Explore the vast range of titles available.

This paper presents a novel real-time algorithm for crack localization in the intersection of steel truss bridges using acoustic emission testing. It is well known that the welded junction or joint of the bridges is vulnerable to cracks due to long-duration dynamic loading. Here, the pencil lead-break-up (PLB) test is used to generate acoustic emission (AE) signals on the joint positions of the steel truss model and recorded using the R6D sensors. Crack location is determined in real-time using the proposed algorithm and a preset range of values for different AE signal parameters. A new modified equation calculates the distance between the source and the nearest sensor. Several experiments are performed with varying positions of sensors and PLB test locations on the model. It helps to set the range of different parameter values of the acquired AE signal by applying signal processing techniques. The proposed algorithm allows for locating the affected node number in the truss model. It also finds the corresponding shortest crack distance from the sensor. At the same time, a reduction in the number of sensors is also given importance.

Acoustic emission (AE) technique has been merged to a promising method for structural health monitoring in non-destructive technique. So an analysis of the AE signal is becoming a very important research component. In this paper, an algorithm is developed for detection of the crack signal among different noise signals since the AE signal is also generated by several means like any impact or rubbing action on the structure which may give erroneous results. An AE monitoring system is developed with three experimental setups to generate three types of AE signals from three dissimilar sources. Thus, an algorithm is developed to identify the crack signal by comparing the parameters of different signals acquired from different sources using some signal processing techniques such as parameter based analysis, waveform based analysis e.g. fast Fourier transform, continuous wavelet transform, cross-correlation coefficient, magnitude coherence coefficient, and energy distribution. After identification of the crack signal, the distance of the crack source has been calculated by analysing the signal in time–frequency domain also an algorithm has been designed to calculate the velocity of the acoustic wave more accurately and consequently the distance of the crack.

The Indian passenger vehicle was witnessing slump in sales even before the pandemic hit shores in March 2020. After the pandemic, the sector witnessed low to negative sales, low consumer trust and confidence and the added fear of the virus. The sudden declaration of the harsh lockdown in March 2020 till May 2020 aggravated the issue further. After May 2020 as the economy was gradually unlocking and most sectors were beginning to open up the study was timed between the period of March 2020 and August 2020. Unstructured textual data from online sources (micro blogging site Twitter, social media and digital media) were scrapped to understand the sentiment with respect to car buying when the lockdown was imposed and when the process of unlocking started. In the second stage, different strategies being adopted by car makers were analyzed and finally, the study concludes with how car buying will take place in a post-COVID world. Based on the analysis, factors that emerged as key to revival of car buying are facelift, spot test, voice bots, discounts, advertising and better financing options. The sentiments associated with these features as identified shall help marketers plan for effectively their market strategy.

In this paper, a complete non-linear symmetric oscillator model using the Hamiltonian approach has been developed and used to describe the cardiovascular conduction process’s dynamics, as the signal generated from the cardiovascular muscle is non-deterministic and random. Electrocardiogram (ECG) signal is a significant factor in the cardiovascular system as most of the medical diagnoses can be well understood by observing the ECG signal’s amplitude. A non-linear cardiovascular muscle model has been proposed in this study, where a modified vanderPol symmetric oscillator-based equation is used. Gone are the days whena non-linear system had been designed using the describing function technique. It is better to design a non-linear model using the Hamiltonian dynamical equation for its high accuracy and flexibility. Varying a non-linear spring constant using this type of approach is more comfortable than the traditional describing function technique. Not only that but different initial conditions can also be taken for experimental purposes. It never affects the overall modeling. The Hamiltonian approach provides the energy of an asymmetric oscillatory system of that cardiovascular conduction system. A non-linear symmetric oscillator was initially depicted by the non-linear mass-spring (two degrees of freedom) model. The motion of an uncertain non-linear cardiovascular system has been solved considering second-order approximation, which also demonstrates the possibility of introducing spatial dimensions. Finally, the model’s natural frequency expression has also been simulated and is composed of the previously published result.

Prion-like domains (PLDs) are low-complexity protein sequences enriched within nucleic acid-binding proteins including those involved in transcription and RNA processing. PLDs of FUS and EWSR1 play key roles in recruiting chromatin remodeler mammalian SWI/SNF (mSWI/SNF) complex to oncogenic FET fusion protein condensates. Here, we show that disordered low-complexity domains of multiple SWI/SNF subunits are prion-like with a strong propensity to undergo intracellular phase separation. These PLDs engage in sequence-specific heterotypic interactions with the PLD of FUS in the dilute phase at sub-saturation conditions, leading to the formation of PLD co-condensates. In the dense phase, homotypic and heterotypic PLD interactions are highly cooperative, resulting in the co-mixing of individual PLD phases and forming spatially homogeneous condensates. Heterotypic PLD-mediated positive cooperativity in protein-protein interaction networks is likely to play key roles in the co-phase separation of mSWI/SNF complex with transcription factors containing homologous low-complexity domains. Prion-like domains are intrinsically disordered regions found in many RNA- and DNA-binding proteins. Here, the authors show that these domains can drive sequence-specific co-phase separation of chromatin remodeling complex with FET oncofusion proteins.

Trogocytosis, a rapid and contact-dependent exchange of plasma membrane fragments and associated molecules between cells, has recently emerged as a critical but underappreciated player in cancer biology. Traditionally studied in the context of immune cell communication, trogocytosis is now recognized for its paradoxical role in modulating tumor progression and therapeutic response across a broad spectrum of malignancies. This review highlights the novel and dynamic functions of trogocytosis in shaping the tumor microenvironment (TME), promoting immune evasion and influencing metastatic potential. Notably, cancer cells exploit trogocytosis to acquire immune regulatory molecules such as CD45, CD4 and checkpoint proteins, effectively dampening anti-tumor responses while enhancing their own survival. Simultaneously, immune effector cells including macrophages, T cells and natural killer (NK) cells leverage trogocytosis to recognize, attack and even kill tumor cells through mechanisms such as trogoptosis. Compelling new evidence also links trogocytosis to therapeutic resistance, particularly in chimeric antigen receptor (CAR-T and CAR-NK) cell therapies, where tumor antigens like CD19 and CD22 are siphoned off by effector cells, leading to T cell fratricide, functional exhaustion and tumor relapse. Beyond its biological significance, trogocytosis is gaining attention as a translational tool in oncology. It offers a novel platform for antigen-specific drug delivery, spatially restricted immune modulation and biomarker discovery through the detection of trogocytosed molecules on circulating immune-cells or extracellular vesicles. These findings redefine trogocytosis as not merely a passive membrane exchange process, but a central mechanism of intercellular communication with profound implications for cancer progression, immunotherapy and precision medicine.

α-Synuclein has a critical role in Parkinson’s disease, but the mechanism of how extracellular α-synuclein aggregates lead to astrocytic degeneration remains unknown. Our recent study in astrocytes highlighted that α-synuclein aggregates undergo lower endocytosis than the monomeric-form, even while displaying a higher impact on glutathione-machinery and glutamate-metabolism under sublethal conditions. As optimal intracellular calcium levels are essential for these functions, we aimed to study the effect of extracellular α-synuclein aggregates on ER calcium entry. We assessed the association of extracellular aggregated-α-synuclein (WT and A30P/A53T double-mutant) with the astrocytic membrane (lipid rafts) and studied its effects on membrane fluidity, ER stress, and ER calcium refilling in three systems—purified rat primary midbrain astrocyte culture, human iPSC-derived astrocytes, and U87 cells. The corresponding timeline effect on mitochondrial membrane potential was also evaluated. Post-24 h exposure to extracellular WT and mutant α-synuclein aggregates, fluorescence-based studies showed a significant increase in astrocyte membrane rigidity over control, with membrane association being significantly higher for the double mutant aggregates. α-Synuclein aggregates also showed preferentially higher association with lipid rafts of astrocytic membrane. A simultaneous increase in ER stress markers (phosphorylated PERK and CHOP) with significantly higher SOCE was also observed in aggregate-treated astrocytes, with higher levels for double mutant variant. These observations correlate with increased expression of SOCE markers, especially Orai3, on plasma membrane. Alterations in mitochondrial membrane potential were only noted post-48 h of exposure to α-synuclein aggregates. We therefore suggest that in astrocytes, α-synuclein-aggregates preferentially associate with lipid rafts of membrane, altering membrane fluidity and consequently inducing ER stress mediated by interaction with membrane SOCE proteins, resulting in higher Ca 2+ entry. A distinct cascade of events of sequential impairment of ER followed by mitochondrial alteration is observed. The study provides novel evidence elucidating relationships between extracellular α-synuclein aggregates and organellar stress in astrocytes and indicates the therapeutic potential in targeting the association of α-synuclein aggregates with astrocytic membrane. Graphical Abstract

Background A key factor in the propagation of α-synuclein pathology is the compromised protein quality control system. Variations in membrane association and astrocytic uptake between different α-synuclein forms suggest differences in exocytosis or membrane cleavage, potentially impacting the secretome's influence on dopaminergic neurons. We aimed to understand differences in protein degradation mechanisms of astrocytes for both wild-type (WT) and mutant forms of α-synuclein, specifically during periods of reduced degradation efficiency. We also investigated α-synuclein release into the secretome and its effects on healthy dopaminergic neurons. Methods Cellular models used were rat primary astrocytes alongside hiPSC-derived astrocytes, whose impact on rat primary dopaminergic neurons and the human SH-SY5Y cell line was investigated. We examined the release and accumulation of α-synuclein resulting from impaired degradatory pathways, including matrix metalloprotease-MMP9, the ubiquitin proteasomal pathway-UPS, and the autophagy-lysosomal pathway-ALP, using immunocytochemical analysis and flow cytometry. Additionally, we explored the effect of astrocytic secretome on dopaminergic-neuronal survival, neurite collapse and function. Results At early stages, astrocytes were able to deal efficiently with monomeric α-synuclein (via UPS), and larger aggregates (through MMP9 and autophagy), clearing extracellular α-synuclein and maintaining neuronal health. However, extended exposure to extracellular monomeric and aggregated α-synuclein compromised their proteasomal activity, inhibiting MMP9 and destabilizing autophagy, transforming astrocytes from protectors to promoters of neurodegeneration. This study is the first to elucidate the astrocytes' preferred degradation pathways for both monomeric and aggregated forms of α-synuclein, along with the subsequent effects of these payloads on the cellular degradation machinery. The astrocytic transformation is characterized by α-synuclein expulsion, increased release of inflammatory cytokines, and diminished secretion of growth factors leading to dopaminergic neuronal apoptosis and dysfunction, particularly neurite collapse, intracellular Ca 2+ response and vesicular dopamine release. The presence of phosphorylated and nitrated α-synuclein species in astrocytes also suggests their potential involvement in modifying both forms of the protein. Conclusion The initial protective action of astrocytes in clearing and degrading extracellular α-synuclein is severely compromised at latter stages, leading to astrocytic dysfunction and impairing neuron-glia cross-talk. This study underscores the criticality of integrating astrocytes into treatment paradigms in synucleinopathies.

Breast cancer (BC) is globally one of the leading killers among women. Within a breast tumor, a minor population of transformed cells accountable for drug resistance, survival, and metastasis is known as breast cancer stem cells (BCSCs). Several experimental lines of evidence have indicated that BCSCs influence the functionality of immune cells. They evade immune surveillance by altering the characteristics of immune cells and modulate the tumor landscape to an immune-suppressive type. They are proficient in switching from a quiescent phase (slowly cycling) to an actively proliferating phenotype with a high degree of plasticity. This review confers the relevance and impact of crosstalk between immune cells and BCSCs as a fate determinant for BC prognosis. It also focuses on current strategies for targeting these aberrant BCSCs that could open avenues for the treatment of breast carcinoma.

Background Protagonistic role of platelets promote capillary infiltration of tumors for distant metastasis along with immunosurveillance. Despite existing reports highlighting role of platelets in tumorigenesis, its impact on breast cancer stem cells (BCSCs) remain underexplored. Our first ever report on murine and human system, accentuate that, tumor educated platelets (TEPs) of luminal A and TNBC subtypes are distinct from healthy counterparts, collaborating with BCSCs to generate sub-variants that elevate tumor aggressiveness. Methods Impact of TEPs on BCSCs was evaluated from primary breast tumor and blood samples of luminal A/TNBC patients along with EC/4T1 murine breast tumor models and MCF-7/MDA-MB-231 cell lines. For downstream assays, TEPs were co-cultured with breast tumor samples or cell lines, followed by magnetic sorting of lin − CD44 + CD24 − BCSCs. TEP induced alterations of BCSCs were evaluated from 3D tumorsphere, colony formation, transwell migration, scratch-wound healing, matrigel invasion, in-vitro tube formation assays. Fluorescence-confocal microscopy, RT-PCR, flow-cytometry, western-blotting was utilized to decipher the role of genes and protein involved in stemness, metastasis along with the transcription factors in the downstream signaling cascade, followed by verifications by RNAi. Results TEPs have elevated expression of P-selectin and interacts with BCSCs via P-selectin and PSGL1 on BCSCs surface. Treatment with aspirin had restorative impact on P-selectin level, converting TEPs from active to resting platelet (RP) state. Under TEPs influence, BCSCs were tumorigenic, clonogenic, multidrug resistant, invasive with numerous invadopodia and remained skewed towards mesenchymal phenotype . Administration of RP reduced TEP associated BCSC virulence both in-vivo and in-vitro. P-selectin-PSGL1 interaction results in binding of WNT to FRIZZLED followed by stabilization and nuclear translocation of β-catenin. Nuclear β-catenin promotes stemness-EMT (Epithelial to mesenchymal transition)-metastasis, along with stimulation of autocrine VEGF-VEGFR2 cascade. Inhibition of WNT and VEGFR2 by RNAi confirmed the critical role of this axis in regulating TEP’s influence on BCSCs. Conclusion These insights into TEP-BCSC interplay, acknowledges TEPs, as-well-as unveils novel receptor-ligand signaling cascade between TEPs and BCSCs, that could be a beneficial therapeutic strategy to target cancer metastasis. Graphical abstract