MODELING AND ANALYSIS OF DEFORMATION ON A FLEXURE BEARING IN LINEAR COMPRESSOR

Flexure bearing is a new concept and used for precision applications such as Programmable Focusing Mechanism (PFM), linear compressor, etc. These bearings are compact and inexpensive. A flexure bearing is designed for specific applications. These designed can usually be done with the advanced design tool like Fine Element Analysis. With the advent of computers Fine Element Analysis has become the most suitable tool for the engineering analysis where the conventional approach is not suitable, geometric complexity are involved etc. This bearing contains three slots having 120 ° apart and 12 peripheral holes are used to clamp the disc rigidly onto a support structure. One central hole made for movement of shaft. The bearings are commonly made by Aluminum material we calculate the deformations in theoretical and FEA method by using Ansys Software. In this paper we are modeling the flexure bearing by using copper material we are calculate the deformations in theoretical and FEA method by using Ansys Software. We are analysis the deflection deformation on the both materials of bearing. We are analysis the deflection deformation on Flexure Bearing at different load (means 1 N to 5 N). Using software’s like CATIA and PROE, modeling of flexure bearing done. Also make Fine Element Method analysis on it by using Ansys software and lastly, this project considers the fatigue life criteria for flexure bearing and tries to optimize it. We are made design calculation and Fine Element Analysis for flexure bearing to make appropriate model and draw the performance charts for linear compressor bearing by comparing the power consumption with different temperatures, and capacity

Studies on the feeding biology of an airbreathing fish Heteropneustes fossilis (Bloch)

The food and feeding habits of an air-breathing fish, Heteropneustes fossilis were studied from an eutrophic lake, Hussainsagar, Hyderabad, (Andhra Pradesh, India), during 1981-1983. The major preferred items of food were insect larvae, insects, ostracods, plant material and gastropods. Due to the mixed feeding habits of both plant and animal matter, this species is considered as an omnivorous feeder. Bryozoans were recorded for the first time in the diet of H. fossilis

Effects of PARP inhibitors, SGLT2 inhibitors, and Colchicine on Doxorubicin-induced Premature Senescence Induced-Phenotype

https://openworks.mdanderson.org/sumexp22/1076/thumbnail.jp

LETKF-ROMS: An improved predictability system for the Indian Ocean

We have developed the assimilation scheme Local Ensemble Transform Kalman Filter (LETKF) and interfaced with the present basin-wide operational ROMS set-up ( 1/12 degree horizontal resolution ) that assimilates in-situ temperature and salinity from RAMA moorings, NIOT buoys and Argo floats. The system also assimilate satellite track data of sea-surface temperature from AMSR-E. The speciality of this assimilation system is that it comprises of ensembles that are initialized with different model coefficients like diffusion parameters and the ensemble members also respond to two different mixing schemes - K profile parameterization and Mellor-Yamada. This aids in maintaining the spread of the ensemble intact - which has always been a challenging task. We have also employed a localization radius of ~200 km, i.e., observations influence the prognostic state variables that fall within this range. The assimilation system is also bestowed with better representative error estimates - a method developed in-house along the likes of Etherton et al. The ensemble members were forced with ensemble atmospheric fluxes provided by National Centre for Medium Range Weather Forecast (NCMRWF). Assimilation was performed every five day. We show that the assimilated system simulates the ocean state better than the present operational basin-wide ROMS. We validate it extensively against multiple observations ranging from RAMA moorings to ADCP observations across both dependent variables like temperature and salinity and independent variables like sealevel anomaly and currents. We show that assimilation improves the overall ocean state except at few isolated locations. It improves the correlation with respect to observations and reduces the root-mean-squared error. We also show that assimilation improves the estimation of mixed layer depth and 20 degree isotherm (which are diagnostic variables) thereby proving that the subsurface conditions are better simulated

Possible Molecular Mechanisms Underlying the Development of Atherosclerosis in Cancer Survivors

Cancer survivors undergone treatment face an increased risk of developing atherosclerotic cardiovascular disease (CVD), yet the underlying mechanisms remain elusive. Recent studies have revealed that chemotherapy can drive senescent cancer cells to acquire a proliferative phenotype known as senescence-associated stemness (SAS). These SAS cells exhibit enhanced growth and resistance to cancer treatment, thereby contributing to disease progression. Endothelial cell (EC) senescence has been implicated in atherosclerosis and cancer, including among cancer survivors. Treatment modalities for cancer can induce EC senescence, leading to the development of SAS phenotype and subsequent atherosclerosis in cancer survivors. Consequently, targeting senescent ECs displaying the SAS phenotype hold promise as a therapeutic approach for managing atherosclerotic CVD in this population. This review aims to provide a mechanistic understanding of SAS induction in ECs and its contribution to atherosclerosis among cancer survivors. We delve into the mechanisms underlying EC senescence in response to disturbed flow and ionizing radiation, which play pivotal role in atherosclerosis and cancer. Key pathways, including p90RSK/TERF2IP, TGFβR1/SMAD, and BH4 signaling are explored as potential targets for cancer treatment. By comprehending the similarities and distinctions between different types of senescence and the associated pathways, we can pave the way for targeted interventions aim at enhancing the cardiovascular health of this vulnerable population. The insights gained from this review may facilitate the development of novel therapeutic strategies for managing atherosclerotic CVD in cancer survivors

Aerobic Exercise Alters the Melanoma Microenvironment and Modulates ERK5 S496 Phosphorylation

Exercise changes the tumor microenvironment by remodeling blood vessels and increasing infiltration by cytotoxic immune cells. The mechanisms driving these changes remain unclear. Herein, we demonstrate that exercise normalizes tumor vasculature and upregulates endothelial expression of VCAM1 in YUMMER 1.7 and B16F10 murine models of melanoma but differentially regulates tumor growth, hypoxia, and the immune response. We found that exercise suppressed tumor growth and increased CD8+ T-cell infiltration in YUMMER but not in B16F10 tumors. Single-cell RNA sequencing and flow cytometry revealed exercise modulated the number and phenotype of tumor-infiltrating CD8+ T cells and myeloid cells. Specifically, exercise caused a phenotypic shift in the tumor-associated macrophage population and increased the expression of MHC class II transcripts. We further demonstrated that ERK5 S496A knock-in mice, which are phosphorylation deficient at the S496 residue, mimicked the exercise effect when unexercised, yet when exercised, these mice displayed a reversal in the effect of exercise on tumor growth and macrophage polarization compared with wild-type mice. Taken together, our results reveal tumor-specific differences in the immune response to exercise and show that ERK5 signaling via the S496 residue plays a crucial role in exercise-induced tumor microenvironment changes. See related Spotlight by Betof Warner, p. 1158

TNIK Regulation of Interferon Signaling and Endothelial Cell Response to Virus Infection

BACKGROUND: Traf2 and Nck-interacting kinase (TNIK) is known for its regulatory role in various processes within cancer cells. However, its role within endothelial cells (ECs) has remained relatively unexplored. METHODS: Leveraging RNA-seq data and Ingenuity Pathway Analysis (IPA), we probed the potential impact of TNIK depletion on ECs. RESULTS: Examination of RNA-seq data uncovered more than 450 Differentially Expressed Genes (DEGs) in TNIK-depleted ECs, displaying a fold change exceeding 2 with a false discovery rate (FDR) below 0.05. IPA analysis unveiled that TNIK depletion leads to the inhibition of the interferon (IFN) pathway [-log ( SUMMARY: Our findings suggest that TNIK plays a crucial role in regulating the EC response to virus infections through modulation of the IFN pathway

MAGI1 Inhibits Interferon Signaling to Promote Influenza a Infection

We have shown that membrane-associated guanylate kinase with inverted domain structure-1 (MAGI1), a scaffold protein with six PSD95/DiscLarge/ZO-1 (PDZ) domains, is involved in the regulation of endothelial cell (EC) activation and atherogenesis in mice. In addition to causing acute respiratory disease, influenza A virus (IAV) infection plays an important role in atherogenesis and triggers acute coronary syndromes and fatal myocardial infarction. Therefore, the aim of this study is to investigate the function and regulation of MAGI1 in IAV-induced EC activation. Whereas, EC infection by IAV increases MAGI1 expression, MAGI1 depletion suppresses IAV infection, suggesting that the induction of MAGI1 may promote IAV infection. Treatment of ECs with oxidized low-density lipoprotein (OxLDL) increases MAGI1 expression and IAV infection, suggesting that MAGI1 is part of the mechanistic link between serum lipid levels and patient prognosis following IAV infection. Our microarray studies suggest that MAGI1-depleted ECs increase protein expression and signaling networks involve in interferon (IFN) production. Specifically, infection of MAGI1-null ECs with IAV upregulates expression of signal transducer and activator of transcription 1 (STAT1), interferon b1 (IFNb1), myxovirus resistance protein 1 (MX1) and 2\u27-5\u27-oligoadenylate synthetase 2 (OAS2), and activate STAT5. By contrast, MAGI1 overexpression inhibits Ifnb1 mRNA and MX1 expression, again supporting the pro-viral response mediated by MAGI1. MAGI1 depletion induces the expression of MX1 and virus suppression. The data suggests that IAV suppression by MAGI1 depletion may, in part, be due to MX1 induction. Lastly, interferon regulatory factor 3 (IRF3) translocates to the nucleus in the absence of IRF3 phosphorylation, and IRF3 SUMOylation is abolished in MAGI1-depleted ECs. The data suggests that MAGI1 inhibits IRF3 activation by maintaining IRF3 SUMOylation. In summary, IAV infection occurs in ECs in a MAGI1 expression-dependent manner by inhibiting anti-viral responses including STATs and IRF3 activation and subsequent MX1 induction, and MAGI1 plays a role in EC activation, and in upregulating a pro-viral response. Therefore, the inhibition of MAGI1 is a potential therapeutic target for IAV-induced cardiovascular disease

Ponatinib Activates an Inflammatory Response in Endothelial Cells via ERK5 SUMOylation

Ponatinib is a multi-targeted third generation tyrosine kinase inhibitor (TKI) used in the treatment of chronic myeloid leukemia (CML) patients harboring the Abelson (Abl)-breakpoint cluster region (Bcr) T315I mutation. In spite of having superb clinical efficacy, ponatinib triggers severe vascular adverse events (VAEs) that significantly limit its therapeutic potential. On vascular endothelial cells (ECs), ponatinib promotes EC dysfunction and apoptosis, and inhibits angiogenesis. Furthermore, ponatinib-mediated anti-angiogenic effect has been suggested to play a partial role in systemic and pulmonary hypertension via inhibition of vascular endothelial growth factor receptor 2 (VEGFR2). Even though ponatinib-associated VAEs are well documented, their etiology remains largely unknown, making it difficult to efficiently counteract treatment-related adversities. Therefore, a better understanding of the mechanisms by which ponatinib mediates VAEs is critical. In cultured human aortic ECs (HAECs) treated with ponatinib, we found an increase in nuclear factor NF-kB/p65 phosphorylation and NF-kB activity, inflammatory gene expression, cell permeability, and cell apoptosis. Mechanistically, ponatinib abolished extracellular signal-regulated kinase 5 (ERK5) transcriptional activity even under activation by its upstream kinase mitogen-activated protein kinase kinase 5α (CA-MEK5α). Ponatinib also diminished expression of ERK5 responsive genes such as Krüppel-like Factor 2/4 (klf2/4) and eNOS. Because ERK5 SUMOylation counteracts its transcriptional activity, we examined the effect of ponatinib on ERK5 SUMOylation, and found that ERK5 SUMOylation is increased by ponatinib. We also found that ponatibib-mediated increased inflammatory gene expression and decreased anti-inflammatory gene expression were reversed when ERK5 SUMOylation was inhibited endogenously or exogenously. Overall, we propose a novel mechanism by which ponatinib up-regulates endothelial ERK5 SUMOylation and shifts ECs to an inflammatory phenotype, disrupting vascular homeostasis