Search results for: adhesion gene
1105 Gene Expression Signature-Based Chemical Genomic to Identify Potential Therapeutic Compounds for Colorectal Cancer
Authors: Yen-Hao Su, Wan-Chun Tang, Ya-Wen Cheng, Peik Sia, Chi-Chen Huang, Yi-Chao Lee, Hsin-Yi Jiang, Ming-Heng Wu, I-Lu Lai, Jun-Wei Lee, Kuen-Haur Lee
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There is a wide range of drugs and combinations under investigation and/or approved over the last decade to treat colorectal cancer (CRC), but the 5-year survival rate remains poor at stages II–IV. Therefore, new, more efficient drugs still need to be developed that will hopefully be included in first-line therapy or overcome resistance when it appears, as part of second- or third-line treatments in the near future. In this study, we revealed that heat shock protein 90 (Hsp90) inhibitors have high therapeutic potential in CRC according to combinative analysis of NCBI's Gene Expression Omnibus (GEO) repository and chemical genomic database of Connectivity Map (CMap). We found that second generation Hsp90 inhibitor, NVP-AUY922, significantly down regulated the activities of a broad spectrum of kinases involved in regulating cell growth arrest and death of NVPAUY922-sensitive CRC cells. To overcome NVP-AUY922-induced upregulation of survivin expression which causes drug insensitivity, we found that combining berberine (BBR), a herbal medicine with potency in inhibiting survivin expression, with NVP-AUY922 resulted in synergistic antiproliferative effects for NVP-AUY922-sensitive and -insensitive CRC cells. Furthermore, we demonstrated that treatment of NVP-AUY922-insensitive CRC cells with the combination of NVP-AUY922 and BBR caused cell growth arrest through inhibiting CDK4 expression and induction of microRNA-296-5p (miR-296-5p)-mediated suppression of Pin1–β-catenin–cyclin D1 signaling pathway. Finally, we found that the expression level of Hsp90 in tumor tissues of CRC was positively correlated with CDK4 and Pin1 expression levels. Taken together, these results indicate that combination of NVP-AUY922 and BBR therapy can inhibit multiple oncogenic signaling pathways of CRC.Keywords: berberine, colorectal cancer, connectivity map, heat shock protein 90 inhibitor
Procedia PDF Downloads 3061104 Prevalence of Pretreatment Drug HIV-1 Mutations in Moscow, Russia
Authors: Daria Zabolotnaya, Svetlana Degtyareva, Veronika Kanestri, Danila Konnov
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An adequate choice of the initial antiretroviral treatment determines the treatment efficacy. In the clinical guidelines in Russia non-nucleoside reverse transcriptase inhibitors (NNRTIs) are still considered to be an option for first-line treatment while pretreatment drug resistance (PDR) testing is not routinely performed. We conducted a cohort retrospective study in HIV-positive treatment naïve patients of the H-clinic (Moscow, Russia) who performed PDR testing from July 2017 to November 2021. All the information was obtained from the medical records anonymously. We analyzed the mutations in reverse transcriptase and protease genes. RT-sequences were obtained by AmpliSens HIV-Resist-Seq kit. Drug resistance was defined using the HIVdb Program v. 8.9-1. PDR was estimated using the Stanford algorithm. Descriptive statistics were performed in Excel (Microsoft Office, 2019). A total of 261 HIV-1 infected patients were enrolled in the study including 197 (75.5%) male and 64 (24.5%) female. The mean age was 34.6±8.3 years. The median CD4 count – 521 cells/µl (IQR 367-687 cells/µl). Data on risk factors of HIV-infection were scarce. The total quantity of strains containing mutations in the reverse transcriptase gene was 75 (28.7%). From these 5 (1.9%) mutations were associated with PDR to nucleoside reverse transcriptase inhibitors (NRTIs) and 30 (11.5%) – with PDR to NNRTIs. The number of strains with mutations in protease gene was 43 (16.5%), from these only 3 (1.1%) mutations were associated with resistance to protease inhibitors. For NNRTIs the most prevalent PDR mutations were E138A, V106I. Most of the HIV variants exhibited a single PDR mutation, 2 were found in 3 samples. Most of HIV variants with PDR mutation displayed a single drug class resistance mutation. 2/37 (5.4%) strains had both NRTIs and NNRTIs mutations. There were no strains identified with PDR mutations to all three drug classes. Though earlier data demonstrated a lower level of PDR in HIV treatment naïve population in Russia and our cohort can be not fully representative as it is taken from the private clinic, it reflects the trend of increasing PDR especially to NNRTIs. Therefore, we consider either pretreatment testing or giving the priority to other drugs as first-line treatment necessary.Keywords: HIV, resistance, mutations, treatment
Procedia PDF Downloads 931103 Phenotypic and Molecular Heterogeneity Linked to the Magnesium Transporter CNNM2
Authors: Reham Khalaf-Nazzal, Imad Dweikat, Paula Gimenez, Iker Oyenarte, Alfonso Martinez-Cruz, Domonik Muller
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Metal cation transport mediator (CNNM) gene family comprises 4 isoforms that are expressed in various human tissues. Structurally, CNNMs are complex proteins that contain an extracellular N-terminal domain preceding a DUF21 transmembrane domain, a ‘Bateman module’ and a C-terminal cNMP-binding domain. Mutations in CNNM2 cause familial dominant hypomagnesaemia. Growing evidence highlights the role of CNNM2 in neurodevelopment. Mutations in CNNM2 have been implicated in epilepsy, intellectual disability, schizophrenia, and others. In the present study, we aim to elucidate the function of CNNM2 in the developing brain. Thus, we present the genetic origin of symptoms in two family cohorts. In the first family, three siblings of a consanguineous Palestinian family in which parents are first cousins, and consanguinity ran over several generations, presented a varying degree of intellectual disability, cone-rod dystrophy, and autism spectrum disorder. Exome sequencing and segregation analysis revealed the presence of homozygous pathogenic mutation in the CNNM2 gene, the parents were heterozygous for that gene mutation. Magnesium blood levels were normal in the three children and their parents in several measurements. They had no symptoms of hypomagnesemia. The CNNM2 mutation in this family was found to locate in the CBS1 domain of the CNNM2 protein. The crystal structure of the mutated CNNM2 protein was not significantly different from the wild-type protein, and the binding of AMP or MgATP was not dramatically affected. This suggests that the CBS1 domain could be involved in pure neurodevelopmental functions independent of its magnesium-handling role, and this mutation could have affected a protein partner binding or other functions in this protein. In the second family, another autosomal dominant CNNM2 mutation was found to run in a large family with multiple individuals over three generations. All affected family members had hypomagnesemia and hypermagnesuria. Oral supplementation of magnesium did not increase the levels of magnesium in serum significantly. Some affected members of this family have defects in fine motor skills such as dyslexia and dyslalia. The detected mutation is located in the N-terminal part, which contains a signal peptide thought to be involved in the sorting and routing of the protein. In this project, we describe heterogenous clinical phenotypes related to CNNM2 mutations and protein functions. In the first family, and up to the authors’ knowledge, we report for the first time the involvement of CNNM2 in retinal photoreceptor development and function. In addition, we report the presence of a neurophenotype independent of magnesium status related to the CNNM2 protein mutation. Taking into account the different modes of inheritance and the different positions of the mutations within CNNM2 and its different structural and functional domains, it is likely that CNNM2 might be involved in a wide spectrum of neuropsychiatric comorbidities with considerable varying phenotypes.Keywords: magnesium transport, autosomal recessive, autism, neurodevelopment, CBS domain
Procedia PDF Downloads 1501102 Nutritional Genomics Profile Based Personalized Sport Nutrition
Authors: Eszter Repasi, Akos Koller
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Our genetic information determines our look, physiology, sports performance and all our features. Maximizing the performances of athletes have adopted a science-based approach to the nutritional support. Nowadays genetics studies have blended with nutritional sciences, and a dynamically evolving, new research field have appeared. Nutritional genomics is needed to be used by nutritional experts. This is a recent field of nutritional science, which can provide a solution to reach the best sport performance using correlations between the athlete’s genome, nutritions, molecules, included human microbiome (links between food, microbiome and epigenetics), nutrigenomics and nutrigenetics. Nutritional genomics has a tremendous potential to change the future of dietary guidelines and personal recommendations. Experts need to use new technology to get information about the athletes, like nutritional genomics profile (included the determination of the oral and gut microbiome and DNA coded reaction for food components), which can modify the preparation term and sports performance. The influence of nutrients on the genes expression is called Nutrigenomics. The heterogeneous response of gene variants to nutrients, dietary components is called Nutrigenetics. The human microbiome plays a critical role in the state of health and well-being, and there are more links between food or nutrition and the human microbiome composition, which can develop diseases and epigenetic changes as well. A nutritional genomics-based profile of athletes can be the best technic for a dietitian to make a unique sports nutrition diet plan. Using functional food and the right food components can be effected on health state, thus sports performance. Scientists need to determine the best response, due to the effect of nutrients on health, through altering genome promote metabolites and result changes in physiology. Nutritional biochemistry explains why polymorphisms in genes for the absorption, circulation, or metabolism of essential nutrients (such as n-3 polyunsaturated fatty acids or epigallocatechin-3-gallate), would affect the efficacy of that nutrient. Controlled nutritional deficiencies and failures, prevented the change of health state or a newly discovered food intolerance are observed by a proper medical team, can support better sports performance. It is important that the dietetics profession informed on gene-diet interactions, that may be leading to optimal health, reduced risk of injury or disease. A special medical application for documentation and monitoring of data of health state and risk factors can uphold and warn the medical team for an early action and help to be able to do a proper health service in time. This model can set up a personalized nutrition advice from the status control, through the recovery, to the monitoring. But more studies are needed to understand the mechanisms and to be able to change the composition of the microbiome, environmental and genetic risk factors in cases of athletes.Keywords: gene-diet interaction, multidisciplinary team, microbiome, diet plan
Procedia PDF Downloads 1721101 DNA Methylation Changes in Response to Ocean Acidification at the Time of Larval Metamorphosis in the Edible Oyster, Crassostrea hongkongensis
Authors: Yong-Kian Lim, Khan Cheung, Xin Dang, Steven Roberts, Xiaotong Wang, Vengatesen Thiyagarajan
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Unprecedented rate of increased CO₂ level in the ocean and the subsequent changes in carbonate system including decreased pH, known as ocean acidification (OA), is predicted to disrupt not only the calcification process but also several other physiological and developmental processes in a variety of marine organisms, including edible oysters. Nonetheless, not all species are vulnerable to those OA threats, e.g., some species may be able to cope with OA stress using environmentally induced modifications on gene and protein expressions. For example, external environmental stressors, including OA, can influence the addition and removal of methyl groups through epigenetic modification (e.g., DNA methylation) process to turn gene expression “on or off” as part of a rapid adaptive mechanism to cope with OA. In this study, the above hypothesis was tested through testing the effect of OA, using decreased pH 7.4 as a proxy, on the DNA methylation pattern of an endemic and a commercially important estuary oyster species, Crassostrea hongkongensis, at the time of larval habitat selection and metamorphosis. Larval growth rate did not differ between control pH 8.1 and treatment pH 7.4. The metamorphosis rate of the pediveliger larvae was higher at pH 7.4 than those in control pH 8.1; however, over one-third of the larvae raised at pH 7.4 failed to attach to an optimal substrate as defined by biofilm presence. During larval development, a total of 130 genes were differentially methylated across the two treatments. The differential methylation in the larval genes may have partially accounted for the higher metamorphosis success rate under decreased pH 7.4 but with poor substratum selection ability. Differentially methylated loci were concentrated in the exon regions and appear to be associated with cytoskeletal and signal transduction, oxidative stress, metabolic processes, and larval metamorphosis, which implies the high potential of C. hongkongensis larvae to acclimate and adapt through non-genetic ways to OA threats within a single generation.Keywords: adaptive plasticity, DNA methylation, larval metamorphosis, ocean acidification
Procedia PDF Downloads 1391100 Introducing Two Species of Parastagonospora (Phaeosphaeriaceae) on Grasses from Italy and Russia, Based on Morphology and Phylogeny
Authors: Ishani D. Goonasekara, Erio Camporesi, Timur Bulgakov, Rungtiwa Phookamsak, Kevin D. Hyde
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Phaeosphaeriaceae comprises a large number of species occurring mainly on grasses and cereal crops as endophytes, saprobes and especially pathogens. Parastagonospora is an important genus in Phaeosphaeriaceae that includes pathogens causing leaf and glume blotch on cereal crops. Currently, there are fifteen Parastagonospora species described, including both pathogens and saprobes. In this study, one sexual morph species and an asexual morph species, occurring as saprobes on members of Poaceae are introduced based on morphology and a combined molecular analysis of the LSU, SSU, ITS, and RPB2 gene sequence data. The sexual morph species Parastagonospora elymi was isolated from a Russian sample of Elymus repens, a grass commonly known as couch grass, and important for grazing animals, as a weed and used in traditional Austrian medicine. P. elymi is similar to the sexual morph of P. avenae in having cylindrical asci, bearing 8, overlapping biseriate, fusiform ascospores but can be distinguished by its subglobose to conical shaped, wider ascomata. In addition, no sheath was observed surrounding the ascospores. The asexual morph species was isolated from a specimen from Italy, on Dactylis glomerata, a commonly found grass distributed in temperate regions. It is introduced as Parastagonospora macrouniseptata, a coelomycete, and bears a close resemblance to P. allouniseptata and P. uniseptata in having globose to subglobose, pycnidial conidiomata and hyaline, cylindrical, 1-septate conidia. However, the new species could be distinguished in having much larger conidiomata. In the phylogenetic analysis which consisted of a maximum likelihood and Bayesian analysis P. elymi showed low bootstrap support, but well segregated from other strains within the Parastagonospora clade. P. neoallouniseptata formed a sister clade with P. allouniseptata with high statistical support.Keywords: dothideomycetes, multi-gene analysis, Poaceae, saprobes, taxonomy
Procedia PDF Downloads 1161099 Investigate the Side Effects of Patients With Severe COVID-19 and Choose the Appropriate Medication Regimens to Deal With Them
Authors: Rasha Ahmadi
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In December 2019, a coronavirus, currently identified as SARS-CoV-2, produced a series of acute atypical respiratory illnesses in Wuhan, Hubei Province, China. The sickness induced by this virus was named COVID-19. The virus is transmittable between humans and has caused pandemics worldwide. The number of death tolls continues to climb and a huge number of countries have been obliged to perform social isolation and lockdown. Lack of focused therapy continues to be a problem. Epidemiological research showed that senior patients were more susceptible to severe diseases, whereas children tend to have milder symptoms. In this study, we focus on other possible side effects of COVID-19 and more detailed treatment strategies. Using bioinformatics analysis, we first isolated the gene expression profile of patients with severe COVID-19 from the GEO database. Patients' blood samples were used in the GSE183071 dataset. We then categorized the genes with high and low expression. In the next step, we uploaded the genes separately to the Enrichr database and evaluated our data for signs and symptoms as well as related medication regimens. The results showed that 138 genes with high expression and 108 genes with low expression were observed differentially in the severe COVID-19 VS control group. Symptoms and diseases such as embolism and thrombosis of the abdominal aorta, ankylosing spondylitis, suicidal ideation or attempt, regional enteritis were observed in genes with high expression and in genes with low expression of acute and subacute forms of ischemic heart, CNS infection and poliomyelitis, synovitis and tenosynovitis. Following the detection of diseases and possible signs and symptoms, Carmustine, Bithionol, Leflunomide were evaluated more significantly for high-expression genes and Chlorambucil, Ifosfamide, Hydroxyurea, Bisphenol for low-expression genes. In general, examining the different and invisible aspects of COVID-19 and identifying possible treatments can help us significantly in the emergency and hospitalization of patients.Keywords: phenotypes, drug regimens, gene expression profiles, bioinformatics analysis, severe COVID-19
Procedia PDF Downloads 1421098 Isolation and Probiotic Characterization of Lactobacillus plantarum and Lactococcus lactis from Gut Microbiome of Rohu (Labeo rohita)
Authors: Prem Kumar, Anuj Tyagi, Harsh Panwar, Vaneet Inder Kaur
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Though aquaculture started as an occupation for poor and weak farmers for livelihood, it has now acquired the shape of one of the biggest industry to grow live protein in the form of aquatic organisms. Industrialization of the aquaculture sector has led to intensification resulting in stress on aquatic organisms and frequent disease outbreaks leading to huge economic impacts. Indiscriminate use of antibiotics as growth promoter and prophylactic agent in aquaculture has resulted in rapid emergence and spread of antibiotic resistance in bacterial pathogens. Over the past few years, use of probiotics (as an alternative of antibiotics) in aquaculture has gained attention due to their immunostimulant and growth promoting properties. It has now well known that after administration, a probiotic bacterium has to compete and establish itself against native microbiota to show its eventual beneficial properties. Due to their non-fish origin, commercial probiotics sometimes may display poor probiotic functionalities and antagonistic effects. Thus, isolation and characterization of probiotic bacteria from same fish host is very much necessary. In this study, attempts were made to isolate potent probiotic lactic acid bacteria (LAB) from intestinal microflora of rohu fish. Twenty-five experimental rohu fishes (mean weight 400 ± 20gm, mean standard length 20 ± 3cm) were used in the study to collect fish gut after dissection in a sterile condition. A total of 150 tentative LAB isolates from selective agar media (de Man-Rogosa-Sharpe (MRS)) were screened for their antimicrobial activity against Aeromonas hydrophila and Microccocus leuteus. A total of 17 isolates, identified as Lactobacillus plantarum and Lactococcus lactis, identified by biochemical tests and PCR amplification and sequencing of 16S rRNA gene fragment, displayed promising antimicrobial activity against both the pathogens. Two isolates from each species (FLB1, FLB2 from L. plantarum; and FLC1, FLC2 from L. lactis) were subjected to downstream probiotic potential characterization. These isolates were compared in vitro for their hemolytic activity, acid and bile tolerance for growth kinetics, auto-aggregation, cell-surface hydrophobicity against xylene, and chloroform, tolerance to phenol, cell adhesion, and safety parameters (by intraperitoneal and intramuscular injections). None of the tested isolates showed any hemolytic activity indicating their potential safety. Moreover, these isolates were tolerant to 0.3% bile (75-82% survival), phenol stress (96-99% survival) with 100% viability at pH 3 over a period of 3 h. Antibiotic sensitivity test revealed that all the tested LAB isolates were resistant to vancomycin, gentamicin, streptomycin, and erythromycin and sensitive to Erythromycin, Chloramphenicol, Ampicillin, Trimethoprim, and Nitrofurantoin. Tetracycline resistance was found in L. plantarum (FLB1 and FLB2 isolates), whereas L. lactis were susceptible to it. Intramuscular and intraperitoneal challenges to fingerlings of rohu fish (5 ± 1gm weight) with FLB1 showed no pathogenicity and occurrence of disease symptoms in fishes over an observation period of 7 days. The results revealed FLB1 as a potential probiotic candidate for aquaculture application among other isolates.Keywords: aquaculture, Lactobacillus plantarum, Lactococcus lactis, probiotics
Procedia PDF Downloads 1361097 Mechanical Characterization of Mango Peel Flour and Biopolypropylene Composites Compatibilized with PP-g-IA
Authors: J. Gomez-Caturla, L. Quiles-Carrillo, J. Ivorra-Martinez, D. Garcia-Garcia, R. Balart
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The present work reports on the development of wood plastic composites based on biopolypropylene (BioPP) and mango peel flour (MPF) by extrusion and injection moulding processes. PP-g-IA and DCP have been used as a compatibilizer and as free radical initiators for reactive extrusion, respectively. Mechanical and morphological properties have been characterized in order to study the compatibility of the blends. The obtained results showed that DCP and PP-g-IA improved the stiffness of BioPP in terms of elastic modulus. Moreover, they positively increased the tensile strength and elongation at the break of the blends in comparison with the sample that only had BioPP and MPF in its composition, improving the affinity between both compounds. DCP and PP-g-IA even seem to have certain synergy, which was corroborated through FESEM analysis. Images showed that the MPF particles had greater adhesion to the polymer matrix when PP-g-IA and DCP were added. This effect was more intense when both elements were added, observing an almost inexistent gap between MPF particles and the BioPP matrix.Keywords: biopolyproylene, compatibilization, mango peel flour, wood plastic composite
Procedia PDF Downloads 1011096 Cell Response on the Ti-15Mo Alloy Surface after Nanotubes Growth
Authors: Ana Paula Rosifini Alves Claro, André Luiz Reis Rangel, Nathan Trujillo, Ketul C. Popat
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In the present work, in vitro cytotoxicity was evaluated after nanotubes growth on Ti15Mo alloy surface. TiO2 nanotubes were obtained by anodizing technique at room temperature in an electrolyte with 0.25 %NH4F and glycerol at a constant anodic potential of 20 V for 24 hours. The morphology of nanotubes was observed by field emission scanning electron microscopy (FE-SEM; XL 30 FEG, Philips). Crystal structure was analyzed by wide-angle X-ray diffraction. A cell culture model using human fibroblast-like cells was used to study the effect of TiO2 nanotubes growth on the cytotoxicity of the Ti15Mo alloy for 1, 4 and 7 days culture period. The MTT assay was used to evaluate cell viability and cell adhesion was evaluated by scanning electron microscopy. Results show that Ti15Mo alloy with TiO2 nanotubes on surface is nontoxic and exhibit good interaction with surface.Keywords: titanium alloys, TiO2 nanotubes, cell growth, Ti-15Mo alloy
Procedia PDF Downloads 4911095 Biological Evaluation of Some Modern Titanium Alloys for Dental Implants
Authors: Roxana Maria Angelescu, Raluca Ion, Anişoara Cîmpean, Doina Răducanu, Mariana Lucia Angelescu
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In an attempt to find titanium alloys that fulfill the requirements for mechanical and biological compatibility, laboratory and material related tests were performed during the years, as well as preclinical and clinical trials. The multidisciplinary scientific research facilitates the global evaluation of biocompatibility and osseointegration regarding the dental implant alloys. The aim of this study was to determine the in vitro biocompatibility of three modern titanium alloys: Ti-31.7Nb-6.21Zr-1.4Fe-0.16O (wt%), Ti-36.5Nb-4.5Zr-3Ta-0.16O (wt%) and Ti-20Nb-5Ta (wt%), in order to establish whether the use of these titanium alloys can have any toxic or injurious effects on biological systems. The commonly used Ti-6Al-4V alloy was investigated as a reference material. The behavior of MC3T3-E1 pre-osteoblasts on all these four metallic surfaces was evaluated. The tests of immunofluorescence, cytotoxicity and cellular proliferation lead to the conclusion that the newly-developed titanium alloys elicit a good cellular response in terms of cellular survival, adhesion, morphology and proliferative potential as well.Keywords: biocompatibility tests, dental implants, titanium alloys, biomedical engineering
Procedia PDF Downloads 5021094 Evaluation of Antimicrobial Efficacy of Nanofluid Containing Carbon Nanotubes Functionalized with Antibiotic on Urinary Tract Infection
Authors: Erfan Rahimi, Hadi Bahari Far, Mojgan Shikhpour
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Background: Urinary tract infection is one of the most common nosocomial infections, especially among women. E. coli is one of the main causes of urinary tract infections and one of the most common antibiotics to fight this bacterium is ampicillin. As conventional antibiotics led to bacterial antibiotic resistance, modification of the pure drugs can address this issue. The aim of this study was to prepare nanofluids containing carbon nanotubes conjugated with ampicillin to improve drug performance and reduce antibiotic resistance. Methods: Multi-walled carbon nanotubes (MWCNTs) were activated with thionyl chloride by reflux system and nanofluids containing antibiotics were prepared by ultrasonic method. The properties of the prepared nano-drug were investigated by general element analysis, infrared spectroscopy, Raman spectroscopy, scanning electron microscopy and transmission electron microscopy. After the treatment of the desired strain with nanofluid, microbial studies were performed to evaluate the antibacterial effects and molecular studies were carried out to measure the expression of the resistance gene AcrAB. Result: We have shown that the antimicrobial effect of ampicillin-functionalized MWCNTs at low concentrations performed better than that of the conventional drug in both resistant and ATCC strains. Also, a decrease in antibiotic resistance of bacteria treated with ampicillin-functionalized MWCNTs compared to the pure drug was observed. Also, ampicillin-functionalized MWCNTs downregulated the expression of AcrAB in treated bacteria. Conclusion: Because carbon nanotubes are capable of destroying the bacterial wall, which provides antibiotic resistance features in bacteria, their usage in the form of nanofluids can make lower dosages (about three times less) than that of the pure drug more effective. Additionally, the expression of the bacterial resistance gene AcrAB decreased, thereby reducing antibiotic resistance and improving drug performance against bacteria.Keywords: urinary tract infection, antibiotic resistance, carbon nanotube, nanofluid
Procedia PDF Downloads 1461093 Assessment of Neurodevelopmental Needs in Duchenne Muscular Dystrophy
Authors: Mathula Thangarajh
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Duchenne muscular dystrophy (DMD) is a severe form of X-linked muscular dystrophy caused by mutations in the dystrophin gene resulting in progressive skeletal muscle weakness. Boys with DMD also have significant cognitive disabilities. The intelligence quotient of boys with DMD, compared to peers, is approximately one standard deviation below average. Detailed neuropsychological testing has demonstrated that boys with DMD have a global developmental impairment, with verbal memory and visuospatial skills most significantly affected. Furthermore, the total brain volume and gray matter volume are lower in children with DMD compared to age-matched controls. These results are suggestive of a significant structural and functional compromise to the developing brain as a result of absent dystrophin protein expression. There is also some genetic evidence to suggest that mutations in the 3’ end of the DMD gene are associated with more severe neurocognitive problems. Our working hypothesis is that (i) boys with DMD do not make gains in neurodevelopmental skills compared to typically developing children and (ii) women carriers of DMD mutations may have subclinical cognitive deficits. We also hypothesize that there may be an intergenerational vulnerability of cognition, with boys of DMD-carrier mothers being more affected cognitively than boys of non-DMD-carrier mothers. The objectives of this study are: 1. Assess the neurodevelopment in boys with DMD at 4-time points and perform baseline neuroradiological assessment, 2. Assess cognition in biological mothers of DMD participants at baseline, 3. Assess possible correlation between DMD mutation and cognitive measures. This study also explores functional brain abnormalities in people with DMD by exploring how regional and global connectivity of the brain underlies executive function deficits in DMD. Such research can contribute to a better holistic understanding of the cognition alterations due to DMD and could potentially allow clinicians to create better-tailored treatment plans for the DMD population. There are four study visits for each participant (baseline, 2-4 weeks, 1 year, 18 months). At each visit, the participant completes the NIH Toolbox Cognition Battery, a validated psychometric measure that is recommended by NIH Common Data Elements for use in DMD. Visits 1, 3, and 4 also involve the administration of the BRIEF-2, ABAS-3, PROMIS/NeuroQoL, PedsQL Neuromuscular module 3.0, Draw a Clock Test, and an optional fMRI scan with the N-back matching task. We expect to enroll 52 children with DMD, 52 mothers of children with DMD, and 30 healthy control boys. This study began in 2020 during the height of the COVID-19 pandemic. Due to this, there were subsequent delays in recruitment because of travel restrictions. However, we have persevered and continued to recruit new participants for the study. We partnered with the Muscular Dystrophy Association (MDA) and helped advertise the study to interested families. Since then, we have had families from across the country contact us about their interest in the study. We plan to continue to enroll a diverse population of DMD participants to contribute toward a better understanding of Duchenne Muscular Dystrophy.Keywords: neurology, Duchenne muscular dystrophy, muscular dystrophy, cognition, neurodevelopment, x-linked disorder, DMD, DMD gene
Procedia PDF Downloads 991092 Targeting Mre11 Nuclease Overcomes Platinum Resistance and Induces Synthetic Lethality in Platinum Sensitive XRCC1 Deficient Epithelial Ovarian Cancers
Authors: Adel Alblihy, Reem Ali, Mashael Algethami, Ahmed Shoqafi, Michael S. Toss, Juliette Brownlie, Natalie J. Tatum, Ian Hickson, Paloma Ordonez Moran, Anna Grabowska, Jennie N. Jeyapalan, Nigel P. Mongan, Emad A. Rakha, Srinivasan Madhusudan
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Platinum resistance is a clinical challenge in ovarian cancer. Platinating agents induce DNA damage which activate Mre11 nuclease directed DNA damage signalling and response (DDR). Upregulation of DDR may promote chemotherapy resistance. Here we have comprehensively evaluated Mre11 in epithelial ovarian cancers. In clinical cohort that received platinum- based chemotherapy (n=331), Mre11 protein overexpression was associated with aggressive phenotype and poor progression free survival (PFS) (p=0.002). In the ovarian cancer genome atlas (TCGA) cohort (n=498), Mre11 gene amplification was observed in a subset of serous tumours (5%) which correlated highly with Mre11 mRNA levels (p<0.0001). Altered Mre11 levels was linked with genome wide alterations that can influence platinum sensitivity. At the transcriptomic level (n=1259), Mre11 overexpression was associated with poor PFS (p=0.003). ROC analysis showed an area under the curve (AUC) of 0.642 for response to platinum-based chemotherapy. Pre-clinically, Mre11 depletion by gene knock down or blockade by small molecule inhibitor (Mirin) reversed platinum resistance in ovarian cancer cells and in 3D spheroid models. Importantly, Mre11 inhibition was synthetically lethal in platinum sensitive XRCC1 deficient ovarian cancer cells and 3D-spheroids. Selective cytotoxicity was associated with DNA double strand break (DSB) accumulation, S-phase cell cycle arrest and increased apoptosis. We conclude that pharmaceutical development of Mre11 inhibitors is a viable clinical strategy for platinum sensitization and synthetic lethality in ovarian cancer.Keywords: MRE11; XRCC1, ovarian cancer, platinum sensitization, synthetic lethality
Procedia PDF Downloads 1291091 Staphylococcal Enterotoxins Play an Important Role in Clinical Signs in Bovine Mastitis
Authors: Stéfani T. A. Dantas, Laura T. S. Takume, Bruna F. Rossi, Érika R. Bonsaglia, Ivana G. Castilho, José C. F. Pantoja, Ary Fernandes Júnior, Juliano L. Gonçalves, Marcos V. Santos, Rinaldo A. Mota, Vera L. M. Rall
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Staphylococcus aureus is one of the main pathogens causing contagious bovine mastitis, being more frequently isolated from subclinical form, although the clinical form also occurs. Clinical mastitis cause visual signs, such as swelling, fever, hardening of the mammary gland, or any change in the characteristics of the milk. Considering the subclinical type, there are no visible signs in the animal nor changes in the milk. S. aureus has many important virulence factors for the establishment of its pathogenicity in animals, such as enterotoxins, which are also responsible for foodborne poisoning. Our objective is to perform a comparative analysis between 103 isolates of S. aureus, obtained from the milk of cows with clinical mastitis and 103 more, from subclinical type, in relation to the presence of these enterotoxins and verify if their presence plays an important role in the signs of illness. We will investigate all enterotoxins described till now, such as sea-see, seg-sez, sel26, sel 27, se01, and se02 (This study was approved by the Sao Paulo State University Animal Use Ethics Committee, No. 0136/2017). For the PCR assay, we used Illustra Bacteria Mini Spin Kit for bacterial DNA. At this moment, we have already tested sea-see, seg-ser, sew, and sex, and the results have already been submitted to Fisher Exact Probability Test or Chi-square Test. Considering the isolates obtained from clinical mastitis, the most frequent enterotoxins were selw (99%), selx (78%) and selh (50.5%), and sec, see, sej, sell, selp,and ser were absent. Among the subclinics, selw (82.5%) selm (15.5%) and selx (14.6%) were the most frequent, and sea-see, seg, sei-sel, sem-ser were absent. We have already observed statistically significant differences for seb, seg, seh, sei, selo, selu, selw and selx. Other interesting results were the low number of genes in each isolate from subclinical mastitis [0 genes: 14 (13.6%); 1 gene: 55 (53.4%); 2 genes: 33 (32%) or 3: 1 (0.97%)] compared to clinical isolates [1 gene: 5 (4.9%); 2 genes: 29 (28.1%); 3 genes: 38 (36.9%); 4 genes: 14 (13.6%); 5 genes: 5 (4.9%); 6 genes: 4 (3.9%); 7 genes: 5 (4.9%); 8 genes: 2 (1.9%) and 9 genes: 1 (1%)]. Based on these results, we can conclude that enterotoxins indeed play an important role in clinical signs in cattle with mastitis.Keywords: mastitis, S. aureus, PCR, staphylococcal enterotoxin
Procedia PDF Downloads 1131090 Packaging Processes for the Implantable Medical Microelectronics
Authors: Chung-Yu Wu, Chia-Chi Chang, Wei-Ming Chen, Pu-Wei Wu, Shih-Fan Chen, Po-Chun Chen
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Electrostimulation medical devices for neural diseases require electroactive and biocompatible materials to transmit signals from electrodes to targeting tissues. Protection of surrounding tissues has become a great challenge for long-term implants. In this study, we designed back-end processes with compatible, efficient, and reliable advantages over the current state-of-the-art. We explored a hermetic packaging process with high quality of adhesion and uniformity as the biocompatible devices for long-term implantation. This approach is able to provide both excellent biocompatibility and protection to the biomedical electronic devices by performing conformal coating of biocompatible materials. We successfully developed a packaging process that is capable of exposing the stimulating electrode and cover all other faces of chip with high quality of protection to prevent leakage of devices and body fluid.Keywords: biocompatible package, medical microelectronics, surface coating, long-term implantation
Procedia PDF Downloads 5241089 Thixomixing as Novel Method for Fabrication Aluminum Composite with Carbon and Alumina Fibers
Authors: Ebrahim Akbarzadeh, Josep A. Picas Barrachina, Maite Baile Puig
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This study focuses on a novel method for dispersion and distribution of reinforcement under high intensive shear stress to produce metal composites. The polyacrylonitrile (PAN)-based short carbon fiber (Csf) and Nextel 610 alumina fiber were dispersed under high intensive shearing at mushy zone in semi-solid of A356 by a novel method. The bundles and clusters were embedded by infiltration of slurry into the clusters, thus leading to a uniform microstructure. The fibers were embedded homogenously into the aluminum around 576-580°C with around 46% of solid fraction. Other experiments at 615°C and 568°C which are contained 0% and 90% solid respectively were not successful for dispersion and infiltration of aluminum into bundles of Csf. The alumina fiber has been cracked by high shearing load. The morphologies and crystalline phase were evaluated by SEM and XRD. The adopted thixo-process effectively improved the adherence and distribution of Csf into Al that can be developed to produce various composites by thixomixing.Keywords: aluminum, carbon fiber, alumina fiber, thixomixing, adhesion
Procedia PDF Downloads 5571088 Evaluation of the Spatial Regulation of Hydrogen Sulphide Producing Enzymes in the Placenta during Labour
Authors: F. Saleh, F. Lyall, A. Abdulsid, L. Marks
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Background: Labour in human is a complex biological process that involves interactions of neurological, hormonal and inflammatory pathways, with the placenta being a key regulator of these pathways. It is known that uterine contractions and labour pain cause physiological changes in gene expression in maternal and fetal blood, and in placenta during labour. Oxidative and inflammatory stress pathways are implicated in labour and they may cause alteration of placental gene expression. Additionally, in placental tissues, labour increases the expression of genes involved in placental oxidative stress, inflammatory cytokines, angiogenic regulators and apoptosis. Recently, Hydrogen Sulphide (H2S) has been considered as an endogenous gaseous mediator which promotes vasodilation and exhibits cytoprotective anti-inflammatory properties. The endogenous H2S is synthesised predominantly by two enzymes: cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE). As the H2S pathway has anti-oxidative and anti-inflammatory characteristics thus, we hypothesised that the expression of CBS and CSE in placental tissues would alter during labour. Methods: CBS and CSE expressions were examined in placentas using western blotting and RT-PCR in inner, middle and outer placental zones in placentas obtained from healthy non labouring women who delivered by caesarian section. These were compared with the equivalent zone of placentas obtained from women who had uncomplicated labour and delivered vaginally. Results: No differences in CBS and CSE mRNA or protein levels were found between the different sites within placentas in either the labour or non-labour group. There were no significant differences in either CBS or CSE expression between the two groups at the inner site and middle site. However, at the outer site there was a highly significant decrease in CBS protein expression in the labour group when compared to the non-labour group (p = 0.002). Conclusion: To the best of author’s knowledge, this is the first report to suggest that, CBS is expressed in a spatial manner within the human placenta. Further work is needed to clarify the precise function and mechanism of this spatial regulation although it is likely that inflammatory pathways regulation is a complex process in which this plays a role.Keywords: anti-inflammatory, hydrogen sulphide, labour, oxidative stress
Procedia PDF Downloads 2411087 Expression of Micro-RNA268 in Zinc Deficient Rice
Authors: Sobia Shafqat, Saeed Ahmad Qaisrani
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MicroRNAs play an essential role in the regulation and development of all processes in most eukaryotes because of their prospective part as mediators controlling cell growth and differentiation towards the exact position of RNAs response in plants under biotic and abiotic factors or stressors. In a few cases, Zn is oblivious poisonous for plants due to its heavy metal status. Some other metals are extremely toxic, like Cd, Hg, and Pb, but these elements require in rice for the programming of genes under abiotic stress resembling Zn stress when micro RNAs268 was importantly introduced in rice. The micro RNAs overexpressed in transgenic plants with an accumulation of a large amount of melanin dialdehyde, hydrogen peroxide, and an excessive quantity of Zn in the seedlings stage. Let out results for rice pliability under Zn stress micro RNAs act as negative controllers. But the role of micro RNA268 act as a modulator in different ecological condition. It has been explained clearly with a long understanding of the role of micro RNA268 under stress conditions; pliability and practically showed outcome to increase plant sufferance under Zn stress because micro RNAs is an intervention technique for gene regulation in gene expression. The proposed study was experimented with by using genetic factors of Zn stress and toxicity effect on rice plants done at District Vehari, Pakistan. The trial was performed randomly with three replications in a complete block design (RCBD). These blocks were controlled with different concentrations of genetic factors. By overexpression of micro RNA268 rice, seedling growth was not stopped under Zn deficiency due to the accumulation of a large amount of melanin dialdehyde, hydrogen peroxide, and an excessive quantity of Zn in their seedlings. Results showed that micro RNA268 act as a negative controller under Zn stress. In the end, under stress conditions, micro RNA268 showed the necessary function in the tolerance of rice plants. The directorial work sketch gave out high agronomic applications and yield outcomes in rice with a specific amount of Zn application.Keywords: micro RNA268, zinc, rice, agronomic approach
Procedia PDF Downloads 611086 Icephobic and Hydrophobic Behaviour of Laser Patterned Transparent Coatings
Authors: Bartłomiej Przybyszewski, Rafał Kozera, Anna Boczkowska, Maciej Traczyk, Paulina Kozera, Malwina Liszewska, Daria Pakuła
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The goal of the work was to reduce or completely eliminate the accumulation of dirt, snow and ice build-up on transparent coatings by achieving self-cleaning and icephobic properties. The research involved the use of laser surface texturing technology for chemically modified coatings of the epoxy materials group and their hybrids used to protect glass surfaces. For this purpose, two methods of surface structuring and the preceding volumetric modification of the chemical composition with proprietary organosilicon compounds and/or mineral additives were used. An attractive approach to the topic was the development of efficient and, most importantly, durable coatings with self-cleaning and ice-phobic properties that reduced or avoided dirt build-up and adhesion of water, snow and ice. With a view to the future industrial application of the developed technologies, all methods meet the requirements in terms of their practical use on a large scale.Keywords: icephobic coatings, hydrophobic coatings, transparent coatings, laser patterning
Procedia PDF Downloads 1051085 Modelling of Atomic Force Microscopic Nano Robot's Friction Force on Rough Surfaces
Authors: M. Kharazmi, M. Zakeri, M. Packirisamy, J. Faraji
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Micro/Nanorobotics or manipulation of nanoparticles by Atomic Force Microscopic (AFM) is one of the most important solutions for controlling the movement of atoms, particles and micro/nano metrics components and assembling of them to design micro/nano-meter tools. Accurate modelling of manipulation requires identification of forces and mechanical knowledge in the Nanoscale which are different from macro world. Due to the importance of the adhesion forces and the interaction of surfaces at the nanoscale several friction models were presented. In this research, friction and normal forces that are applied on the AFM by using of the dynamic bending-torsion model of AFM are obtained based on Hurtado-Kim friction model (HK), Johnson-Kendall-Robert contact model (JKR) and Greenwood-Williamson roughness model (GW). Finally, the effect of standard deviation of asperities height on the normal load, friction force and friction coefficient are studied.Keywords: atomic force microscopy, contact model, friction coefficient, Greenwood-Williamson model
Procedia PDF Downloads 1991084 A Comparative CFD Study on the Hemodynamics of Flow through an Idealized Symmetric and Asymmetric Stenosed Arteries
Authors: B. Prashantha, S. Anish
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The aim of the present study is to computationally evaluate the hemodynamic factors which affect the formation of atherosclerosis and plaque rupture in the human artery. An increase of atherosclerosis disease in the artery causes geometry changes, which results in hemodynamic changes such as flow separation, reattachment, and adhesion of new cells (chemotactic) in the artery. Hence, geometry plays an important role in the determining the nature of hemodynamic patterns. Influence of stenosis in the non-bifurcating artery, under pulsatile flow condition, has been studied on an idealized geometry. Analysis of flow through symmetric and asymmetric stenosis in the artery revealed the significance of oscillating shear index (OSI), flow separation, low WSS zones and secondary flow patterns on plaque formation. The observed characteristic of flow in the post-stenotic region highlight the importance of plaque eccentricity on the formation of secondary stenosis on the arterial wall.Keywords: atherosclerotic plaque, oscillatory shear index, stenosis nature, wall shear stress
Procedia PDF Downloads 3501083 Effect of Post Treatment Temperature on Ni-20Cr Wire Arc Spray Coating to Thermal Resistance
Authors: Ken Ninez Nurpramesti Prinindya, Yuli Setiyorini
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Crown enclosure high temperature flares damaged and reduced dimensions crown. Generally crown on EHTF could have a life time up to twenty years. Therefore, this study aims to increase the value of thermal resistance with the effect post treatment on NiCr coated arc spray method. The variation of post treatment temperature, was at 650°C, 750°C, and 850°C. Morphology on the surface and the adhesion strength was analyzed by SEM-EDX, Surface Roughness and Pull - off test. XRD testing was conducted to determine the contained in NiCr coated. Thermal stability of NiCr coated was tested by DSC-TGA. The most optimal results was owned by NiCr coating with post treated at 850°C. It has good thermal stability until 1000°C because of Cr2O3 formation in coated specimen. The higher temperature of post treatment coating was showed better result on porosity and roughness surface value.Keywords: Arc spray process, NiCr wire, post-treatment coating, high temperature-corrosion resistance
Procedia PDF Downloads 4761082 Effects of Pterostilbene in Brown Adipose Tissue from Obese Rats
Authors: Leixuri Aguirre, Iñaki Milton-Laskibar, Elizabeth Hijona, Luis Bujanda, Agnes M. Rimando, Maria P. Portillo
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Introduction: In recent years great attention has been paid by scientific community to phenolic compounds as active biomolecules naturally present in foodstuffs due to their beneficial effects on health. Pterostilbene is a resveratrol dimethylether derivative which shows higher biodisponibility. Objective. To analyze the effects of two doses of pterostilbene on several markers of thermogenic capacity in a model of genetic obesity, which shows reduced thermogenesis. Methods: The experiment was conducted with thirty Zucker (fa/fa) rats that were distributed in 3 experimental groups, the control group and two groups orally administered with pterostilbene at 15 and 30 mg/kg body weight/day for 6 weeks. Gene expression of Ucp1, Pgc-1α, Cpt1b, Pparα, Nfr1, Tfam and Cox-2 were assessed by RT-PCR, protein expression of UCP1 and GLUT4 by western blot and enzyme activity of carnitine palmitoyl transferase 1b and citrate synthase by spectrophotometry in interscapular brown adipose tissue (iBAT). Statistical analysis was performed by using one way ANOVA and Newman-Keuls as post-hoc test. Results: Pterostilbene did not change gene expression of Pgc-1α. However, significant increases were found in the expression of Ucp1, Pparα, Nfr-1 and Cox-2. Protein expression of UCP1 and GLUT4 was increased in animals treated with pterostilbene, as well as the activities of CPT-1b and CS. These effects were observed with both doses of pterostilbene, without differences between them. Conclusions: These results show that pterostilbene increases thermogenic and oxidative capacity of brown adipose tissue in obese rats. Whether these effects effectively contribute to the anti-obesity properties of these compound needs further research. Acknowledgments: MINECO-FEDER (AGL2015-65719-R), Basque Government (IT-572-13), University of the Basque Country (ELDUNANOTEK UFI11/32), Institut of Health Carlos III (CIBERobn). Iñaki Milton is a fellowship from the Basque Government.Keywords: brown adipose tissue, pterostilbene, thermogenesis, uncoupling protein 1
Procedia PDF Downloads 2951081 Effect of Surface Treatment on Physico-Mechanical Properties of Sisal Fiber-Unsaturated Polyester Composites
Authors: A. H. Birniwa, A. A. Salisu, M. Y. Yakasai, A. Sabo, K. Aujara, A. Isma’il
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Sisal fibre was extracted from Sisal leaves by enzymatic retting method. A portion of the fibre was subjected to treatment with alkali, benzoyl chloride and silane compounds. Sisal fibre composites were fabricated using unsaturated polyester resin, by hand lay-up technique using both the treated and untreated fibre. Tensile, flexural and water absorption tests were conducted and evaluated on the composites. The results obtained were found to increase in the treated fibre compared to untreated fibre. Surface morphology of the fibre was observed using scanning electron microscopy (SEM) and the result obtained showed variation in the morphology of the treated and untreated fibre. FT-IR results showed inclusion of benzoyl and silane groups on the fibre surface. The fibre chemical modification improves its adhesion to the matrix, mechanical properties of the composites were also found to improve.Keywords: composite, flexural strength, matrix, sisal fibre
Procedia PDF Downloads 3951080 The Importance of including All Data in a Linear Model for the Analysis of RNAseq Data
Authors: Roxane A. Legaie, Kjiana E. Schwab, Caroline E. Gargett
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Studies looking at the changes in gene expression from RNAseq data often make use of linear models. It is also common practice to focus on a subset of data for a comparison of interest, leaving aside the samples not involved in this particular comparison. This work shows the importance of including all observations in the modeling process to better estimate variance parameters, even when the samples included are not directly used in the comparison under test. The human endometrium is a dynamic tissue, which undergoes cycles of growth and regression with each menstrual cycle. The mesenchymal stem cells (MSCs) present in the endometrium are likely responsible for this remarkable regenerative capacity. However recent studies suggest that MSCs also plays a role in the pathogenesis of endometriosis, one of the most common medical conditions affecting the lower abdomen in women in which the endometrial tissue grows outside the womb. In this study we compared gene expression profiles between MSCs and non-stem cell counterparts (‘non-MSC’) obtained from women with (‘E’) or without (‘noE’) endometriosis from RNAseq. Raw read counts were used for differential expression analysis using a linear model with the limma-voom R package, including either all samples in the study or only the samples belonging to the subset of interest (e.g. for the comparison ‘E vs noE in MSC cells’, including only MSC samples from E and noE patients but not the non-MSC ones). Using the full dataset we identified about 100 differentially expressed (DE) genes between E and noE samples in MSC samples (adj.p-val < 0.05 and |logFC|>1) while only 9 DE genes were identified when using only the subset of data (MSC samples only). Important genes known to be involved in endometriosis such as KLF9 and RND3 were missed in the latter case. When looking at the MSC vs non-MSC cells comparison, the linear model including all samples identified 260 genes for noE samples (including the stem cell marker SUSD2) while the subset analysis did not identify any DE genes. When looking at E samples, 12 genes were identified with the first approach and only 1 with the subset approach. Although the stem cell marker RGS5 was found in both cases, the subset test missed important genes involved in stem cell differentiation such as NOTCH3 and other potentially related genes to be used for further investigation and pathway analysis.Keywords: differential expression, endometriosis, linear model, RNAseq
Procedia PDF Downloads 4321079 Flexural Analysis of Palm Fiber Reinforced Hybrid Polymer Matrix Composite
Authors: G.Venkatachalam, Gautham Shankar, Dasarath Raghav, Krishna Kuar, Santhosh Kiran, Bhargav Mahesh
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Uncertainty in the availability of fossil fuels in the future and global warming increased the need for more environment-friendly materials. In this work, an attempt is made to fabricate a hybrid polymer matrix composite. The blend is a mixture of General Purpose Resin and Cashew Nut Shell Liquid, a natural resin extracted from cashew plant. Palm fiber, which has high strength, is used as a reinforcement material. The fiber is treated with alkali (NaOH) solution to increase its strength and adhesiveness. Parametric study of flexure strength is carried out by varying alkali concentration, duration of alkali treatment and fiber volume. Taguchi L9 Orthogonal array is followed in the design of experiments procedure for simplification. With the help of ANOVA technique, regression equations are obtained which gives the level of influence of each parameter on the flexure strength of the composite.Keywords: Adhesion, CNSL, Flexural Analysis, Hybrid Matrix Composite, Palm Fiber
Procedia PDF Downloads 4051078 Investigation on Mesh Sensitivity of a Transient Model for Nozzle Clogging
Authors: H. Barati, M. Wu, A. Kharicha, A. Ludwig
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A transient model for nozzle clogging has been developed and successfully validated against a laboratory experiment. Key steps of clogging are considered: transport of particles by turbulent flow towards the nozzle wall; interactions between fluid flow and nozzle wall, and the adhesion of the particle on the wall; the growth of the clog layer and its interaction with the flow. The current paper is to investigate the mesh (size and type) sensitivity of the model in both two and three dimensions. It is found that the algorithm for clog growth alone excluding the flow effect is insensitive to the mesh type and size, but the calculation including flow becomes sensitive to the mesh quality. The use of 2D meshes leads to overestimation of the clog growth because the 3D nature of flow in the boundary layer cannot be properly solved by 2D calculation. 3D simulation with tetrahedron mesh can also lead to an error estimation of the clog growth. A mesh-independent result can be achieved with hexahedral mesh, or at least with triangular prism (inflation layer) for near-wall regions.Keywords: clogging, continuous casting, inclusion, simulation, submerged entry nozzle
Procedia PDF Downloads 2831077 Prevalence and Molecular Characterization of Extended-Spectrum–β Lactamase and Carbapenemase-Producing Enterobacterales from Tunisian Seafood
Authors: Mehdi Soula, Yosra Mani, Estelle Saras, Antoine Drapeau, Raoudha Grami, Mahjoub Aouni, Jean-Yves Madec, Marisa Haenni, Wejdene Mansour
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Multi-resistance to antibiotics in gram-negative bacilli and particularly in enterobacteriaceae, has become frequent in hospitals in Tunisia. However, data on antibiotic resistant bacteria in aquatic products are scarce. The aims of this study are to estimate the proportion of ESBL- and carbapenemase-producing Enterobacterales in seafood (clams and fish) in Tunisia and to molecularly characterize the collected isolates. Two types of seafood were sampled in unrelated markets in four different regions in Tunisia (641 pieces of farmed fish and 1075 mediterranean clams divided into 215 pools, and each pool contained 5 pieces). Once purchased, all samples were incubated in tubes containing peptone salt broth for 24 to 48h at 37°C. After incubation, overnight cultures were isolated on selective MacConkey agar plates supplemented with either imipenem or cefotaxime, identified using API20E test strips (bioMérieux, Marcy-l’Étoile, France) and confirmed by Maldi-TOF MS. Antimicrobial susceptibility was determined by the disk diffusion method on Mueller-Hinton agar plates and results were interpreted according to CA-SFM 2021. ESBL-producing Enterobacterales were detected using the Double Disc Synergy Test (DDST). Carbapenem-resistance was detected using an ertapenem disk and was respectively confirmed using the ROSCO KPC/MBL and OXA-48 Confirm Kit (ROSCO Diagnostica, Taastrup, Denmark). DNA was extracted using a NucleoSpin Microbial DNA extraction kit (Macherey-Nagel, Hoerdt, France), according to the manufacturer’s instructions. Resistance genes were determined using the CGE online tools. The replicon content and plasmid formula were identified from the WGS data using PlasmidFinder 2.0.1 and pMLST 2.0. From farmed fishes, nine ESBL-producing strains (9/641, 1.4%) were isolated, which were identified as E. coli (n=6) and K. pneumoniae (n=3). Among the 215 pools of 5 clams analyzed, 18 ESBL-producing isolates were identified, including 14 E. coli and 4 K. pneumoniae. A low isolation rate of ESBL-producing Enterobacterales was detected 1.6% (18/1075) in clam pools. In fish, the ESBL phenotype was due to the presence of the blaCTX-M-15 gene in all nine isolates, but no carbapenemase gene was identified. In clams, the predominant ESBL phenotype was blaCTX-M-1 (n=6/18). blaCPE (NDM1, OXA48) was detected only in 3 isolates ‘K. pneumoniae isolates’. Replicon typing on the strains carring the ESBL and carbapenemase gene revelead that the major type plasmid carried ESBL were IncF (42.3%) [n=11/26]. In all, our results suggest that seafood can be a reservoir of multi-drug resistant bacteria, most probably of human origin but also by the selection pressure of antibiotic. Our findings raise concerns that seafood bought for consumption may serve as potential reservoirs of AMR genes and pose serious threat to public health.Keywords: BLSE, carbapenemase, enterobacterales, tunisian seafood
Procedia PDF Downloads 1081076 Quantitative Changes in Biofilms of a Seawater Tubular Heat Exchanger Subjected to Electromagnetic Fields Treatment
Authors: Sergio Garcia, Alfredo Trueba, Luis M. Vega, Ernesto Madariaga
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Biofilms adhesion is one of the more important cost of industries plants on wide world, which use to water for cooling heat exchangers or are in contact with water. This study evaluated the effect of Electromagnetic Fields on biofilms in tubular heat exchangers using seawater cooling. The results showed an up to 40% reduction of the biofilm thickness compared to the untreated control tubes. The presence of organic matter was reduced by 75%, the inorganic mater was reduced by 87%, and 53% of the dissolved solids were eliminated. The biofilm thermal conductivity in the treated tube was reduced by 53% as compared to the control tube. The hardness in the effluent during the experimental period was decreased by 18% in the treated tubes compared with control tubes. Our results show that the electromagnetic fields treatment has a great potential in the process of removing biofilms in heat exchanger.Keywords: biofilm, heat exchanger, electromagnetic fields, seawater
Procedia PDF Downloads 191