Important Functions Research Articles

Natural Compounds that Modulate Circadian Rhythms.

Circadian rhythms of innate 24 h cycles comprise well-conserved biological phenomena from cyanobacteria to mammalian. They are driven by light and regulated by clock genes that work as transcription factors and control the expression of many other genes and physiological functions in the cells. The expression of ~ 40% of protein-coding genes shows 24 h oscillation patterns in mice, implying their importance in normal body functions. Indeed, the physiological and behavioural rhythmicity generated through clock genes-mediated multiple mechanisms affects the quality of life at large. Disrupted circadian rhythmicity is associated with several kinds of diseases. For example, cancer cells show abnormal expression patterns for circadian rhythm genes that have been shown to regulate oncogenesis, drug responses, and disease prognosis. Furthermore, the modern globalisation of human lifestyle and business and social activities have disrupted innate circadian rhythm, resulting in a variety of diseases through disrupted humoral, immunological, and neuronal pathways. Safe and sustainable modulation of circadian rhythm has become a prevalent need that warrants basic and interventional research, as well as clinical investigations. Although traditional systems of medicine suggest some natural compounds with circadian rhythmmodulating potential, most of these have not been validated in laboratory or clinical studies. Reliable read-outs of the effects of test compounds on circadian rhythmicity have been limited by the availability of live cell assays. We have, herein, provided an overview of living cell-embedded real- time reporter gene assays designed for screening compounds that modulate circadian rhythm, and discussed the potential of some natural compounds for circadian rhythm modulation as validated by cell-based assay systems, and their role in disease therapeutics.

Co-habiting ants and silverfish display a converging feeding ecology

BackgroundVarious animal taxa have specialized to living with social hosts. Depending on their level of specialization, these symbiotic animals are characterized by distinct behavioural, chemical, and morphological traits that enable close heterospecific interactions. Despite its functional importance, our understanding of the feeding ecology of animals living with social hosts remains limited. We examined how host specialization of silverfish co-habiting with ants affects several components of their feeding ecology. We combined stable isotope profiling, feeding assays, phylogenetic reconstruction, and microbial community characterization of the Neoasterolepisma silverfish genus and a wider nicoletiid and lepismatid silverfish panel where divergent myrmecophilous lifestyles are observed.ResultsStable isotope profiling (δ13C and δ15N) showed that the isotopic niches of granivorous Messor ants and Messor-specialized Neoasterolepisma exhibit a remarkable overlap within an ant nest. Trophic experiments and gut dissections further supported that these specialized Neoasterolepisma silverfish transitioned to a diet that includes plant seeds. In contrast, the isotopic niches of generalist Neoasterolepisma silverfish and generalist nicoletiid silverfish were clearly different from their ant hosts within the shared nest environment. The impact of the myrmecophilous lifestyle on feeding ecology was also evident in the internal silverfish microbiome. Compared to generalists, Messor-specialists exhibited a higher bacterial density and a higher proportion of heterofermentative lactic acid bacteria. Moreover, the nest environment explained the infection profile (or the 16S rRNA genotypes) of Weissella bacteria in Messor-specialized silverfish and the ant hosts.ConclusionsTogether, we show that social hosts are important determinants for the feeding ecology of symbiotic animals and can induce diet convergence.

The mediating role of ICT learning confidence and technostress between executive functions and digital skills

Having good digital skills is essential today, yet little is known about the cognitive factors that influence the development of these skills. Given the importance of executive functions (EFs) in adapting to environmental changes and acquiring skills, EFs might contribute to acquiring digital skills too. EFs might also influence people’s approach toward ICTs and affect digital skills through emotional variables. Therefore, here, we tested whether cognitive control and flexibility are connected to computer and smartphone skills through emotional factors (learning confidence, stress, and attitude). A total of 269 participants (56 males, M = 30 years) filled out our survey which included questionnaires on demographic variables (age, education, and socioeconomic status), ICT motivation, digital skills, EFs, and technology-related emotional factors. EFs were also investigated through two performance-based measures. We used generalized linear models and structural equation modeling to test the associations between these variables. The results showed that smartphone skills were positively associated with self-reported cognitive flexibility through ICT learning confidence and technology-induced stress. Self-reported cognitive control and age were connected to smartphone skills directly. Self-reported cognitive flexibility was also associated with computer skills through ICT learning confidence. In addition, performance-based cognitive control and the level of education were directly linked to computer skills. These results may provide guidance to support digital skills and create digital skill training.

Proteomics is advancing the understanding of stallion sperm biology.

The mammalian ejaculate is very well suited to proteomics studies. As such, research concerning sperm proteomics is offering a huge amount of new information on the biology of spermatozoa. Among domestic animals, horses represent a species of special interest, in which reproductive technologies and a sizeable market of genetic material have grown exponentially in the last decade. Studies using proteomic approaches have been conducted in recent years, showing that proteomics is a potent tool to dig into the biology of the stallion spermatozoa. The aim of this review is to present an overview of the research conducted, and how these studies have improved our knowledge of stallion sperm biology. The main outcomes of the research conducted so far have been an improved knowledge of metabolism, and its importance in sperm functions, the impact of different technologies on the sperm proteome, and the identification of potential biomarkers. Moreover, proteomics of seminal plasma and phosphoproteomics are identified as areas of major interest.

Kidney Organoid Modeling of WT1 Mutations Reveals Key Regulatory Paths Underlying Podocyte Development.

Wilms tumor-1(WT1) is a crucial transcription factor that regulates podocyte development. However, the epigenomic mechanism underlying the function of WT1 during podocyte development has yet to be fully elucidated. Here, single-cell chromatin accessibilityand gene expressionmaps of foetal kidneys and kidney organoids are generated. Functional implications of WT1-targeted genes, which are crucial for the development of podocytes and the maintenance of their structure, including BMPER/PAX2/MAGI2 that regulates WNT signaling pathway, MYH9 that maintains actin filament organization and NPHS1 that modulates cell junction assembly are identified. To further illustrate the functional importance of WT1-mediated transcriptional regulation during podocyte development, cultured and implanted patient-derived kidney organoids derived from the Induced Pluripotent Stem Cell (iPSCs) of a patient with a heterozygous missense mutation in WT1 are generated. Results from single-cell RNA sequencing (scRNA-seq)and functional assays confirm that the WT1 mutation leads to delays in podocyte development and causes damage to cell structures, due to its failure to activate the targeting genes MAGI2, MYH9, and NPHS1. Notably, correcting the mutation in the patient iPSCs using CRISPR-Cas9 gene editing rescues the podocyte phenotype. Collectively, this work elucidates the WT1-related epigenomic landscape with respect to human podocyte development and identifies the disease-causing role of a WT1 mutation.

Removal of the large inverted repeat from the plastid genome reveals gene dosage effects and leads to increased genome copy number

The chloroplast genomes of most plants and algae contain a large inverted repeat (IR) region that separates two single-copy regions and harbours the ribosomal RNA operon. We have addressed the functional importance of the IR region by removing an entire copy of the 25.3-kb IR from the tobacco plastid genome. Using plastid transformation and subsequent selectable marker gene elimination, we precisely excised the IR, thus generating plants with a substantially reduced plastid genome size. We show that the lack of the IR results in a mildly reduced plastid ribosome number, suggesting a gene dosage benefit from the duplicated presence of the ribosomal RNA operon. Moreover, the IR deletion plants contain an increased number of plastid genomes, suggesting that genome copy number is regulated by measuring total plastid DNA content rather than by counting genomes. Together, our findings (1) demonstrate that the IR can enhance the translation capacity of the plastid, (2) reveal the relationship between genome size and genome copy number, and (3) provide a simplified plastid genome structure that will facilitate future synthetic biology applications.

Celiac Disease: The Importance of Studying the Duodenal Mucosa-Associated Microbiota.

There is increasing evidence indicating that changes in both the composition and functionality of the intestinal microbiome are closely associated with the development of several chronic inflammatory diseases, with celiac disease (CeD) being particularly noteworthy. Thanks to the advent of culture-independent methodologies, the ability to identify and quantify the diverse microbial communities residing within the human body has been significantly improved. However, in the context of CeD, a notable challenge lies in characterizing the specific microbiota present on the mucosal surfaces of the intestine, rather than relying solely on fecal samples, which may not fully represent the relevant microbial populations. Currently, our comprehension of the composition and functional importance of mucosa-associated microbiota (MAM) in CeD remains an ongoing field of research because the limited number of available studies have reported few and sometimes contradictory results. MAM plays a crucial role in the development and progression of CeD, potentially acting as both a trigger and modulator of the immune response within the intestinal mucosa, given its proximity to the epithelial cells and direct interaction. According to this background, this review aims to consolidate the existing literature specifically focused on MAM in CeD. By elucidating the complex interplay between the host immune system and the gut microbiota, we aim to pave the way for new interventions based on novel therapeutic targets and diagnostic biomarkers for MAM in CeD.

HtrA4 is well conserved only in higher primates and functionally important for EVT differentiation

IntroductionThe placenta differs greatly among species, and deep extra-villous trophoblast (EVT) invasion is a unique feature of placentation of higher primates including humans. We reported serine protease HtrA4 being found predominantly in human placentas with aberrant expression linked to preeclampsia. However, it remains unclear where HtrA4 is produced in the placenta, how it is expressed in other species, and whether it is essential for human placentation. MethodsWe first compared HtrA4 protein sequences of over 100 species, then scrutinized the key characteristics of HtrA4 in the human, rhesus macaque and mouse, and determined cellular localization in the placenta. We next investigated functional significance of HtrA4 in EVT differentiation using human trophoblast stem cells (TSCs). ResultsAcross broader species HtrA4 is well conserved only in higher primates. In humans, only the placenta expressed HtrA4, localising to trophoblasts of villous as well as extra-villous lineages. Rhesus macaques produced HtrA4 but again only in placentas, whereas mice showed no abundant HtrA4 expression anywhere including the placenta, yet it was an active protease if produced. The functional importance of HtrA4 in human EVT was demonstrated using TSCs, which expressed low levels of HtrA4 but significantly up-regulated it during EVT differentiation, and knockdown of HtrA4 severely inhibited the differentiation process. DiscussionHtrA4 is expressed in placentas of humans and macaques but not mice; it is critical for human EVT differentiation. Together with previous reports showing HtrA4 is also indispensable for syncytialization, this study further revealed HtrA4 as a functionally important protease for human placentation.

#2062 Protein interactome and trafficking of uromodulin in HEK and MDCK cell model

Abstract Background and Aims Uromodulin (UMOD) is a kidney-specific glycoprotein and the most abundant urinary protein in healthy individuals. Genome-wide association studies have shown an association between UMOD variants, kidney diseases, and hypertension. UMOD exhibits bidirectional secretion as it releases into the renal interstitium and circulation. However, the molecular trafficking of UMOD and its interaction remains poorly defined. We aimed to establish a stable Human Embryonic Kidney (HEK293) cell line expressing human UMOD to identify the potential regulators of UMOD expression or secretion. This study will provide significant implications for conditions such as hypertension, chronic kidney diseases, acute kidney injury, or UMOD-autosomal dominant tubulointerstitial kidney disease (UMOD-ADTKD). Method A HEK-UMOD-expressing cell line was generated by introducing human UMOD transcript 1 expression and using a tetracycline-inducible expression vector (pcDNA™FRT⁄TO vector) with yellow fluorescent protein tag at the C-terminal and previously established MDCK-UMOD cell line was also used. An untargeted proteomic approach was used to identify proteins, using GFP trap co-immunoprecipitation assay followed by mass spectrometry analysis. Results We identified 1367 and 1140 UMOD interacting proteins in HEK and MDCK cell models respectively. There were 620 proteins common to both these models. Through gene ontology, we unravel the molecular mechanisms involved in the biosynthesis, folding, and transport of UMOD. We observed several proteins associated with clathrin-mediated transporting. To study the role of clathrin in UMOD transport, we treated the polarised MDCK-UMOD cells with pitstop 2. There was significantly more secretion of UMOD with pitstop 2 treatment in the apical compartment compared to untreated cells however there was no significant difference in UMOD secretion in the basolateral compartment. Conclusion These results suggested that clathrin-coated vesicles are involved in transporting and sorting UMOD. Further studies need to investigate the functional importance of these proteins in UMOD trafficking and their implications in different physiological processes.

Cutting Edge: LAG3 Dimerization Is Required for TCR/CD3 Interaction and Inhibition of Antitumor Immunity.

Lymphocyte activation gene 3 (LAG3) is an inhibitory receptor that plays a critical role in controlling T cell tolerance and autoimmunity and is a major immunotherapeutic target. LAG3 is expressed on the cell surface as a homodimer but the functional relevance of this is unknown. In this study, we show that the association between the TCR/CD3 complex and a murine LAG3 mutant that cannot dimerize is perturbed in CD8+ T cells. We also show that LAG3 dimerization is required for optimal inhibitory function in a B16-gp100 tumor model. Finally, we demonstrate that a therapeutic LAG3 Ab, C9B7W, which does not block LAG3 interaction with its cognate ligand MHC class II, disrupts LAG3 dimerization and its association with the TCR/CD3 complex. These studies highlight the functional importance of LAG3 dimerization and offer additional approaches to therapeutically target LAG3.

TAF2, within the TFIID complex, regulates the expression of a subset of protein-coding genes

TFIID, one of the general transcription factor (GTF), regulates transcriptional initiation of protein-coding genes through direct binding to promoter elements and subsequent recruitment of other GTFs and RNA polymerase II. Although generally required for most protein-coding genes, accumulated studies have also demonstrated promoter-specific functions for several TFIID subunits in gene activation. Here, we report that TBP-associated factor 2 (TAF2) specifically regulates TFIID binding to a small subset of protein-coding genes and is essential for cell growth of multiple cancer lines. Co-immunoprecipitation assays revealed that TAF2 may be sub-stoichiometrically associated with the TFIID complex, thus indicating a minor fraction of TAF2-containing TFIID in cells. Consistently, integrated genome-wide profiles show that TAF2 binds to and regulates only a small subset of protein-coding genes. Furthermore, through the use of an inducible TAF2 degradation system, our results reveal a reduction of TBP/TFIID binding to several ribosomal genes upon selective ablation of TAF2. In addition, depletion of TAF2, as well as the TAF2-regulated ribosomal protein genes RPL30 and RPL39, decreases ribosome assembly and global protein translation. Collectively, this study suggests that TAF2 within the TFIID complex is of functional importance for TBP/TFIID binding to and expression of a small subset of protein-coding genes, thus establishing a previously unappreciated promoter-selective function for TAF2.

In vitro fertilization outcome based on the detailed early luteal phase trajectory of hormones: a prospective cohort study

BackgroundOvarian stimulation and the use of human chorionic gonadotropin (hCG) for triggering oocyte maturation in women undergoing in vitro fertilisation (IVF) introduces several differences in luteal phase hormone levels compared with natural cycles that may negatively impact on endometrial receptivity and pregnancy rates after fresh embryo transfer. Exogenous luteal phase support is given to overcome these issues. The suitability of a pragmatic approach to luteal phase support is not known due to a lack of data on early phase luteal hormone levels and their association with fertility outcomes during IVF with fresh embryo transfer. This study determined early luteal phase profiles of serum progesterone, 17-hydroxyprogesterone and hCG, and associations between hormone levels/hormone level profile after hCG trigger and the live birth rate in women undergoing IVF with fresh embryo transfer.MethodsThis prospective single center, cohort study was conducted in Vietnam from January 2021 to December 2022. Women aged 18–38 years with normal ovarian reserve and undergoing controlled ovarian stimulation using a gonadotropin-releasing hormone antagonist protocol were included. Serum hormone levels were determined before trigger, at 12, 24 and 36 h after hCG, and daily from 1 to 6 days after oocyte pick-up. Serum hormone level profiles were classified as lower or upper. The primary outcome was live birth rate based on early luteal phase hormone level profile.ResultsNinety-five women were enrolled. Live birth occurred in 19/69 women (27.5%) with a lower progesterone profile and 13/22 (59.1%) with an upper progesterone profile (risk ratio [RR] 2.15; 95% confidence interval [CI] 1.28–3.60), and in 6/31 (19.4%) versus 26/60 (43.3%) with a lower versus upper serum 17-hydroxyprogesterone profile (RR 2.24; 95% CI 1.03–4.86). Nearly 20% of women had peak progesterone concentration on or before day 3 after oocyte pick-up, and this was associated with significantly lower chances of having a life birth.ConclusionsThese data show the importance of proper corpus luteum function with sufficient progesterone/17-hydroxyprogesterone production for achievement of pregnancy and to maximize the chance of live birth during IVF.Trial RegistrationNCT04693624 (www.clinicaltrials.gov).

Evolutionary trends in the elasmobranch neurocranium

The neurocranium (braincase) is one of the defining vertebrate characters. Housing the brain and other key sensory organs, articulating with the jaws and contributing to the shape of the anteriormost portion of the body, the braincase is undoubtedly of great functional importance. Through studying relationships between braincase shape and ecology we can gain an improved understanding of form-function relationships in extant and fossil taxa. Elasmobranchii (sharks and rays) represent an important case study of vertebrate braincase diversity as their neurocranium is simplified and somewhat decoupled from other components of the cranium relative to other vertebrates. Little is known about the associations between ecology and braincase shape in this clade. In this study we report patterns of mosaic cranial evolution in Elasmobranchii that differ significantly from those present in other clades. The degree of evolutionary modularity also differs between Selachii and Batoidea. In both cases innovation in the jaw suspension appears to have driven shifts in patterns of integration and modularity, subsequently facilitating ecological diversification. Our results confirm the importance of water depth and biogeography as drivers of elasmobranch cranial diversity and indicate that skeletal articulation between the neurocranium and jaws represents a major constraint upon the evolution of braincase shape in vertebrates.

Machine Learning-Based Mortality Prediction in Chronic Kidney Disease among Heart Failure Patients: Insights and Outcomes from the Jordanian Heart Failure Registry

Background and Objectives: Heart failure (HF) is a prevalent and debilitating condition that imposes a significant burden on healthcare systems and adversely affects the quality of life of patients worldwide. Comorbidities such as chronic kidney disease (CKD), arterial hypertension, and diabetes mellitus (DM) are common among HF patients, as they share similar risk factors. This study aimed to identify the prognostic significance of multiple factors and their correlation with disease prognosis and outcomes in a Jordanian cohort. Materials and Methods: Data from the Jordanian Heart Failure Registry (JoHFR) were analyzed, encompassing medical records from acute and chronic HF patients attending public and private cardiology clinics and hospitals across Jordan. An online form was utilized for data collection, focusing on three kidney function tests, estimated glomerular filtration rate (eGFR), blood urea nitrogen (BUN), and creatinine levels, with the eGFR calculated using the Cockcroft–Gault formula. We also built six machine learning models to predict mortality in our cohort. Results: From the JoHFR, 2151 HF patients were included, with 644, 1799, and 1927 records analyzed for eGFR, BUN, and creatinine levels, respectively. Age negatively impacted all measures (p ≤ 0.001), while smokers surprisingly showed better results than non-smokers (p ≤ 0.001). Males had more normal eGFR levels compared to females (p = 0.002). Comorbidities such as hypertension, diabetes, arrhythmias, and implanted devices were inversely related to eGFR (all with p-values <0.05). Higher BUN levels were associated with chronic HF, dyslipidemia, and ASCVD (p ≤ 0.001). Higher creatinine levels were linked to hypertension, diabetes, dyslipidemia, arrhythmias, and previous HF history (all with p-values <0.05). Low eGFR levels were associated with increased mechanical ventilation needs (p = 0.049) and mortality (p ≤ 0.001), while BUN levels did not significantly affect these outcomes. Machine learning analysis employing the Random Forest Classifier revealed that length of hospital stay and creatinine >115 were the most significant predictors of mortality. The classifier achieved an accuracy of 90.02% with an AUC of 80.51%, indicating its efficacy in predictive modeling. Conclusions: This study reveals the intricate relationship among kidney function tests, comorbidities, and clinical outcomes in HF patients in Jordan, highlighting the importance of kidney function as a predictive tool. Integrating machine learning models into clinical practice may enhance the predictive accuracy of patient outcomes, thereby supporting a more personalized approach to managing HF and related kidney dysfunction. Further research is necessary to validate these findings and to develop innovative treatment strategies for the CKD population within the HF cohort.

Individual differences in autonomy and sociotropy in relation to autistic traits, camouflaging and interpersonal functioning

The social motivation hypothesis has proposed that autism/autistic traits result developmentally from lower motivation to interact socially. However, counter to this hypothesis, a growing body of research on ‘camouflaging’ suggests many autistic people or those with high autistic traits work hard to appear more ‘neurotypical’ to foster friendships. “Sociotropy/dependency” and “autonomy/self-reliance” characterise different attachment styles. Despite their importance for understanding interpersonal functioning, their relationship with autistic traits and camouflaging is unknown. To investigate this question in 168 participants (71 % females, Mean age = 30; SD = 10), we used online self-reported measures including depressive and social anxiety (i.e. affective) symptoms. A large fraction of variability in interpersonal functioning and camouflaging in the respective models was explained (R-square: 0.40 and 0.50, respectively). Autistic traits and autonomy were both negatively and independently associated with interpersonal functioning (β = −0.23, p = .002 and β = −0.14, p = .045, respectively) after controlling for the influence of sociotropy and affective symptoms. Furthermore, sociotropy was independently associated with camouflaging (β = 0.22, p = .001) after controlling for autonomy and affective symptoms. This may suggest that social motivation is dissociable from autistic traits which could explain why a subgroup of people with autistic traits is highly motivated to camouflage.

FvMbp1-Swi6 complex regulates vegetative growth, stress tolerance, and virulence in Fusarium verticillioides

The mycotoxigenic fungus Fusarium verticillioides is a common pathogen of grain and medicine that contaminates the host with fumonisin B1 (FB1) mycotoxin, poses serious threats to human and animal health. Therefore, it is crucial to unravel the regulatory mechanisms of growth, and pathogenicity of F. verticillioides. Mbp1 is a component of the MluI cell cycle box binding factor complex and acts as an APSES-type transcription factor that regulates cell cycle progression. However, no information is available regarding its role in F. verticillioides. In this study, we demonstrate that FvMbp1 interacts with FvSwi6 that acts as the cell cycle transcription factor, to form the heteromeric transcription factor complexes in F. verticillioides. Our results show that ΔFvMbp1 and ΔFvSwi6 both cause a severe reduction of vegetative growth, conidiation, and increase tolerance to diverse environmental stresses. Moreover, ΔFvMbp1 and ΔFvSwi6 dramatically decrease the virulence of the pathogen on the stalk and ear of maize. Transcriptome profiling show that FvMbp1-Swi6 complex co-regulates the expression of genes associated with multiple stress responses. These results indicate the functional importance of the FvMbp1-Swi6 complex in the filamentous fungi F. verticillioides and reveal a potential target for the effective prevention and control of Fusarium diseases.

Untangling Structural and Functional Diversity of Prokaryotic Microbial Assemblage on Mangrove Pneumatophores

Untangling Structural and Functional Diversity of Prokaryotic Microbial Assemblage on Mangrove Pneumatophores

PiR-hsa-23533 promotes malignancy in head and neck squamous cell carcinoma via USP7

BackgroundWith regard to head and neck squamous cell carcinoma (HNSCC), its occurrence and advancement are controlled by genetic and epigenetic anomalies. PIWI-interacting RNAs (piRNAs) are recognized with significance in tumor, but the precise molecular mechanisms of piRNAs in HNSCC largely remain undisclosed. MethodsDifferentially expressed piRNAs were identified by RNA sequencing. The expression of piR-hsa-23533 was evaluated using quantitative real-time PCR and RNA in situ hybridization. The impacts of piR-hsa-23533 on the proliferation and apoptosis of HNSCC cells were investigated by a series of in vitro and in vivo assays. ResultspiR-hsa-23533 exhibits upregulation within HNSCC cells and tissues. Besides, piR-hsa-23533 overexpression promotes proliferation while inhibiting apoptosis in vitro and in vivo, while piR-hsa-23533 silencing has an opposite function. From the mechanistic perspective, piR-hsa-23533 can bind to Ubiquitin-specific protease 7 (USP7), as shown through RNA pull-down and RNA immunoprecipitation assays, promoting USP7 mRNA and protein expression. ConclusionsThese findings highlight the functional importance of piR-hsa-23533 in HNSCC and may assist in the development of anti-HNSCC therapeutic target.

DEPLOYMENT OF ENHANCED DEEP LEARNING MODEL WITH THE BEST ESTIMATORS ON OPTIMIZERS AND ACTIVATION FUNCTIONS FOR HEALTHCARE IN WEB APPLICATION

Breast cancer and brain tumor stand as leading global causes of mortality. Brain tumor uses Magnetic Resonance Imaging (MRI) which offers superior clarity in visualizing brain structures compared to other imaging modalities, while Breast cancer uses ultrasonography (US) serves as a common tool for detecting breast cancer despite its inherent limitations in image quality. Motion artifacts frequently hinder MRI scans, necessitating skilled radiologists for accurate interpretation. Computer-aided diagnosis (CAD) systems driven by artificial intelligence, present a promising solution by consistently assisting radiologists in analyzing US images. Convolutional neural networks (CNNs) leverage various optimizers like Adam and Stochastic Gradient Descent (SGD), RMSprop, Adagrad, and Adadelta as well as activation functions including PReLu, LeakyReLu, Elu, and ReLu for their construction and training. The comparative analysis highlights the importance of optimizers and activation functions in deep learning algorithms for predicting brain tumors and breast cancer. The Adam optimizer combined with the ReLU activation function achieved an accuracy of 85% for breast cancer prediction, while RMSprop combined with ReLU activation function achieved a higher accuracy of 93% for brain tumor classification. From this research, considerable deep learning configurations are identified for both breast cancer and brain tumor prediction, facilitating more precise and efficient diagnoses. The comparative analysis provides valuable insights for those involved in medical imaging applications. Furthermore, The CNN model is deployed in web interface using flask framework to streamline the integration of these models into healthcare systems. This interface simplifies the input of medical data including image data and provides real-time predictions. KEYWORDS—Convolutional neural networks, Comparative Analysis, Activation functions, Optimizers, Ultrasound images, MRI images, Breast cancer, Brain tumor, medical imaging applications, FLASK.

Development of Risk Informed Aging Management Program in Decommissioning

Abstract This paper proposes to solve the issues related to aging management program (AMP) during the decommissioning phase by using risk information. The AMP for the decommissioning plants has not been established while the number of permanently shut down and decommissioned nuclear power plants are increasing in the world. The first issue is the change of the functional importance of the safety systems at the beginning of decommissioning. We propose to evaluate the importance using the probabilistic risk assessment (PRA) model with the change of specification in the decommissioning plant and to determine new importance grade. The second issue is to make the maintenance based on the appropriate risk information. This risk information should be based on the progress of decommissioning, reflected and evaluated in the PRA model, as well as information obtained from maintenance inspections, including the ROP process, and failure experience during routine operation. To address these issues, the maintenance program in decommissioning that uses the evaluation of risk information according to the decommissioning phase is proposed in this paper.