Search results for: glioma invasion
52 Update on Epithelial Ovarian Cancer (EOC), Types, Origin, Molecular Pathogenesis, and Biomarkers
Authors: Salina Yahya Saddick
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Ovarian cancer remains the most lethal gynecological malignancy due to the lack of highly sensitive and specific screening tools for detection of early-stage disease. The OSE provides the progenitor cells for 90% of human ovarian cancers. Recent morphologic, immunohistochemical and molecular genetic studies have led to the development of a new paradigm for the pathogenesis and origin of epithelial ovarian cancer (EOC) based on a ualistic model of carcinogenesis that divides EOC into two broad categories designated Types I and II which are characterized by specific mutations, including KRAS, BRAF, ERBB2, CTNNB1, PTEN PIK3CA, ARID1A, and PPPR1A, which target specific cell signaling pathways. Type 1 tumors rarely harbor TP53. type I tumors are relatively genetically stable and typically display a variety of somatic sequence mutations that include KRAS, BRAF, PTEN, PIK3CA CTNNB1 (the gene encoding beta catenin), ARID1A and PPP2R1A but very rarely TP53 . The cancer stem cell (CSC) hypothesis postulates that the tumorigenic potential of CSCs is confined to a very small subset of tumor cells and is defined by their ability to self-renew and differentiate leading to the formation of a tumor mass. Potential protein biomarker miRNA, are promising biomarkers as they are remarkably stable to allow isolation and analysis from tissues and from blood in which they can be found as free circulating nucleic acids and in mononuclear cells. Recently, genomic anaylsis have identified biomarkers and potential therapeutic targets for ovarian cancer namely, FGF18 which plays an active role in controlling migration, invasion, and tumorigenicity of ovarian cancer cells through NF-κB activation, which increased the production of oncogenic cytokines and chemokines. This review summarizes update information on epithelial ovarian cancers and point out to the most recent ongoing research.Keywords: epithelial ovarian cancers, somatic sequence mutations, cancer stem cell (CSC), potential protein, biomarker, genomic analysis, FGF18 biomarker
Procedia PDF Downloads 38051 Engineering a Tumor Extracellular Matrix Towards an in vivo Mimicking 3D Tumor Microenvironment
Authors: Anna Cameron, Chunxia Zhao, Haofei Wang, Yun Liu, Guang Ze Yang
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Since the first publication in 1775, cancer research has built a comprehensive understanding of how cellular components of the tumor niche promote disease development. However, only within the last decade has research begun to establish the impact of non-cellular components of the niche, particularly the extracellular matrix (ECM). The ECM, a three-dimensional scaffold that sustains the tumor microenvironment, plays a crucial role in disease progression. Cancer cells actively deregulate and remodel the ECM to establish a tumor-promoting environment. Recent work has highlighted the need to further our understanding of the complexity of this cancer-ECM relationship. In vitro models use hydrogels to mimic the ECM, as hydrogel matrices offer biological compatibility and stability needed for long term cell culture. However, natural hydrogels are being used in these models verbatim, without tuning their biophysical characteristics to achieve pathophysiological relevance, thus limiting their broad use within cancer research. The biophysical attributes of these gels dictate cancer cell proliferation, invasion, metastasis, and therapeutic response. Evaluating the three most widely used natural hydrogels, Matrigel, collagen, and agarose gel, the permeability, stiffness, and pore-size of each gel were measured and compared to the in vivo environment. The pore size of all three gels fell between 0.5-6 µm, which coincides with the 0.1-5 µm in vivo pore size found in the literature. However, the stiffness for hydrogels able to support cell culture ranged between 0.05 and 0.3 kPa, which falls outside the range of 0.3-20,000 kPa reported in the literature for an in vivo ECM. Permeability was ~100x greater than in vivo measurements, due in large part to the lack of cellular components which impede permeation. Though, these measurements prove important when assessing therapeutic particle delivery, as the ECM permeability decreased with increasing particle size, with 100 nm particles exhibiting a fifth of the permeability of 10 nm particles. This work explores ways of adjusting the biophysical characteristics of hydrogels by changing protein concentration and the trade-off, which occurs due to the interdependence of these factors. The global aim of this work is to produce a more pathophysiologically relevant model for each tumor type.Keywords: cancer, extracellular matrix, hydrogel, microfluidic
Procedia PDF Downloads 9150 Russian pipeline natural gas export strategy under uncertainty
Authors: Koryukaeva Ksenia, Jinfeng Sun
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Europe has been a traditional importer of Russian natural gas for more than 50 years. In 2021, Russian state-owned company Gazprom supplied about a third of all gas consumed in Europe. The Russia-Europe mutual dependence in terms of natural gas supplies has been causing many concerns about the energy security of the two sides for a long period of time. These days the issue has become more urgent than ever considering recent Russian invasion in Ukraine followed by increased large-scale geopolitical conflicts, making the future of Russian natural gas supplies and global gas markets as well highly uncertain. Hence, the main purpose of this study is to get insight into the possible futures of Russian pipeline natural gas exports by a scenario planning method based on Monte-Carlo simulation within LUSS model framework, and propose Russian pipeline natural gas export strategies based on the obtained scenario planning results. The scenario analysis revealed that recent geopolitical disputes disturbed the traditional, longstanding model of Russian pipeline gas exports, and, as a result, the prospects and the pathways for Russian pipeline gas on the world markets will differ significantly from those before 2022. Specifically, our main findings show, that (i) the events of 2022 generated many uncertainties for the long-term future of Russian pipeline gas export perspectives on both western and eastern supply directions, including geopolitical, regulatory, economic, infrastructure and other uncertainties; (ii) according to scenario modelling results, Russian pipeline exports will face many challenges in the future, both on western and eastern directions. A decrease in pipeline gas exports will inevitably affect country’s natural gas production and significantly reduce fossil fuel export revenues, jeopardizing the energy security of the country; (iii) according to proposed strategies, in order to ensure the long-term stable export supplies in the changing environment, Russia may need to adjust its traditional export strategy by performing export flows and product diversification, entering new markets, adapting its contracting mechanism, increasing competitiveness and gaining a reputation of a reliable gas supplier.Keywords: Russian natural gas, Pipeline natural gas, Uncertainty, Scenario simulation, Export strategy
Procedia PDF Downloads 6049 Cocoa Stimulates the Production Bioactive Components of Lactobacillus Casei and Competitively Excludes Foodborne Pathogens
Authors: Mengfei Peng, Serajus Salaheen, Debabrata Biswas
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Lactobacillus casei found in the human intestine and mouth is commonly applied for dairy production. Recently, it was found that some byproducts produced by Lactobacillus exhibited antimicrobial activities against multiple bacteria. Meanwhile, introduction of prebiotic-like foods (e.g. cocoa) or probiotics or both of them as food supplements in human diets as well as in farm animal feeds is believed to be an effective ways in control/reduce the colonization of foodborne bacterial pathogens infection in the gut environment. We hypothesized that cocoa may stimulate the production antimicrobial components of Lactobacillus casei and may potentially inhibit/reduce the colonization and infection of foodborne bacterial pathogens in the gut. Mixed culture of L. casei (LC) with enterohemorrhagic E. coli EDL933 (EHEC), Salmonella Typhimurium LT2 (ST), or Listeria monocytogenes LM2 (LM) showed that LC could competitively exclude (100%) them within 72 h. Further, investigation of cell-free culture supernatant (CFCS) revealed that the antimicrobial effects of LC came from CFCS. CFCS of LC eliminated (100%) EHEC, ST, and LM within 72 h, and 2 h CFCS treatment increased the hydrophobicity of EHEC (5.10 folds), ST (8.48 folds), and LM (2.03 folds). In addition, LC cells exhibited more inhibitive effects than CFCS on cell adhesive and invasive activities of EHEC (52.14% & 90.45%), ST (66.89% & 93.83%), and LM (61.10% & 83.40%). Two clusters of poly-peptides in CFCS were identified by SDS-PAGE, the molecular weights of which are ≈5 KD and 40-45 KD. LC CFCS with overnight growth in the presence of 3% strengthened all of the antimicrobial activities (growth inhibition, outer membrane disruption, and cell infective ability reduction). Liquid chromatography/Mass spectrometry analysis detected 5 unique components in class of flavonoids in LC CFCS with overnight 3% cocoa supplement. Furthermore, qPCR results showed that CFCSs up-regulated the expression level of genes responsible for flagellin synthesis and motility, but down-regulated genes for specific binding and invasion-associated proteins synthesis. The stimulatory effects of cocoa in producing bioactive components of probiotics may aid prevention of foodborne illness caused by major foodborne enteric bacterial pathogens.Keywords: foodborne pathogens, probiotics, prebiotics, pathogen exclusion
Procedia PDF Downloads 43348 Investigating the Use of Seaweed Extracts as Biopesticides
Authors: Emma O’ Keeffe, Helen Hughes, Peter McLoughlin, Shiau Pin Tan, Nick McCarthy
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Biosecurity is emerging as one of the most important issues facing the agricultural and forestry community. This is as a result of increased invasion from new pests and diseases with the main protocol for dealing with these species being the use of synthetic pesticides. However, these chemicals have been shown to exhibit negative effects on the environment. Seaweeds represent a vast untapped resource of bio-molecules with a broad range of biological activities including pesticidal. This project investigated both the antifungal and antibacterial activity of seaweed species against two problematic root rot fungi, Armillaria mellea and Heterobasidion annosum and ten quarantine bacterial plant pathogens including Xanthomonas arboricola, Xanthomonas fragariae, and Erwinia amylovora. Four seaweed species were harvested from the South-East coast of Ireland including brown, red and green varieties. The powdered seaweeds were extracted using four different solvents by liquid extraction. The poisoned food technique was employed to establish the antifungal efficacy, and the standard disc diffusion assay was used to assess the antibacterial properties of the seaweed extracts. It was found that extracts of the green seaweed exhibited antifungal activity against H. annosum, with approximately 50% inhibition compared to the negative control. The protectant activities of the active extracts were evaluated on disks of Picea sitchensis, a plant species sensitive to infection from H. annosum and compared to the standard chemical control product urea. The crude extracts exhibited very similar activity to the 10% and 20% w/v concentrations of urea, demonstrating the ability of seaweed extracts to compete with commercially available products. Antibacterial activity was exhibited by a number of seaweed extracts with the red seaweed illustrating the strongest activity, with a zone of inhibition of 15.83 ± 0.41 mm exhibited against X. arboricola whilst the positive control (10 μg/disk of chloramphenicol) had a zone of 26.5 ± 0.71 mm. These results highlight the potential application of seaweed extracts in the forestry and agricultural industries for use as biopesticides. Further work is now required to identify the bioactive molecules that are responsible for this antifungal and antibacterial activity in the seaweed extracts, including toxicity studies to ensure the extracts are non-toxic to plants and humans.Keywords: antibacterial, antifungal, biopesticides, seaweeds
Procedia PDF Downloads 17347 The Second Generation of Tyrosine Kinase Inhibitor Afatinib Controls Inflammation by Regulating NLRP3 Inflammasome Activation
Authors: Shujun Xie, Shirong Zhang, Shenglin Ma
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Background: Chronic inflammation might lead to many malignancies, and inadequate resolution could play a crucial role in tumor invasion, progression, and metastases. A randomised, double-blind, placebo-controlled trial shows that IL-1β inhibition with canakinumab could reduce incident lung cancer and lung cancer mortality in patients with atherosclerosis. The process and secretion of proinflammatory cytokine IL-1β are controlled by the inflammasome. Here we showed the correlation of the innate immune system and afatinib, a tyrosine kinase inhibitor targeting epidermal growth factor receptor (EGFR) in non-small cell lung cancer. Methods: Murine Bone marrow derived macrophages (BMDMs), peritoneal macrophages (PMs) and THP-1 were used to check the effect of afatinib on the activation of NLRP3 inflammasome. The assembly of NLRP3 inflammasome was check by co-immunoprecipitation of NLRP3 and apoptosis-associated speck-like protein containing CARD (ASC), disuccinimidyl suberate (DSS)-cross link of ASC. Lipopolysaccharide (LPS)-induced sepsis and Alum-induced peritonitis were conducted to confirm that afatinib could inhibit the activation of NLRP3 in vivo. Peripheral blood mononuclear cells (PBMCs) from non-small cell lung cancer (NSCLC) patients before or after taking afatinib were used to check that afatinib inhibits inflammation in NSCLC therapy. Results: Our data showed that afatinib could inhibit the secretion of IL-1β in a dose-dependent manner in macrophage. Moreover, afatinib could inhibit the maturation of IL-1β and caspase-1 without affecting the precursors of IL-1β and caspase-1. Next, we found that afatinib could block the assembly of NLRP3 inflammasome and the ASC speck by blocking the interaction of the sensor protein NLRP3 and the adaptor protein ASC. We also found that afatinib was able to alleviate the LPS-induced sepsis in vivo. Conclusion: Our study found that afatinib could inhibit the activation of NLRP3 inflammasome in macrophage, providing new evidence that afatinib could target the innate immune system to control chronic inflammation. These investigations will provide significant experimental evidence in afatinib as therapeutic drug for non-small cell lung cancer or other tumors and NLRP3-related diseases and will explore new targets for afatinib.Keywords: inflammasome, afatinib, inflammation, tyrosine kinase inhibitor
Procedia PDF Downloads 11846 Antiangiogenic and Pro-Apoptotic Properties of Shemamruthaa: An Herbal Preparation in Experimental Mammary Carcinoma-Bearing Rats and Breast Cancer Cell Line In vitro
Authors: Nandhakumar Elumalai, Purushothaman Ayyakannu, Sachidanandam T. Panchanatham
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Background: Understanding the basic mechanisms and factors underlying the tumor growth and invasion has gained attention in recent times. The processes of angiogenesis and apoptosis are known to play a vital role in various stages of cancer. The vascular endothelial growth factor (VEGF) is well established as one of the key regulators of tumor angiogenesis while MMPs are known for their exclusive ability to degrade ECM. Objective: The present study was designed to evaluate the pro apoptotic and anti angiogenic activity of the herbal formulation Shemamruthaa. The anticancer activity of Shemamruthaa was tested in breast cancer cell line (MCF-7). Results of MTT, trypan blue and flow cytometric analysis of apoptotis suggested that Shemamruthaa can induce cytotoxicity in cancer cells, in a concentration- and time dependent manner and induce apoptosis. With these results, we further evaluated the antiangiogenic and pro-apoptotic activities of Shemamruthaa in DMBA induced mammary carcinoma in Sprague Dawley rats. Flavono tumour was induced in 8-week-old Sprague-Dawley rats by gastric intubation of 25 mg DMBA in 1ml olive oil. After 90 days of induction period, the rats were orally administered with Shemamruthaa (400 mg/kg body wt) for 45 days. Treatment with the drug SM significantly modulated the expression of p53, MMP-2, MMP-3, MMP-9 and VEGF by means of its anti angiogenic and protease inhibiting activity. Conclusion: Based on these results, it might be concluded that the formulation, Shemamruthaa, constituted of dried flowers of Hibiscus rosa-sinensis, fruits of Emblica officinalis, and honey has been found to exhibit pronounced antiproliferative and apoptotic effects. This enhanced anticancer effect of Shemamruthaa might be attributed to the synergistic action of polyphenols such as flavonoids, tannins, alkaloids, glycosides, saponins, steroids, terpenoids, vitamin C, niacin, pyrogallol, hydroxymethylfurfural, trilinolein, and other compounds present in the formulation. Collectively, these results demonstrate that Shemamruthaa holds potential to be developed as a potent chemotherapeutic agent against mammary carcinoma.Keywords: Shemamruthaa, flavonoids, MCF-7 cell line, mammary cancer
Procedia PDF Downloads 25245 Comparison of Home Ranges of Radio Collared Jaguars (Panthera onca L.) in the Dry Chaco and Wet Chaco of Paraguay
Authors: Juan Facetti, Rocky McBride, Karina Loup
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The Chaco Region of Paraguay is a key biodiverse area for the conservation of jaguars (Panthera onca), the largest feline of the Americas. It comprises five eco-regions, which holds important but decreasing populations of this species. The last decades, the expansion of soybean over the Atlantic Forest, forced the translocation of cattle-ranches towards the Chaco. Few studies of Jaguar's population densities in the American hemisphere were done until now. In the region, the specie is listed as vulnerable or threatened and more information is needed to implement any conservation policy. Among the factors that threaten the populations are land-use change, habitat fragmentation, prey depletion and illegal hunting. Two largest eco-regions were studied: the Wet Chaco and the Dry Chaco. From 2002 more than 20 jaguars were captured and fitted with GPS-collar. Data collected from 11 GPS-collars were processed, transformed numerically and finally converted into maps for analyzing. 8.092 locations were determined for four adult females (AF) and one adult male (AM) in the Wet Chaco, and one AF, one juvenile male (JM) and four AM in the Dry Chaco, during 1,867 days. GIS and kernel methodology were used to calculate daily distance of movement, home range-HR (95% isopleth), and core area (considered as 50% isopleth). In the Wet Chaco HR were 56 Km2 and 238 km2 for females and males respectively; while in the Dry Chaco HR were 685 Km2 and 844.5 km2 for females and males respectively, and 172 Km2 for a juvenile. Core areas of individual activity for each jaguar, were on average 11.5 Km2 and 33.55 km2 for AF and AM respectively in the Wet Chaco, while in the Dry Chaco were larger: 115 km2 for five AM and 225 Km2 for an AF and 32.4 Km2 for a JM. In both ecoregions, only one relevant overlap of HR of adults was reported. During the reproduction season, the HR (95% K) of one AM overlapped 49.83% with that of one AF. At the Wet Chaco, the maximum daily distance moved by an AF was 14.5 Km and 11.6 Km for the AM, while the Maximum Mean Daily Moved (MMDM) distance was 5.6 km for an AF and 3.1 km for an AM. At the Dry Chaco, the maximum daily distance for an AF was 61.7Km., 50.9Km for the AM and 6.6 Km for the JM, while the MMDM distance was 13.2 km for an AM and 8.4 km for an AF. This study confirmed that, as the invasion to jaguar habitat increased, it resulted in fragmented landscapes that influence spacing patterns of jaguars. Males used largest HR that of the smaller females and males covers largest distances that of the females. There appeared to be important spatial segregation between not only females but also males. It is likely that the larger areas used by males are partly caused by the sexual dimorphism in body size that entails differences in prey requirements. These could explain the larger distances travelled daily by males.Keywords: Chaco ecoregions, Jaguar, home range, Panthera onca, Paraguay
Procedia PDF Downloads 30244 Microalgae Hydrothermal Liquefaction Process Optimization and Comprehension to Produce High Quality Biofuel
Authors: Lucie Matricon, Anne Roubaud, Geert Haarlemmer, Christophe Geantet
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Introduction: This case discusses the management of two floor of mouth (FOM) Squamous Cell Carcinomas (SCC) not identified upon initial biopsy. Case Report: A 51 year-old male presented with right FOM erythroleukoplakia. Relevant medical history included alcoholic dependence syndrome and alcoholic liver disease. Relevant drug therapy encompassed acamprosate, folic acid, hydroxocobalamin and thiamine. The patient had a 55.5 pack-year smoking history and alcohol dependence from age 14, drinking 16 units/day. FOM incisional biopsy and histopathological analysis diagnosed Carcinoma in situ. Treatment involved wide local excision. Specimen analysis revealed two separate foci of pT1 moderately differentiated SCCs. Carcinoma staging scans revealed no pathological lymphadenopathy, no local invasion or metastasis. SCCs had been excised in completion with narrow margins. MDT discussion concluded that in view of the field changes it would be difficult to identify specific areas needing further excision, although techniques such as Lugol’s Iodine were considered. Further surgical resection, surgical neck management and sentinel lymph node biopsy was offered. The patient declined intervention, primary management involved close monitoring alongside alcohol and smoking cessation referral. Discussion: Narrow excisional margins can increase carcinoma recurrence risk. Biopsy failed to identify SCCs, despite sampling an area of clinical concern. For gross field change multiple incisional biopsies should be considered to increase chance of accurate diagnosis and appropriate treatment. Coupling of tobacco and alcohol has a synergistic effect, exponentially increasing the relative risk of oral carcinoma development. Tobacco and alcoholic control is fundamental in reducing treatment‑related side effects, recurrence risk, and second primary cancer development.Keywords: microalgae, biofuels, hydrothermal liquefaction, biomass
Procedia PDF Downloads 13343 Influence of Various Disaster Scenarios Assumption to the Advance Creation of Wide-Area Evacuation Plan Confronting Natural Disasters
Authors: Nemat Mohammadi, Yuki Nakayama
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After occurring Great East Japan earthquake and as a consequence the invasion of an extremely large Tsunami to the city, obligated many local governments to take into account certainly these kinds of issues. Poor preparation of local governments to deal with such kinds of disasters at that time and consequently lack of assistance delivery for local residents caused thousands of civilian casualties as well as billion dollars of economic damages. Those local governments who are responsible for governing such coastal areas, have to consider some countermeasures to deal with these natural disasters, prepare a comprehensive evacuation plan and contrive some feasible emergency plans for the purpose of victims’ reduction as much as possible. Under this evacuation plan, the local government should contemplate more about the traffic congestion during wide-area evacuation operation and estimate the minimum essential time to evacuate the whole city completely. This challenge will become more complicated for the government when the people who are affected by disasters are not only limited to the normal informed citizens but also some pregnant women, physically handicapped persons, old age citizens and foreigners or tourists who are not familiar with that conditions as well as local language are involved. The important issue to deal with this challenge is that how to inform these people to take a proper action right away noticing the Tsunami is coming. After overcoming this problem, next significant challenge is even more considerable. Next challenge is to evacuate the whole residents in a short period of time from the threated area to the safer shelters. In fact, most of the citizens will use their own vehicles to evacuate to the designed shelters and some of them will use the shuttle buses which are provided by local governments. The problem will arise when all residents want to escape from the threated area simultaneously and consequently creating a traffic jam on evacuation routes which will cause to prolong the evacuation time. Hence, this research mostly aims to calculate the minimum essential time to evacuate each region inside the threated area and find the evacuation start point for each region separately. This result will help the local government to visualize the situations and conditions during disasters and assist them to reduce the possible traffic jam on evacuation routes and consequently suggesting a comprehensive wide-area evacuation plan during natural disasters.Keywords: BPR formula, disaster scenarios, evacuation completion time, wide-area evacuation
Procedia PDF Downloads 21342 Chronic Progressive External Ophthalmoplegia (CPEO)
Authors: Gagandeep Singh Digra, Pawan Kumar, Mandeep Kaur Sidhu
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INTRODUCTION: Chronic Progressive External Ophthalmoplegia (CPEO), also known as Progressive External Ophthalmoplegia (PEO), is a type of eye disorder characterized by a loss of the muscle functions involved in eye and eyelid movement. CPEO can be caused by mutations in mitochondrial DNA. It typically manifests in young adults with bilateral and progressive ptosis as the most common presentation but can also present with difficulty swallowing (dysphagia) and general weakness of the skeletal muscles (myopathy), particularly in the neck, arms, or legs. CASE PRESENTATION: This is a case discussion of 3 cousins who presented to our clinic. A 23-year-old male with past surgical history (PSH) of ptosis repair 2 years ago presented with a chief complaint of nasal intonation for 1.5 years associated with difficulty swallowing. The patient also complained of nasal regurgitation of liquids. He denied any headaches, fever, seizures, weakness of arms or legs, urinary complaints or changes in bowel habits. Physical Examination was positive for facial muscle weakness, including an inability to lift eyebrows (Frontalis), inability to close eyes tightly (Orbicularis Oculi), corneal reflex absent bilaterally, difficulty clenching jaw (Masseter muscle), difficulty smiling (Zygomaticus major), inability to elevate upper lip (Zygomaticus minor). Another cousin of the first patient, a 25-year-old male with no past medical history, presented with complaints of nasal intonation for 2 years associated with difficulty swallowing. He denied a history of nasal regurgitation, headaches, fever, seizures, weakness, urinary complaints or changes in bowel habits. Physical Examination showed facial muscle weakness of the Frontalis muscle, Orbicularis Oculi muscle, Masseter Muscle, Zygomaticus Major, Zygomaticus Minor and absent corneal reflexes. A 28-year-old male, a cousin of the first two patients, presented with chief complaints of ptosis and nasal intonation for the last 8 years. He also complained of difficulty swallowing and nasal regurgitation of liquids. His physical examination showed facial muscle weakness, including frontalis muscle (inability to lift eyebrows), Orbicularis Oculi (inability to close eyes tightly), absent corneal reflexes bilaterally, Zygomaticus Major (difficulty smiling), and Zygomaticus Minor (inability to elevate upper lip). MRI brain and visual field of all the patients were normal. Differential diagnoses, including Grave’s disease, Myasthenia Gravis and Glioma, were ruled out. Due to financial reasons, muscle biopsy could not be pursued. Pedigree analysis revealed only males were affected, likely due to maternal inheritance, so the clinical diagnosis of CPEO was made. The patients underwent symptomatic management, including ptosis surgical correction for the third patient. CONCLUSION: Chronic Progressive External Ophthalmoplegia (CPEO), a rare case entity, occurs in young adults as a manifestation of mitochondrial myopathy. There are three modes of transmission- maternal transmission associated with mitochondrial point mutations, autosomal recessive, and autosomal dominant. CPEO can sometimes be difficult to diagnose, especially in asymmetric presentation. Therefore, it is crucial to keep it in differential diagnosis to avoid delay in diagnosis.Keywords: neurology, chronic, progressive, ophthalmoplegia
Procedia PDF Downloads 11041 Expression of miRNA 335 in Gall Bladder Cancer: A Correlative Study
Authors: Naseem Fatima, A. N. Srivastava, Tasleem Raza, Vijay Kumar
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Introduction: Carcinoma gallbladder is third most common gastrointestinal lethal disease with the highest incidence and mortality rate among women in Northern India. Scientists have found several risk factors that make a person more likely to develop gallbladder cancer; among these risk factors, deregulation of miRNAs has been demonstrated to be one of the most crucial factors. The changes in the expression of specific miRNA genes result in the control of inflammation, cell cycle regulation, stress response, proliferation, differentiation, apoptosis and invasion thus mediate the process in tumorgenesis. The aim of this study was to investigate the role of MiRNA-335 and may as a molecular marker in early detection of gallbladder cancer in suspected cases. Material and Methods: A total of 20 consecutive patients with gallbladder cancer aged between 30-75 years were registered for the study. Total RNA was extracted from tissue by using the mirVANA MiRNA isolation Kit according to the manufacturer’s protocol. The MiRNA- 335 and U6 snRNA-specific cDNA were reverse-transcribed from total RNA using Taqman microRNA reverse-transcription kit according to the manufacturer’s protocol. TaqMan MiRNA probes hsa-miR-335 and Taqman Master Mix without AmpEase UNG, Individual real-time PCR assays were performed in a 20 μL reaction volume on a Real-Time PCR system (Applied Biosystems StepOnePlus™) to detect MiRNA-335 expression in tissue. Relative quantification of target MiRNA expression was evaluated using the comparative cycle threshold (CT) method. The correlation was done in between cycle threshold (CT Value) of target MiRNA in gallbladder cancer with respect to non-cancerous Cholelithiasis gallbladder. Each sample was examined in triplicate. The Newman-Keuls Multiple Comparison Test was used to determine the expression of miR-335. Results: MiRNA335 was found to be significantly downregulated in the gallbladder cancer tissue (P<0.001), when compared with non-cancerous Cholelithiasis gallbladder cases. Out of 20 cases, 75% showed reduced expression of MiRNA335, were at last stage of disease with low overall survival rate and remaining 25% were showed up-regulated expression of MiRNA335 with high survival rate. Conclusion: The present study showed that reduced expression of MiRNA335 is associated with the advancement of the disease, and its deregulation may provide important clues to understanding it as a prognostic marker and opportunities for future research.Keywords: carcinoma gallbladder, downregulation, MiRNA-335, RT-PCR assay
Procedia PDF Downloads 36040 Synthesis of Temperature Sensitive Nano/Microgels by Soap-Free Emulsion Polymerization and Their Application in Hydrate Sediments Drilling Operations
Authors: Xuan Li, Weian Huang, Jinsheng Sun, Fuhao Zhao, Zhiyuan Wang, Jintang Wang
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Natural gas hydrates (NGHs) as promising alternative energy sources have gained increasing attention. Hydrate-bearing formation in marine areas is highly unconsolidated formation and is fragile, which is composed of weakly cemented sand-clay and silty sediments. During the drilling process, the invasion of drilling fluid can easily lead to excessive water content in the formation. It will change the soil liquid plastic limit index, which significantly affects the formation quality, leading to wellbore instability due to the metastable character of hydrate-bearing sediments. Therefore, controlling the filtrate loss into the formation in the drilling process has to be highly regarded for protecting the stability of the wellbore. In this study, the temperature-sensitive nanogel of P(NIPAM-co-AMPS-co-tBA) was prepared by soap-free emulsion polymerization, and the temperature-sensitive behavior was employed to achieve self-adaptive plugging in hydrate sediments. First, the effects of additional amounts of AMPS, tBA, and cross-linker MBA on the microgel synthesis process and temperature-sensitive behaviors were investigated. Results showed that, as a reactive emulsifier, AMPS can not only participate in the polymerization reaction but also act as an emulsifier to stabilize micelles and enhance the stability of nanoparticles. The volume phase transition temperature (VPTT) of nanogels gradually decreased with the increase of the contents of hydrophobic monomer tBA. An increase in the content of the cross-linking agent MBA can lead to a rise in the coagulum content and instability of the emulsion. The plugging performance of nanogel was evaluated in a core sample with a pore size distribution range of 100-1000nm. The temperature-sensitive nanogel can effectively improve the microfiltration performance of drilling fluid. Since a combination of a series of nanogels could have a wide particle size distribution at any temperature, around 200nm to 800nm, the self-adaptive plugging capacity of nanogels for the hydrate sediments was revealed. Thermosensitive nanogel is a potential intelligent plugging material for drilling operations in natural gas hydrate-bearing sediments.Keywords: temperature-sensitive nanogel, NIPAM, self-adaptive plugging performance, drilling operations, hydrate-bearing sediments
Procedia PDF Downloads 17239 “Japan’s New Security Outlook: Implications for the US-Japan Alliance”
Authors: Agustin Maciel-Padilla
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This paper explores the most significant change to Japan’s security strategy since the end of World War II, in particular Prime Minister Fumio Kishida’s government publication, in late 2022, of 3 policy documents (the National Security Strategy [NSS], the National Defense Strategy and the Defense Buildup Program) that basically propose to expand the country’s military capabilities and to increase military spending over a 5-year period. These policies represent a remarkable transformation of Japan’s defense-oriented policy followed since 1946. These proposals have been under analysis and debate since they were announced, as it was also Japan’s historic ambition to strengthening its deterrence capabilities in the context of a more complex regional security environment. Even though this new defense posture has attracted significant international attention, it is far from representing a done deal because of the fact that there is still a long way to go to implement this vision because of a wide variety of political and economic issues. Japan is currently experiencing the most dangerous security environment since the end of World War II, and this situation led Japan to intensify its dialogue with the United States to reflect a re-evaluation of deterrence in the face of a rapidly worsening security environment, a changing balance of power in East Asia, and the arrival of a new era of “great power competition”. Japan’s new documents, for instance, identify China and North Korea’s as posing, respectively, a strategic challenge and an imminent threat. Japan has also noted that Russia’s invasion of Ukraine has contributed to erode the foundation of the international order. It is considered that Russia’s aggression was possible because Ukraine’s defense capability was not enough for effective deterrence. Moreover, Japan’s call for “counterstrike capabilities” results from a recognition that China and North Korea’s ballistic and cruise missiles could overwhelm Japan’s air and missile defense systems, and therefore there is an urgent need to strengthen deterrence and resilience. In this context, this paper will focus on the impact of these changes on the US-Japan alliance. Adapting this alliance to Tokyo’s new ambitions and capabilities could be critical in terms of updating their traditional protection/access to bases arrangement, interoperability and joint command and control issues, as well as regarding the security–economy nexus. While China is Japan’s largest trading partner, and trade between the two has been growing, US-Japan economic relationship has been slower, notwithstanding the fact that US-Japan security cooperation has strengthened significantly in recent years.Keywords: us-japan alliance, japan security, great power competition, interoperability
Procedia PDF Downloads 6538 Colonization of Non-Planted Mangrove Species in the “Rehabilitation of Aquaculture Ponds to Mangroves” Projects in China
Authors: Yanmei Xiong, Baowen Liao, Kun Xin, Zhongmao Jiang, Hao Guo, Yujun Chen, Mei Li
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Conversion of mangroves to aquaculture ponds represented as one major reason for mangrove loss in Asian countries in the 20th century. Recently the Chinese government has set a goal to increase 48,650 ha (more than the current mangrove area) of mangroves before the year of 2025 and “rehabilitation of aquaculture ponds to mangroves” projects are considered to be the major pathway to increase the mangrove area of China. It remains unclear whether natural colonization is feasible and what are the main influencing factors for mangrove restoration in these projects. In this study, a total of 17 rehabilitation sites in Dongzhai Bay, Hainan, China were surveyed for vegetation, soil and surface elevation five years after the rehabilitation project was initiated. Colonization of non-planted mangrove species was found at all sites and non-planted species dominated over planted species at 14 sites. Mangrove plants could only be found within the elevation range of -20 cm to 65 cm relative to the mean sea level. Soil carbon and nitrogen contents of the top 20 cm were generally low, ranging between 0.2%–1.4% and 0.03%–0.09%, respectively, and at each site, soil carbon and nitrogen were significantly lower at elevations with mangrove plants than lower elevations without mangrove plants. Seven sites located at the upper stream of river estuaries, where soil salinity was relatively lower, and nutrient was relatively higher, was dominated by non-planted Sonneratia caseolaris. Seven sites located at the down-stream of river estuaries or in the inner part of the bay, where soil salinity and nutrient were intermediate, were dominated by non-planted alien Sonneratia apetala. Another three sites located at the outer part of the bay, where soil salinity was higher and nutrient was lower, were dominated by planted species (Rhizophora stylosa, Kandelia obovata, Aegiceras corniculatum and Bruguiera sexangula) with non-planted S. apetala and Avicennia marina also found. The results suggest that natural colonization of mangroves is feasible in pond rehabilitation projects given the rehabilitation of tidal activities and appropriate elevations. Surface elevation is the major determinate for the success of mangrove rehabilitation, and soil salinity and nutrients are important in shaping vegetation structure. The colonization and dominance of alien species (Sonneratia apetala in this case) in some rehabilitation sites poses invasion risks and thus cautions should be taken when introducing alien mangrove species.Keywords: coastal wetlands, ecological restoration, mangroves, natural colonization, shrimp pond rehabilitation, wetland restoration
Procedia PDF Downloads 13437 The Use of Geographic Information System in Spatial Location of Waste Collection Points and the Attendant Impacts in Bida Urban Centre, Nigeria
Authors: Daramola Japheth, Tabiti S. Tabiti, Daramola Elizabeth Lara, Hussaini Yusuf Atulukwu
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Bida urban centre is faced with solid waste management problems which are evident in the processes of waste generation, onsite storage, collection, transfer and transport, processing and disposal of solid waste. As a result of this the urban centre is defaced with litters of garbage and offensive odours due to indiscriminate dumping of refuse within the neighborhood. The partial removal of the fuel subsidy by the Federal Government in January 2012 leads to the formation of Subsidy Reinvestment Programmes (SURE-P), the Federal Government’s share is 41 per cent of the savings while the States and Local Government shared the remaining 59 percent. The SURE-P Committee in carrying out the mandate entrusted upon it by the President by identifying few critical infrastructure and social Safety nets that will ameliorate the sufferings of Nigerians. Waste disposal programme as an aspect of Solid waste management is one of the areas of focus for Niger State SURE-programmes incorporated under Niger State Environmental Protection Agency. The emergence of this programme as related to waste management in Bida has left behind a huge refuse spots along major corridors leading to a serious state of mess. Major roads within the LGA is now turned to dumping site, thereby obstructing traffic movements, while the aesthetic nature of the town became something else with offensive odours all over. This paper however wishes to underscore the use of geographical Information System in identifying solid waste sports towards effective solid waste management in the Bida urban centre. The paper examined the spatial location of dumping points and its impact on the environment. Hand held Global Position System was use to pick the dumping points location; where a total number of 91 dumping points collected were uploaded to ArcGis 10.2 for analysis. Interview method was used to derive information from households living near the dumping site. It was discovered that the people now have to cope with offensive odours, rodents invasion, dog and cats coming around the house as a result of inadequate and in prompt collection of waste around the neighborhood. The researchers hereby recommend that more points needs to be created with prompt collections of waste within the neighborhood by the necessary SURE - P agencies.Keywords: dumping site, neighborhood, refuse, waste
Procedia PDF Downloads 52936 Triazenes: Unearthing Their Hidden Arsenal Against Malaria and Microbial Menace
Authors: Frans J. Smit, Wisdom A. Munzeiwa, Hermanus C. M. Vosloo, Lyn-Marie Birkholtz, Richard K. Haynes
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Malaria and antimicrobial infections remain significant global health concerns, necessitating the continuous search for novel therapeutic approaches. This abstract presents an overview of the potential use of triazenes as effective agents against malaria and various antimicrobial pathogens. Triazenes are a class of compounds characterized by a linear arrangement of three nitrogen atoms, rendering them structurally distinct from their cyclic counterparts. This study investigates the efficacy of triazenes against malaria and explores their antimicrobial activity. Preliminary results revealed significant antimalarial activity of the triazenes, as evidenced by in vitro screening against P. falciparum, the causative agent of malaria. Furthermore, the compounds exhibited broad-spectrum antimicrobial activity, indicating their potential as effective antimicrobial agents. These compounds have shown inhibitory effects on various essential enzymes and processes involved in parasite survival, replication, and transmission. The mechanism of action of triazenes against malaria involves interactions with critical molecular targets, such as enzymes involved in the parasite's metabolic pathways and proteins responsible for host cell invasion. The antimicrobial activity of the triazenes against bacteria and fungi was investigated through disc diffusion screening. The antimicrobial efficacy of triazenes has been observed against both Gram-positive and Gram-negative bacteria, as well as multidrug-resistant strains, making them potential candidates for combating drug-resistant infections. Furthermore, triazenes possess favourable physicochemical properties, such as good stability, solubility, and low toxicity, which are essential for drug development. The structural versatility of triazenes allows for the modification of their chemical composition to enhance their potency, selectivity, and pharmacokinetic properties. These modifications can be tailored to target specific pathogens, increasing the potential for personalized treatment strategies. In conclusion, this study highlights the potential of triazenes as promising candidates for the development of novel antimalarial and antimicrobial therapeutics. Further investigations are necessary to determine the structure-activity relationships and optimize the pharmacological properties of these compounds. The results warrant additional research, including MIC studies, to further explore the antimicrobial activity of the triazenes. Ultimately, these findings contribute to the development of more effective strategies for combating malaria and microbial infections.Keywords: malaria, anti-microbials, triazene, resistance
Procedia PDF Downloads 10335 Study of Biofouling Wastewater Treatment Technology
Authors: Sangho Park, Mansoo Kim, Kyujung Chae, Junhyuk Yang
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The International Maritime Organization (IMO) recognized the problem of invasive species invasion and adopted the "International Convention for the Control and Management of Ships' Ballast Water and Sediments" in 2004, which came into force on September 8, 2017. In 2011, the IMO approved the "Guidelines for the Control and Management of Ships' Biofouling to Minimize the Transfer of Invasive Aquatic Species" to minimize the movement of invasive species by hull-attached organisms and required ships to manage the organisms attached to their hulls. Invasive species enter new environments through ships' ballast water and hull attachment. However, several obstacles to implementing these guidelines have been identified, including a lack of underwater cleaning equipment, regulations on underwater cleaning activities in ports, and difficulty accessing crevices in underwater areas. The shipping industry, which is the party responsible for understanding these guidelines, wants to implement them for fuel cost savings resulting from the removal of organisms attached to the hull, but they anticipate significant difficulties in implementing the guidelines due to the obstacles mentioned above. Robots or people remove the organisms attached to the hull underwater, and the resulting wastewater includes various species of organisms and particles of paint and other pollutants. Currently, there is no technology available to sterilize the organisms in the wastewater or stabilize the heavy metals in the paint particles. In this study, we aim to analyze the characteristics of the wastewater generated from the removal of hull-attached organisms and select the optimal treatment technology. The organisms in the wastewater generated from the removal of the attached organisms meet the biological treatment standard (D-2) using the sterilization technology applied in the ships' ballast water treatment system. The heavy metals and other pollutants in the paint particles generated during removal are treated using stabilization technologies such as thermal decomposition. The wastewater generated is treated using a two-step process: 1) development of sterilization technology through pretreatment filtration equipment and electrolytic sterilization treatment and 2) development of technology for removing particle pollutants such as heavy metals and dissolved inorganic substances. Through this study, we will develop a biological removal technology and an environmentally friendly processing system for the waste generated after removal that meets the requirements of the government and the shipping industry and lays the groundwork for future treatment standards.Keywords: biofouling, ballast water treatment system, filtration, sterilization, wastewater
Procedia PDF Downloads 10934 The Role of the Indigenous Radio Today and Its Impact on the Audience: The Case of Dambana FM in Sri Lanka
Authors: Dammika Bandara Herath
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A group of people who inherits a long history of existence within a particular country may be known as early inhabitants or indigenous peoples. In other words, they have not migrated to the particular territory from another part of the world and at the same time, they have inhabited the territory in issue prior to the time of a major invasion/migration. According to the UN, there are a number of unique attributes of the indigenous peoples: Self-identification as indigenous people,Historical continuity with pre-colonial and/or pre-settler societies, Distinct social, economic or political systems, Distinct language, culture and beliefs, Form non-dominant groups of society, Resolve to maintain and reproduce their ancestral environments and systems as distinctive peoples and communities. Indigenous peoples constitute 5% of the world’s population. They are also known as tribal people, first people, native people, and indigenous people. Various indigenous communities can be found in about 90 countries in the world. Asia is home to approximately 70 % of these indigenous communities who have their own unique socio-cultural identities. Most indigenous communities remain isolated from the mainstream social, cultural, and economic institutions of their homeland. Yet, they inherited their own unique rights and responsible peculiar to their own group. These include: Protecting the socio-cultural heritage of the group, Protecting the unique identity of their community from socio-cultural changes in the mainstream communities,Protecting their land, Diffusing their cultural heritage to the future generation, Co-existing peacefully with other community .However, indigenous peoples encounter a lot of challenges as a result of socio-cultural change and legal restrictions in the world today. To assist the communities to face these challenges, the mass –media can play a significant role and the radio media has a purpose-built mechanism for this mission, known as the indigenous radio. In Sri Lanka, Dambana FM is such a radio channel based on the indigenous radio model. The target audience of this channel is the vedda / indigenous community of Sri Lanka. This study intends to the current role of the indigenous radio based on Dambana FM, of which the target audience is the indigenous community of Dambana. For the purpose of this study, interviews were conducted among fifty randomly selected respondents from the indigenous community of Dambana. As far as the findings of this study are concerned, problems in the quality of the programmed broadcasted and problems of transmission are the key issues faced by the indigenous radio in Sri Lanka. Based on the findings, the researcher seeks to develop a model to enhance the impact of the indigenous radio on its listeners in Sri Lanka.Keywords: indigenous, communities, radio, vedda, culture
Procedia PDF Downloads 40933 Identification of Potent and Selective SIRT7 Anti-Cancer Inhibitor via Structure-Based Virtual Screening and Molecular Dynamics Simulation
Authors: Md. Fazlul Karim, Ashik Sharfaraz, Aysha Ferdoushi
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Background: Computational medicinal chemistry approaches are used for designing and identifying new drug-like molecules, predicting properties and pharmacological activities, and optimizing lead compounds in drug development. SIRT7, a nicotinamide adenine dinucleotide (NAD+)-dependent deacylase which regulates aging, is an emerging target for cancer therapy with mounting evidence that SIRT7 downregulation plays important roles in reversing cancer phenotypes and suppressing tumor growth. Activation or altered expression of SIRT7 is associated with the progression and invasion of various cancers, including liver, breast, gastric, prostate, and non-small cell lung cancer. Objectives: The goal of this work was to identify potent and selective bioactive candidate inhibitors of SIRT7 by in silico screening of small molecule compounds obtained from Nigella sativa (N. sativa). Methods: SIRT7 structure was retrieved from The Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB), and its active site was identified using CASTp and metaPocket. Molecular docking simulation was performed with PyRx 0.8 virtual screening software. Drug-likeness properties were tested using SwissADME and pkCSM. In silico toxicity was evaluated by Osiris Property Explorer. Bioactivity was predicted by Molinspiration software. Antitumor activity was screened for Prediction of Activity Spectra for Substances (PASS) using Way2Drug web server. Molecular dynamics (MD) simulation was carried out by Desmond v3.6 package. Results: A total of 159 bioactive compounds from the N. Sativa were screened against the SIRT7 enzyme. Five bioactive compounds: chrysin (CID:5281607), pinocembrin (CID:68071), nigellidine (CID:136828302), nigellicine (CID:11402337), and epicatechin (CID:72276) were identified as potent SIRT7 anti-cancer candidates after docking score evaluation and applying Lipinski's Rule of Five. Finally, MD simulation identified Chrysin as the top SIRT7 anti-cancer candidate molecule. Conclusion: Chrysin, which shows a potential inhibitory effect against SIRT7, can act as a possible anti-cancer drug candidate. This inhibitor warrants further evaluation to check its pharmacokinetics and pharmacodynamics properties both in vitro and in vivo.Keywords: SIRT7, antitumor, molecular docking, molecular dynamics simulation
Procedia PDF Downloads 7932 A Battle of Identity(ies): Deconstructing Spaces of Belonging in Saleem Haddad’s Guapa and Hasan Namir’s God in Pink
Authors: Nour Aladdin
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This paper explores the interconnectedness of belonging, space, and identity in Anglo Arab literature, particularly Saleem Haddad’s Guapa and Hasan Namir’sGod in Pink. This paper suggest that Rasa and Ramy, the queer Arab characters respectively, do not belong in either the Middle East or the West. Using Amin Maalouf’s analysis of the Arab identity, specifically his argument that an individual identifies strongly with the aspect of their identity that is under attack, this paper argues that all of Rasa and Ramy’s spaces are politically charged - a term that denotes that all values and beliefs instilled in Arabs and their spaces are heavily influenced by Arab politics, culture, and, often times religion. Therefore, the politically charged environments Rasa and Ramy inhabit will always be against one part of their identity, which is why they cannot identify as queer and Arab simultaneously. For Rasa, the unnamed Middle Eastern country, his home environment, as well as the so-called safe space nightclub, condemn his queerness, leading him to connect more to his sexual orientation. However, Rasa associates himself with his Arab roots when he migrates to America, a different form of politically charged space that minoritizes his ethnicity. Similarly, Ramy’s spaces are naturally religiopolitical after Islam heightened in Iraq during the Iraq War; as a result, Ramy’s home environment, Sheikh Ammar’s house, the mosque, and the nightclub are influenced by the religiopolitics and bombard his ability to identify as not only a queer Arab but a queer Arab Muslim. Ultimately, because Rasa and Ramy are constantly in movement, their identity attributes are also in movement. This paper is divided into three sections. The first section focuses on Guapa and the Arab Spring’s politics, mainly its influence on queer Arabs in and around the Middle East. Drawing from a number of queer and Arab gender theories, I analyze all of Rasa’s spaces as politically charged that prevent him from the means to be queer and Arab. The second section examines God in Pink in close connection to the 2003 invasion of Iraq. Ramy’s spaces are religiopolitically charged, that prevent him to embrace all of his identity attributes – nationality, ethnicity, sexual orientation, and religious affiliation – concomitantly. The last section considers the rapid use of technology and social media in the Middle East as a means to provide deviant heterotopic spaces for queer Arabs. With the rise of subtle and covert queer heterotopias, there is a slow and steady shift of queer tolerance in the Arab world.Keywords: belonging, identity, spaces, queer, arabness, middle east, orientalism
Procedia PDF Downloads 11431 Quercetin and INT3 Inhibits Endocrine Therapy Resistance and Epithelial to Mesenchymal Transition in MCF7 Breast Cancer Cells
Authors: S. Pradhan, D. Pradhan, G. Tripathy
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Anti-estrogen treatment resistant is a noteworthy reason for disease relapse and mortality in estrogen receptor alpha (ERα)- positive breast cancers. Tamoxifen or estrogen withdrawal increases the dependance of breast malignancy cells on INT3 signaling. Here, we researched the contribution of Quercetin and INT3 signaling in endocrine resistant breast cancer cells. Methods: We utilized two models of endocrine therapies resistant (ETR-) breast cancer: tamoxifen-resistant (TamR) and long term estrogen-deprived (LTED) MCF7 cells. We assessed the migratory and invasive limit of these cells by Transwell assay. Expression of epithelial to mesenchymal transition (EMT) controllers and in addition INT3 receptors and targets were assessed by real-time PCR and western blot analysis. Besides, we tried in vitro anti-Quercetin monoclonal antibodies (mAbs) and gamma secretase inhibitors (GSIs) as potential EMT reversal therapeutic agents. At last, we created stable Quercetin over expessing MCF7 cells and assessed their EMT features and response to tamoxifen. Results:We found that ETR cells acquired an epithelial to mesenchymal transition (EMT) phenotype and showed expanded levels of Quercetin and INT3 targets. Interestingly, we detected higher level of INT3 however lower levels of INT31 and INT32 proposing a switch to targeting through distinctive INT3 receptors after obtaining of resistance. Anti-Quercetin monoclonal antibodies and the GSI PF03084014 were effective in obstructing the Quercetin/INT3 axis and in part inhibiting the EMT process. As a consequence of this, cell migration and invasion were weakened and the stem cell like population was considerably decreased. Genetic hushing of Quercetin and INT3 prompted proportionate impacts. Finally, stable overexpression of Quercetin was adequate to make MCF7 lethargic to tamoxifen by INT3 activation. Conclusions: ETR cells express abnormal amounts of Quercetin and INT3, whose actuation eventually drives invasive conduct. Anti-Quercetin mAbs and GSI PF03084014 lessen expression of EMT molecules decreasing cellular invasiveness. Quercetin overexpression instigates tamoxifen resistance connected to obtaining of EMT phenotype. Our discovering propose that focusing on Quercetin and/or INT3 warrants further clinical assessment as substantial therapeutic methodologies in endocrine-resistant breast cancer.Keywords: quercetin, INT3, mesenchymal transition, MCF7 breast cancer cells
Procedia PDF Downloads 31130 Concrete Compressive Strengths of Major Existing Buildings in Kuwait
Authors: Zafer Sakka, Husain Al-Khaiat
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Due to social and economic considerations, owners all over the world desire to keep and use existing structures, including aging ones. However, these structures, especially those that are dear, need accurate condition assessment, and proper safety evaluation. More than half of the budget spent on construction activities in developed countries is related to the repair and maintenance of these reinforced concrete (R/C) structures. Also, periodical evaluation and assessment of relatively old concrete structures are vital and imperative. If the evaluation and assessment of structural components of a particular aging R/C structure reveal that repairs are essential for these components, these repairs should not be delayed. Delaying the repairs has the potential of losing serviceability of the whole structure and/or causing total failure and collapse of the structure. In addition, if repairs are delayed, the cost of maintenance will skyrocket as well. It can also be concluded from the above that the assessment of existing needs to receive more consideration and thought from the structural engineering societies and professionals. Ten major existing structures in Kuwait city that were constructed in the 1970s were assessed for structural reliability and integrity. Numerous concrete samples were extracted from the structural systems of the investigated buildings. This paper presents the results of the compressive strength tests that were conducted on the extracted cores. The results are compared for the buildings’ columns and beams elements and compared with the design strengths. The collected data were statistically analyzed. The average compressive strengths of the concrete cores that were extracted from the ten buildings had a large variation. The lowest average compressive strength for one of the buildings was 158 kg/cm². This building was deemed unsafe and economically unfeasible to be repaired; accordingly, it was demolished. The other buildings had an average compressive strengths fall in the range 215-317 kg/cm². Poor construction practices were the main cause for the strengths. Although most of the drawings and information for these buildings were lost during the invasion of Kuwait in 1990, however, information gathered indicated that the design strengths of the beams and columns for most of these buildings were in the range of 280-400 kg/cm². Following the study, measures were taken to rehabilitate the buildings for safety. The mean compressive strength for all cores taken from beams and columns of the ten buildings was 256.7 kg/cm². The values range was 139 to 394 kg/cm². For columns, the mean was 250.4 kg/cm², and the values ranged from 137 to 394 kg/cm². However, the mean compressive strength for the beams was higher than that of columns. It was 285.9 kg/cm², and the range was 181 to 383 kg/cm². In addition to the concrete cores that were extracted from the ten buildings, the 28-day compressive strengths of more than 24,660 concrete cubes were collected from a major ready-mixed concrete supplier in Kuwait. The data represented four different grades of ready-mix concrete (250, 300, 350, and 400 kg/cm²) manufactured between the year 2003 and 2018. The average concrete compressive strength for the different concrete grades (250, 300, 350 and 400 kg/cm²) was found to be 318, 382, 453 and 504 kg/cm², respectively, and the coefficients of variations were found to be 0.138, 0.140, 0.157 and 0.131, respectively.Keywords: concrete compressive strength, concrete structures, existing building, statistical analysis.
Procedia PDF Downloads 11629 Zoledronic Acid with Neoadjuvant Chemotherapy in Advanced Breast Cancer Prospective Study 2011–2014
Authors: S. Sakhri
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Background: The use of Zoledronic acid (ZA) is an established place in the treatment of malignant tumors with a predilection for the skeleton of interest (in particular metastasis). Although the main target of Zoledronic acid was osteoclasts, there are preclinical data suggest that Zoledronic acid may have an antitumor effect on cells other than osteoclasts, including tumor cells. Antitumor activity, including the inhibition of tumor cell growth and the induction of apoptosis of tumor cells, inhibition of tumor cell adhesion and invasion, and anti-angiogenic effects have been demonstrated. Methods. From (2012 to 2014), 438 patients were included respondents the inclusion criteria, respectively. This is a prospective study over a 4 year period. Of all patients (N=438), 432 received neoadjuvant chemotherapy with Zoledronic acid. The primary end point was the pathologic complete response in advancer breast cancer stage. The secondary end point is to evaluate Clinical response according to RECIST criteria; estimate the bone density before and at the end of chemotherapy in women with locally advanced breast cancer, Toxicity Evaluation and Overall survival using Kaplan-Meier and log test. Result: The Objective response rate was 97% after (C4) with 3% stabilizations and 99, 3% of which 0.7% C8 after stabilization. The clinical complete response was 28% after C4 respectively, and 46.8% after C8, the pathologic complete response rate was 40.13% according to the classification Sataloff. We observed that the pathologic complete response rate was the most raised in the group including Her2 (luminal Her2 and Her2) the lowest in the triple negative group as classified by Sataloff. We found that the pCR is significantly higher in the age group (35-50 years) with 53.17%. Those who have more than 50 years in 2nd place with 27.7% and the lower in young woman 35 years pCR was 19%, not statistically significant, -The pCR was also in favor of the menopausal group in 51, 4%, and 48, 55% for non-menopausal women. The average duration of overall survival was also significantly in the subgroup (Luminal -Her2, Her2) compared with triple negative. It is 47.18 months in the luminal group vs. 38.95 in the triple negative group. -Was observed in our study a difference in quality of life between (C1) was the admission of the patient, and after (C8), we found an increase in general signs and a deterioration in the psychological state C1, in contrast to the C8 these general signs and mental status improves, up to 12, and 24 months. Conclusion The results of this study suggest that the addition of ZA to néoadjuvant CT has potential anti-cancer benefit in patients (Luminal -Her2, Her2) compared with triple negative with or without menopause status.Keywords: HER2+, RH+, breast cancer, tyrosine kinase
Procedia PDF Downloads 20928 An Audit on the Role of Sentinel Node Biopsy in High-Risk Ductal Carcinoma in Situ and Intracystic Papillary Carcinoma
Authors: M. Sulieman, H. Arabiyat, H. Ali, K. Potiszil, I. Abbas, R. English, P. King, I. Brown, P. Drew
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Introduction: The incidence of breast ductal Carcinoma in Situ (DCIS) has been increasing; it currently represents up 20-25% of all breast carcinomas. Some aspects of DCIS management are still controversial, mainly due to the heterogeneity of its clinical presentation and of its biological and pathological characteristics. In DCIS, histological diagnosis obtained preoperatively, carries the risk of sampling error if the presence of invasive cancer is subsequently diagnosed. The mammographic extent over than 4–5 cm and the presence of architectural distortion, focal asymmetric density or mass on mammography are proven important risk factors of preoperative histological under staging. Intracystic papillary cancer (IPC) is a rare form of breast carcinoma. Despite being previously compared to DCIS it has been shown to present histologically with invasion of the basement membrane and even metastasis. SLNB – Carries the risk of associated comorbidity that should be considered when planning surgery for DCIS and IPC. Objectives: The aim of this Audit was to better define a ‘high risk’ group of patients with pre-op diagnosis of non-invasive cancer undergoing breast conserving surgery, who would benefit from sentinel node biopsy. Method: Retrospective data collection of all patients with ductal carcinoma in situ over 5 years. 636 patients identified, and after exclusion criteria applied: 394 patients were included. High risk defined as: Extensive micro-calcification >40mm OR any mass forming DCIS. IPC: Winpath search from for the term ‘papillary carcinoma’ in any breast specimen for 5 years duration;.29 patients were included in this group. Results: DCIS: 188 deemed high risk due to >40mm calcification or a mass forming (radiological or palpable) 61% of those had a mastectomy and 32% BCS. Overall, in that high-risk group - the number with invasive disease was 38%. Of those high-risk DCIS pts 85% had a SLN - 80% at the time of surgery and 5% at a second operation. For the BCS patients - 42% had SLN at time of surgery and 13% (8 patients) at a second operation. 15 (7.9%) pts in the high-risk group had a positive SLNB, 11 having a mastectomy and 4 having BCS. IPC: The provisional diagnosis of encysted papillary carcinoma is upgraded to an invasive carcinoma on final histology in around a third of cases. This has may have implications when deciding whether to offer sentinel node removal at the time of therapeutic surgery. Conclusions: We have defined a ‘high risk’ group of pts with pre-op diagnosis of non-invasive cancer undergoing BCS, who would benefit from SLNB at the time of the surgery. In patients with high-risk features; the risk of invasive disease is up to 40% but the risk of nodal involvement is approximately 8%. The risk of morbidity from SLN is up to about 5% especially the risk of lymphedema.Keywords: breast ductal carcinoma in Situ (DCIS), intracystic papillary carcinoma (IPC), sentinel node biopsy (SLNB), high-risk, non-invasive, cancer disease
Procedia PDF Downloads 11127 Immuno-Protective Role of Mucosal Delivery of Lactococcus lactis Expressing Functionally Active JlpA Protein on Campylobacter jejuni Colonization in Chickens
Authors: Ankita Singh, Chandan Gorain, Amirul I. Mallick
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Successful adherence of the mucosal epithelial cells is the key early step for Campylobacter jejuni pathogenesis (C. jejuni). A set of Surface Exposed Colonization Proteins (SECPs) are among the major factors involved in host cell adherence and invasion of C. jejuni. Among them, constitutively expressed surface-exposed lipoprotein adhesin of C. jejuni, JlpA, interacts with intestinal heat shock protein 90 (hsp90α) and contributes in disease progression by triggering pro-inflammatory response via activation of NF-κB and p38 MAP kinase pathway. Together with its ability to express in the bacterial surface, higher sequence conservation and predicted predominance of several B cells epitopes, JlpA protein reserves its potential to become an effective vaccine candidate against wide range of Campylobacter sps including C. jejuni. Given that chickens are the primary sources for C. jejuni and persistent gut colonization remain as major cause for foodborne pathogenesis to humans, present study explicitly used chickens as model to test the immune-protective efficacy of JlpA protein. Taking into account that gastrointestinal tract is the focal site for C. jejuni colonization, to extrapolate the benefit of mucosal (intragastric) delivery of JlpA protein, a food grade Nisin inducible Lactic acid producing bacteria, Lactococcus lactis (L. lactis) was engineered to express recombinant JlpA protein (rJlpA) in the surface of the bacteria. Following evaluation of optimal surface expression and functionality of recombinant JlpA protein expressed by recombinant L. lactis (rL. lactis), the immune-protective role of intragastric administration of live rL. lactis was assessed in commercial broiler chickens. In addition to the significant elevation of antigen specific mucosal immune responses in the intestine of chickens that received three doses of rL. lactis, marked upregulation of Toll-like receptor 2 (TLR2) gene expression in association with mixed pro-inflammatory responses (both Th1 and Th17 type) was observed. Furthermore, intragastric delivery of rJlpA expressed by rL. lactis, but not the injectable form, resulted in a significant reduction in C. jejuni colonization in chickens suggesting that mucosal delivery of live rL. lactis expressing JlpA serves as a promising vaccine platform to induce strong immune-protective responses against C. jejuni in chickens.Keywords: chickens, lipoprotein adhesion of Campylobacter jejuni, immuno-protection, Lactococcus lactis, mucosal delivery
Procedia PDF Downloads 13926 To Live on the Margins: A Closer Look at the Social and Economic Situation of Illegal Afghan Migrants in Iran
Authors: Abdullah Mohammadi
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Years of prolong war in Afghanistan has led to one of the largest refugee and migrant populations in the contemporary world. During this continuous unrest which began in 1970s (by military coup, Marxist revolution and the subsequent invasion of USSR), over one-third of the population migrated to neighboring countries, especially Pakistan and Iran. After the Soviet Army withdrawal in 1989, a new wave of conflicts emerged between rival Afghan groups and this led to new refugees. Taliban period, also, created its own refugees. During all these years, I.R. of Iran has been one of the main destinations of Afghan refugees and migrants. At first, due to the political situation after Islamic Revolution, Iran government didn’t restrict the entry of Afghan refugees. Those who came first in Iran received ID cards and had access to education and healthcare services. But in 1990s, due to economic and social concerns, Iran’s policy towards Afghan refugees and migrants changed. The government has tried to identify and register Afghans in Iran and limit their access to some services and jobs. Unfortunately, there are few studies on Afghan refugees and migrants’ situation in Iran and we have a dim and vague picture of them. Of the few studies done on this group, none of them focus on the illegal Afghan migrants’ situation in Iran. Here, we tried to study the social and economic aspects of illegal Afghan migrants’ living in Iran. In doing so, we interviewed 24 illegal Afghan migrants in Iran. The method applied for analyzing the data is thematic analysis. For the interviews, we chose family heads (17 men and 7 women). According to the findings, illegal Afghan migrants’ socio-economic situation in Iran is very undesirable. Its main cause is the marginalization of this group which is resulted from government policies towards Afghan migrants. Most of the illegal Afghan migrants work in unskilled and inferior jobs and live in rent houses on the margins of cities and villages. None of them could buy a house or vehicle due to law. Based on their income, they form one of the lowest, unprivileged groups in the society. Socially, they face many problems in their everyday life: social insecurity, harassment and violence, misuse of their situation by police and people, lack of education opportunity, etc. In general, we may conclude that illegal Afghan migrant have little adaptation with Iran’s society. They face severe limitations compared to legal migrants and refugees and have no opportunity for upward social mobility. However, they have managed some strategies to face these difficulties including: seeking financial and emotional helps from family and friendship networks, sending one of the family members to third country (mostly to European countries), establishing self-administered schools for children (schools which are illegal and run by Afghan educated youth).Keywords: illegal Afghan migrants, marginalization, social insecurity, upward social mobility
Procedia PDF Downloads 31725 Non-Melanoma Skin Cancer of Cephalic Extremity – Clinical and Histological Aspects
Authors: Razvan Mercut, Mihaela Ionescu, Vlad Parvanescu, Razvan Ghita, Tudor-Gabriel Caragea, Cristina Simionescu, Marius-Eugen Ciurea
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Introduction: Over the past years, the incidence of non-melanoma skin cancer (NMSC) has continuously increased, being one of the most commonly diagnosed carcinomasofthe cephalic extremity. NMSC regroups basal cell carcinoma (BCC), squamous cell carcinoma (SCC), Merkel cell carcinoma, cutaneous lymphoma, and sarcoma. The most common forms are BCC and SCC, both still implying a significant level of morbidity due to local invasion (especially BCC), even if the overall death rates are declining. The objective of our study was the evaluation of clinical and histological aspects of NMSC for a group of patients with BCC and SCC, from Craiova, a south-western major city in Romania. Materialand method: Our study lot comprised 65 patients, with an almost equal distribution of sexes, and ages between 23-91 years old (mean value±standard deviation62.61±16.67), all treated within the Clinic of Plastic Surgery and Reconstructive Microsurgery, Clinical Emergency County Hospital Craiova, Romania, between 2019-2020. In order to determine the main morphological characteristics of both studied cancers, we used paraffin embedding techniques, with various staining methods:hematoxylin-eosin, Masson's trichrome stain with aniline blue, and Periodic acid-schiffAlcian Blue. The statistical study was completed using Microsoft Excel (Microsoft Corp., Redmond, WA, USA), with XLSTAT (Addinsoft SARL, Paris, France). Results: The overall results of our study indicate that BCC accounts for 67.69% of all NMSC forms; SCC covers 27.69%, while 4.62% are representedby other forms. The most frequent site is the nose for BCC (27.69%, 18 patients), being followed by preauricular regions, forehead, and periorbital areas. For patients with SCC, tumors were mainly located at lips level (66.67%, 12 patients). The analysis of NMSC histological forms indicated that nodular BCC is predominant (45.45%, 20 patients), as well as ulcero-vegetant SCC (38.89%, 7 patients). We have not identified any topographic characteristics or NMSC forms significantly related to age or sex. Conclusions: The most frequent NMSC form identified for our study lot was BCC. The preferred location was the nose for BCC. For SCC, the oral cavity is the most frequent anatomical site, especially the lips level. Nodular BCC and ulcero-vegetant SCC were the most commonly identified histological types. Our findings emphasize the need for periodic screening, in order to improve prevention and early treatment for these malignancies.Keywords: non-melanoma skin cancer, basal cell carcinoma, squamous cell carcinoma, histological
Procedia PDF Downloads 18924 The Association between Prior Antibiotic Use and Subsequent Risk of Infectious Disease: A Systematic Review
Authors: Umer Malik, David Armstrong, Mark Ashworth, Alex Dregan, Veline L'Esperance, Lucy McDonnell, Mariam Molokhia, Patrick White
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Introduction: The microbiota lining epithelial surfaces is thought to play an important role in many human physiological functions including defense against pathogens and modulation of immune response. The microbiota is susceptible to disruption from external influences such as exposure to antibiotic medication. It is thought that antibiotic-induced disruption of the microbiota could predispose to pathogen overgrowth and invasion. We hypothesized that antibiotic use would be associated with increased risk of future infections. We carried out a systematic review of evidence of associations between antibiotic use and subsequent risk of community-acquired infections. Methods: We conducted a review of the literature for observational studies assessing the association between antibiotic use and subsequent community-acquired infection. Eligible studies were published before April 29th, 2016. We searched MEDLINE, EMBASE, and Web of Science and screened titles and abstracts using a predefined search strategy. Infections caused by Clostridium difficile, drug-resistant organisms and fungal organisms were excluded as their association with prior antibiotic use has been examined in previous systematic reviews. Results: Eighteen out of 21,518 retrieved studies met the inclusion criteria. The association between past antibiotic exposure and subsequent increased risk of infection was reported in 16 studies, including one study on Campylobacter jejuni infection (Odds Ratio [OR] 3.3), two on typhoid fever (ORs 5.7 and 12.2), one on Staphylococcus aureus skin infection (OR 2.9), one on invasive pneumococcal disease (OR 1.57), one on recurrent furunculosis (OR 16.6), one on recurrent boils and abscesses (Risk ratio 1.4), one on upper respiratory tract infection (OR 2.3) and urinary tract infection (OR 1.1), one on invasive Haemophilus influenzae type b (Hib) infection (OR 1.51), one on infectious mastitis (OR 5.38), one on meningitis (OR 2.04) and five on Salmonella enteric infection (ORs 1.4, 1.59, 1.9, 2.3 and 3.8). The effect size in three studies on Salmonella enteric infection was of marginal statistical significance. A further two studies on Salmonella infection did not demonstrate a statistically significant association between prior antibiotic exposure and subsequent infection. Conclusion: We have found an association between past antibiotic exposure and subsequent risk of a diverse range of infections in the community setting. Our findings provide evidence to support the hypothesis that prior antibiotic usage may predispose to future infection risk, possibly through antibiotic-induced alteration of the microbiota. The findings add further weight to calls to minimize inappropriate antibiotic prescriptions.Keywords: antibiotic, infection, risk factor, side effect
Procedia PDF Downloads 22523 Nanomechanical Characterization of Healthy and Tumor Lung Tissues at Cell and Extracellular Matrix Level
Authors: Valeria Panzetta, Ida Musella, Sabato Fusco, Paolo Antonio Netti
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The study of the biophysics of living cells drew attention to the pivotal role of the cytoskeleton in many cell functions, such as mechanics, adhesion, proliferation, migration, differentiation and neoplastic transformation. In particular, during the complex process of malignant transformation and invasion cell cytoskeleton devolves from a rigid and organized structure to a more compliant state, which confers to the cancer cells a great ability to migrate and adapt to the extracellular environment. In order to better understand the malignant transformation process from a mechanical point of view, it is necessary to evaluate the direct crosstalk between the cells and their surrounding extracellular matrix (ECM) in a context which is close to in vivo conditions. In this study, human biopsy tissues of lung adenocarcinoma were analyzed in order to define their mechanical phenotype at cell and ECM level, by using particle tracking microrheology (PTM) technique. Polystyrene beads (500 nm) were introduced into the sample slice. The motion of beads was obtained by tracking their displacements across cell cytoskeleton and ECM structures and mean squared displacements (MSDs) were calculated from bead trajectories. It has been already demonstrated that the amplitude of MSD is inversely related to the mechanical properties of intracellular and extracellular microenvironment. For this reason, MSDs of particles introduced in cytoplasm and ECM of healthy and tumor tissues were compared. PTM analyses showed that cancerous transformation compromises mechanical integrity of cells and extracellular matrix. In particular, the MSD amplitudes in cells of adenocarcinoma were greater as compared to cells of normal tissues. The increased motion is probably associated to a less structured cytoskeleton and consequently to an increase of deformability of cells. Further, cancer transformation is also accompanied by extracellular matrix stiffening, as confirmed by the decrease of MSDs of matrix in tumor tissue, a process that promotes tumor proliferation and invasiveness, by activating typical oncogenic signaling pathways. In addition, a clear correlation between MSDs of cells and tumor grade was found. MSDs increase when tumor grade passes from 2 to 3, indicating that cells undergo to a trans-differentiation process during tumor progression. ECM stiffening is not dependent on tumor grade, but the tumor stage resulted to be strictly correlated with both cells and ECM mechanical properties. In fact, a greater stage is assigned to tumor spread to regional lymph nodes and characterized by an up-regulation of different ECM proteins, such as collagen I fibers. These results indicate that PTM can be used to get nanomechanical characterization at different scale levels in an interpretative and diagnostic context.Keywords: cytoskeleton, extracellular matrix, mechanical properties, particle tracking microrheology, tumor
Procedia PDF Downloads 280