tissues. Creating functional microvascular networks within these constructs is crucial for promoting integration with host vessels and ensuring successful engraftment. Here, we present a hybrid 3D system in which poly (ethylene oxide terephthalate)/poly (butylene terephthalate) fibrous scaffolds are combined with pectin hydrogels to provide internal topography and guide the formation of microvascular beds. The sequence/method of seeding human endothelial cells (EC) and mesenchymal stromal cells (MSC) into the system had a significant impact on microvessel formation. Optimal results were obtained when EC were directly seeded onto the fibrous scaffold, followed by the addition of hydrogel-embedded MSC. This approach facilitated the development of highly oriented microvascular networks along the fibers. These networks were lumenized, supported by a basement membrane, and stabilized by pericyte-like cells, persisting for at least 28 days in vitro. Furthermore, culture under pro-angiogenic and osteoinductive conditions induced MSC osteogenic differentiation without impairing microvessel formation. Upon subcutaneous implantation in mice, the pre-vascularized constructs were infiltrated by host vessels, and human microvessels were still present after 2 weeks. Overall, the proposed hybrid 3D system, combined with an optimized cell-seeding protocol, offers an effective approach for directing the formation of robust and geometrically oriented microvessels, making it promising for tissue engineering applications.

Self-identified Race and Ethnicity and How this is Perceived: Associations with the Physical and Mental Health of Incarcerated Individuals.

The singular focus on self-identified race and ethnicity in health disparities research may not fully convey the individual and structural components of experiencing race in society, or in a racialized context such as prison. Processes of racialization create boundaries between incarcerated individuals and regulate their daily interactions and access to resources, with possible effects on well-being. However, the relationship between perceived race and health has not been examined within the imprisoned population. We used data from the 2016 Survey of Prison Inmates (n = 23,010) to assess how self-identified race, perceived race, and the discordance between racial self-identification and perception were associated with the physical (number of chronic conditions) and mental health (psychological distress) of American Indian and Alaska Native, Asian, Black, Latino, White, and multiracial incarcerated individuals. Reported perception as Latino was associated with better mental and physical health relative to perception as White. Perceived Latino identity was more strongly associated with physical and mental health than a Latino self-identity. Reported perception as Black was associated with less psychological distress than perception as White, but this relationship dissipated after accounting for self-identified race. In contrast, perceived and self-identified multiracial incarcerated individuals reported worse health than their White counterparts. Having a discordant (vs. concordant) racial identity was associated with worse physical and mental health among imprisoned persons regardless of race. The use of a single, unidimensional measure of race and ethnicity in health disparities research does not fully reveal racialization's influence on health, specifically for those experiencing incarceration.

Possibilities of the electronic educational environment in increasing the efficiency of the military education system

The presented article examines innovative ways to develop military education in the context of digitalization and digital transformation. Specific technical solutions have been proposed to increase the efficiency of future officers' mastery of military-technical specialties. The pedagogical experience of using the designed library of 3D-models of military hand-held small arms in the officer training system is summarized and presented. This library is described in detail and its place in the structure of the electronic educational environment of a military educational organization of higher education of a law enforcement agency is highlighted. The logical sequence of studying a sample of military hand-held small arms in the system technical description – 3D-model – real sample is revealed. The positive aspects of using the developed library in the preparation system are highlighted. Directions for further development of the structural component of the electronic educational environment of a military educational organization are proposed.

Structural and non-structural fragility curves for low-rise mainshock-damaged buildings subjected to aftershocks

The seismic response of mainshock-damaged buildings under aftershocks is an important topic in terms of the lateral response of damaged structures. The majority of current seismic design standards just consider a single earthquake (mainshock/design earthquake) and they don’t take into account the influence of aftershocks on the seismic design process. The aftershocks could have significant effects on the seismic response of mainshock-damaged structures. This situation was reported in some of the previous earthquake events in which the aftershocks caused additional damage to the structures. In this study, the fragility curves for structural and non-structural Drift-Sensitive Components (DSCs) and Acceleration-Sensitive Components (ASCs) of two low-rise mainshock-damaged moment resisting steel and reinforcement concrete buildings under the effect of aftershocks with different intensities were presented. The intensity of the mainshocks was adjusted until the intact buildings experienced three levels of damage states including slight, moderate and extensive damage states. After that, the fragility curve of the structural and non-structural components of the mainshock-damaged buildings under the effect of aftershocks was evaluated by the Incremental Dynamic Analysis (IDA). The results show that the effect of aftershocks on the probability of damage to structural and non-structural components of mainshock-damaged structures is related to the level of the initial damage. For slightly and moderately mainshock-damaged buildings, the probability of exceedance of the damage under aftershocks is relatively similar to the intact buildings, however, the aftershocks significantly increase the probability of damage to the extensively mainshock-damaged buildings. Although extensive initial damage causes a significant increase in the probability of damage to non-structural DSCs, the damage probability of non-structural ASCs remains relatively as similar to intact buildings. Regarding the HAZUS manual, the results show that the probability of damage exceedance of the structural components is higher than non-structural ASCs, however, the opposite observation was reported from the previous earthquakes. Therefore, in this study, four levels of damage threshold for non-structural ASCs are proposed.

Uncertainty and Latin Hypercube Sampling in Geotechnical Earthquake Engineering

A soil–foundation–structure system (SFSS) often exhibits different responses compared to a fixed-base structure when subjected to earthquake ground motion. Both kinematic and inertial soil–foundation–structure interactions can significantly influence the structural performance of buildings. Numerous parameters within an SFSS affect its overall response, introducing inherent uncertainty into the solution. Performing time history analyses, even for a linear elastic coupled SFSS, requires considerable computational effort. To reduce the computational cost without compromising accuracy, the use of the Latin Hypercube Sampling (LHS) technique is proposed herein. Sampling techniques are rarely employed in soil–foundation–structure interaction analyses, yet they are highly beneficial. These methodologies allow analyses determined by sampling to be conducted using commercial codes designed for deterministic analyses, without requiring any modifications. The advantage is that the number of analyses determined by the sampling size is significantly reduced as compared to considering all combinations of input parameters. After identifying the important samples, one can evaluate the seismic demand of selected soil–foundation–bridge pier systems using finite element numerical software. This paper indicates that LHS reduces computational effort by 60%, whereas structural response components (translation, rocking) show distinct trends for different systems.

Malate dehydrogenase: a story of diverse evolutionary radiation.

Malate dehydrogenase (MDH) is a ubiquitous enzyme involved in cellular respiration across all domains of life. MDH's ubiquity allows it to act as an excellent model for considering the history of life and how the rise of aerobic respiration and eukaryogenesis influenced this evolutionary process. Here, we present the diversity of the MDH family of enzymes across bacteria, archaea, and eukarya, the relationship between MDH and lactate dehydrogenase (LDH) in the formation of a protein superfamily, and the connections between MDH and endosymbiosis in the formation of mitochondria and chloroplasts. The development of novel and powerful DNA sequencing techniques has challenged some of the conventional wisdom underlying MDH evolution and suggests a history dominated by gene duplication, horizontal gene transfer, and cryptic endosymbiosis events and adaptation to a diverse range of environments across all domains of life over evolutionary time. The data also suggest a superfamily of proteins that do not share high levels of sequential similarity but yet retain strong conservation of core function via key amino acid residues and secondary structural components. As DNA sequencing and 'big data' analysis techniques continue to improve in the life sciences, it is likely that the story of MDH will continue to refine as more examples of superfamily diversity are recovered from nature and analyzed.

Seismic behavior of composite shear walls with post-casting UHPC boundary elements and CRB600H steel bars

This study investigates the seismic behavior of composite shear walls reinforced with post-casting Ultra-High Performance Concrete (UHPC) boundary elements and Colded-Rolled Ribbed Bars (CRB600H). The research aims to explore the synergistic effects of UHPC and CRB600H bars on seismic performance. Six shear wall specimens with a shear span ratio of 1.56 were subjected to cyclic loading to evaluate their failure modes, crack patterns, hysteresis behavior, stiffness degradation, ductility, residual deformation, and energy dissipation capacity. The results demonstrated that the use of CRB600H bars in boundary elements of normal concrete specimens improved post-yield stiffness and reduced residual deformation. Conversely, incorporating UHPC in boundary elements enhanced load-bearing capacity and crack control but slightly reduced ductility due to the weaker interfacial connection between UHPC and the foundation. Additionally, CRB600H bars in the web region improved load-bearing capacity while maintaining ductility comparable to HRB400 bars. The findings suggest that substituting CRB600H for HRB400 in shear-dominant regions can enhance the seismic performance of shear walls. Finally, the multi-layer shell element numerical model validated by the experimental results was encouraged to conduct parametric analysis in the future. This research supports the development of more resilient building structures by integrating high-performance materials in key structural components.

Crevice corrosion behavior of 316L austenitic steel in static liquid lead-bismuth eutectic at 550°C

Crevice corrosion is a significant form of localized corrosion that can lead to failures in structural components. However, there is a lack of research on this phenomenon in liquid lead-bismuth eutectic (LBE). In this study, the crevice corrosion behavior of 316 L exposed to stagnant LBE with the oxygen concentration of 1 × 10–6 wt.% at 550 °C for 500 h was examined for the first time. Microstructural characterizations indicated 316 L is susceptible to crevice corrosion and reducing the crevices size facilitates a transition from oxidation to dissolution corrosion. Grain boundaries are able to provide more diffusion channels for oxygen, thereby promoting the development of Cr-rich oxides and chemical segregations beneath the surface scale. A simplified model elucidating the transportation of dissolved oxygen within the crevice environment of LBE has been developed.

Sphingolipid Analysis in Clinical Research.

Sphingolipids are the most diverse class of lipids due to the numerous variations in their structural components. This diversity is also reflected in their extremely different functions. Sphingolipids are not only constituents of cell membranes but have emerged as key signaling molecules involved in a variety of cellular functions, such as cell growth and differentiation, proliferation and apoptotic cell death. Lipidomic analyses in clinical research have identified pathways and products of sphingolipid metabolism that are altered in several human pathologies. In this article, we describe how to properly design a lipidomic experiment in clinical research, how to handle plasma and serum samples for this purpose, and how to measure sphingolipids using liquid chromatography-mass spectrometry.

B-082 Clinical Investigation of Rods and Rings Pattern in Anti-Nuclear Antibody Test in Korean Patients

Abstract Background In the mid-2000s, a novel pattern in antinuclear antibody (ANA) testing was reported. Indirect immunofluorescence assays on HEp-2 cells, conducted with sera from patients with Hepatitis C virus (HCV) infection, revealed cytoplasmic structures in the form of rods and rings (RR). These structures typically displayed rod lengths of 3-10μm and ring diameters of 2-5μm. Inosine monophosphate dehydrogenase (IMPDH) was identified as the primary component of the RR structures. Research on the administration of interferon/ribavirin (IFN/RBV) showed that ribavirin, an IMPDH inhibitor, induced RR formation in over 95% of cells. Additionally, RR patterns were reported in patients receiving other IMPDH inhibitors such as mycophenolic acid and azathioprine. While cytidine triphosphate synthase 1 (CTPS1) was suggested to be associated with RR structures, there were no reported cases in patients. Interestingly, patients receiving methotrexate, which does not directly inhibit IMPDH but hinders GTP biosynthesis, also exhibited RR structures. To explore the clinical implications of specimens showing RR patterns, a study was conducted to investigate the actual clinical scenarios associated with these findings. Methods This is a retrospective study conducted at a single center, covering the period from January 2022 to December 2023, focusing on the results of ANA testing. The ANA tests were performed using HEp-2 cells (FLUORO HEPANA TEST, MBL, Nagoya, Japan) on slides manufactured with AP 16 IF Plus (das, Palombara Sabina, RM, Italy). ANA results were obtained through qualitative testing, ranging from 1+ to 4+, or quantitative testing based on dilutions ranging from 1:40 to 1:640, depending on clinical requirements. Results Out of the 7,648 ANA test results, the RR pattern was observed in 40 cases (0.5%). Among these, 2.5% had a history of HCV infection with IFN/RBV treatment, and an additional 2.5% had concurrent use of IMPDH inhibitors. There were no reported cases of medication history related to the synthetic pathway of nucleic acids, including CTPS1. Cases where RR patterns coexisted with autoimmune diseases accounted for 35%, infections for 25%, and other inflammatory conditions for 22.5%. RR patterns reported with an intensity of 3+ or at dilutions of 1:160 or higher constituted 27.5%. Among cases displaying strong fluorescence, 45% were associated with infections, 18% with autoimmune conditions, and another 18% with unexplained inflammatory causes. In the overall sample, elevated CRP or ESR was noted in 54.5% of cases with infections, autoimmune diseases, or other inflammatory conditions. Among samples with intense intensity, 55.5% showed elevated CRP or ESR when inflammatory conditions were present. Conclusions The majority of cases exhibiting the RR pattern showed no history of exposure to IMPDH inhibitors or drugs affecting the nucleic acid synthetic pathway. A high proportion of cases clinically diagnosed with inflammation showed a concurrent RR pattern, with only approximately half of them demonstrating elevated CRP or ESR levels. This study suggests the possibility of identifying inflammatory responses not captured by conventional acute inflammation markers through the RR pattern observed in ANA testing.