The fatigue life of welded joints under cyclic loading is a complex process that can be roughly divided into fatigue crack initiation, crack propagation and final fracture. Usually, these phases are evaluated separately. Several methods are available to estimate the extent of the different phases in welded components, such as stress-based fatigue concepts for crack initiation or linear elastic fracture mechanics for crack propagation; however, distinguishing these phases in welded components is a complex procedure and often relies on assumptions such as transition crack sizes. The objective of this study is to investigate the relationship between fatigue crack initiation and propagation in welded joints using artificially notched specimens with welded joints characteristics of different notch acuity (different radii and opening angle). The experiments show that the investigated relationship basically depends on the notch acuity, the load level and the stress ratio.

This study aims to explore the effect of microstructural parameters on notch fatigue damage behavior of the TC21 alloy. Different levels of lamellar microstructures were achieved through distinct aging temperatures of 550, 600, and 650 °C. The findings reveal that increasing aging temperature primarily contributes to the augmentation of α colony (αc) thickness, grain boundaries α phase (GBα) thickness, and α fine (αfine) size, alongside a reduction in α lath (αlath) thickness and αfine content. The notch alters stress distribution and relaxation effects at the root, enhancing notched tensile strength while weakening plasticity. Moreover, the increased thickness of GBα emerges as a critical factor leading to the increase area of intergranular cleavage fracture. It is noteworthy that more thickness αlath and smaller αfine facilitate deformation coordination and enhance dislocation accumulation at the interface, leading to a higher propensity for microvoids and microcracks to propagate along the interface. Conversely, at elevated aging temperatures, thinner αlath and larger αfine are more susceptible to fracture, resulting in the liberation of dislocations at the interface. The reduction in αlath thickness is crucial for triggering the initiation of multi-system dislocations at the interface, which promotes the development of persistent slip bands (PSBs) and dislocation nets within αlath. This phenomenon induces inhomogeneous plastic deformation and localized hardening, fostering the formation of microvoids and microcracks.

Fatigue failure remains a critical concern in structural engineering and material science, prompting extensive research to understand and predict the behaviour of materials under cyclic loading conditions. The present study aims to investigate the fatigue life of carbon steel specimens containing opposite semicircular edge notches through a comprehensive experimental and numerical analysis. In this study, stress concentration factors (SCF, K_t) of rectangular plate with opposite semicircular notches are considered under uniform tensile stress to analyse the notch deformation because of stretching of plate. Furthermore, the research focuses on quantifying stress concentration factors (SCFs) for these notches based on S-N curves of carbon steel. The study employs a combination of experimental and numerical techniques to understand the influence of these notches on the fatigue performance of carbon steel structures. A plate with opposite semicircular edge single notches under the axial load creates stress concentration near the notch and it is much larger than the average stress on the plate. Both analytical and finite element methods are used to calculate the maximum stress around the notch. SOLIDWORKS Premium Student Edition 2023 has been employed for modelling and SOLIDWORKS Simulation Premium Student Edition 2023 has been used for stress analysis and fatigue notch factor of rectangular plate of size 31 mm x 25.4 mm x 6.35 mm. The uniform tensile load with a magnitude of 20195 N is applied on one sides of rectangular plate normal to the sides of notches with ratio h/r = 1, for the semicircular notch. The result obtained on both analytical and finite element methods are compared and the percentage of error has been evaluated. Subsequently, these specimens undergo fatigue testing under varying loading conditions to capture their fatigue behaviour. The acquired fatigue data is then plotted against stress amplitude to construct S-N curves, forming the foundation for assessing the fatigue life of the notched specimens. To complement the experimental findings and to gain a deeper understanding of the stress concentration phenomenon, numerical simulations are conducted using advanced finite element analysis (FEA) techniques. The finite element models are carefully calibrated against the experimental results to ensure their accuracy and reliability. The FEA simulations enable the determination of stress concentration factors at critical locations within the notched specimens, further validating the experimental observations. The investigation reveals crucial insights into the effect of opposite semicircular edge notches on the fatigue life of carbon steel structures. The obtained S-N curves allow engineers and designers to predict the fatigue life of components with similar notches, aiding in the development of reliable and durable structures in practical applications. Moreover, the stress concentration factors determined from the numerical simulations provide valuable data to assess the potential failure modes and to optimise designs, effectively mitigating fatigue-related failures. The combination of experimental and numerical approaches ensures a comprehensive and rigorous analysis of the fatigue behaviour in notched specimens, offering a reliable basis for making informed engineering decisions. The comparison between the analytical method and the Finite Element Method (FEM) demonstrated good agreement, with an error percentage of 4.272%. The analysis revealed that the specimen would experience failure after approximately 2882 cycles, with a maximum stress of 395.914 MPa. This research study enhances the understanding of fatigue life in carbon steel structures containing opposite semicircular edge notches and contributes valuable data to the field of fatigue mechanics. The outcomes serve as a valuable resource for professionals engaged in structural engineering, material science, and design optimisation, ultimately leading to safer and more durable industrial components in critical applications. The findings of this research contribute to the understanding of fatigue behaviour in carbon steel components with stress concentration effects caused by semicircular notches. Moreover, the validated numerical simulations and data curves facilitate the prediction of fatigue life and aid in determining the critical conditions leading to fatigue failure. In conclusion, this research highlights the significance of combining experimental testing with numerical simulations to comprehensively analyse the fatigue life of carbon steel specimens with opposite semicircular edge notches. The obtained stress concentration factors provide crucial information for structural integrity assessment and offer potential for further optimising design criteria to mitigate fatigue-related failures. The findings of this study could play a vital role in enhancing the reliability and safety of carbon steel structures subjected to cyclic loading conditions. The comprehensive experimental and numerical analyses establish a foundation for future studies exploring other materials and geometries with notches, fostering advancements in fatigue life prediction and structural integrity assessment.

Abstract—In the present paper the static and fatigue analysis of plates with holes is conducted. Structures are made of 2D woven roving composites. The parametrization of convex holes is proposed. Experimental results of specimens without holes and with different shapes of notches under static and fatigue tensile loads are presented. The fatigue behaviour of structures is analysed with the use of the low cycle fatigue method. The attention is focused on the nonlinear deformations of 2D woven roving structures leading to the scatter of results. The analysis is supplemented by the numerical finite element modeling. The agreement between experimental and finite element modeling is very good. Since we do not intend to repeat in the abstract the review of the existing literature I would like to emphasize only that the present work is a continuation and extension of the results discussed in the literature – see the next sections of the paper. The finite element modeling of plates with holes is presented in details by Muc [1], Muc, Ulatowska [2] and Muc, Romanowicz [3] including also the problems of the accuracy. The mesh correctness and accuracy is discussed in Ref [2] where the results are compared to the analytical results illustrated in the Soviet Union literature. The experimental results and the form of specimens are shown by Pandita et al. [4] and they are fundaments for our present experimental investigations. Two parametrical description of static and fatigue behaviour of plates with holes characterizes the goal and the novelty of the paper. The analysis demonstrates how those parameters affect on the variations of static and fatigue failure loads. In addition, it should be emphasized that the fuzzy approach is employed herein to reduce the number of experimental data and to avoid statistical analysis of experimental results – see e.g. Muc [5]. In the mesoscale modeling and using the fuzzy approach it is possible to achieve a very good description of static and fatigue behavior of plates with convex holes subjected to tension.

Glioblastoma multiforme (GBM) is a highly invasive brain malignancy originating from astrocytes, accounting for approximately 30% of central nervous system malignancies. Despite advancements in therapeutic strategies including surgery, chemotherapy, and radiopharmaceutical drugs, the prognosis for GBM patients remains dismal. The aggressive nature of GBM necessitates the identification of molecular targets and the exploration of effective treatments to inhibit its proliferation. The Notch signaling pathway, which plays a critical role in cellular homeostasis, becomes deregulated in GBM, leading to increased expression of pathway target genes such as MYC, Hes1, and Hey1, thereby promoting cellular proliferation and differentiation. Recent research has highlighted the regulatory role of non-coding RNAs (ncRNAs) in modulating Notch signaling by targeting critical mRNA expression at the post-transcriptional or transcriptional levels. Specifically, various types of ncRNAs, including long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), have been shown to control multiple target genes and significantly contribute to the carcinogenesis of GBM. Furthermore, these ncRNAs hold promise as prognostic and predictive markers for GBM. This review aims to summarize the latest studies investigating the regulatory effects of ncRNAs on the Notch signaling pathway in GBM.

Notch signaling is a highly conserved pathway which occurs between adjacent cells to distinguish them. The Notch signaling cascade operates in a simple mechanism, yet Notch plays remarkably diverse roles in development to regulate cell fate determination, organ growth and tissue patterning. Originally isolated and characterized in the model insect Drosophila melanogaster, recent studies in various insect species have revealed that Notch signaling is broadly involved in the construction of insect tissues. This review focuses on providing a molecular mechanistic and developmental picture regarding the roles of Notch pathway in insects. The functions of Notch in the formation and patterning of insect embryo, wing, leg, ovary and several specific structures as well as in stress responses are summarized. These results are discussed in developmental context with an eye toward understanding the functionality of Notch signaling pathway in different insect species.

Metastasis is a major cause factor for breast cancer (BC)-associated mortality. During the metastatic process, disseminated tumor cells (DTCs) detach from the primary sites, and enter the bloodstream and establish the secondary colonies. Recent studies have provided substantial evidence for the importance of Notch signaling in BC metastasis. Therefore, this review focuses on the mechanisms by which Notch contributes to the origin of BC DTCs, increases their motility, regulates their intravasation and extravasation, protects them from host surveillance, and finally facilitates colonization. Identification of the mechanisms underlying Notch-related BC metastasis will lead to the development of novel Notch-targeted therapeutic strategies to reduce metastasis and significantly improve outcomes.

A study was conducted to predict failure stresses, failure locations, and their paths of initiation of perforated polymethyl methacrylate (PMMA) specimens as they were loaded using pins inserted into the holes. First, a series of experiments were conducted for perforated PMMA coupons. There were six different types of coupons. The test specimens had three different widths with a circular hole of a diameter of 8 mm, which was placed at two different locations along the specimen length. All the specimens were loaded using a pin inserted into the hole with three different pins of nominal diameters of 8 mm, 6 mm, and 5 mm, respectively. To predict the failure and compare the results against the experimental data, the recently proposed universal failure criterion was used in the study using finite element analyses. The failure criteria gave acceptable results as compared to the experimental data.

To enhance the uplift capacity and facilitate the installation of multi-row perfobond connectors at shallow burial depths, this study puts forward a novel notched T-perfobond connector. The design incorporates an integrated flange at the bottom of the connector and a notch at the edge of the hole. Through pull-out model tests on four notched T-perfobond connectors, this research investigates their failure mechanisms and pull-out capacities. Utilizing the explicit dynamics method in Abaqus, a finite element model of the pull-out resistance test for the notched T-perfobond connector is established and verified against experimental data. Furthermore, a detailed parametric analysis involving 54 models is conducted, examining crucial parameters such as rib dimensions, hole geometry, flange size, notch width, bar diameter, and material properties. Based on the combined experimental and numerical results, the paper assesses the suitability of current formulas for calculating the pull-out capacity of perfobond connectors and proposes a refined calculation method specifically for notched T-perfobond connectors. All the findings in this paper can serve as a reference in the design and construction of composite structures.

Crescentic glomerulonephritis is a devastating autoimmune disease that without early and properly treat-ment may rapidly progress to end-stage renal disease and death. Current immunosuppressive treatment provided limited efficacy and an important burden of adverse events. Epigenetic drugs are a source of novel therapeutic tools. Among them, bromodomain and extraterminal domain (BET) inhibitors (iBETs) block the interaction between bromodomains and acetylated proteins, including histones and transcription factors. iBETs have demonstrated protective effects on malignancy, inflammatory conditions and experi-mental kidney disease. Recently, Gremlin-1 was proposed as a urinary biomarker of disease progression in human anti-neutrophil cytoplasmic antibody (ANCA)-associated crescentic glomerulonephritis. We have now evaluated whether iBETs regulate Gremlin-1 in experimental anti-glomerular basement membrane nephritis induced by nephrotoxic serum (NTS) in mice, a model of human crescentic glomerulonephritis. In NTS-injected mice, the iBET JQ1 inhibited renal Gremlin-1 overexpression and diminished glomerular damage, including podocyte loss. Chromatin immunoprecipitation assay demonstrated BRD4 enrichment of the Grem-1 gene promoter in injured kidneys, consistent with Gremlin-1 epigenetic regulation. Moreover, JQ1 blocked BRD4 binding and inhibited Grem-1 gene transcription. The beneficial effect of iBETs was also mediated by targeting NOTCH signaling pathway. JQ1 inhibited the gene expression of the NOTCH effec-tors Hes-1 and Hey-1 in NTS-injured kidneys. Our results further support the role for epigenetic drugs, such as iBETs, in the treatment of rapidly progressive crescentic glomerulonephritis.

Glaucoma is a multifactorial neurodegenerative disease, characterized by degeneration of the retinal ganglion cells (RGCs). There has been little progress in developing efficient strategies for neuroprotection in glaucoma. We profiled the retina transcriptome of Lister Hooded rats at 2 weeks after optic nerve crush (ONC) and analyzed the data from the Genomic Fabric Paradigm (GFP) to bring additional insights into the molecular mechanisms of the retinal remodeling after induction of RGC degeneration. GFP considers for the expression of each gene 3 independent characteristics: level, variability and correlation with each other gene. Thus, the 17,657 quantified genes our study generated a total of 155,911,310 values to analyze. This represents 8,830x more data per condition than a traditional transcriptomic analysis. ONC led to a 57% reduction in RGC numbers as detected by retrograde labeling with DiI. We observed a higher Relative Expression Variability after ONC. Gene expression stability was used as a measure of transcription control and disclosed a robust reduction in the number of very stably expressed genes. Predicted Protein-Protein interaction (PPI) analysis with STRING revealed axon and neuron projection as mostly decreased processes, consistent with RGC degeneration. Conversely, immune response PPIs were found among up-regulated genes. Enrichment analysis showed that Complement Cascade and Notch Signaling Pathway, as well as Oxidative Stress and Kit Receptor Pathway were affected after ONC. To expand our studies of altered molecular pathways, we examined the pair-wise coordination of gene expressions within each pathway and within the entire transcriptome using Pearson correlations. ONC increased the number of synergistically coordinated pairs of genes and the number of similar profiles mainly in Complement Cascade and Notch Signaling Pathway. This deep bioinformatic study provides novel insights beyond the regulation of individual gene expression and discloses changes in the control of expression of Complement Cascade and Notch Signaling functional pathways that may be relevant for both RGC degeneration and remodeling of the retinal tissue after ONC.

Because most of the recognized causes of superior gluteal nerve (SGN) injury are iatrogenic, detailed knowledge of the anatomy of the SGN is crucial to prevent its injury associated with surgical procedures. This study aims to describe the precise location of SGN or its branches at the greater sciatic foramen, measure the distances of these nervous structures to palpable bony landmarks, and evaluate the possible correlation between these parameters and pelvis size. Twenty human cadaveric hemipelvises were studied. After dissection to expose the SGN or its branches at the greater sciatic foramen, the distances from these nervous structures to the greater trochanter (GT), to the anterior superior iliac spine (ASIS), to the posterior superior iliac spine (PSIS), to the ischial tuberosity (IT), and to the greater sciatic notch were measured. We found that at the greater sciatic foramen the SGN emerges as a common trunk in 75% of hemipelvises, and already divided in its superior and inferior branches in 25% of hemipelvises. When the SGN exits the pelvis as a common trunk, it does so, in most cases, in contact with the bone at the apex of the greater sciatic notch or superior to it. The median distance from the SGN at the greater sciatic notch to the PSIS, ASIS, GT and IT is 7.6 cm, 10.9 cm, 7.5 cm and 10.8 cm, respectively. We found a positive correlation between some of the analyzed parameters and the size of the pelvis. The anatomical data of this study may serve as pivotal guides during orthopedic pelvic surgery, contributing to minimize SNG iatrogenic lesions with significant implications in the patient's quality of life.

Hidradenitis suppurativa (HS) is a chronic skin disease characterized by painful, recurrent abscesses, nodules, and scarring, primarily in skin folds. The exact causes of HS are multifactorial, involving genetic, hormonal, and environmental factors. It is associated with systemic diseases like metabolic syndrome and inflammatory bowel disease. Genetic studies have identified mutations in the γ-secretase complex, which affects Notch signaling pathways critical for skin cell regulation. Despite its high heritability, most HS reported cases do not follow a simple genetic pattern. In this article, we performed a whole-exome sequencing (WES) on a cohort of 100 individuals with HS and we provide a comprehensive review of the variants known to be described or associated with HS, referencing 91 of them in the γ-secretase and 78 in other genes involved in the Notch pathway, keratinization, or immune response. From this new genetic analysis, we add ten new variants to these catalogs.

In voice analysis, the electroglottographic (EGG) signal has long been recognized as a useful complement to the acoustic signal, if only when the vocal folds are actually contacting, such that this signal has an appreciable amplitude. However, phonation can occur also without vocal fold contacting, as in breathy voice, in which case the EGG amplitude is low, but not zero. It is of great interest to identify the transition from non-contacting to contacting, because this will substantially change the nature of the vocal fold oscillations; yet that transition is not in itself audible. The magnitude of the normalized peak derivative of the EGG signal is a convenient indicator of contacting, but no current EGG hardware has a sufficient signal-to-noise ratio of the derivative. The textbook techniques of spectral thresholding and static notch filtering are straightforward to implement, can run in real time, and can mitigate several noise problems in EGG hardware.

The early detection of small cracks in large structures is a crucial requirement for the implementation of structural health monitoring (SHM) system with a low transducer density. This work presents the results of the analysis of scattering of a submillimeter notch type defect with semielliptical shape with a groove at constant width 100µm in a 4.1mm thick aluminum plate. The defect is investigated with an ultrasonic guided wave (UGW) A0 mode at 550 kHz to cover long range in a thick plate. The mode selection is obtained by interdigital transducers designed to operate with 5mm central wavelength. The novel contribution is the assessment of the scattering amplitudes at different orientations of the defect when the distance is large as 35 cm in pulse-echo mode or 70 cm in pitch-catch mode. The system model is based on Finite Element Model (FEM) simulations and the results are in good agreement with experimental tests. The detection of the defect is obtained by comparing the scattered signals from the defect with base line signals of the pristine laminate. The analysis of scattering features and the efficient excitation with a probing UGW show the potential implementation in real structural health monitoring (SHM) systems.

Oestrogen receptor expression in breast cancer (BC) cells is a marker of high cellular differentiation and allows the identification of two BC groups (ER-positive and ER-negative) that, although not completely homogeneous, differ in biological characteristics, clinical behaviour and therapeutic options. The study, based on three publicly available EWAS datasets, focuses on the comparison between these two groups of breast cancer using an epimutation score. The score is calculated not only based on the presence of the epimutation but also on the deviation amplitude of the methylation outlier value. For each dataset, we performed a functional analysis based first on the functional gene region of each annotated gene (we aggregated the data per gene region TSS1500, TSS200, first-exon, body-gene identified by the information from the Illumina Data Sheet) and then we performed a pathway enrichment analysis through the REACTOME database based on the genes with the highest epimutation score. Thus, we blended our results and found common pathways for all three data sets. We found that a higher and significant epimutation score due to hypermethylation in ER-positive BC is present in the promoter region of the genes belonging to the SUMOylation pathway, the NOTCH pathway, the IFN-$\gamma$ signalling pathway and the deubiquitination protease pathway; while a higher and significant level of epimutation due to hypomethylation in ER-positive BC is present in the promoter region of the genes belonging to the ESR-mediated pathway. The presence of this state of promoter hypomethylation in the ESR-mediated signalling genes is consistent and coherent with an active signalling pathway mediated by oestrogen function in the group of ER-positive BC. SUMOylation and NOTCH pathways are associated with BC pathogenesis and have been found to play distinct roles in the two BC subgroups. We speculated that the altered methylation profile may play a role in regulating signalling pathways with specific functions in the two subgroups of ER-BC.

Tumor cells display abnormal growth and division, avoiding the natural process of cell death. These cells can be benign (non-cancerous growth) or malignant (cancerous growth). Over the past few decades, numerous in vitro or in vivo tumor models have been employed to understand the molecular mechanisms associated with tumorigenesis in diverse aspects. However, our comprehension of how non-tumor cells transform into tumor cells at molecular and cellular levels remains incomplete. The nematode C. elegans has emerged as an excellent model organism for exploring various phenomena, including tumorigenesis. Although C. elegans does not naturally develop cancer, it serves as a valuable platform for identifying oncogenes and the underlying mechanisms within a live organism. In this review, we describe three distinct germline tumor models in C. elegans, highlighting their associated mechanisms and related regulators. Given the conservation of many of the regulators implicated in C. elegans tumorigenesis, it is proposed that these unique models hold significant potential for enhancing our comprehension of the broader control mechanisms governing tumorigenesis.

It is not understood how the numbers and identities of vertebrae are controlled during mammalian development. The remarkable robustness and conservation of segmental numbers may suggest a digital nature of the underlying process. Here I propose a mechanism that allows cells to obtain and store the segmental information in digital form, and to produce a pattern of chromatin accessibility that in turn regulates Hox gene expression specific to the metameric segment. The model requires that a regulatory element be present such that the number of occurrences of the motif between two consecutive Hox genes equals the number of segments under the control of the anterior gene. This is true for the recently discovered HRC3 motif, associated with histone modifications and developmental genes. The finding not only allows correctly predicting the numbers of segments using only sequence information, but also resolves the 40-year-old enigma of the function of temporal and spatial collinearity of Hox genes. The logic of the mechanism is illustrated in an animated video: https://youtu.be/4a3XOQ7Lz28. I also discuss how different aspects of the proposed mechanism can be tested experimentally.

The Notch signaling pathway plays a major role in embryological development and in the ongoing life processes of many animals. Its role is to provide cell-to-cell communication in which a Sender cell, bearing membrane -embedded ligands, instructs a Receiver cell, bearing membrane- embedded receptors, to adopt one of two available fates. Elucidating the evolution of this pathway is the topic of this paper, which uses an orthologs approach to build a firm base for such a study. Using BLAST searches, orthologs were identified for all of the 49 listed components of the Notch signaling pathway. The time course of the integration of these proteins as animal evolution proceeded was elucidated. Insofar as cell –to-cell communication is only of relevance in multicellular animals, it is not surprising that the Notch system reached a fully-working configuration only with the evolutionary appearance of the Metazoa, the first multicellular animals The roles of the Notch system’s 49 components in contemporary descendants of the ortholog-contributing ancestors were ascertained from a survey of the literature. A single protein, the protein tyrosine kinase (PTK) of the protozoan Ministeria vibrans was identified as a possible pre-Metazoan ancestor of the DLL, JAG, and NOTCH proteins. A scenario for the evolution of the Notch signaling pathway is presented and described as the co-option of its components, clade by clade, in a repurposing of genes already present in the ancestral unicellular organisms.

In this study, the fundamentals of electroencephalography signals, their categorization into frequency sub-bands, the circuitry used for their acquisition, and the impact of noise interference on signal acquisition are examined. Additionally, design specifications for medical-grade and research-grade EEG circuits and a comprehensive analysis of various analog front-end architectures for electroencephalograph (EEG) circuit design are presented. Three distinct selected case studies are examined in terms of comparative evaluation with generic EEG circuit design templates. Moreover, a novel one-channel battery-supplied EEG analog front-end circuit designed to address the requirements of usage protocols containing strong com-pound muscle movements is introduced. Furthermore, a realistic input signal generator circuit is proposed that models the human body and the Electromagnetic Interference from its surroundings. Experimental simulations are conducted in 50 Hz and 60 Hz electrical grid environments to evaluate the performance of the novel design. The results demonstrate the efficacy of the proposed system, particularly in terms of bandwidth, portability, common mode rejection ratio , gain, suppression of muscle movement artifacts, electrostatic discharge and leakage current protection. Conclusively, the novel design is cost-effective and suitable for both commercial and research single-channel EEG applications. It can be easily incorporated in Brain Computer Interfaces and neurofeedback training systems.

Abstract: The pathobiology of ascending aorta aneurysms (AAA) onset and progression is not well understood and only partially characterized. AAA are also complicated in case of bicuspid aorta valve (BAV) anatomy. There is emerging evidence about the crucial role of endothelium-related pathways, which show in AAA an altered expression and function. Here, we examined the involvement of ERG-related pathways in the differential progression of disease in aortic tissues from patients having a BAV or tricuspid aorta valve (TAV) with or without AAA. Our findings identified ERG as a novel endothelial-specific regulator of TGF-β-SMAD, Notch, and NO pathways, by modulating a differential fibrotic or calcified AAA progression in BAV and TAV aortas. We provided evidence that calcification is correlated to different ERG expression (as gene and protein), which appears to be under control of Notch signaling. The latter, when increased, associated with an early calcification in aortas with BAV valve and aneurysmatic, was demonstrated to favor the progression versus severe complications, i.e., dissection or rupture. In TAV aneurysmatic aortas, ERG appeared to modulate fibrosis. Therefore, we proposed that ERG may represent a sensitive tissue biomarker to monitor AAA progression and a target to develop therapeutic strategies and influence surgical procedures.

Neuroendocrine neoplasms (NENs) comprise a heterogeneous group of rare malignancies mainly originated from hormones secreting cells, which are widespread in human tissues. The identification of mutations in ATRX/DAXX genes in sporadic NENs, as well as the high burden of mutations scattered throughout MEN-1 gene in both sporadic and inherited syndromes, provided new insights into the molecular biology of tumour development. Other molecular mechanisms, such as the NOTCH signaling pathway, have shown to play an important role in the pathogenesis of NENs. NOTCH receptors are expressed on neuroendocrine cells and generally, act as tumour suppressor proteins, but in some contexts can function as oncogenes. The biological heterogeneity of NENs suggests that to fully understand the roles and the potential therapeutic implications of gene mutations and NOTCH signaling in NENs, a comprehensive analysis of genetic alterations, NOTCH expression patterns and their potential roles across all NEN subtypes is required.

Robots in space are necessarily extremely light and lack structural stiffness resulting in natural frequencies of resonance so low as to reside inside the attitude controller’s bandwidth. A variety of input trajectories can be used to drive a controller’s attempt to ameliorate the control-structural interactions where feedback is provided by low-quality, noisy sensors. Traditionally, step functions are used as the ideal input trajectory. However, step functions are not ideal in many applications, as they are discontinuous. Alternative input trajectories are explored in this manuscript and applied to an example system that includes a flexible appendage attached to a rigid main body. The main body is controlled by a reaction wheel. The equations of motion of the flexible appendage, rigid body, and reaction wheel are derived. A feedback controller is developed to account for the rigid body modes. Additional filters are added to compensate for the system’s flexible modes. Sinusoidal trajectories are autonomously generated to feed the controller. Whiplash compensation is additionally implemented for comparison. The control method without random errors with the smallest error is the sinusoidal trajectory method, which showed a 97.39% improvement when compared to the baseline response when step trajectories were commanded, while the sinusoidal method was inferior to traditional step trajectories when sensor noise and random errors were present.