Natural Frequency based delamination estimation in GFRP beams using RSM and ANN

The importance of delamination detection can be understood from aircraft components like Vertical Stabilizer, which is subjected to heavy vibration during the flight movement and it may lead to delamination and finally even flight crash can happen because of that. Any solid structure's vibration behaviour discloses specific dynamic characteristics and property parameters of that structure. This research investigates the detection of delamination in composites using a method based on vibration signals.  The composite material's flexural stiffness and strength are reduced as a result of delaminations, and vibration properties such as natural frequency responses are altered. In inverse problems involving vibration response, the response signals such as natural frequencies are utilized to find the location and magnitude of delaminations. For different delaminated beams with varying position and size, inverse approaches such as Response Surface Methodology (RSM) and Artificial Neural Network (ANN) are utilized to address the inverse problem, which aids in the prediction of delamination size and location

Artificial neural network based delamination prediction in composite plates using vibration signals

Dynamic loading on composite components may induce damages such as cracks, delaminations, etc. and development of an early damage detection technique for delaminations is one of the most important aspects in ensuring the integrity and safety of composite components. The presence of damages such as delaminations on the composites reduces its stiffness and further changes the dynamic behaviour of the structures. As the loss in stiffness leads to changes in the natural frequencies, mode shapes, and other aspects of the structure, vibration analysis may be the ideal technique to employ in this case. In this research work, the supervised feed-forward multilayer back-propagation Artificial Neural Network (ANN) is used to determine the position and area of delaminations in GFRP plates using changes in natural frequencies as inputs. The natural frequencies were obtained by finite element analysis and results are validated by experimentation. The findings show that the suggested technique can satisfactorily estimate the location and extent of delaminations in composite plates

FABRICATION OF DRUG DELIVERY SYSTEM FOR CONTROLLED RELEASE OF CURCUMIN, INTERCALATED WITH MAGNETITE NANOPARTICLES THROUGH SODIUM ALGINATE/POLYVINYLPYRROLIDONE-CO-VINYL ACETATE SEMI IPN MICROBEADS

Objective: The aim of the present work is to fabricate curcumin (CUR) encapsulated microbeads in the polymer matrix of sodium alginate (SA)/poly(vinylpyrrolidone)-co-vinyl acetate (PVP-co-VAc) intercalated with magnetite nanoparticles (MNPs) using glutaraldehyde (GA)/calcium chloride CaCl2 as the crosslinker. Methods: Magnetite nanoparticles (MNPs) were synthesized by a modified co-precipitation method. Curcumin encapsulated SA/PVP-co-VAc microbeads, intercalated with MNPs were prepared by simple ionotropic gelation technique. The formation of microbeads and uniform distribution of curcumin were characterized using spectroscopic methods. In addition, swelling and drug release kinetic studies of the microbeads were performed in simulated intestinal fluid (pH 7.4) and simulated gastric fluid (pH 1.2) at 37 °C. Results: Microbeads formation was confirmed by Fourier Transform Infrared (FTIR). Differential Scanning Calorimetry (DSC) studies reveal that the peak at 181 °C of CUR was not observed in CUR loaded microbeads, which confirms that CUR was encapsulated at the molecular level in the polymer matrix. The X-Ray diffraction (X-RD) diffractograms of CUR shows 2Ө peaks between 12-28 °, which indicated the crystalline nature of CUR, these peaks are not found in CUR loaded microbeads, suggesting that the drug has been molecularly dispersed in the polymer matrix. The X-RD 2Ө peaks of MNPs are observed in the MNPs loaded microbeads, which confirms that MNPs are successfully loaded in the microbeads. The swelling studies and in vitro release studies were performed at pH 1.2 and 7.4. The results reveal that at pH 7.4 highest swelling and release was observed, which confirms that the developed microbeads are pH sensitive and are suitable for intestinal drug delivery. The drug release kinetics fit into the Korsmeyer-Peppas equation, indicating non-Fickian diffusion. Conclusion: The results concluded that the present system as dependent on pH of the test medium and hence suggest suitability for intestinal drug delivery

Artificial neural network based delamination prediction in composite plates using vibration signals

Dynamic loading on composite components may induce damages such as cracks, delaminations, etc. and development of an early damage detection technique for delamination prediction is one of the most important aspects in ensuring the integrity and safety of such components. The presence of damages such as delaminations on the composites reduces its stiffness and changes the dynamic behaviour of the structures. As the loss in stiffness leads to changes in the natural frequencies, mode shapes, and other aspects of the structure, vibration analysis may be the ideal technique for delamination prediction. In this research work, the supervised feed-forward multilayer back-propagation Artificial Neural Network is used to determine the position and area of delaminations in glass fiber-reinforced polymer (GFRP) plates using changes in natural frequencies as inputs. The natural frequencies were obtained by finite element analysis and results are validated experimentally. The findings show that the suggested technique can satisfactorily estimate the location and extent of delaminations in composite plates

SODIUM ALGINATE/GELATIN MICROBEADS-INTERCALATED WITH KAOLIN NANOCLAY FOR EMERGING DRUG DELIVERY IN WILSON’S DISEASE

Objective: The aim of the present study was to fabricate and evaluate the drug release studies using Sodium Alginate (SA) and Gelatin (GE) microbeads intercalated with Kaolin (KA) nanoclay for sustained release of D-Penicillamine (D-PA). Methods: Sodium alginate/gelatin/Kaolin blend microbeads were prepared by an extrusion method by using glutaraldehyde (GA) as a crosslinker. The obtained microbeads were characterized by Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM) and X–ray diffraction (XRD). Drug release kinetics of the microbeads was investigated in simulated intestinal fluid (pH 7.4) at 37 °C. Results: Microbeads formation was confirmed by FTIR spectroscopy. X-RD reveals that the KA should be intercalated with the drug and also it confirms the molecular level dispersion of D-Penicillamine into microbeads. Scanning Electron Microscopy (SEM) studies reveal that the beads were in spherical shape with some wrinkled depressions on the surface. The in vitro release study indicates the D-Penicillamine released in a controlled manner. The in vitro release kinetics was assessed by Korsmeyer-Peppas equation and the ‘n’ value lies in between 0.557-0.693 indicates Non-Fickian diffusion process. Conclusion: The results suggest that the developed KA intercalated microbeads are good potential drug carrier for the controlled release of D-PA

PBEF1/NAmPRTase/Visfatin: a potential malignant astrocytoma/glioblastoma serum marker with prognostic value

Malignant astrocytomas comprise anaplastic astrocytoma (AA; grade III) and Glioblastoma (GBM; grade IV). GBM is the most malignant with a median survival of 10-12 months in patients. Using cDNA microarray based expression profiling of different grades of astrocytomas, we identified several fold increased levels of PBEF1 transcripts in GBM samples. Pre-B-cell colony enhancing factor 1 gene (PBEF1) encodes Nicotinamide phosphoribosyltransferase (NAmPRTase), which catalyses the rate limiting step in the salvage pathway of NAD metabolism in mammalian cells. Further validation using real time RT-qPCR on an independent set of tumor samples (n=91) and normal brain samples (n=9), GBM specific higher expression of PBEF1 was confirmed. Immunohistochemical staining for PBEF1 on a subset of the above samples largely reinforced our finding. We carried out ELISA analysis on serum samples of astrocytoma patients to determine whether this protein levels would correlate with the presence of tumor and tumor grade. PBEF1 serum levels were substantially elevated in many of the AA and GBM patients. Statistical analysis of these data indicates that in patients with astrocytoma, serum PBEF1 levels correlate with tumor grade and is highest in GBM. Immunohistochemical analysis of an independent set of 51 retrospective GBM cases with known survival data revealed that PBEF1 expression in the tumor tissue along with its co-expression with p53 was associated with poor survival. Thus, we have identified PBEF1 as a potential malignant astrocytoma serum marker and prognostic indicator among GBMs

Upregulation of ASCL1 and inhibition of Notch signaling pathway characterize progressive astrocytoma

Astrocytoma is the most common type of brain cancer constituting more than half of all brain tumors. With an aim to identify markers describing astrocytoma progression, we have carried out microarray analysis of astrocytoma samples of different grades using cDNA microarray containing 1152 cancer-specific genes. Data analysis identified several differentially regulated genes between normal brain tissue and astrocytoma as well as between grades II/III astrocytoma and glioblastoma multiforme (GBM; grade IV). We found several genes known to be involved in malignancy including Achaete-scute complex-like 1 (Drosophila) (ASCL1; Hash 1). As ASCL has been implicated in neuroendocrine, medullary thyroid and small-cell lung cancers, we chose to examine the role of ASCL1 in the astrocytoma development. Our data revealed that ASCL1 is overexpressed in progressive astrocytoma as evidenced by increased levels of ASCL1 transcripts in 85.71% (6/7) of grade II diffuse astrocytoma (DA), 90% (9/10) of grade III anaplastic astrocytoma (AA) and 87.5% (7/8) of secondary GBMs, while the majority of primary de novo GBMs expressed similar to or less than normal brain levels (66.67%; 8/12). ASCL1 upregulation in progressive astrocytoma is accompanied by inhibition of Notch signaling as seen by uninduced levels of HES1, a transcriptional target of Notch1, increased levels of HES6, a dominant-negative inhibitor of HES1-mediated repression of ASCL1, and increased levels of Notch ligand Delta1, which is capable of inhibiting Notch signaling by forming intracellular Notch ligand autonomous complexes. Our results imply that inhibition of Notch signaling may be an important early event in the development of grade II DA and subsequent progression to grade III AA and secondary GBM. Furthermore, ASCL1 appears to be a putative marker to distinguish primary GBM from secondary GBM

Novel glioblastoma markers with diagnostic and prognostic value identified through transcriptome analysis

Purpose: Current methods of classification of astrocytoma based on histopathologic methods are often subjective and less accurate. Although patients with glioblastoma have grave prognosis, significant variability in patient outcome is observed. Therefore, the aim of this study was to identify glioblastoma diagnostic and prognostic markers through microarray analysis. Experimental Design: We carried out transcriptome analysis of 25 diffusely infiltrating astrocytoma samples [WHO grade II - diffuse astrocytoma, grade III - anaplastic astrocytoma, and grade IV - glioblastoma (GBM)] using cDNA microarrays containing 18,981 genes. Several of the markers identified were also validated by real-time reverse transcription quantitative PCR and immunohistochemical analysis on an independent set of tumor samples (n = 100). Survival analysis was carried out for two markers on another independent set of retrospective cases (n = 51). Results: We identified several differentially regulated grade-specific genes. Independent validation by real-time reverse transcription quantitative PCR analysis found growth arrest and DNA-damage-inducible α (GADD45α) and follistatin-like 1 (FSTL1) to be up-regulated in most GBMs (both primary and secondary), whereas superoxide dismutase 2 and adipocyte enhancer binding protein 1 were up-regulated in the majority of primary GBM. Further, identification of the grade-specific expression of GADD45α and FSTL1 by immunohistochemical staining reinforced our findings. Analysis of retrospective GBM cases with known survival data revealed that cytoplasmic overexpression of GADD45α conferred better survival while the coexpression of FSTL1 with p53 was associated with poor survival. Conclusions: Our study reveals that GADD45α and FSTLI are GBM-specific whereas superoxide dismutase 2 and adipocyte enhancer binding protein 1 are primary GBM-specific diagnostic markers. Whereas GADD45α overexpression confers a favorable prognosis, FSTL1 overexpression is a hallmark of poor prognosis in GBM patients

Trilaciclib prior to chemotherapy and atezolizumab in patients with newly diagnosed extensive-stage small cell lung cancer: A multicentre, randomised, double-blind, placebo-controlled Phase II trial

Trilaciclib is an intravenous CDK4/6 inhibitor administered prior to chemotherapy to preserve haematopoietic stem and progenitor cells and immune system function from chemotherapy-induced damage (myelopreservation). The effects of administering trilaciclib prior to carboplatin, etoposide and atezolizumab (E/P/A) were evaluated in a randomised, double-blind, placebo-controlled Phase II study in patients with newly diagnosed extensive-stage small cell lung cancer (ES-SCLC) (NCT03041311). The primary endpoints were duration of severe neutropenia (SN; defined as absolute neutrophil count <0.5 × 109 cells per L) in Cycle 1 and occurrence of SN during the treatment period. Other endpoints were prespecified to assess the effects of trilaciclib on additional measures of myelopreservation, patient-reported outcomes, antitumour efficacy and safety. Fifty-two patients received trilaciclib prior to E/P/A and 53 patients received placebo. Compared to placebo, administration of trilaciclib resulted in statistically significant decreases in the mean duration of SN in Cycle 1 (0 vs 4 days; P < .0001) and occurrence of SN (1.9% vs 49.1%; P < .0001), with additional improvements in red blood cell and platelet measures and health-related quality of life (HRQoL). Trilaciclib was well tolerated, with fewer grade ≥3 adverse events compared with placebo, primarily due to less high-grade haematological toxicity. Antitumour efficacy outcomes were comparable. Administration of trilaciclib vs placebo generated more newly expanded peripheral T-cell clones (P = .019), with significantly greater expansion among patients with an antitumour response to E/P/A (P = .002). Compared with placebo, trilaciclib administered prior to E/P/A improved patients' experience of receiving treatment for ES-SCLC, as shown by reduced myelosuppression, and improved HRQoL and safety profiles