Search results for: receptor diffusion

Authors: Mukurdipi Ray, Seema Singh

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Extrauterine endometrial stromal sarcoma (ESS) is a rare entity and typified by delayed recurrence of primary ESS. Here, we present an unusual case of uterine ESS in a woman with a history of hysterectomy. A 19-year-old girl, underwent a hysterectomy and bilateral salpingo-oophorectomy for uterine ESS 12 months ago and now after remaining disease free for nine months ago she presented with ascites along with pelvic and peritoneal mass. Intraoperatively, the large omental mass was found, and optimal cytoreduction with total omentomy (supracolic and infracolic ) total peritonectomy and hyperthermic intraperitoneal chemotherapy (HIPEC) was offered to the patient. Final histopathology report showed the involvement of only omentum by ESS cells. Immunohistochemistry (IHC) and receptor study were done and it was positive for CD-10 and desmin and negative for CK- 7. This case highlights the rarity of extrauterine ESS in the omentum with a known history of primary uterine ESS which was treated successfully with the above-mentioned procedure. Though active and long-term surveillance is recommended to monitor for late recurrences.

Keywords: endrometrial stromal sarcoma, complete cytoreduction, hyperthermic intra peritoneal chemotherapy, total omentectomy

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Authors: Hakan Akin

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The aim of this study was to examine the policy making process in Turkish Health System. This policy making process will be examined through public policy change theories. Since political actors played in the formulation of public policies also explains the type of policy change, this actors will be inspected in the supranational and national basis. Also the transformation of public policy in the Turkish health care system will be analysed under the concepts of New right ideology, neo-liberalism, neo-conservatism and governance. And after this analyse, the outputs and outcomes of this transformation will be discussed in the context of developing countries.

Keywords: policy transfer, policy diffusion, policy convergence, new right, governance

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Authors: Mouna Mesbahi, M. Loutfi Benkhedir

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In CZTS films solar cell, the preferable reaction between Cu and sulfur vapor was likely to be induced by out diffusion of the bottom Cu component to the surface; this would lead to inhomogeneous distribution of the Cu component to form the Cu2SnS3 secondary phase and formation of many voids and crevices in the resulting CZTS film; which is also the cause of the decline in performance. In this work we study the electronic and optical properties of Cu2SnS3. For this purpose we used the Wien2k code based on the theory of density functional theory (DFT) with the modified Becke-Johnson exchange potential mBJ and the Hubbard potential individually or combined. We have found an energy gap 0.92 eV. The results are in good agreement with experimental results.

Keywords: Cu2SnS3, DFT, electronic and optical properties, mBJ+U, WIEN2K

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Authors: Mehrnaz Mostafavi, Mahtab Shabani, Alireza Azani, Fatemeh Ghafari

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Artificial intelligence (AI) can transform breast cancer diagnosis and therapy by providing sophisticated solutions for screening, imaging interpretation, histopathological analysis, and treatment planning. This literature review digs into the many uses of AI in breast cancer treatment, highlighting the need for collaboration between AI scientists and healthcare practitioners. It emphasizes advances in AI-driven breast imaging interpretation, such as computer-aided detection and diagnosis (CADe/CADx) systems and deep learning algorithms. These have shown significant potential for improving diagnostic accuracy and lowering radiologists' workloads. Furthermore, AI approaches such as deep learning have been used in histopathological research to accurately predict hormone receptor status and categorize tumor-associated stroma from regular H&E stains. These AI-powered approaches simplify diagnostic procedures while providing insights into tumor biology and prognosis. As AI becomes more embedded in breast cancer care, it is crucial to ensure its ethical, efficient, and patient-focused implementation to improve outcomes for breast cancer patients ultimately.

Keywords: breast cancer, artificial intelligence, cancer diagnosis, clinical practice

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Authors: Jahanshah Ashkani, Kevin J. Naidoo

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Glycosylation is the major posttranslational modification (PTM) process in cellular development. In tumour development, it is marked by structural alteration of carbohydrates (glycans) that is the result of aberrant glycosylation. Altered glycan structures affect cell surface ligand-receptor interactions that interfere with the regulation of cell adhesion, migration, and proliferation. The resulting changes in glycan biosynthesis pathways originate from altered expression of glycosyltransferases and glycosidases. While the alteration in glycosylation patterns is a recognized “hallmark of cancer”, the influential overview of the biology of cancer proposes eight hallmarks with no explicit suggestion to connectivity with glycosylation. Recently, we have discovered a connection between the glycosyltransferase gene expression and cancer type and subtype. Here we present an association between aberrant glycosylation and the biological hallmarks of breast cancer by exploring the common regulatory mechanisms at the genomic scale. The result of this study bridges the glycobiological and biological pathways that are accepted hallmarks of cancer by connecting their common regulatory pathways. This is an impetus for further investigation as target therapies of breast cancer are very likely to be uncovered from this.

Keywords: aberrant glycosylation, biological hallmarks, breast cancer, regulatory mechanism

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Authors: Shikha Masand, Sudesh Kumar Yadav

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Certain protein kinases have been shown to be crucial for plant cell signaling pathways associated with plant immune responses. Here we identified a horsegram [Macrotyloma uniflorum (Lam.) Verdc.] malectin-like leucine rich receptor-like protein kinase (RLK) gene MuRLK. The functional MuRLK protein preferentially binds to mannose and N-acetyl glucosamine residues. MuRLK exists in the cytoplasm and also localizes to the plasma membrane of plant cells via its N-terminus. Over-expression of MuRLK in Arabidopsis enhances the basal resistance to infection with Pseudomonas syringae pv. tomato, Alternaria brassicicola and Hyaloperonospora arabidopsidis, are associated with elevated ROS bursts, MAPK activation, thus ultimately leading to hypersensitive cell death. Moreover, salicylic acid-dependent and jasmonic acid-dependent defense responses are also enhanced in the MuRLK-overexpressed plants that lead to HR-induced cell death. Together, these results suggest that MuRLK plays a key role in the regulation of plant cell death, early and late defense responses after the recognition of microbial pathogens.

Keywords: horsegram, Pseudomonas syringae pv. tomato, MuRLK, ROS burst, cell death, plant defense

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Authors: Farzad Khajavi, Farzaneh Jalilfar, Faranak Jafari, Leila Shokrani

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Formulation of Ranolazine in the form of extended-release tablet in 500 mg dosage form was performed using Eudragit L100-55 as a retarding agent. Drug-release profiles were investigated in comparison with the reference Ranexa extended-release 500 mg tablet. F₂ and f₁ were calculated as 64.16 and 8.53, respectively. According to Peppas equation, the release of drug is controlled by diffusion (n=0.5). The tablets were put into accelerated stability conditions (40 °C, 75% humidity) for 3 and 6 months. The dissolution release profiles and other physical and chemical characteristics of the tablets confirmed the robustness and stability of formulation in this condition.

Keywords: drug release, extended-release tablet, ranolazine, stability

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Authors: Jeremy J. Johnson

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Mediterranean herbs including rosemary (Rosmarinus officinalis) contain a variety of phytochemicals including diterpenes that possess extensive biological activity. Applications of diterpenes, including the more abundant forms carnosol and carnosic acid, have been shown to possess anti-cancer, anti-inflammatory, anti-oxidant, and anti-proliferation properties. To confirm these properties, we have evaluated rosemary extract and selected diterpenes for biological activity in cancer and inflammatory models. Our preliminary data have revealed that select diterpenes can disrupt androgen receptor functionality in prostate and breast cancer cells. This property is unique among natural products for hormone-responsive cancers. The second area of interest has been evaluating rosemary extract and selected diterpenes for activation of sestrin-2, an antioxidant protein, in colon cancer cells. A combination of in vitro and in vivo approaches have been utilized to characterize the activity of rosemary diterpenes in rosemary. Taken together, these results suggest that phytochemicals found in rosemary have distinct pharmacological actions for disrupting cell-signaling pathways in cancer and inflammatory bowel disease.

Keywords: rosemary, diterpene, cancer, inflammation

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Authors: Nendouvhada Livhuwani Portia, Nicole Sibuyi, Kwazikwakhe Gabuza, Adewale Fadaka

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Metabolic dysfunction-associated liver disease (MASLD) is a chronic condition characterized by excessive fat accumulation in the liver, distinct from conditions caused by alcohol, viral hepatitis, or medications. MASLD is often linked with metabolic syndrome, including obesity, diabetes, hyperlipidemia, and hypertriglyceridemia. This disease can progress to metabolic dysfunction-associated steatohepatitis (MASH), marked by liver inflammation and scarring, potentially leading to cirrhosis. However, only 43-44% of patients with steatosis develop MASH, and 7-30% of those with MASH progress to cirrhosis. The exact mechanisms underlying MASLD and its progression remain unclear, and there are currently no specific therapeutic strategies for MASLD/MASH. While anti-obesity and anti-diabetic medications can reduce progression, they do not fully treat or reverse the disease. As an alternative, green-synthesized metal nanoparticles (MNPs) are emerging as potential treatments for liver diseases due to their anti-diabetic, anti-inflammatory, and anti-obesity properties with minimal side effects. MNPs like gold nanoparticles (AuNPs) and silver nanoparticles (AgNPs) have been shown to improve metabolic processes by lowering blood glucose, body fat, and inflammation. The study aimed to explore the effects of green-synthesized MNPs on gene expression in an in vitro model of MASH using C3A/HepG2 liver cells. The MASH model was created by exposing these cells to free fatty acids (FFAs) followed by lipopolysaccharide (LPS) to induce inflammation. Cell viability was assessed with the Water-Soluble Tetrazolium (WST)-1 assay, and lipid accumulation was measured using the Oil Red O (ORO) assay. Additionally, mitochondrial membrane potential was assessed by the tetramethyl rhodamine, methyl ester (TMRE) assay, and inflammation was measured with an Enzyme-Linked Immunosorbent Assay (ELISA). The study synthesized AuNPs from Carpobrotus edulis fruit (CeF) and avocado seed (AvoSE) and AgNPs from Salvia africana-lutea (SAL) using optimized conditions. The MNPs were characterized by UV-Vis spectrophotometry and Dynamic Light Scattering (DLS). The nanoparticles were tested at various concentrations for their impact on the C3A/HepG2-induced MASH model. Among the MNPs tested, AvoSE-AuNPs showed the most promise. They reduced cell proliferation and intracellular lipid content more effectively than CeFE-AuNPs and SAL-AgNPs. Molecular analysis using real-time polymerase chain reaction revealed that AvoSE-AuNPs could potentially reverse MASH effects by reducing the expression of key pro-inflammatory and metabolic genes, including tumor necrosis factor-alpha (TNF-α), Fas cell surface death receptor (FAS), Peroxisome proliferator-activated receptor (PPAR)-α, PPAR-γ, and Sterol regulatory element-binding protein (SREBPF)-1. Further research is needed to confirm the molecular mechanisms behind the effects of these MNPs and to identify the specific phytochemicals responsible for their synthesis and bioactivities.

Keywords: gold nanoparticles, green nanotechnology, metal nanoparticles, obesity

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Authors: L. Torchane

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This study is devoted to defining the optimal conditions for the nitriding of pure iron at atmospheric pressure by using NH3-Ar-C3H8 gas mixtures. After studying the mechanisms of phase formation and mass transfer at the gas-solid interface, a mathematical model is developed in order to predict the nitrogen transfer rate in the solid, the ε-carbonitride layer growth rate and the nitrogen and carbon concentration profiles. In order to validate the model and to show its possibilities, it is compared with thermogravimetric experiments, analyses and metallurgical observations (X-ray diffraction, optical microscopy and electron microprobe analysis). Results obtained allow us to demonstrate the sound correlation between the experimental results and the theoretical predictions.

Keywords: gaseous nitrocarburizing, kinetic model, diffusion, layer growth kinetic

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Authors: Maha Mourad, Fady Todros

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The objective of this research is to find an explanatory model to define the most important variables and factors that affect the acceptance of Mobile Internet in the Egyptian market. A qualitative exploratory research was conducted to support the conceptual framework followed with a quantitative research in the form of a survey distributed among 411 respondents. It was clear that relative advantage, complexity, compatibility, perceived price level and perceived playfulness have a dominant role in influencing consumers to adopt mobile internet, while observability is correlated to the adoption but when measured with the other factors it lost its value. The perceived price level has a negative relationship with the adoption as well the compatibility.

Keywords: innovation, Egypt, communication technologies, diffusion, innovation adoption, emerging market

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Authors: G. E. Sharaf El-Deen, S. E. A. Sharaf El-Deen

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Activated carbon was prepared from coconut shell (ACS); a discarded agricultural waste was used to produce bioadsorbent through easy and environmental friendly processes. This activated carbon based biosorbent was evaluated for adsorptive removal of lead from water. The characterisation results showed this biosorbent had very high specific surface area and functional groups. The adsorption equilibrium data was well described by Langmuir, whilst kinetics data by pseudo-first order, pseudo-second order and Intraparticle diffusion models. The adsorption process could be described by the pseudo-second order kinetic.

Keywords: coconut shell, activated carbon, adsorption isotherm and kinetics, lead removal

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Authors: Marina Passero, Tianhua Zhai, Zuyi (Jacky) Huang

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Alzheimer’s disease has become a major public health issue, as indicated by the increasing populations of Americans living with Alzheimer’s disease. After decades of extensive research in Alzheimer’s disease, only seven drugs have been approved by Food and Drug Administration (FDA) to treat Alzheimer’s disease. Five of these drugs were designed to treat the dementia symptoms, and only two drugs (i.e., Aducanumab and Lecanemab) target the progression of Alzheimer’s disease, especially the accumulation of amyloid-b plaques. However, controversial comments were raised for the accelerated approvals of either Aducanumab or Lecanemab, especially with concerns on safety and side effects of these two drugs. There is still an urgent need for further drug discovery to target the biological processes involved in the progression of Alzheimer’s disease. Excessive cholesterol has been found to accumulate in the brain of those with Alzheimer’s disease. Cholesterol can be synthesized in both the blood and the brain, but the majority of biosynthesis in the adult brain takes place in astrocytes and is then transported to the neurons via ApoE. The blood brain barrier separates cholesterol metabolism in the brain from the rest of the body. Various proteins contribute to the metabolism of cholesterol in the brain, which offer potential targets for Alzheimer’s treatment. In the astrocytes, SREBP cleavage-activating protein (SCAP) binds to Sterol Regulatory Element-binding Protein 2 (SREBP2) in order to transport the complex from the endoplasmic reticulum to the Golgi apparatus. Cholesterol is secreted out of the astrocytes by ATP-Binding Cassette A1 (ABCA1) transporter. Lipoprotein receptors such as triggering receptor expressed on myeloid cells 2 (TREM2) internalize cholesterol into the microglia, while lipoprotein receptors such as Low-density lipoprotein receptor-related protein 1 (LRP1) internalize cholesterol into the neuron. Cytochrome P450 Family 46 Subfamily A Member 1 (CYP46A1) converts excess cholesterol to 24S-hydroxycholesterol (24S-OHC). Cholesterol has been approved for its direct effect on the production of amyloid-beta and tau proteins. The addition of cholesterol to the brain promotes the activity of beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), secretase, and amyloid precursor protein (APP), which all aid in amyloid-beta production. The reduction of cholesterol esters in the brain have been found to reduce phosphorylated tau levels in mice. In this work, a computational pipeline was developed to identify the protein targets involved in cholesterol regulation in brain and further to identify chemical compounds as the inhibitors of a selected protein target. Since extensive evidence shows the strong correlation between brain cholesterol regulation and Alzheimer’s disease, a detailed literature review on genes or pathways related to the brain cholesterol synthesis and regulation was first conducted in this work. An interaction network was then built for those genes so that the top gene targets were identified. The involvement of these genes in Alzheimer’s disease progression was discussed, which was followed by the investigation of existing clinical trials for those targets. A ligand-protein docking program was finally developed to screen 1.5 million chemical compounds for the selected protein target. A machine learning program was developed to evaluate and predict the binding interaction between chemical compounds and the protein target. The results from this work pave the way for further drug discovery to regulate brain cholesterol to combat Alzheimer’s disease.

Keywords: Alzheimer’s disease, drug discovery, ligand-protein docking, gene-network analysis, cholesterol regulation

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Authors: Leena Ahmad Khaleel Alfarani, Maggie McPherson, Neil Morris

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Over the last decade, m-learning has been widely accepted and utilized by many western universities. However, Saudi universities face many challenges in utilizing such technology, a central one being to encourage teachers to use such technology. Although there are several factors that affect faculty members’ participation in the adoption of m-learning, this paper focuses merely on two factors, the usefulness and ease of using m-learning. A sample of 279 faculty members in one Saudi university has responded to the online survey. The results of the study have revealed that there is a statistically significant relationship (at the 0.05 level) between both usefulness and ease of using m-learning factors and the intention of teachers to use m-learning currently and in the future.

Keywords: mobile learning, diffusion of innovation theory, technology acceptance, faculty adoption

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Authors: Yisau Adelaja Odusote, Olakanmi Felix Akinto

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The associative tendency between like atoms in molten Cd-Ga and Cd-In alloy systems has been studied by using the Quasi-Chemical Approximation Model (QCAM). The concentration dependence of the microscopic functions (the concentration-concentration fluctuations in the long-wavelength limits, Scc(0), the chemical short-range order (CSRO) parameter α1 as well as the chemical diffusion) and the mixing properties as the free energy of mixing, GM, enthalpy of mixing and entropy of mixing of the two molten alloys have been determined. Thermodynamic properties of both systems deviate positively from Raoult's law, while the systems are characterized by positive interaction energy. The role of atomic size ratio on the alloying properties was discussed.

Keywords: homo-pairs, interchange energy, enthalpy, entropy, Cd-Ga, Cd-In

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Authors: Kuei-Ling Sun, Emily Chia-Yu Su

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Allergy is a hypersensitive overreaction of the immune system to environmental stimuli, and a major health problem. These overreactions include rashes, sneezing, fever, food allergies, anaphylaxis, asthmatic, shock, or other abnormal conditions. Allergies can be caused by food, insect stings, pollen, animal wool, and other allergens. Their development of allergies is due to both genetic and environmental factors. Allergies involve immunoglobulin E antibodies, a part of the body’s immune system. Immunoglobulin E antibodies will bind to an allergen and then transfer to a receptor on mast cells or basophils triggering the release of inflammatory chemicals such as histamine. Based on the increasingly serious problem of environmental change, changes in lifestyle, air pollution problem, and other factors, in this study, we both collect allergens and non-allergens from several databases and use several machine learning methods for classification, including logistic regression (LR), stepwise regression, decision tree (DT) and neural networks (NN) to do the model comparison and determine the permutations of allergen amino acid’s sequence.

Keywords: allergy, classification, decision tree, logistic regression, machine learning

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Authors: Xingxin Wu, Fenli Shao, Tao Tan, Yang Tan, Yang Sun, Qiang Xu

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Psoriasis is a chronic inflammatory skin disease that affects about 2% of the world's population. IL-23 signaling plays a key role in the pathogenesis of psoriasis. Control of IL-23 release by small molecule compounds during developing psoriasis has not been well established. Here, we show that compound 1, a small molecule nature product, protected mice from imiquimod-induced psoriasis with improved skin lesions, reduced skin thickness, and reduced IL-23 mRNA expression in the skin tissue. FACS results showed compound 1 reduced the number of dendritic cells in the skin. Interestingly, compound 1 was not able to ameliorate IL-23-induced psoriasis-like skin inflammation in mice. Further, compound 1 inhibited MyD88-dependent IL-23 mRNA expression induced by LPS, CpG and imiquimod in BMDC cells, but not MyD88-independent CD80 and CD86 expression induced by LPS. The methods included real-time PCR, western blot, H & E staining, FACS and ELISA et al. In conclusion, compound 1 regulates MyD88-dependent signaling to control IL-23 release in dendritic cells, which improves imiquimod-induced psoriasis.

Keywords: dendritic cells, IL-23, toll-like receptor signaling, psoriasis

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Authors: Muhammad Asif Rasheed

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Newcastle disease virus (NDV), an avian orthoavulavirus, is a causative agent of Newcastle disease named (NDV) and can cause even the epidemics when the disease is not treated. Previously several vaccines based on attenuated and inactivated viruses have been reported, which are rendered useless with the passage of time due to versatile changes in viral genome. Therefore, we aimed to develop an effective multi-epitope vaccine against the haemagglutinin neuraminidase (HN) protein of 26 NDV strains from Pakistan through a modern immunoinformatic approaches. As a result, a vaccine chimaera was constructed by combining T-cell and B-cell epitopes with the appropriate linkers and adjuvant. The designed vaccine was highly immunogenic, non-allergen, and antigenic; therefore, the potential 3D-structureof multi epitope vaccine was constructed, refined, and validated. A molecular docking study of a multiepitope vaccine candidate with the chicken Toll-like receptor-4 indicated successful binding. An In silico immunological simulation was used to evaluate the candidate vaccine's ability to elicit an effective immune response. According to the computational studies, the proposed multiepitope vaccine is physically stable and may induce immune responses, whichsuggested it a strong candidate against 26 Newcastle disease virus strains from Pakistan. A wet lab study is under process to confirm the results.

Keywords: epitopes, newcastle disease virus, paramyxovirus virus, vaccine

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Authors: Sarah E. Nelson, Casey Weiner, Alexander Sigmon, Jun Hua, Haris I. Sair, Jose I. Suarez, Robert D. Stevens

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Graph-theoretical information from structural connectomes indicated significant connectivity changes and improved acute prognostication in a Random Forest (RF) model in aneurysmal subarachnoid hemorrhage (aSAH), which can lead to significant morbidity and mortality and has traditionally been fraught by poor methods to predict outcome. This study’s hypothesis was that structural connectivity changes occur in canonical brain networks of acute aSAH patients, and that these changes are associated with functional outcome at six months. In a prospective cohort of patients admitted to a single institution for management of acute aSAH, patients underwent diffusion tensor imaging (DTI) as part of a multimodal MRI scan. A weighted undirected structural connectome was created of each patient’s images using Constant Solid Angle (CSA) tractography, with 176 regions of interest (ROIs) defined by the Johns Hopkins Eve atlas. ROIs were sorted into four networks: Default Mode Network, Executive Control Network, Salience Network, and Whole Brain. The resulting nodes and edges were characterized using graph-theoretic features, including Node Strength (NS), Betweenness Centrality (BC), Network Degree (ND), and Connectedness (C). Clinical (including demographics and World Federation of Neurologic Surgeons scale) and graph features were used separately and in combination to train RF and Logistic Regression classifiers to predict two outcomes: dichotomized modified Rankin Score (mRS) at discharge and at six months after discharge (favorable outcome mRS 0-2, unfavorable outcome mRS 3-6). A total of 56 aSAH patients underwent DTI a median (IQR) of 7 (IQR=8.5) days after admission. The best performing model (RF) combining clinical and DTI graph features had a mean Area Under the Receiver Operator Characteristic Curve (AUROC) of 0.88 ± 0.00 and Area Under the Precision Recall Curve (AUPRC) of 0.95 ± 0.00 over 500 trials. The combined model performed better than the clinical model alone (AUROC 0.81 ± 0.01, AUPRC 0.91 ± 0.00). The highest-ranked graph features for prediction were NS, BC, and ND. These results indicate reorganization of the connectome early after aSAH. The performance of clinical prognostic models was increased significantly by the inclusion of DTI-derived graph connectivity metrics. This methodology could significantly improve prognostication of aSAH.

Keywords: connectomics, diffusion tensor imaging, graph theory, machine learning, subarachnoid hemorrhage

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Authors: Hind O. Osman, Tilal Elsaman, Bashir A. Yousef, Esraa Elhadi, Aimun A. E. Ahmed, Eyman Mohamed Eltayib, Malik Suliman Mohamed, Magdi Awadalla Mohamed

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Epilepsy is the most common neurological condition and cause of substantial morbidity and mortality. In the present study, the molecular hybridization tool was adopted to obtain six Schiff bases of isatin and adamantane-1-carbohydrazide (18–23). Then, their anticonvulsant activity was evaluated using a pentylenetetrazole- (PTZ-) induced seizure model using phenobarbitone as a positive control. Our findings showed that compounds 18–23 provided significant protection against PTZ-induced seizure, and maximum activities were associated with compound 23. Moreover, all investigated compounds increased the latency of induced convulsion and reduced the duration of epilepsy, with compound 23 being the best. Interestingly, most of the synthesized molecules showed a reduction in neurological symptoms and severity of the seizure. Molecular docking studies suggest GABA-A receptor as a potential target, and in silico ADME screening revealed that the pharmaceutical properties of compound 23 are within the specified limit. Thus, compound 23 was identified as a promising candidate that warrants further drug discovery processes.

Keywords: isatin and adamantane, anticonvulsant activity, PTZ-induced seizure, molecular docking

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Authors: Manal Kamel, Sara Maher

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Development of sensitive non-invasive tests for detection of SARS-CoV-2 antigens is imperative to manage the extent of infection throughout the population, yet, it is still challenging. Here, we designed and optimized a sandwich enzyme-linked immunosorbent assay (ELISA) for SARS-CoV-2 S1 antigen detection in saliva. Both saliva samples and nasopharyngeal swapswere collected from 170 PCR-confirmed positive and negative cases. Gold nanoparticles (AuNPs) were conjugated with S1protein receptor binding domain (RBD) nanobodies. Recombinant S1 monoclonal antibodies (S1mAb) as primery antibody and gold conjugated nanobodies as secondary antibody were employed in sandwich ELISA. Our developed system were optimized to achieve 87.5 % sensitivity and 100% specificity for saliva samples compared to 89 % and 100% for nasopharyngeal swaps, respectively. This means that saliva could be a suitable replacement for nasopharyngeal swaps No cross reaction was detected with other corona virus antigens. These results revealed that our developed ELISAcould be establishedas a new, reliable, sensitive, and non-invasive test for diagnosis of SARS-CoV-2 infection, using the easily collected saliva samples.

Keywords: COVID 19, diagnosis, ELISA, nanobodies

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Authors: Rajeswari Raguraman, Sowmya Parameswaran, Krishnakumar Subramanian, Jagat Kanwar, Rupinder Kanwar

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Background: Tumor microenvironment has been implicated in several cancers to regulate cell growth, invasion and metastasis culminating in outcome of therapy. Tumor stroma consists of multiple cell types that are in constant cross-talk with the tumor cells to favour a pro-tumorigenic environment. Not much is known about the existence of tumor microenvironment in the pediatric intraocular malignancy, Retinoblastoma (RB). In the present study, we aim to understand the multiple stromal cellular subtypes and tumor stromal interactions expressed in RB tumors. Materials and Methods: Immunohistochemistry for stromal cell markers CD31, CD68, alpha-smooth muscle (α-SMA), vimentin and glial fibrillary acidic protein (GFAP) was performed on formalin fixed paraffin embedded tissues sections of RB (n=12). The differential expression of stromal target molecules; fibroblast activation protein (FAP), tenascin-C (TNC), osteopontin (SPP1), bone marrow stromal antigen 2 (BST2), stromal derived factor 2 and 4 (SDF2 and SDF4) in primary RB tumors (n=20) and normal retina (n=5) was studied by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and Western blotting. The differential expression was correlated with the histopathological features of RB. The interaction between RB cell lines (Weri-Rb-1, NCC-RbC-51) and Bone marrow stromal cells (BMSC) was also studied using direct co-culture and indirect co-culture methods. The functional effect of the co-culture methods on the RB cells was evaluated by invasion and proliferation assays. Global gene expression was studied by using Affymetrix 3’ IVT microarray. Pathway prediction was performed using KEGG and the key molecules were validated using qRT-PCR. Results: The immunohistochemistry revealed the presence of several stromal cell types such as endothelial cells (CD31+;Vim+/-); macrophages (CD68+;Vim+/-); Fibroblasts (Vim+; CD31-;CD68- );myofibroblasts (α-SMA+/ Vim+) and invading retinal astrocytes/ differentiated retinal glia (GFAP+; Vim+). A characteristic distribution of these stromal cell types was observed in the tumor microenvironment, with endothelial cells predominantly seen in blood vessels and macrophages near actively proliferating tumor or necrotic areas. Retinal astrocytes and glia were predominant near the optic nerve regions in invasive tumors with sparse distribution in tumor foci. Fibroblasts were widely distributed with rare evidence of myofibroblasts in the tumor. Both gene and protein expression revealed statistically significant (P<0.05) up-regulation of FAP, TNC and BST2 in primary RB tumors compared to the normal retina. Co-culture of BMSC with RB cells promoted invasion and proliferation of RB cells in direct and indirect contact methods respectively. Direct co-culture of RB cell lines with BMSC resulted in gene expression changes in ECM-receptor interaction, focal adhesion, IL-8 and TGF-β signaling pathways associated with cancer. In contrast, various metabolic pathways such a glucose, fructose and amino acid metabolism were significantly altered under the indirect co-culture condition. Conclusion: The study suggests that the close interaction between RB cells and the stroma might be involved in RB tumor invasion and progression which is likely to be mediated by ECM-receptor interactions and secretory factors. Targeting the tumor stroma would be an attractive option for redesigning treatment strategies for RB.

Keywords: gene expression profiles, retinoblastoma, stromal cells, tumor microenvironment

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Authors: Veronique Jubera, Ka-Young Kim, U-Chan Chung, Amelie Veillere, Jean-Marc Heintz

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Emitting materials and all solid state lasers are widely used in the field of optical applications and materials science as a source of excitement, instrumental measurements, medical applications, metal shaping etc. Recently promising optical efficiencies were recorded on ceramics which result from a cheaper and faster ways to obtain crystallized materials. The choice and optimization of the sintering process is the key point to fabricate transparent ceramics. It includes a high control on the preparation of the powder with the choice of an adequate synthesis, a pre-heat-treatment, the reproducibility of the sintering cycle, the polishing and post-annealing of the ceramic. The densification is the main factor needed to reach a satisfying transparency, and many technologies are now available. The symmetry of the unit cell plays a crucial role in the diffusion rate of the material. Therefore, the cubic symmetry compounds having an isotropic refractive index is preferred. The cubic Y3NbO7 matrix is an interesting host which can accept a high concentration of rare earth doping element and it has been demonstrated that SPS is an efficient way to sinter this material. The optimization of diffusion losses requires a microstructure of fine ceramics, generally less than one hundred nanometers. In this case, grain growth is not an obstacle to transparency. The ceramics properties are then isotropic thereby to free-shaping step by orienting the ceramics as this is the case for the compounds of lower symmetry. After optimization of the synthesis route, several SPS parameters as heating rate, holding, dwell time and pressure were adjusted in order to increase the densification of the Eu3+ doped Y3NbO7 pellets. The luminescence data coupled with X-Ray diffraction analysis and electronic diffraction microscopy highlight the existence of several distorted environments of the doping element in the studied defective fluorite-type host lattice. Indeed, the fast and high crystallization rate obtained to put in evidence a lack of miscibility in the phase diagram, being the final composition of the pellet driven by the ratio between niobium and yttrium elements. By following the luminescence properties, we demonstrate a direct impact on the SPS process on this material.

Keywords: emission, niobate of rare earth, Spark plasma sintering, lack of miscibility

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Authors: Waheed Zahra, Mohamed El-Beltagy, Ashraf El Mhlawy, Reda Elkhadrawy

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In this paper, we consider singular perturbation reaction-diffusion boundary value problems, which contain a small uncertain perturbation parameter. To solve these problems, we propose a numerical method which is based on an exponential spline and Shishkin mesh discretization. While interval analysis principle is used to deal with the uncertain parameter, sensitivity analysis has been conducted using different methods. Numerical results are provided to show the applicability and efficiency of our method, which is ε-uniform convergence of almost second order.

Keywords: singular perturbation problem, shishkin mesh, two small parameters, exponential spline, interval analysis, sensitivity analysis

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Authors: N. Ibrahim-Rassoul, A. Kessi, E. K. Si-Ahmed, N. Djilali, J. Legrand

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The static and dynamic formation of liquid water bridges is analyzed using a combination of visualization experiments in a microchannel with a mathematical model. This paper presents experimental and theoretical findings of water plug/capillary bridge formation in a 250 μm squared microchannel. The approach combines mathematical and numerical modeling with experimental visualization and measurements. The generality of the model is also illustrated for flow conditions encountered in manipulation of polymeric materials and formation of liquid bridges between patterned surfaces. The predictions of the model agree favorably the observations as well as with the experimental recordings.

Keywords: green energy, mathematical modeling, fuel cell, water plug, gas diffusion layer, surface of revolution

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Authors: Remi Safi, Aline Hamade, Najat Bteich, Jamal El Saghir, Mona Diab Assaf, Marwan El-Sabban, Fadia Najjar

Abstract:

Estrogen is considered a risk factor for breast cancer since it promotes breast-cell proliferation. The jaesckeanadiol-3-p-hydroxyphenylpropanoate, a hemi-synthetic analogue of the natural phytoestrogen ferutinin (jaesckeanadiol-p-hydroxybenzoate), is designed to be devoid of estrogenic activity. This analogue induces a cytotoxic effect 30 times higher than that of ferutinin towards MCF-7 breast cancer cell line. We compared these two compounds with respect to their effect on proliferation, cell cycle distribution and cancer stem-like cells in the MCF-7 cell line. Treatment with ferutinin (30 μM) and its analogue (1 μM) produced a significant accumulation of cells at the pre G0/G1 cell cycle phase and triggered apoptosis. Importantly, this compound retains its anti-proliferative activity against breast cancer stem/progenitor cells that are naturally insensitive to ferutinin at the same dose. These results position ferutinin analogue as an effective compound inhibiting the proliferation of estrogen-dependent breast cancer cells and consistently targeting their stem-like cells.

Keywords: ferutinin, hemi-synthetic analogue, breast cancer, estrogen, stem/progenitor cells

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Authors: Daniel Osorio, Janneth Gonzalez, Andres Pinzon

Abstract:

In this work, proteins and metabolic pathways associated with the neuroprotective response mediated by the synthetic neurosteroid tibolone under a palmitate-induced inflammatory model were identified by flux balance analysis (FBA). Three different metabolic scenarios (‘healthy’, ‘inflamed’ and ‘medicated’) were modeled over a gene expression data-driven constructed tissue-specific metabolic reconstruction of mature astrocytes. Astrocyte reconstruction was built, validated and constrained using three open source software packages (‘minval’, ‘g2f’ and ‘exp2flux’) released through the Comprehensive R Archive Network repositories during the development of this work. From our analysis, we predict that tibolone executes their neuroprotective effects through a reduction of neurotoxicity mediated by L-glutamate in astrocytes, inducing the activation several metabolic pathways with neuroprotective actions associated such as taurine metabolism, gluconeogenesis, calcium and the Peroxisome Proliferator Activated Receptor signaling pathways. Also, we found a tibolone associated increase in growth rate probably in concordance with previously reported side effects of steroid compounds in other human cell types.

Keywords: astrocytes, flux balance analysis, genome scale metabolic reconstruction, inflammation, neuroprotection, tibolone

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Authors: Subhayan Maity

Abstract:

Complete scenario of cosmic evolution from emergent phase to late time acceleration (i.e. non-singular ever expanding Universe) is a popular preference in the recent cosmology. Yet one can’t exclude the idea that other type of evolution pattern of the Universe may also be possible. Especially, the bouncing scenario is becoming a matter of interest now a days. The present work is an exhibition of such a different pattern of cosmic evolution where the evolution of Universe has been shown as a cyclic thermodynamic process. Under diffusion mechanism (non-equilibrium thermodynamic process), the cosmic evolution has been modelled as [ emergent - accelerated expansion - decelerated expansion - decelerated contraction - accelerated contraction - emergent] .

Keywords: non-equilibrium thermodynamics, non singular evolution of universe, cyclic evolution, diffusive fluid

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Authors: Feng Zhang, Li Chen, Desong Kong, Xiaoping Zhang, Xiaojing Zhu, Yin Lu, Shizhong Zheng

Abstract:

Sinusoidal pathological angiogenesis is a novel therapeutic target for liver fibrosis. We demonstrated that curcumin ameliorated fibrotic injury and sinusoidal angiogenesis in rat liver with fibrosis caused by carbon tetrachloride. Curcumin reduced the expression of angiogenic markers in fibrotic liver. Experiments in vitro showed that the viability and vascularization of rat liver sinusoidal endothelial cells (LSECs) were not impaired by curcumin. Further investigations showed that curcumin inhibited VEGF expression in hepatic stellate cells (HSCs) by disrupting PDGF-βR/ERK and mTOR pathways. HSC motility and vascularization were also suppressed by curcumin via blocking PDGF-βR/FAK/RhoA cascade. Gain- or loss-of-function analyses revealed that activation of PPARγ was required for curcumin to inhibit angiogenic properties of HSCs. We concluded that curcumin attenuated sinusoidal angiogenesis in liver fibrosis possibly by targeting HSCs via a PPARγ activation-dependent mechanism. PPARγ could be a target molecule for reducing pathological angiogenesis during liver fibrosis.

Keywords: angiogenesis, hepatic stellate cell, curcumin, peroxisome proliferator-activated receptor-γ

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Authors: Arpita Roy, Navneeta Bharadvaja

Abstract:

Cancer is an uncontrolled growth of abnormal cells in the body. It is one of the most serious diseases on which extensive research work has been going on all over the world. Structure-based drug designing is a computational approach which helps in the identification of potential leads that can be used for the development of a drug. Plumbagin is a naphthoquinone derivative from Plumbago zeylanica roots and belongs to one of the largest and diverse groups of plant metabolites. Anticancer and antiproliferative activities of plumbagin have been observed in animal models as well as in cell cultures. Plumbagin shows inhibitory effects on multiple cancer-signaling proteins; however, the binding mode and the molecular interactions have not yet been elucidated for most of these protein targets. In this investigation, an attempt to provide structural insights into the binding mode of plumbagin against four cancer receptors using molecular docking was performed. Plumbagin showed minimal energy against targeted cancer receptors, therefore suggested its stability and potential towards different cancers. The least binding energies of plumbagin with COX-2, TACE, and CDK6 are -5.39, -4.93, -and 4.81 kcal/mol, respectively. Comparison studies of plumbagin with different receptors showed that it is a promising compound for cancer treatment. It was also found that plumbagin obeys the Lipinski’s Rule of 5 and computed ADMET properties which showed drug likeliness and improved bioavailability. Since plumbagin is from a natural source, it has reduced side effects, and these results would be useful for cancer treatment.

Keywords: cancer, receptor, plumbagin, docking

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