577 research outputs found
Mutual Coupling Reduction of DRA for MIMO Applications
In this paper, A multiple input Multiple Output (MIMO) antenna using two Square Dielectric Resonators (SDRs) is introduced. The mutual coupling between the two SDRAs is reduced using two different methods; the first method is based on splitting a spiral slot in the ground plane, then filling the slot with dielectric material, "E.=2.2". The second method is based on inserting a copper parasitic element, having the same shape of the splitted Spiral, between the two SDRAs. The effect of replacing the copper parasitic element with Carbon nanotubes (CNTs) parasitic element "SOC12 doped long-MWCNT BP" is also studied. The antenna system is designed to operate at 6 GHz. The analysis and simulations are carried out using finite element method (FEM). The defected ground plane method gives a maximum isolation of l8dB at element spacing of 30mm (0.6λo), whereas the parasitic element method gives a maximum isolation of 42.5dB at the same element spacing
Multi-Classification Model for Brain Tumor Early Prediction Based on Deep Learning Techniques
Brain tumor early prediction is a critical task in medical imaging, as early detection and classification of tumors can significantly improve patient outcomes and treatment planning. In this study, we propose multi-classification models based on deep learning techniques for early prediction of brain tumors using magnetic resonance imaging (MRI) scans. Specifically, we investigate the effectiveness of Convolutional Neural Networks (CNN) in the You Only Look Once (YOLO) approach for an accurate classification of brain tumors into multiple classes based on their morphological characteristics. The proposed model is designed to extract spatial features from MRI images, capturing local patterns and structures indicative of different tumor types. Moreover, the model is employed to analyze sequential MRI images over time, capturing temporal dynamics and changes in tumor characteristics. Experimental results on a large dataset of labelled MRI scans demonstrate the effectiveness of the proposed multi-classification model in accurately predicting brain tumor types at an early stage. Comparative analysis and evaluation metrics such as accuracy, validation, and losses\u27 curves versus epochs, in addition to a confusion matrix, are presented to assess the performance of each model. Results have indicated that YOLO v8 yielded 96% accuracy in training samples and up to 100% accuracy in testing samples
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2D versus 3D human induced pluripotent stem cell-derived cultures for neurodegenerative disease modelling
Neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and amyotrophic lateral sclerosis (ALS), affect millions of people every year and so far, there are no therapeutic cures available. Even though animal and histological models have been of great aid in understanding disease mechanisms and identifying possible therapeutic strategies, in order to find disease-modifying solutions there is still a critical need for systems that can provide more predictive and physiologically relevant results. One possible avenue is the development of patient-derived models, e.g. by reprogramming patient somatic cells into human induced pluripotent stem cells (hiPSCs), which can then be differentiated into any cell type for modelling. These systems contain key genetic information from the donors, and therefore have enormous potential as tools in the investigation of pathological mechanisms underlying disease phenotype, and progression, as well as in drug testing platforms. hiPSCs have been widely cultured in 2D systems, but in order to mimic human brain complexity, 3D models have been proposed as a more advanced alternative. This review will focus on the use of patient-derived hiPSCs to model AD, PD, HD and ALS. In brief, we will cover the available stem cells, types of 2D and 3D culture systems, existing models for neurodegenerative diseases, obstacles to model these diseases in vitro, and current perspectives in the field
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A report of novel STIM1 deficiency and 6 year follow up of two previous cases associated with mild immunological phenotype
Loss of function or null mutations of Stromal interaction molecule 1 (STIM1) are known to cause early-onset combined immunodeficiency (CID) disease with recurrent and chronic infections, autoimmunity, haemolytic anaemia, ectodermal dysplasia, muscular weakness and myalgia. here we report of novel STIM1 deficiency and 6 year follow up of two previous cases associated with mild immunological phenotyp
Functionalized poly(N-isopropylacrylamide)-based microgels in tumor targeting and drug delivery
Over the past several decades, the development of engineered small particles as targeted and drug delivery systems (TDDS) has received great attention thanks to the possibility to overcome the limitations of classical cancer chemotherapy, including targeting incapability, nonspecific action and, consequently, systemic toxicity. Thus, this research aims at using a novel design of Poly(N-isopropylacrylamide) p(NIPAM)-based microgels to specifically target cancer cells and avoid the healthy ones, which is expected to decrease or eliminate the side effects of chemotherapeutic drugs. Smart NIPAM-based microgels were functionalized with acrylic acid and coupled to folic acid (FA), targeting the folate receptors overexpressed by cancer cells and to the chemotherapeutic drug doxorubicin (Dox). The successful conjugation of FA and Dox was demonstrated by dynamic light scattering (DLS), Fourier-transform infrared (FTIR) spectroscopy, thermogravimetric analysis (TGA), UV-VIS analysis, and differential scanning calorimetry (DSC). Furthermore, viability assay performed on cancer and healthy breast cells, suggested the microgels’ biocompatibility and the cytotoxic effect of the conjugated drug. On the other hand, the specific tumor targeting of synthetized microgels was demonstrated by a co-cultured (healthy and cancer cells) assay monitored using confocal microscopy and flow cytometry. Results suggest successful targeting of cancer cells and drug release. These data support the use of pNIPAM-based microgels as good candidates as TDDS
Expanding clinical phenotype and novel insights into the pathogenesis of ICOS deficiency
Background: Inducible T cell co-stimulator (ICOS) deficiency has been categorized as a combined immunodeficiency often complicated by enteropathies, autoimmunity, lymphoproliferation, and malignancy. We report seven new patients and four novel ICOS mutations resulting in a common variable immunodeficiency (CVID)–like phenotype and show that dysregulated IL-12 release, reduced cytotoxic T lymphocyte–associated protein 4 (CTLA4) expression, and skewing towards a Th1-dominant phenotype are all associated with inflammatory complications in this condition.
Methods: A combination of whole exome and Sanger sequencing was used to identify novel mutations. Standard clinical and immunological evaluation was performed. FACS and ELISA-based assays were used to study cytokine responses and ICOS/ICOSL/CTLA4 expression following stimulation of whole blood and PBMCs with multiple TLR ligands, anti-CD3, and PHA.
Results: Four novel ICOS mutations included homozygous c.323_332del, homozygous c.451C>G, and compound heterozygous c.58+1G>A/c.356T>C. The predominant clinical phenotype was that of antibody deficiency associated with inflammatory complications in 4/7 patients. Six out of seven patients were treated with immunoglobulin replacement and one patient died from salmonella sepsis. All patients who were tested showed reduced IL-10 and IL-17 cytokine responses, normal IL-1β, IL6, and TNF release following LPS stimulation and highly elevated IL-12 production in response to combined LPS/IFNγ stimulation. This was associated with skewing of CD4+ T cells towards Th1 phenotype and increased expression of ICOSL on monocytes. Lastly, reduced CTLA4 expression was found in 2 patients. One patient treated with ustekinumab for pancytopenia due to granulomatous bone marrow infiltration failed to respond to this targeted therapy.
Conclusions: ICOS deficiency is associated with defective T cell activation, with simultaneously enhanced stimulation of monocytes. The latter is likely to result from a lack of ICOS/ICOSL interaction which might be necessary to provide negative feedback which limits monocytes activation
T cells are depleted in HCV-induced hepatocellular carcinoma patients: possible role of apoptosis and p53
A lipidomic screen of hyperglycemia-treated HRECs links 12/15-Lipoxygenase to microvascular dysfunction during diabetic retinopathy via NADPH oxidase
Retinal hyperpermeability and subsequent macular edema is a cardinal feature of early diabetic retinopathy (DR). Here, we investigated the role of bioactive lipid metabolites, in particular 12/15-lipoxygenase (LOX)-derived metabolites, in this process. LC/MS lipidomic screen of human retinal endothelial cells (HRECs) demonstrated that 15-HETE was the only significantly increased metabolite (2.4 ± 0.4-fold, P = 0.0004) by high glucose (30 mM) treatment. In the presence of arachidonic acid, additional eicosanoids generated by 12/15-LOX, including 12- and 11-HETEs, were significantly increased. Fluorescein angiography and retinal albumin leakage showed a significant decrease in retinal hyperpermeability in streptozotocin-induced diabetic mice lacking 12/15-LOX compared with diabetic WT mice. Our previous studies demonstrated the potential role of NADPH oxidase in mediating the permeability effect of 12- and 15-HETEs, therefore we tested the impact of intraocular injection of 12-HETE in mice lacking the catalytic subunit of NADPH oxidase (NOX2). The permeability effect of 12-HETE was significantly reduced in NOX2−/− mice compared with the WT mice. In vitro experiments also showed that 15-HETE induced HREC migration and tube formation in a NOX-dependent manner. Taken together our data suggest that 12/15-LOX is implicated in DR via a NOX-dependent mechanism.National Institutes of Health Grant 5R01EY023315 and National Priorities Research Program Grant 4-1046-3-284 from the Qatar National Research Fund (a member of Qatar Foundation). This study was also supported in part by the National Center for Research Resources, National Institutes of Health Grant S10RR027926
Evidence on the inhibitory effect of Brassica plants against Acinetobacter baumannii lipases: phytochemical analysis, in vitro, and molecular docking studies
Background
Infections caused by Acinetobacter baumannii are becoming a rising public health problem due to its high degree of acquired and intrinsic resistance mechanisms. Bacterial lipases penetrate and damage host tissues, resulting in multiple infections. Because there are very few effective inhibitors of bacterial lipases, new alternatives for treating A. baumannii infections are urgently needed. In recent years, Brassica vegetables have received a lot of attention since their phytochemical compounds have been directly linked to diverse antimicrobial actions by inhibiting the growth of various Gram-positive and Gram-negative bacteria, yeast, and fungi. Despite their longstanding antibacterial history, there is currently a lack of scientific evidence to support their role in the management of infections caused by the nosocomial bacterium, A. baumannii. This study aimed to address this gap in knowledge by examining the antibacterial and lipase inhibitory effects of six commonly consumed Brassica greens, Chinese cabbage (CC), curly and Tuscan kale (CK and TK), red and green Pak choi (RP and GP), and Brussels sprouts (BR), against A. baumannii in relation to their chemical profiles.
Methods
The secondary metabolites of the six extracts were identified using LC-QTOF-MS/MS analysis, and they were subsequently correlated with the lipase inhibitory activity using multivariate data analysis and molecular docking.
Results
In total, 99 metabolites from various chemical classes were identified in the extracts. Hierarchical cluster analysis (HCA) and principal component analysis (PCA) revealed the chemical similarities and variabilities among the specimens, with glucosinolates and phenolic compounds being the major metabolites. RP and GP showed the highest antibacterial activity against A. baumannii, followed by CK. Additionally, four species showed a significant effect on the bacterial growth curves and demonstrated relevant inhibition of A. baumannii lipolytic activity. CK showed the greatest inhibition (26%), followed by RP (21%), GP (21%), and TK (15%). Orthogonal partial least squares-discriminant analysis (OPLS-DA) pinpointed 9 metabolites positively correlated with the observed bioactivities. Further, the biomarkers displayed good binding affinities towards lipase active sites ranging from −70.61 to −30.91 kcal/mol, compared to orlistat.
Conclusion
This study emphasizes the significance of Brassica vegetables as a novel natural source of potential inhibitors of lipase from A. baumannii
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