Search results for: endothelial cell

Authors: Yihenew Simegniew Birhan, Hsieh Chih Tsai

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The recent advancements in synthetic chemistry and nanotechnology fostered the development of different nanocarriers for enhanced intracellular delivery of pharmaceutical agents to tumor cells. Polymeric micelles (PMs), characterized by small size, appreciable drug loading capacity (DLC), better accumulation in tumor tissue via enhanced permeability and retention (EPR) effect, and the ability to avoid detection and subsequent clearance by the mononuclear phagocyte (MNP) system, are convenient to improve the poor solubility, slow absorption and non-selective biodistribution of payloads embedded in their hydrophobic cores and hence, enhance the therapeutic efficacy of chemotherapeutic agents. Recently, redox-responsive polymeric micelles have gained significant attention for the delivery and controlled release of anticancer drugs in tumor cells. In this study, we synthesized redox-responsive diselenide bond containing amphiphilic polymer, Bi(mPEG-PLGA)-Se₂ from mPEG-PLGA, and 3,3'-diselanediyldipropanoic acid (DSeDPA) using DCC/DMAP as coupling agents. The successful synthesis of the copolymers was verified by different spectroscopic techniques. Above the critical micelle concentration, the amphiphilic copolymer, Bi(mPEG-PLGA)-Se₂, self-assembled into stable micelles. The DLS data indicated that the hydrodynamic diameter of the micelles (123.9 ± 0.85 nm) was suitable for extravasation into the tumor cells through the EPR effect. The drug loading content (DLC) and encapsulation efficiency (EE) of DOX-loaded micelles were found to be 6.61 wt% and 54.9%, respectively. The DOX-loaded micelles showed initial burst release accompanied by sustained release trend where 73.94% and 69.54% of encapsulated DOX was released upon treatment with 6mM GSH and 0.1% H₂O₂, respectively. The biocompatible nature of Bi(mPEG-PLGA)-Se₂ copolymer was confirmed by the cell viability study. In addition, the DOX-loaded micelles exhibited significant inhibition against HeLa cells (44.46%), at a maximum dose of 7.5 µg/mL. The fluorescent microscope images of HeLa cells treated with 3 µg/mL (equivalent DOX concentration) revealed efficient internalization and accumulation of DOX-loaded Bi(mPEG-PLGA)-Se₂ micelles in the cytosol of cancer cells. In conclusion, the intelligent, biocompatible, and the redox stimuli-responsive behavior of Bi(mPEG-PLGA)-Se₂ copolymer marked the potential applications of diselenide-linked mPEG-PLGA micelles for the delivery and on-demand release of chemotherapeutic agents in cancer cells.

Keywords: anticancer drug delivery, diselenide bond, polymeric micelles, redox-responsive

Procedia PDF Downloads 110

Authors: Sabri Serkan Gulluoglu

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The study is aimed at examining the effects of internet marketing with IPTV on human beings. Internet marketing with IPTV is emerging as an integral part of business strategies in today’s technologically advanced world and the business activities all over the world are influences with the emergence of this modern marketing tool. As the population of the Internet and on-line users’ increases, new research issues have arisen concerning the demographics and psychographics of the on-line user and the opportunities for a product or service. In recent years, we have seen a tendency of various services converging to the ubiquitous Internet Protocol based networks. Besides traditional Internet applications such as web browsing, email, file transferring, and so forth, new applications have been developed to replace old communication networks. IPTV is one of the solutions. In the future, we expect a single network, the IP network, to provide services that have been carried by different networks today. For finding some important effects of a video based technology market web site on internet, we determine to apply a questionnaire on university students. Recently some researches shows that in Turkey the age of people 20 to 24 use internet when they buy some electronic devices such as cell phones, computers, etc. In questionnaire there are ten categorized questions to evaluate the effects of IPTV when shopping. There were selected 30 students who are filling the question form after watching an IPTV channel video for 10 minutes. This sample IPTV channel is “buy.com”, it look like an e-commerce site with an integrated IPTV channel on. The questionnaire for the survey is constructed by using the Likert scale that is a bipolar scaling method used to measure either positive or negative response to a statement (Likert, R) it is a common system that is used is the surveys. By following the Likert Scale “the respondents are asked to indicate their degree of agreement with the statement or any kind of subjective or objective evaluation of the statement. Traditionally a five-point scale is used under this methodology”. For this study also the five point scale system is used and the respondents were asked to express their opinions about the given statement by picking the answer from the given 5 options: “Strongly disagree, Disagree, Neither agree Nor disagree, Agree and Strongly agree”. These points were also rates from 1-5 (Strongly disagree, Disagree, Neither disagree Nor agree, Agree, Strongly agree). On the basis of the data gathered from the questionnaire some results are drawn in order to get the figures and graphical representation of the study results that can demonstrate the outcomes of the research clearly.

Keywords: IPTV, internet marketing, online, e-commerce, video based technology

Procedia PDF Downloads 240

Authors: Agnieszka H. Ludwig-Slomczynska, Michal T. Seweryn, Przemyslaw Kapusta, Ewelina Pitera, Katarzyna Cyganek, Urszula Mantaj, Lucja Dobrucka, Ewa Wender-Ozegowska, Maciej T. Malecki, Pawel Wolkow

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Obesity results from an imbalance between energy intake and its expenditure. Genome-Wide Association Study (GWAS) analyses have led to discovery of only about 100 variants influencing body mass index (BMI), which explain only a small portion of genetic variability. Analysis of gene epistasis gives a chance to discover another part. Since it was shown that interaction and communication between nuclear and mitochondrial genome are indispensable for normal cell function, we have looked for epistatic interactions between the two genomes to find their correlation with BMI. Methods: The analysis was performed on 366 T1DM patients using Illumina Infinium OmniExpressExome-8 chip and followed by imputation on Michigan Imputation Server. Only genes which influence mitochondrial functioning (listed in Human MitoCarta 2.0) were included in the analysis – variants of nuclear origin (MAF > 5%) in 1140 genes and 42 mitochondrial variants (MAF > 1%). Gene expression analysis was performed on GTex data. Association analysis between genetic variants and BMI was performed with the use of Linear Mixed Models as implemented in the package 'GENESIS' in R. Analysis of association between mRNA expression and BMI was performed with the use of linear models and standard significance tests in R. Results: Among variants involved in epistasis between mitochondria and nucleus we have identified one in mitochondrial transcription factor, TFB2M (rs6701836). It interacted with mitochondrial variants localized to MT-RNR1 (p=0.0004, MAF=15%), MT-ND2 (p=0.07, MAF=5%) and MT-ND4 (p=0.01, MAF=1.1%). Analysis of the interaction between nuclear variant rs6701836 (nuc) and rs3021088 localized to MT-ND2 mitochondrial gene (mito) has shown that the combination of the two led to BMI decrease (p=0.024). Each of the variants on its own does not correlate with higher BMI [p(nuc)=0.856, p(mito)=0.116)]. Although rs6701836 is intronic, it influences gene expression in the thyroid (p=0.000037). rs3021088 is a missense variant that leads to alanine to threonine substitution in the MT-ND2 gene which belongs to complex I of the electron transport chain. The analysis of the influence of genetic variants on gene expression has confirmed the trend explained above – the interaction of the two genes leads to BMI decrease (p=0.0308). Each of the mRNAs on its own is associated with higher BMI (p(mito)=0.0244 and p(nuc)=0.0269). Conclusıons: Our results show that nuclear-mitochondrial epistasis can influence BMI in T1DM patients. The correlation between transcription factor expression and mitochondrial genetic variants will be subject to further analysis.

Keywords: body mass index, epistasis, mitochondria, type 1 diabetes

Procedia PDF Downloads 175

Authors: Aminu Mohammed, Shahidul Islam

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Aframomum melegueta K.Schum commonly known as Grains of Paradise has been a popularly used spice in most of the African food preparation. Available data have shown that ethyl acetate fraction from crude ethanolic extract exhibited α-amylase and α-glucosidase inhibitory actions, improved pancreatic β-cell damage and ameliorated insulin resistance in diabetic rats. Additionally, 6-gingerol, 6-shogaol, 6-paradol and oleanolic acid are shown to be the compounds responsible for the antidiabetic action of A. melegueta. However, detail antioxidant potential of this spice in a diabetic animal model has not yet been reported. Thus, the present study investigates the effect of oral consumption of A. melegueta fruit on the in vivo antioxidant status of type 2 diabetes (T2D) model of rats. T2D was induced in rats by feeding a 10% fructose solution ad libitum for two weeks followed by a single intraperitoneal injection of streptozotocin (40 mg/kg body weight (bw)). The animals were orally administered with 150 (DAML) or 300 mg/kg bw (DAMH) of the fraction once daily for four weeks. Data were analyzed by using a statistical software package (SPSS for Windows, version 22, IBM Corporation, NY, USA) using Tukey’s-HSD multiple range post-hoc test. Values were considered significantly different at p < 0.05. According to the data, after four weeks of intervention, diabetic untreated animals showed significantly (p < 0.05) elevation of blood glucose levels. The levels of thiobarbituric acid reactive substances (TBARS) were observed to increase with concomitant reduction of reduced glutathione (GSH) levels in the serum and organs (liver, kidney, heart and pancreas) of diabetic untreated animals. The activities of endogenous antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, and reductase) were greatly reduced in the serum and organs of diabetic untreated animals compared to the normal animals. These alterations were reverted to near-normal after the treatment of A. melegueta fruit in the treated groups (DAML & DAMH) within the study period, especially at the dose of 300 mg/kg bw. This potent antioxidant action may partly be attributed to the presence of the 6-Gingerol, 6-shogaol and 6-paradol are known to possess antioxidant action. The results of our study showed that A. melegueta intake improved the antioxidant status of T2D rats and therefore could be used to ameliorate the diabetes-induced oxidative damage.

Keywords: Aframomum melegueta, antioxidant, ethyl acetate extract, type 2 diabetes

Procedia PDF Downloads 301

Authors: Antonis Elia, Theo Loizou, Gladys Onambele-Pearson, Matthew Barlow, Georgina Stebbings

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Hypoxic conditions have been reported to enhance red blood cell production in both acclimatised low-landers and altitude adapted populations. This process is mediated by the erythropoietin hormone, which is released predominantly by the hypoxic kidney. A higher haemoglobin concentration was previously reported in elite breath-hold divers when compared to elite-skiers and untrained individuals. Therefore, the present study aimed to investigate whether apnoea induced hypoxia could induce a significant increase in serum erythropoietin concentration in recreational breath-hold divers which would provide an explanation to the higher haemoglobin levels observed in elite breath-hold divers. Identifying whether apnoea induced hypoxia induces a significant increase in serum erythropoietin might suggest that apnoea can be used as an alternative acclimatisation method to high altitude exposure. Seven healthy, recreational male breath-hold divers performed two sets of five 180 second breath-holds with a ten-minute supine rest between each set and a two-minute seated rest between each apnoea. During each breath-hold, participant’s heart rate and peripheral oxygen saturation levels were recorded every subsequent 10 seconds until the end of the 180 second breath-hold. After each 180 second breath-hold a capillary blood sample was collected from the finger to identify circulating haemoglobin levels. Following completion of the apnoeic protocol, three blood samples were collected at 30, 90 and 180 minutes to measure circulating erythropoietin levels. A significant interaction between erythropoietin and time was observed (F(3,18)= 4.72, p < 0.001), with significant increases in erythropoietin evident at 30 (t(6)= -5.035, p < 0.0590 (t(6)= -6.162, p < 0.05) and 180 (t(6)= - 7.232, p < 0.001) minutes post the last apnoea when compared to baseline. Corresponding average increases when compared to baseline were 16% at 30, 23% at 90 and 40% at 180 minutes post the last apnoea. A significant interaction between haemoglobin and time was observed (F(78,84)= 20.814, p < 0.001), with significant increases in haemoglobin evident at the fifth (t(29)= -1.124, p < 0.001), ninth (t(29)= -1.357, p < 0.001) and tenth (t(29)= -1.211, p < 0.05) apnoeas when compared to baseline. A significant interaction between peripheral oxygen saturation and time was observed (F(10,60)= 408.23, p < 0.001). The present study demonstrates that a series of ten 180 second breath-holds is sufficient to induce a significant increase in the circulating erythropoietin concentration of recreational breath hold divers. These observations may suggest that apnoea induced hypoxia may be used as an alternative acclimatisation method to high altitude exposure.

Keywords: apnoea, breath-holding, diving reflex, erythropoietin, haemoglobin

Procedia PDF Downloads 180

Authors: Susana Gonçalves, Joana Lencart, Anabela Gregório Dias

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Introduction: In combination with chemotherapy, Total Body Irradiation (TBI) is most used as part of the conditioning regimen prior to allogeneic hematopoietic stem cell transplantation. Conventional TBI techniques have a long application time but non-conformality of beam-application with the inability to individually spare organs at risk. Our institution’s intention is to start using Volumetric Modulated Arc Therapy (VMAT) techniques to increase homogeneity of delivered radiation. As a first approach, a dosimetric plan was performed on a computed tomography (CT) scan of a Rando Alderson antropomorfic phantom (head and torso), using a set of six arcs distributed along the phantom. However, a full body anthropomorphic phantom is essential to carry out technique validation and implementation. Our aim is to define the physical and chemical characteristics and the ideal manufacturing procedure of upper and lower limbs to our anthropomorphic phantom, for later validate TBI using VMAT. Materials and Methods: To study the better fit between our phantom and limbs, a CT scan of Rando Alderson anthropomorphic phantom was acquired. CT was performed on GE Healthcare equipment (model Optima CT580 W), with slice thickness of 2.5 mm. This CT was also used to access the electronic density of soft tissue and bone through Hounsfield units (HU) analysis. Results: CT images were analyzed and measures were made for the ideal upper and lower limbs. Upper limbs should be build under the following measures: 43cm length and 7cm diameter (next to the shoulder section). Lower limbs should be build under the following measures: 79cm length and 16.5cm diameter (next to the thigh section). As expected, soft tissue and bone have very different electronic density. This is important to choose and analyze different materials to better represent soft tissue and bone characteristics. The approximate HU values of the soft tissue and for bone shall be 35HU and 250HU, respectively. Conclusion: At the moment, several compounds are being developed based on different types of resins and additives in order to be able to control and mimic the various constituent densities of the tissues. Concurrently, several manufacturing techniques are being explored to make it possible to produce the upper and lower limbs in a simple and non-expensive way, in order to finally carry out a systematic and appropriate study of the total body irradiation. This preliminary study was a good starting point to demonstrate the feasibility of TBI with VMAT.

Keywords: TBI, VMAT, anthropomorphic phantom, tissue equivalent materials

Procedia PDF Downloads 80

Authors: Santi Maneewatchararangsri, Wanpen Chaicumpa, Patcharin Saengjaruk, Urai Chaisri

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Leptospirosis is a globally neglected disease that continues to be a significant public health and veterinary burden, with millions of cases reported each year. Early and accurate differential diagnosis of leptospirosis from other febrile illnesses and the development of a broad spectrum of leptospirosis vaccines are needed. The LipL32 outer membrane lipoprotein is a member of Leptospira adhesive matrices and has been found to exert hemolytic activity to erythrocytes in vitro. Therefore, LipL32 is regarded as a potential target for diagnosis, broad-spectrum leptospirosis vaccines, and for passive immunotherapy. In this study, we established LipL32-specific mouse monoclonal antibodies, mAbLPF1 and mAbLPF2, and their respective mouse- and humanized-engineered single chain variable fragment (ScFv). Their antibodies’ neutralizing activities against Leptospira-mediated hemolysis in vitro, and the therapeutic efficacy of mAbs against heterologous Leptospira infected hamsters were demonstrated. The epitope peptide of mAb LPF1 was mapped to a non-contiguous carboxy-terminal β-turn and amphipathic α-helix of LipL32 structure contributing to phospholipid/host cell adhesion and membrane insertion. We found that the mAbLPF2 epitope was located on the interacting loop of peptide binding groove of the LipL32 molecule responsible for interactions with host constituents. Epitope sequences are highly conserved among Leptospira spp. and are absent from the LipL32 superfamily of other microorganisms. Both epitopes are surface-exposed, readily accessible by mAbs, and immunogenic. However, they are less dominant when revealed by LipL32-specific immunoglobulins from leptospirosis-patient sera and rabbit hyperimmune serum raised by whole Leptospira. Our study also demonstrated an adhesion inhibitory activity of LipL32 protein to host membrane components and cells mediated by mAbs as well as an anti-hemolytic activity of the respective antibodies. The therapeutic antibodies, particularly the humanized-ScFv, have a potential for further development as non-drug therapeutic agent for human leptospirosis, especially in subjects allergic to antibiotics. The epitope peptides recognized by two therapeutic mAbs have potential use as tools for structure-function studies. Finally, protective peptides may be used as a target for epitope-based vaccines for control of leptospirosis.

Keywords: leptospira lipl32-specific antibodies, therapeutic epitopes, epitopes characterization, immunotherapy

Procedia PDF Downloads 297

Authors: Umut Kokbas, Mustafa Nisari

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Immunoglobulins, also known as antibodies, are glycoprotein molecules produced by activated B cells that transform into plasma cells and result in them. Antibodies are critical molecules of the immune response to fight, which help the immune system specifically recognize and destroy antigens such as bacteria, viruses, and toxins. Immunoglobulin classes differ in their biological properties, structures, targets, functions, and distributions. Five major classes of antibodies have been identified in mammals: IgA, IgD, IgE, IgG, and IgM. Evaluation of the immunoglobulin isotype can provide a useful insight into the complex humoral immune response. Evaluation and knowledge of immunoglobulin structure and classes are also important for the selection and preparation of antibodies for immunoassays and other detection applications. The immunoglobulin test measures the level of certain immunoglobulins in the blood. IgA, IgG, and IgM are usually measured together. In this way, they can provide doctors with important information, especially regarding immune deficiency diseases. Hypogammaglobulinemia (HGG) is one of the main groups of primary immunodeficiency disorders. HGG is caused by various defects in B cell lineage or function that result in low levels of immunoglobulins in the bloodstream. This affects the body's immune response, causing a wide range of clinical features, from asymptomatic diseases to severe and recurrent infections, chronic inflammation and autoimmunity Transient infant hypogammaglobulinemia (THGI), IgM deficiency (IgMD), Bruton agammaglobulinemia, IgA deficiency (SIgAD) HGG samples are a few. Most patients can continue their normal lives by taking prophylactic antibiotics. However, patients with severe infections require intravenous immune serum globulin (IVIG) therapy. The IgE level may rise to fight off parasitic infections, as well as a sign that the body is overreacting to allergens. Also, since the immune response can vary with different antigens, measuring specific antibody levels also aids in the interpretation of the immune response after immunization or vaccination. Immune deficiencies usually occur in childhood. In Immunology and Allergy clinics, apart from the classical methods, it will be more useful in terms of diagnosis and follow-up of diseases, if it is fast, reliable and especially in childhood hypogammaglobulinemia, sampling from children with a method that is more convenient and uncomplicated. The antibodies were attached to the electrode surface via the poly hydroxyethyl methacrylamide cysteine nanopolymer. It was used to evaluate the anodic peak results obtained in the electrochemical study. According to the data obtained, immunoglobulin determination can be made with a biosensor. However, in further studies, it will be useful to develop a medical diagnostic kit with biomedical engineering and to increase its sensitivity.

Keywords: biosensor, immunosensor, immunoglobulin, infection

Procedia PDF Downloads 107

Authors: Jamshid Hussain, Kuen Song Lin

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Over one thousand tons of pig hair biowaste (PHB) are produced yearly in Taiwan. The improper disposal of PHB can have a negative impact on the environment, consequently contributing to the spread of diseases. The treatment of PHB has become a major environmental and economic challenge. Innovative treatments must be developed because of the heavy metal and sulfur content of PHB. Like most organic materials, PHB is composed of many organic volatiles that contain large amounts of hydrogen. Hydrogen gas can be effectively produced by the catalytic gasification of PHB using a laboratory-scale fixed-bed gasifier, employing 15 wt% NiO/Al₂O₃ catalyst at 753–913 K. The derived kinetic parameters were obtained and refined using simulation calculations. FE–SEM microphotograph showed that NiO/Al₂O₃ catalyst particles are Spherical or irregularly shaped with diameters of 10–20 nm. HR–TEM represented that the fresh Ni particles were evenly dispersed and uniform in the microstructure of Al₂O₃ support. The sizes of the NiO nanoparticles were vital in determining catalyst activity. As displayed in the pre-edge XANES spectra of the NiO/Al₂O₃ catalysts, it exhibited a non-intensive absorbance nature for the 1s to 3d transition, which is prohibited by the selection rule for an ideal octahedral symmetry. Similarly, the populace of Ni(II) and Ni(0) onto Al₂O₃ supports are proportional to the strength of the 1s to 4pxy transition, respectively. The weak shoulder at 8329–8334 eV and a strong character at 8345–8353 eV were ascribed to the 1s to 4pxy shift, which suggested the presence of NiO types onto Al₂O₃ support in PHB catalytic gasification. As determined by the XANES analyses, Ni(II)→Ni(0) reduction was mostly observed. The oxidation of PHB onto the NiO/Al₂O₃ surface may have resulted in Ni(0) and the formation of tar during the gasification process. The EXAFS spectra revealed that the Ni atoms with Ni–Ni/Ni–O bonds were found. The Ni–O bonding proved that the produced syngas were unable to reduce NiO to Ni(0) completely. The weakness of the Ni–Ni bonds may have been caused by the highly dispersed Ni in the Al₂O₃ support. The central Ni atoms have Ni–O (2.01 Å) and Ni–Ni (2.34 Å) bond distances in the fresh NiO/Al₂O₃ catalyst. The PHB was converted into hydrogen-rich syngas (CO + H₂, >89.8% dry basis). When PHB (250 kg h−1) was catalytically gasified at 753–913 K, syngas was produced at approximately 5.45 × 105 kcal h−1 of heat recovery with 76.5%–83.5% cold gas efficiency. The simulation of the pilot-scale PHB catalytic gasification demonstrated that the system could provide hydrogen (purity > 99.99%) and generate electricity for an internal combustion engine of 100 kW and a proton exchange membrane fuel cell (PEMFC) of 175 kW. A projected payback for a PHB catalytic gasification plant with a capacity of 10- or 20-TPD (ton per day) was around 3.2 or 2.5 years, respectively.

Keywords: pig hair biowaste, catalytic gasification, hydrogen production, PEMFC, resource recovery

Procedia PDF Downloads 15

Authors: Pamela R. Jackson, Andrea Hawkins-Daarud, Cassandra R. Rickertsen, Kamala Clark-Swanson, Scott A. Whitmire, Kristin R. Swanson

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Glioblastoma Multiforme (GBM), the most common primary brain tumor, often presents with hyperintensity on T2-weighted or T2-weighted fluid attenuated inversion recovery (T2/FLAIR) magnetic resonance imaging (MRI). This hyperintensity corresponds with vasogenic edema, however there are likely many infiltrating tumor cells within the hyperintensity as well. While MRIs do not directly indicate tumor cells, MRIs do reflect the microenvironmental water abnormalities caused by the presence of tumor cells and edema. The inherent heterogeneity and resulting MRI features of GBMs complicate assessing disease response. To understand how hyperintensity on T2/FLAIR MRI may correlate with edema in the extracellular space (ECS), a multi-compartmental MRI signal equation which takes into account tissue compartments and their associated volumes with input coming from a mathematical model of glioma growth that incorporates edema formation was explored. The reasonableness of two possible extracellular space schema was evaluated by varying the T2 of the edema compartment and calculating the possible resulting T2s in tumor and peripheral edema. In the mathematical model, gliomas were comprised of vasculature and three tumor cellular phenotypes: normoxic, hypoxic, and necrotic. Edema was characterized as fluid leaking from abnormal tumor vessels. Spatial maps of tumor cell density and edema for virtual tumors were simulated with different rates of proliferation and invasion and various ECS expansion schemes. These spatial maps were then passed into a multi-compartmental MRI signal model for generating simulated T2/FLAIR MR images. Individual compartments’ T2 values in the signal equation were either from literature or estimated and the T2 for edema specifically was varied over a wide range (200 ms – 9200 ms). T2 maps were calculated from simulated images. T2 values based on simulated images were evaluated for regions of interest (ROIs) in normal appearing white matter, tumor, and peripheral edema. The ROI T2 values were compared to T2 values reported in literature. The expanding scheme of extracellular space is had T2 values similar to the literature calculated values. The static scheme of extracellular space had a much lower T2 values and no matter what T2 was associated with edema, the intensities did not come close to literature values. Expanding the extracellular space is necessary to achieve simulated edema intensities commiserate with acquired MRIs.

Keywords: extracellular space, glioblastoma multiforme, magnetic resonance imaging, mathematical modeling

Procedia PDF Downloads 235

Authors: Gaweł Magdalena, Lipkowska Anna, Olbert Magdalena, Frąckiewicz Ewelina, Librowski Tadeusz, Nowak Gabriel, Pilc Andrzej

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Heme oxygenase-1 (HO-1), also known as heat shock protein 32 (HSP32), has been shown to be implicated in cytoprotection in various organs. Its activation plays a significant role in acute and chronic inflammation, protecting cells from oxidative injury and apoptosis. This inducible isoform of HO catalyzes the first and rate-limiting step in heme degradation to produce equimolar quantities of biologically active products: carbon monoxide (CO), free iron and biliverdin. CO has been reported to possess anti-apoptotic properties. Moreover, it inhibits the production of proinflammatory cytokines and stimulates the synthesis of the anti-inflammatory interleukin-10 (IL-10), as well as promotes vasodilatation at sites of inflammation. The second product of catalytic HO-1 activity, free cytotoxic iron, is promptly sequestered into the iron storage protein ferritin, which lowers the pro-oxidant state of the cell. The third product, biliverdin, is subsequently converted by biliverdin reductase into the bile pigment bilirubin, the most potent endogenous antioxidant among the constituents of human serum, which modulates immune effector functions and suppresses inflammatory response. Furthermore, being one of the so-called stress proteins, HO-1 adaptively responds to different stressors, such as reactive oxygen species (ROS), inflammatory cytokines and heavy metals and thus protects cells against such conditions as ischemia, hemorrhagic shock, heat shock or hypoxia. It is suggested that pharmacologic modulation of HO-1 may represent an effective strategy for prevention of stress and drug-induced gastrointestinal toxicity. HO-1 is constitutively expressed in normal gastric, intestinal and colonic mucosa and up-regulated during inflammation. It has been proven that HO-1 up-regulated by hemin, heme and cobalt-protoporphyrin ameliorates experimental colitis. In addition, the up-regulation of HO-1 partially explains the mechanism of action of 5-aminosalicylic acid (5-ASA), which is used clinically as an anti-colitis agent. In 2009 Ueda et al. has reported for the first time that mucosal protection by Polaprezinc, a chelate compound of zinc and L-carnosine used as an anti-ulcer drug in Japan, is also attributed to induction of HO-1 in the stomach. Since then, inducers of HO-1 are desired subject of research, as they may constitute therapeutically effective anti-ulcer drugs.

Keywords: heme oxygenase-1, gastric lesions, gastroprotection, Polaprezinc

Procedia PDF Downloads 504

Authors: Andreea Molnar, Amalia Ardeljan, Lexi Frankel, Marissa Dallara, Brittany Nagel, Omar Rashid

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Background: Escherichia coli is a gram-negative, facultative anaerobic bacteria that belongs to the family Enterobacteriaceae and resides in the intestinal tracts of individuals. E.Coli has numerous strains grouped into serogroups and serotypes based on differences in antigens in their cell walls (somatic, or “O” antigens) and flagella (“H” antigens). More than 700 serotypes of E. coli have been identified. Although most strains of E. coli are harmless, a few strains, such as E. coli O157:H7 which produces Shiga toxin, can cause intestinal infection with symptoms of severe abdominal cramps, bloody diarrhea, and vomiting. Infection with E. Coli can lead to the development of systemic inflammation as the toxin exerts its effects. Chronic inflammation is now known to contribute to cancer development in several organs, including the prostate. The purpose of this study was to evaluate the correlation between E. Coli and the incidence of prostate cancer. Methods: Data collected in this cohort study was provided by a Health Insurance Portability and Accountability Act (HIPAA) compliant national database to evaluate patients infected with E.Coli infection and prostate cancer using the International Classification of Disease (ICD-10 and ICD-9 codes). Permission to use the database was granted by Holy Cross Health, Fort Lauderdale for the purpose of academic research. Data analysis was conducted through the use of standard statistical methods. Results: Between January 2010 and December 2019, the query was analyzed and resulted in 81, 037 patients after matching in both infected and control groups, respectively. The two groups were matched by Age Range and CCI score. The incidence of prostate cancer was 2.07% and 1,680 patients in the E. Coli group compared to 5.19% and 4,206 patients in the control group. The difference was statistically significant by a p-value p<2.2x10-16 with an Odds Ratio of 0.53 and a 95% CI. Based on the specific treatment for E.Coli, the infected group vs control group were matched again with a result of 31,696 patients in each group. 827 out of 31,696 (2.60%) patients with a prior E.coli infection and treated with antibiotics were compared to 1634 out of 31,696 (5.15%) patients with no history of E.coli infection (control) and received antibiotic treatment. Both populations subsequently developed prostate carcinoma. Results remained statistically significant (p<2.2x10-16), Odds Ratio=0.55 (95% CI 0.51-0.59). Conclusion: This retrospective study shows a statistically significant correlation between E.Coli infection and a decreased incidence of prostate cancer. Further evaluation is needed in order to identify the impact of E.Coli infection and prostate cancer development.

Keywords: E. Coli, prostate cancer, protective, microbiology

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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 140

Authors: Beate Englich, Linda Schlittenbauer, Christiane Pfeifer, Isabel Kratochvil, Michael Borte, Gabriele I. Stangl, Martin von Bergen, Thorsten Reemtsma, Irina Lehmann, Kristin M. Junge

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The worldwide production of endocrine disrupting compounds (EDC) has risen dramatically over the last decades, as so has the prevalence for obesity. Many EDCs are believed to contribute to this obesity epidemic, by enhancing adipogenesis or disrupting relevant metabolism. This effect is most tremendous in the early prenatal period when priming effects find a highly vulnerable time window. Therefore, we investigate the impact of parabens on childhood overweight development and adipogenesis in general. Parabens are ester of 4-hydroxy-benzoic acid and part of many cosmetic products or food packing. Therefore, ubiquitous exposure can be found in the westernized world, with exposure already starting during the sensitive prenatal period. We assessed maternal cosmetic product consumption, prenatal paraben exposure and infant BMI z-scores in the prospective German LINA cohort. In detail, maternal urinary concentrations (34 weeks of gestation) of methyl paraben (MeP), ethyl paraben (EtP), n-propyl paraben (PrP) and n-butyl paraben (BuP) were quantified using UPLC-MS/MS. Body weight and height of their children was assessed during annual clinical visits. Further, we investigated the direct influence of those parabens on adipogenesis in-vitro using a human mesenchymal stem cell (MSC) differentiation assay to mimic a prenatal exposure scenario. MSC were exposed to 0.1 – 50 µM paraben during the entire differentiation period. Differentiation outcome was monitored by impedance spectrometry, real-time PCR and triglyceride staining. We found that maternal cosmetic product consumption was highly correlated with urinary paraben concentrations at pregnancy. Further, prenatal paraben exposure was linked to higher BMI Z-scores in children. Our in-vitro analysis revealed that especially the long chained paraben BuP stimulates adipogenesis by increasing the expression of adipocyte specific genes (PPARγ, ADIPOQ, LPL, etc.) and triglyceride storage. Moreover, we found that adiponectin secretion is increased whereas leptin secretion is reduced under BuP exposure in-vitro. Further mechanistic analysis for receptor binding and activation of PPARγ and other key players in adipogenesis are currently in process. We conclude that maternal cosmetic product consumption is linked to prenatal paraben exposure of children and contributes to the development of infant overweight development by triggering key pathways of adipogenesis.

Keywords: adipogenesis, endocrine disruptors, paraben, prenatal exposure

Procedia PDF Downloads 274

Authors: Hyuk Sung Yoon, In-Lee Choi, Mohammad Zahirul Islam, Jun Pill Baek, Ho-Min Kang

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The strawberry ‘Maehyang’ cultivated in South Korea has been increased to export to Southeast Asia. The degradation of quality often occurs in strawberries during short export period. Botrytis cinerea has been known to cause major damage to the export strawberries and the disease was caused during shipping and distribution. This study was conducted to find out the sterilized effect of chlorine dioxide(ClO2) gas and high concentration of CO2 gas injection for ‘Maehyang’ strawberry and it was packaged with oxygen transmission rate (OTR) films. The strawberry was harvested at 80% color changed stage and packaged with OTR film and perforated film (control). The treatments were a MAP used by with 20,000 cc·m-2·day·atm OTR film and gas injection in packages. The gas type of ClO2 and CO2 were injected into OTR film packages, and treatments were 6 mg/L ClO2, 15% CO2, and they were combined. The treated strawberries were stored at 3℃ for 30 days. Fresh weight loss rate was less than 1% in all OTR film packages but it was more than 15% in a perforated film treatment that showed severe deterioration of visual quality during storage. Carbon dioxide concentration within a package showed approximately 15% of the maximum CO2 concentration in all treatments except control until the 21st day, it was the tolerated range of maximum CO2 concentration of strawberry in recommended CA or MA conditions. But, it increased to almost 50% on the 30th day. Oxygen concentration showed a decrease down to approximately 0% in all treatments except control for 25 days. Ethylene concentration was shown to be steady until the 17th day, but it quickly increased on the 17th day and dropped down on the final storage day (30th day). All treatments did not show any significant differences in gas treatments. Firmness increased in CO2 (15%) and ClO2 (6mg/L) + CO2 (15%) treatments during storage. It might be the effect of high concentration CO2 known by reducing decay and cell wall degradation. The soluble solid decreased in all treatments during storage. These results were caused to use up the sugar by the increase of respiration during storage. The titratable acidity showed a similarity in all treatments. Incidence of fungi was 0% in CO2 (15%) and ClO2 (6mg/L)+ CO2 (15%), but was more than 20% in a perforated film treatment. Consequently, The result indicates that Chloride Dioxide(ClO2) and high concentration of CO2 inhibited fungi growth. Due to the fact that fresh weight loss rate and incidence of fungi were lower, the ClO2(6mg/L)+ CO2(15%) prove to be most efficient in sterilization. These results suggest that Chloride Dioxide (ClO2) and high concentration of CO2 gas injection treatments were an effective decontamination technique for improving the safety of strawberries.

Keywords: chloride dioxide, high concentration of CO2, modified atmosphere condition, oxygen transmission rate films

Procedia PDF Downloads 339

Authors: Apeng Dong, Shu Li, Wenguo Zhu, Ming Qi, Qiuyi Xu

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The primary objective of this paper is to focus on the elasticity properties of three-dimensional full five directional (3Df5d) braided composite. A large body of research has been focused on the 3D four directional (4d) and 3D five directional (5d) structure but not much research on the 3Df5d material. Generally, the influence of the yarn shape on mechanical properties of braided materials tends to be ignored, which makes results too ideal. Besides, with the improvement of the computational ability, people are accustomed to using computers to predict the material parameters, which fails to give an explicit and concise result facilitating production and application. Based on the traditional mechanics, this paper firstly deduced the functional relation between elasticity properties and braiding parameters. In addition, considering the actual shape of yarns after consolidation, the longitudinal modulus is modified and defined practically. Firstly, the analytic model is established based on the certain assumptions for the sake of clarity, this paper assumes that: A: the cross section of axial yarns is square; B: The cross section of braiding yarns is hexagonal; C: the characters of braiding yarns and axial yarns are the same; D: The angle between the structure boundary and the projection of braiding yarns in transverse plane is 45°; E: The filling factor ε of composite yarns is π/4; F: The deformation of unit cell is under constant strain condition. Then, the functional relation between material constants and braiding parameters is systematically deduced aimed at the yarn deformation mode. Finally, considering the actual shape of axial yarns after consolidation, the concept of technology factor is proposed and the longitudinal modulus of the material is modified based on the energy theory. In this paper, the analytic solution of material parameters is given for the first time, which provides a good reference for further research and application for 3Df5d materials. Although the analysis model is established based on certain assumptions, the analysis method is also applicable for other braided structures. Meanwhile, it is crucial that the cross section shape and straightness of axial yarns play dominant roles in the longitudinal elastic property. So in the braiding and solidifying process, the stability of the axial yarns should be guaranteed to increase the technology factor to reduce the dispersion of material parameters. Overall, the elastic properties of this materials are closely related to the braiding parameters and can be strongly designable, and although the longitudinal modulus of the material is greatly influenced by the technology factors, it can be defined to certain extent.

Keywords: analytic solution, braided composites, elasticity properties, technology factor

Procedia PDF Downloads 237

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

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

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

Procedia PDF Downloads 268

Authors: M. Gowri, E. K. Girija, V. Ganesh

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Background and Significance: Among the dental infections, inflammation and infection of the root canal are common among all age groups. Currently, the management of root canal infections involves cleaning the canal with powerful irrigants followed by intracanal medicament application. Though these treatments have been in vogue for a long time, root canal failures do occur. Treatment for root canal infections is limited due to the anatomical complexity in terms of small micrometer volumes and poor penetration of drugs. Thus, infections of the root canal seem to be a challenge that demands development of new agents that can eradicate C. albicans. Methodology: In the present study, we synthesized and screened silver-curcumin nanoparticle against Candida albicans. Detailed molecular studies were carried out with silver-curcumin nanoparticle on C. albicans pathogenicity. Morphological cell damage and antibiofilm activity of silver-curcumin nanoparticle on C. albicans was studied using scanning electron microscopy (SEM). Biochemical evidence for membrane damage was studied using flow cytometry. Further, the antifungal activity of silver-curcumin nanoparticle was evaluated in an ex vivo dentinal tubule infection model. Results: Screening data showed that silver-curcumin nanoparticle was active against C. albicans. Silver-curcumin nanoparticle exerted time kill effect and post antifungal effect. When used in combination with fluconazole or nystatin, silver-curcumin nanoparticle revealed a minimum inhibitory concentration (MIC) decrease for both drugs used. In-depth molecular studies with silver-curcumin nanoparticle on C. albicans showed that silver-curcumin nanoparticle inhibited yeast to hyphae (Y-H) conversion. Further, SEM images of C. albicans showed that silver-curcumin nanoparticle caused membrane damage and inhibited biofilm formation. Biochemical evidence for membrane damage was confirmed by increased propidium iodide (PI) uptake in flow cytometry. Further, the antifungal activity of silver-curcumin nanoparticle was evaluated in an ex vivo dentinal tubule infection model, which mimics human tooth root canal infection. Confocal laser scanning microscopy studies showed eradication of C. albicans and reduction in colony forming unit (CFU) after 24 h treatment in the infected tooth samples in this model. Conclusion: The results of this study can pave the way for developing new antifungal agents with well deciphered mechanisms of action and can be a promising antifungal agent or medicament against root canal infection.

Keywords: C. albicans, ex vivo dentine model, inhibition of biofilm formation, root canal infection, yeast to hyphae conversion inhibition

Procedia PDF Downloads 208

Authors: Z. Razi, S. M. J. Mortazavi, N. Shokrpour, Z. Shayan, F. Amiri

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Long-term exposure to low doses of ionizing radiation occurs in radiation health care workplaces. Although doses in health professions are generally very low, there are still matters of concern. The radiation safety program promotes occupational radiation safety through accurate and reliable monitoring of radiation workers in order to effectively manage radiation protection. To achieve this goal, it has become mandatory to implement health examination periodically. As a result, based on the hematological alterations, working populations with a common occupational radiation history are screened. This paper calls into question the effectiveness of blood component analysis as a screening program which is mandatory for medical radiation workers in some countries. This study details the distribution and trends of changes in blood components, including white blood cells (WBCs), red blood cells (RBCs) and platelets as well as received cumulative doses from occupational radiation exposure. This study was conducted among 199 participants and 100 control subjects at the medical imaging departments at the central hospital of Shiraz University of Medical Sciences during the years 2006–2010. Descriptive and analytical statistics, considering the P-value<0.05 as statistically significance was used for data analysis. The results of this study show that there is no significant difference between the radiation workers and controls regarding WBCs and platelet count during 4 years. Also, we have found no statistically significant difference between the two groups with respect to RBCs. Besides, no statistically significant difference was observed with respect to RBCs with regards to gender, which has been analyzed separately because of the lower reference range for normal RBCs levels in women compared to men and. Moreover, the findings confirm that in a separate evaluation between WBCs count and the personnel’s working experience and their annual exposure dose, results showed no linear correlation between the three variables. Since the hematological findings were within the range of control levels, it can be concluded that the radiation dosage (which was not more than 7.58 mSv in this study) had been too small to stimulate any quantifiable change in medical radiation worker’s blood count. Thus, use of more accurate method for screening program based on the working profile of the radiation workers and their accumulated dose is suggested. In addition, complexity of radiation-induced functions and the influence of various factors on blood count alteration should be taken into account.

Keywords: blood cell count, mandatory testing, occupational exposure, radiation

Procedia PDF Downloads 462

Authors: Francisco J. Cedano, Laura M. Pinzón, Camila I. Castro, Felipe Salcedo, Juan P. Casas, Juan C. Briceño

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Complex fractures located in articular surfaces are challenging to treat and their reduction with conventional treatments could compromise the functionality of the affected limb. An adhesive material to treat those fractures is desirable for orthopedic surgeons. This adhesive must be biocompatible and have a high adhesion to bone surface in an aqueous environment. The proposed adhesive is based on chitosan, given its adhesive and biocompatibility properties. Chitosan is mixed with calcium carbonate and hydroxyapatite, which contribute to structural support and a gel like behavior, and glutaraldehyde is used as a cross-linking agent to keep the adhesive mechanical performance in aqueous environment. This work aims to evaluate the rheological, adhesion strength and biocompatibility properties of the proposed adhesive using in vitro tests. The gelification process of the adhesive was monitored by oscillatory rheometry in an ARG-2 TA Instruments rheometer, using a parallel plate geometry of 22 mm and a gap of 1 mm. Time sweep experiments were conducted at 1 Hz frequency, 1% strain and 37°C from 0 to 2400 s. Adhesion strength is measured using a butt joint test with bovine cancellous bone fragments as substrates. The test is conducted at 5 min, 20min and 24 hours after curing the adhesive under water at 37°C. Biocompatibility is evaluated by a cytotoxicity test in a fibroblast cell culture using MTT assay and SEM. Rheological results concluded that the average gelification time of the adhesive is 820±107 s, also it reaches storage modulus magnitudes up to 106 Pa; The adhesive show solid-like behavior. Butt joint test showed 28.6 ± 9.2 kPa of tensile bond strength for the adhesive cured for 24 hours. Also there was no significant difference in adhesion strength between 20 minutes and 24 hours. MTT showed 70 ± 23 % of active cells at sixth day of culture, this percentage is estimated respect to a positive control (only cells with culture medium and bovine serum). High vacuum SEM observation permitted to localize and study the morphology of fibroblasts presented in the adhesive. All captured fibroblasts presented in SEM typical flatted structure with filopodia growth attached to adhesive surface. This project reports an adhesive based on chitosan that is biocompatible due to high active cells presented in MTT test and these results were correlated using SEM. Also, it has adhesion properties in conditions that model the clinical application, and the adhesion strength do not decrease between 5 minutes and 24 hours.

Keywords: bioadhesive, bone adhesive, calcium carbonate, chitosan, hydroxyapatite, glutaraldehyde

Procedia PDF Downloads 321

Authors: Anuranjani Kumar, Madhu Bala

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Ionising radiation exposure induces generation of free radicals and the oxidative DNA damage. SBL-1, a radioprotective leaf extract prepared from leaves Hippophae rhamnoides L. (Common name; Seabuckthorn), showed > 90% survival in mice population that was treated with lethal dose (10 Gy) of ⁶⁰Co gamma irradiation. In this study, early effects of pre-treatment with or without SBL-1 in blood peripheral blood lymphocytes (PBMCs) were investigated by cell viability assays (trypan blue and MTT). The quantitative in vitro study of Hoescht/PI staining was performed to check the apoptosis/necrosis in PBMCs irradiated at 2 Gy with or without pretreatment of SBL-1 (at different concentrations) up to 24 and 48h. Comet assay was performed in vivo, to detect the DNA strands breaks and its repair mechanism on peripheral blood lymphocytes at lethal dose (10 Gy). For this study, male mice (wt. 28 ± 2g) were administered radioprotective dose (30mg/kg body weight) of SBL-1, 30 min prior to irradiation. Animals were sacrificed at 24h and 48h. Blood was drawn through cardiac puncture, and blood lymphocytes were separated using histopaque column. Both neutral and alkaline comet assay were performed using standardized technique. In irradiated animals, alkaline comet assay revealed single strand breaks (SSBs) that showed significant (p < 0.05) increase in percent DNA in tail and Olive tail moment (OTM) at 24 h while at 48h the percent DNA in tail further increased significantly (p < 0.02). The double strands breaks (DSBs) increased significantly (p < 0.01) at 48 h in neutral assay, in comparison to untreated control. The animals pre-treated with SBL-1 before irradiation showed significantly (p < 0.05) less DSBs at 48 h treatment in comparison to irradiated group of animals. The SBL-1 alone treated group itself showed no toxicity. The antioxidant potential of SBL-1 were also investigated by in vitro biochemical assays such as DPPH (p < 0.05), ABTS, reducing ability (p < 0.09), hydroxyl radical scavenging (p < 0.05), ferric reducing antioxidant power (FRAP), superoxide radical scavenging activity (p < 0.05), hydrogen peroxide scavenging activity (p < 0.05) etc. SBL-1 showed strong free radical scavenging power that plays important role in the studies of radiation-induced injuries. The SBL-1 treated PBMCs showed significant (p < 0.02) viability in trypan blue assay at 24-hour incubation.

Keywords: radiation, SBL-1, SSBs, DSBs, FRAP, PBMCs

Procedia PDF Downloads 154

Authors: Vanessa Castro, Liria H. Okuda, Daniela P. Chiebao, Adriana H. C. N. Romaldini, Harumi Hojo, Marina Grandi, Joao Paulo A. Silva, Alessandra F. C. Nassar

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The Biological Institute of Sao Paulo, in partnership with a private company, develops an Animal Health Family Farming Program (Prosaf) to enable communication among smallholder farmers and scientists, on-farm consulting and lectures, solving health questions that will benefit agricultural productivity. In Vale do Paraiba region, a dairy region of Sao Paulo State, southern Brazil, many of these types of farms are found with several milk quality problems. Most of these farms are profit-based business; however, with non-technified cattle rearing systems and uncertain veterinary assistance. Feedback from Prosaf showed that the biggest complaints from farmers were low milk production, sick animals and, mainly, loss of selling price due to a high somatic cell count (SCC) and a total bacterial count (TBC). The aims of this study were to improve milk quality, animal hygiene and herd health status by adjustments into general management practices and introducing techniques of sanitary control and milk monitoring in five dairy farms from Sao Jose do Barreiro municipality, Sao Paulo State, Brazil, to increase their profits. A total of 119 milk samples from 56 animals positive for California Mastitis Test (CMT) were collected. The positive CMT indicates subclinical mastitis, therefore laboratorial exams were performed in the milk (microbiological, biochemical and antibiogram test) detect the presence of Staphylococcus aureus (41.8%), Bacillus sp. (11.8%), Streptococcus sp. (2.1%), nonfermenting, motile and oxidase-negative Gram-negative Bacilli (2.1%) and Enterobacter (2.1%). Antibiograms revealed high resistance to gentamicin and streptomycin, probably due to indiscriminate use of antibiotics without veterinarian prescription. We suggested the improvement of hygiene management in the complete milking and cooling tanks system. Using the results of the laboratory tests, animals were properly treated, and the effects observed were better CMT outcomes, lower SCCs, and TBCs leading to an increase in milk pricing. This study will have a positive impact on the family farmers from Sao Paulo State dairy region by improving their market milk competitiveness.

Keywords: milk, family farming, food quality, antibiogram, profitability

Procedia PDF Downloads 155

Authors: Ashima Sharma, Tapan K. Chaudhuri

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Human Serum Albumin (HSA) is one of the most demanded therapeutic protein with immense biotechnological applications. The current source of HSA is human blood plasma. Blood is a limited and an unsafe source as it possesses the risk of contamination by various blood derived pathogens. This issue led to exploitation of various hosts with the aim to obtain an alternative source for the production of the rHSA. But, till now no host has been proven to be effective commercially for rHSA production because of their respective limitations. Thus, there exists an indispensable need to promote non-animal derived rHSA production. Of all the host systems, Escherichia coli is one of the most convenient hosts which has contributed in the production of more than 30% of the FDA approved recombinant pharmaceuticals. E. coli grows rapidly and its culture reaches high cell density using inexpensive and simple substrates. The fermentation batch turnaround number for E. coli culture is 300 per year, which is far greater than any of the host systems available. Therefore, E. coli derived recombinant products have more economical potential as fermentation processes are cheaper compared to the other expression hosts available. Despite of all the mentioned advantages, E. coli had not been successfully adopted as a host for rHSA production. The major bottleneck in exploiting E. coli as a host for rHSA production was aggregation i.e. majority of the expressed recombinant protein was forming inclusion bodies (more than 90% of the total expressed rHSA) in the E. coli cytosol. Recovery of functional rHSA form inclusion body is not preferred because it is tedious, time consuming, laborious and expensive. Because of this limitation, E. coli host system was neglected for rHSA production for last few decades. Considering the advantages of E. coli as a host, the present work has targeted E. coli as an alternate host for rHSA production through resolving the major issue of inclusion body formation associated with it. In the present study, we have developed a novel and innovative method for enhanced soluble and functional production of rHSA in E.coli (~60% of the total expressed rHSA in the soluble fraction) through modulation of the cellular growth, folding and environmental parameters, thereby leading to significantly improved and enhanced -expression levels as well as the functional and soluble proportion of the total expressed rHSA in the cytosolic fraction of the host. Therefore, in the present case we have filled in the gap in the literature, by exploiting the most well studied host system Escherichia coli which is of low cost, fast growing, scalable and ‘yet neglected’, for the enhancement of functional production of HSA- one of the most crucial biomolecule for clinical and biotechnological applications.

Keywords: enhanced functional production of rHSA in E. coli, recombinant human serum albumin, recombinant protein expression, recombinant protein processing

Procedia PDF Downloads 347

Authors: S. Mehrab Amiri, Nasser Talebbeydokhti

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Modeling sediment transport processes by means of numerical approach often poses severe challenges. In this way, a number of techniques have been suggested to solve flow and sediment equations in decoupled, semi-coupled or fully coupled forms. Furthermore, in order to capture flow discontinuities, a number of techniques, like artificial viscosity and shock fitting, have been proposed for solving these equations which are mostly required careful calibration processes. In this research, a numerical scheme for solving shallow water and Exner equations in fully coupled form is presented. First-Order Centered scheme is applied for producing required numerical fluxes and the reconstruction process is carried out toward using Monotonic Upstream Scheme for Conservation Laws to achieve a high order scheme.  In order to satisfy C-property of the scheme in presence of bed topography, Surface Gradient Method is proposed. Combining the presented scheme with fourth order Runge-Kutta algorithm for time integration yields a competent numerical scheme. In addition, to handle non-prismatic channels problems, Cartesian Cut Cell Method is employed. A trained Multi-Layer Perceptron Artificial Neural Network which is of Feed Forward Back Propagation (FFBP) type estimates sediment flow discharge in the model rather than usual empirical formulas. Hydrodynamic part of the model is tested for showing its capability in simulation of flow discontinuities, transcritical flows, wetting/drying conditions and non-prismatic channel flows. In this end, dam-break flow onto a locally non-prismatic converging-diverging channel with initially dry bed conditions is modeled. The morphodynamic part of the model is verified simulating dam break on a dry movable bed and bed level variations in an alluvial junction. The results show that the model is capable in capturing the flow discontinuities, solving wetting/drying problems even in non-prismatic channels and presenting proper results for movable bed situations. It can also be deducted that applying Artificial Neural Network, instead of common empirical formulas for estimating sediment flow discharge, leads to more accurate results.

Keywords: artificial neural network, morphodynamic model, sediment continuity equation, shallow water equations

Procedia PDF Downloads 188

Authors: M. Khorshed Alam, H. Takaba

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The catalytic properties of metal usually change by intermixturing with another metal in polymer electrolyte fuel cells. Pt-Ru alloy is one of the much-talked used alloy to enhance the CO oxidation. In this work, we have investigated the CO coverage on the Pt2Ru3 nanoparticle with different atomic conformation of Pt and Ru using a combination of material informatics with computational chemistry. Density functional theory (DFT) calculations used to describe the adsorption strength of CO and H with different conformation of Pt Ru ratio in the Pt2Ru3 slab surface. Then through the Monte Carlo (MC) simulations we examined the segregation behaviour of Pt as a function of surface atom ratio, subsurface atom ratio, particle size of the Pt2Ru3 nanoparticle. We have constructed a regression equation so as to reproduce the results of DFT only from the structural descriptors. Descriptors were selected for the regression equation; xa-b indicates the number of bonds between targeted atom a and neighboring atom b in the same layer (a,b = Pt or Ru). Terms of xa-H2 and xa-CO represent the number of atoms a binding H2 and CO molecules, respectively. xa-S is the number of atom a on the surface. xa-b- is the number of bonds between atom a and neighboring atom b located outside the layer. The surface segregation in the alloying nanoparticles is influenced by their component elements, composition, crystal lattice, shape, size, nature of the adsorbents and its pressure, temperature etc. Simulations were performed on different size (2.0 nm, 3.0 nm) of nanoparticle that were mixing of Pt and Ru atoms in different conformation considering of temperature range 333K. In addition to the Pt2Ru3 alloy we also considered pure Pt and Ru nanoparticle to make comparison of surface coverage by adsorbates (H2, CO). Hence, we assumed the pure and Pt-Ru alloy nanoparticles have an fcc crystal structures as well as a cubo-octahedron shape, which is bounded by (111) and (100) facets. Simulations were performed up to 50 million MC steps. From the results of MC, in the presence of gases (H2, CO), the surfaces are occupied by the gas molecules. In the equilibrium structure the coverage of H and CO as a function of the nature of surface atoms. In the initial structure, the Pt/Ru ratios on the surfaces for different cluster sizes were in range of 0.50 - 0.95. MC simulation was employed when the partial pressure of H2 (PH2) and CO (PCO) were 70 kPa and 100-500 ppm, respectively. The Pt/Ru ratios decrease as the increase in the CO concentration, without little exception only for small nanoparticle. The adsorption strength of CO on the Ru site is higher than the Pt site that would be one of the reason for decreasing the Pt/Ru ratio on the surface. Therefore, our study identifies that controlling the nanoparticle size, composition, conformation of alloying atoms, concentration and chemical potential of adsorbates have impact on the steadiness of nanoparticle alloys which ultimately and also overall catalytic performance during the operations.

Keywords: anode catalysts, fuel cells, material informatics, Monte Carlo

Procedia PDF Downloads 192

Authors: Caiyun Liu, A. Hernandez-Manas, N. Grimi, E. Vorobiev

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Drying is one of the most used methods for food preservation, which extend shelf life of food and makes their transportation, storage and packaging easier and more economic. The commonly dried method is hot air drying. However, its disadvantages are low energy efficiency and long drying times. Because of the high temperature during the hot air drying, the undesirable changes in pigments, vitamins and flavoring agents occur which result in degradation of the quality parameters of the product. Drying process can also cause shrinkage, case hardening, dark color, browning, loss of nutrients and others. Recently, new processes were developed in order to avoid these problems. For example, the application of pulsed electric field provokes cell membrane permeabilisation, which increases the drying kinetics and moisture diffusion coefficient. Microwave drying technology has also several advantages over conventional hot air drying, such as higher drying rates and thermal efficiency, shorter drying time, significantly improved product quality and nutritional value. Rehydration kinetics of dried product is a very important characteristic of dried products. Current research has indicated that the rehydration ratio and the coefficient of rehydration are dependent on the processing conditions of drying. The present study compares the efficiency of two processes (1: room temperature air drying, 2: microwave/air drying) in terms of drying rate, product quality and rehydration ratio. In this work, potato slices (≈2.2g) with a thickness of 2 mm and diameter of 33mm were placed in the microwave chamber and dried. Drying kinetics and drying rates of different methods were determined. The process parameters included inlet air velocity (1 m/s, 1.5 m/s, 2 m/s) and microwave power (50 W, 100 W, 200 W and 250 W) were studied. The evolution of temperature during microwave drying was measured. The drying power had a strong effect on drying rate, and the microwave-air drying resulted in 93% decrease in the drying time when the air velocity was 2 m/s and the power of microwave was 250 W. Based on Lewis model, drying rate constants (kDR) were determined. It was observed an increase from kDR=0.0002 s-1 to kDR=0.0032 s-1 of air velocity of 2 m/s and microwave/air (at 2m/s and 250W) respectively. The effective moisture diffusivity was calculated by using Fick's law. The results show an increase of effective moisture diffusivity from 7.52×10-11 to 2.64×10-9 m2.s-1 for air velocity of 2 m/s and microwave/air (at 2m/s and 250W) respectively. The temperature of the potato slices increased for higher microwaves power, but decreased for higher air velocity. The rehydration ratio, defined as the weight of the the sample after rehydration per the weight of dried sample, was determined at different water temperatures (25℃, 50℃, 75℃). The rehydration ratio increased with the water temperature and reached its maximum at the following conditions: 200 W for the microwave power, 2 m/s for the air velocity and 75°C for the water temperature. The present study shows the interest of microwave drying for the food preservation.

Keywords: drying, microwave, potato, rehydration

Procedia PDF Downloads 270

Authors: Mina Rabipour, Elena Pallaske, Floyd Hassenrück, Rocio Rebollido-Rios

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Protein tyrosine kinases, including Lyn kinase of the Src family kinases (SFK), regulate cell proliferation, survival, and differentiation. Lyn kinase has been implicated in various cancers, positioning it as a promising therapeutic target. However, the conserved ATP-binding pocket across SFKs makes developing selective inhibitors challenging. This study aims to address this limitation by exploring the potential for allosteric modulation of Lyn kinase, focusing on how its structural dynamics and specific oncogenic mutations impact its conformation and function. To achieve this, we combined homology modeling, molecular dynamics simulations, and data science techniques to conduct microsecond-length simulations. Our approach allowed a detailed investigation into the interplay between Lyn’s catalytic and regulatory domains, identifying key conformational states involved in allosteric regulation. Additionally, we evaluated the structural effects of Dasatinib, a competitive inhibitor, and ATP binding on Lyn active conformation. Notably, our simulations show that cancer-related mutations, specifically I364L/N and E290D/K, shift Lyn toward an inactive conformation, contrasting with the active state of the wild-type protein. This may suggest how these mutations contribute to aberrant signaling in cancer cells. We conducted a dynamical network analysis to assess residue-residue interactions and the impact of mutations on the Lyn intramolecular network. This revealed significant disruptions due to mutations, especially in regions distant from the ATP-binding site. These disruptions suggest potential allosteric sites as therapeutic targets, offering an alternative strategy for Lyn inhibition with higher specificity and fewer off-target effects compared to ATP-competitive inhibitors. Our findings provide insights into Lyn kinase regulation and highlight allosteric sites as avenues for selective drug development. Targeting these sites may modulate Lyn activity in cancer cells, reducing toxicity and improving outcomes. Furthermore, our computational strategy offers a scalable approach for analyzing other SFK members or kinases with similar properties, facilitating the discovery of selective allosteric modulators and contributing to precise cancer therapies.

Keywords: lyn tyrosine kinase, mutation analysis, conformational changes, dynamic network analysis, allosteric modulation, targeted inhibition

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Authors: Alan Ruiz-Padilla, Brando Villalobos-Villalobos, Yeniley Ruiz-Noa, Claudia Mendoza-Macías, Claudia Palafox-Sánchez, Miguel Marín-Rosales, Álvaro Cruz, Rubén Rangel-Salazar

Abstract:

Introduction: In patients with rheumatoid arthritis, resistance or poor response to disease modifying antirheumatic drugs (DMARD) may be a reflection of the increase in g-P. The expression of g-P may be important in mediating the effluence of DMARD from the cell. In addition, P-glycoprotein is involved in the transport of cytokines, IL-1, IL-2 and IL-4, from normal lymphocytes activated to the surrounding extracellular matrix, thus influencing the activity of RA. The involvement of P-glycoprotein in the transmembrane transport of cytokines can serve as a modulator of the efficacy of DMARD. It was shown that a number of lymphocytes with glycoprotein P activity is increased in patients with RA; therefore, P-glycoprotein expression could be related to the activity of RA and could be a predictor of poor response to therapy. Objective: To evaluate in RA patients, if the G2677T/A MDR1 polymorphisms is associated with differences in the rate of therapeutic response to disease-modifying antirheumatic agents in patients with rheumatoid arthritis. Material and Methods: A prospective cohort study was conducted. Fifty seven patients with RA were included. They had an active disease according to DAS-28 (score >3.2). We excluded patients receiving biological agents. All the patients were followed during 6 months in order to identify the rate of therapeutic response according to the American College of Rheumatology (ACR) criteria. At the baseline peripheral blood samples were taken in order to identify the G2677T/A MDR1 polymorphisms using PCR- Specific allele. The fragment was identified by electrophoresis in polyacrylamide gels stained with ethidium bromide. For statistical analysis, the genotypic and allelic frequencies of MDR1 gene polymorphism between responders and non-responders were determined. Chi-square tests as well as, relative risks with 95% confidence intervals (95%CI) were computed to identify differences in the risk for achieving therapeutic response. Results: RA patients had a mean age of 47.33 ± 12.52 years, 87.7% were women with a mean for DAS-28 score of 6.45 ± 1.12. At the 6 months, the rate of therapeutic response was 68.7 %. The observed genotype frequencies were: for G/G 40%, T/T 32%, A/A 19%, G/T 7% and for A/A genotype 2%. Patients with G allele developed at 6 months of treatment, higher rate for therapeutic response assessed by ACR20 compared to patients with others alleles (p=0.039). Conclusions: Patients with G allele of the - G2677T/A MDR1 polymorphisms had a higher rate of therapeutic response at 6 months with DMARD. These preliminary data support the requirement for a deep evaluation of these and other genotypes as factors that may influence the therapeutic response in RA.

Keywords: pharmacogenetics, MDR1, P-glycoprotein, therapeutic response, rheumatoid arthritis

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Authors: Sultan Z. Mahmud, Emily C. Graff, Adil Bashir

Abstract:

Phosphoprotein enriched in astrocytes 15 kDa (PEA-15) is a multifunctional adapter protein which is associated with the regulation of apoptotic cell death. Recently it has been discovered that PEA-15 is crucial in normal neurodevelopment of domestic cats, a gyrencephalic animal model, although the exact function of PEA-15 in neurodevelopment is unknown. This study investigates how PEA-15 affects the blood-brain barrier (BBB) permeability in cat brain, which can cause abnormalities in tissue metabolite and energy supplies. Severe polymicrogyria and microcephaly have been observed in cats with a loss of function PEA-15 mutation, affecting the normal neurodevelopment of the cat. This suggests that the vital role of PEA-15 in neurodevelopment is associated with gyrification. Neurodevelopment is a highly energy demanding process. The mammalian brain depends on glucose as its main energy source. PEA-15 plays a very important role in glucose uptake and utilization by interacting with phospholipase D1 (PLD1). Mitochondria also plays a critical role in bioenergetics and essential to supply adequate energy needed for neurodevelopment. Cerebral blood flow regulates adequate metabolite supply and recent findings also showed that blood plasma contains mitochondria as well. So the BBB can play a very important role in regulating metabolite and energy supply in the brain. In this study the blood-brain permeability in cat brain was measured using MRI magnetization transfer (MT) effect on the perfusion signal. Perfusion is the tissue mass normalized supply of blood to the capillary bed. Perfusion also accommodates the supply of oxygen and other metabolites to the tissue. A fraction of the arterial blood can diffuse to the tissue, which depends on the BBB permeability. This fraction is known as water extraction fraction (EF). MT is a process of saturating the macromolecules, which has an effect on the blood that has been diffused into the tissue while having minimal effect on intravascular blood water that has not been exchanged with the tissue. Measurement of perfusion signal with and without MT enables to estimate the microvascular blood flow, EF and permeability surface area product (PS) in the brain. All the experiments were performed with Siemens 7T Magnetom with 32 channel head coil. Three control cats and three PEA-15 mutant cats were used for the study. Average EF in white and gray matter was 0.9±0.1 and 0.86±0.15 respectively, perfusion in white and gray matter was 85±15 mL/100g/min and 97±20 mL/100g/min respectively, PS in white and gray matter was 201±25 mL/100g/min and 225±35 mL/100g/min respectively for control cats. For PEA-15 mutant cats, average EF in white and gray matter was 0.81±0.15 and 0.77±0.2 respectively, perfusion in white and gray matter was 140±25 mL/100g/min and 165±18 mL/100g/min respectively, PS in white and gray matter was 240±30 mL/100g/min and 259±21 mL/100g/min respectively. This results show that BBB is compromised in PEA-15 mutant cat brain, where EF is decreased and perfusion as well as PS are increased in the mutant cats compared to the control cats. This findings might further explain the function of PEA-15 in neurodevelopment.

Keywords: BBB, cat brain, magnetization transfer, PEA-15

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Authors: Cecile Edel, Sandrine Giscard D'Estaing, Elsa Labrune, Jacqueline Lornage, Mehdi Benchaib

Abstract:

Introduction: The use of incubator equipped with time-lapse technology in Artificial Reproductive Technology (ART) allows a continuous surveillance. With morphocinetic parameters, algorithms are available to predict the potential outcome of an embryo. However, the different proposed time-lapse algorithms do not take account the missing data, and then some embryos could not be classified. The aim of this work is to construct a predictive model even in the case of missing data. Materials and methods: Patients: A retrospective study was performed, in biology laboratory of reproduction at the hospital ‘Femme Mère Enfant’ (Lyon, France) between 1 May 2013 and 30 April 2015. Embryos (n= 557) obtained from couples (n=108) were cultured in a time-lapse incubator (Embryoscope®, Vitrolife, Goteborg, Sweden). Time-lapse incubator: The morphocinetic parameters obtained during the three first days of embryo life were used to build the predictive model. Predictive model: A quadratic regression was performed between the number of cells and time. N = a. T² + b. T + c. N: number of cells at T time (T in hours). The regression coefficients were calculated with Excel software (Microsoft, Redmond, WA, USA), a program with Visual Basic for Application (VBA) (Microsoft) was written for this purpose. The quadratic equation was used to find a value that allows to predict the blastocyst formation: the synthetize value. The area under the curve (AUC) obtained from the ROC curve was used to appreciate the performance of the regression coefficients and the synthetize value. A cut-off value has been calculated for each regression coefficient and for the synthetize value to obtain two groups where the difference of blastocyst formation rate according to the cut-off values was maximal. The data were analyzed with SPSS (IBM, Il, Chicago, USA). Results: Among the 557 embryos, 79.7% had reached the blastocyst stage. The synthetize value corresponds to the value calculated with time value equal to 99, the highest AUC was then obtained. The AUC for regression coefficient ‘a’ was 0.648 (p < 0.001), 0.363 (p < 0.001) for the regression coefficient ‘b’, 0.633 (p < 0.001) for the regression coefficient ‘c’, and 0.659 (p < 0.001) for the synthetize value. The results are presented as follow: blastocyst formation rate under cut-off value versus blastocyst rate formation above cut-off value. For the regression coefficient ‘a’ the optimum cut-off value was -1.14.10-3 (61.3% versus 84.3%, p < 0.001), 0.26 for the regression coefficient ‘b’ (83.9% versus 63.1%, p < 0.001), -4.4 for the regression coefficient ‘c’ (62.2% versus 83.1%, p < 0.001) and 8.89 for the synthetize value (58.6% versus 85.0%, p < 0.001). Conclusion: This quadratic regression allows to predict the outcome of an embryo even in case of missing data. Three regression coefficients and a synthetize value could represent the identity card of an embryo. ‘a’ regression coefficient represents the acceleration of cells division, ‘b’ regression coefficient represents the speed of cell division. We could hypothesize that ‘c’ regression coefficient could represent the intrinsic potential of an embryo. This intrinsic potential could be dependent from oocyte originating the embryo. These hypotheses should be confirmed by studies analyzing relationship between regression coefficients and ART parameters.

Keywords: ART procedure, blastocyst formation, time-lapse incubator, quadratic model

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