Search results for: cancer stem cell (CSC)

Authors: Vincent Murray

Abstract:

The glycopeptide bleomycin is used in the treatment of testicular cancer, Hodgkin's lymphoma, and squamous cell carcinoma. Bleomycin damages and cleaves DNA in human cells, and this is considered to be the main mode of action for bleomycin's anti-tumor activity. In particular, double-strand breaks are thought to be the main mechanism for the cellular toxicity of bleomycin. Using Illumina next-generation DNA sequencing techniques, the genome-wide sequence specificity of bleomycin-induced double-strand breaks was determined in human cells. The degree of bleomycin cleavage was also assessed at the transcription start sites (TSSs) of actively transcribed genes and compared with non-transcribed genes. It was observed that bleomycin preferentially cleaved at the TSSs of actively transcribed human genes. There was a correlation between the degree of this enhanced cleavage at TSSs and the level of transcriptional activity. Bleomycin cleavage is also affected by chromatin structure and at TSSs, the peaks of bleomycin cleavage were approximately 200 bp apart. This indicated that bleomycin was able to detect phased nucleosomes at the TSSs of actively transcribed human genes. The genome-wide cleavage pattern of the bleomycin analogues 6′-deoxy-BLM Z and zorbamycin was also investigated in human cells. As found for bleomycin, these bleomycin analogues also preferentially cleaved at the TSSs of actively transcribed human genes. The cytotoxicity (IC₅₀ values) of these bleomycin analogues was determined. It was found that the degree of enhanced cleavage at TSSs was inversely correlated with the IC₅₀ values of the bleomycin analogues. This suggested that the level of cleavage at the TSSs of actively transcribed human genes was important for the cytotoxicity of bleomycin and analogues. Hence this study provided a deeper understanding of the cellular processes involved in the cancer chemotherapeutic activity of bleomycin.

Keywords: anti-tumour activity, bleomycin analogues, chromatin structure, genome-wide study, Illumina DNA sequencing

Procedia PDF Downloads 106

Authors: Yosika Dian Komala, Uke Kurniawan Usman, Yuyun Siti Rohmah

Abstract:

The enable technology fills up needs of high-speed data service is Universal Mobile Telecommunications Service (UMTS). UMTS has a data rate up to 2Mbps.UMTS terrestrial system has a coverage area about 1-2km. High Altitude Platform Station (HAPS) can be built by a macro cell that is able to serve the wider area. Design method of UMTS using HAPS is planning base on coverage and capacity. The planning method is simulated with 2.8.1 Atoll’s software. Determination of radius of the cell based on the coverage uses free space loss propagation model. While the capacity planning to determine the average cell through put is available with the Offered Bit Quantity (OBQ).

Keywords: UMTS, HAPS, coverage planning, capacity planning, signal level, Ec/Io, overlapping zone, throughput

Procedia PDF Downloads 618

Authors: Anthara Vivek, Manisha Shukla, Mahesh Narayan, Prakash Narayan

Abstract:

Sickle cell disease disproportionately affects sub-Saharan Africa and certain tribal populaces in India and has consequently drawn little intertest from Pharma. In sickle cell patients, adhesion of erythrocytes or reticulocytes to one another and the vessel wall results in painful ischemic episodes with few, if any, effective treatments for vaso-occlusive crises. Identification of disease-associated adhesion markers on erythrocytes or reticulocytes might inform the use of more effective therapies against vaso-occlusive crises. Increased expression of one or more of bcam, itga4, cd44, cd47, rap1a, vcam1, or icam4 has been reported in sickle cell subjects. Using the miRNet ontology knowledgebase, peripheral blood interactomes were generated by seeding various combinations of the afore-referenced mRNA. These interactomes yielded an array of miR targets. As examples, targeting hsa-miR-155-5p can potentially neutralize the rap1a-bcam-cd44-itga4-vcam1 erythrocyte/reticulocyte adhesion interactome whereas targeting hsa-miRs-103a-3p or 107 can potentially neutralize adhesion in cells overexpressing icam4-cd47-bcam-itga4-cd36. AM3380 (MIRacle™) is an off-the shelf hsa-miR-155-5p agomiR that can potentially neutralize the rap1a-bcam-cd44-itga4-vcam1 signaling axis. Phlebotomy coupled with transcriptomics represents a potentially feasible and effective precision medicine strategy to mitigate vaso-occlusive crises in sickle cell patients.

Keywords: adhesion, interactome, precision, medicine

Procedia PDF Downloads 57

Authors: Mohammed Al-Zubaidi, Katherine Ong, Pravin Viswambaram, Steve McCombie, Oliver Oey, Jeremy Ong, Richard Gauci, Ronny Low, Dickon Hayne

Abstract:

Objective: Lymph node involvement along with distant metastasis in a patient with invasive bladder cancer determines the disease survival, therefeor, it is an essential determinant of the therapeutic management and outcome. This retrospective study aims to determine the accuracy of FDG PET scan in detecting lymphatic involvement and distant metastatic urothelial cancer compared to conventional CT staging. Method: A retrospective review of 76 patients with UC or BC who underwent surgery or confirmatory biopsy that was staged with both CT and 18F-FDG-PET (up to 8 weeks apart) between 2015 and 2020. Fifty-sevenpatients (75%) had formal pelvic LN dissection or biopsy of suspicious metastasis. 18F-FDG-PET reports for positive sites were qualitative depending on SUV Max. On the other hand, enlarged LN by RECIST criteria 1.1 (>10 mm) and other qualitative findings suggesting metastasis were considered positive in CT scan. Histopathological findings from surgical specimens or image-guided biopsies were considered the gold standard in comparison to imaging reports. 18F-FDG-avid or enlarged pelvic LNs with surgically proven nodal metastasis were considered true positives. Performance characteristics of 18F-FDG-PET and CT, including sensitivity, specificity, positive predictive value (PPV), and negative predictive value (PPV), were calculated. Results: Pelvic LN involvement was confirmed histologically in 10/57 (17.5%) patients. Sensitivity, specificity, PPV and NPV of CT for detecting pelvic LN metastases were 41.17% (95% CI:18-67%), 100% (95% CI:90-100%) 100% (95% CI:59-100%) and 78.26% (95% CI:64-89%) respectively. Sensitivity, specificity, PPV and NPV of 18F-FDG-PET for detecting pelvic LN metastases were 62.5% (95% CI:35-85%), 83.78% (95% CI:68-94%), 62.5% (95% CI:35-85%), and 83.78% (95% CI:68-94%) respectively. Pre-operative staging with 18F-FDG-PET identified the distant metastatic disease in 9/76 (11.8%) patients who were occult on CT. This retrospective study suggested that 18F-FDG-PET may be more sensitive than CT for detecting pelvic LN metastases. 7/76 (9.2%) patients avoided cystectomy due to 18F-FDG-PET diagnosed metastases that were not reported on CT. Conclusion: 18F-FDG-PET is more sensitive than CT for pelvic LN metastases, which can be used as the standard modality of bladder cancer staging, as it may change the treatment by detecting lymph node metastasis that was occult in CT. Further research involving randomised controlled trials comparing the diagnostic yield of 18F-FDG-PET and CT in detecting nodal and distant metastasis in UC or BC is warranted to confirm our findings.

Keywords: FDG PET, CT scan, urothelial cancer, bladder cancer

Procedia PDF Downloads 104

Authors: Richard Harrison

Abstract:

Developing competency in mathematics and related critical thinking skills is essential to the education of undergraduate students of Science, Technology, Engineering and Mathematics (STEM). Recently, the HE sector has been impacted by a seemingly widening disconnect between the mathematical competency of incoming first-year STEM students and their entrance qualification tariffs. Despite relatively high grades in A-Level Mathematics, students may initially lack fundamental skills in key areas such as algebraic manipulation and have limited capacity to apply problem solving strategies. Compounded by compensatory measures applied to entrance qualifications during the pandemic, there has been an associated decline in student performance on introductory university mathematics modules. In the UK, a number of online resources have been developed to help scaffold the transition to university mathematics. However, in general, these do not offer a structured learning journey focused on individual developmental needs, nor do they offer an experience coherent with the teaching and learning characteristics of the destination institution. In order to address some of these issues, a bespoke framework has been designed and implemented on our VLE in the Faculty of Engineering & Physical Sciences (FEPS) at the University of Surrey. Called the FEPS Maths Support Framework, it was conceived to scaffold the mathematical development of individuals prior to entering the university and during the early stages of their transition to undergraduate studies. More than 90% of our incoming STEM students voluntarily participate in the process. Students complete a set of initial diagnostic questions in the late summer. Based on their performance and feedback on these questions, they are subsequently guided to self-select specific mathematical topic areas for review using our proprietary resources. This further assists students in preparing for discipline related diagnostic tests. The framework helps to identify students who are mathematically weak and facilitates early intervention to support students according to their specific developmental needs. This paper presents a summary of results from a rich data set captured from the framework over a 3-year period. Quantitative data provides evidence that students have engaged and developed during the process. This is further supported by process evaluation feedback from the students. Ranked performance data associated with seven key mathematical topic areas and eight engineering and science discipline areas reveals interesting patterns which can be used to identify more generic relative capabilities of the discipline area cohorts. In turn, this facilitates evidence based management of the mathematical development of the new cohort, informing any associated adjustments to teaching and learning at a more holistic level. Evidence is presented establishing our framework as an effective early intervention strategy for addressing the sector-wide issue of supporting the mathematical development of STEM students transitioning to HE

Keywords: competency, development, intervention, scaffolding

Procedia PDF Downloads 50

Authors: Sri Rahayu, M. Dwi Susan, Aris Soewondo, W. M. Agung Pramana

Abstract:

Semen is an organic fluid (seminal plasma) that contain spermatozoa. Proteins are one of the major seminal plasma components that modulate sperm functionality, influence sperm capacitation and maintaining the stability of the membrane. Semen freezing is a procedure to preserve sperm cells. The process causes decrease in sperm viability due to temperature shock and oxidation stress. Oxidation stress is a disturbance on phosphorylation that increases ROS concentration, and it produces lipid peroxide in spermatozoa membrane resulted in high MDA (malondialdehyde) concentration. The objective of this study was to examine the effect of freezing on protein and MDA profile of bovine sperm cell and seminal plasma after freezing. Protein and MDA of sperm cell and seminal plasma were isolated from 10 sample. Protein profiles was analyzed by SDS PAGE with separating gel 12,5 %. The concentration of MDA was measured by spectrophotometer. The results of the research indicated that freezing of semen cause lost of the seminal plasma proteins with molecular with 20, 10, and 9 kDa. In addition, the result research showed that protein of the sperm (26, 10, 9, 7, and 6 kDa) had been lost. There were difference MDA concentration of seminal plasma and sperm cell were increase after freezing. MDA concentration of seminal plasma before and after freezing were 2.2 and 2.4 nmol, respectively. MDA concentration of sperm cell before and after freezing were 1,5 and 1.8 nmol, respectively. In conclusion, there were differences protein profiles of spermatozoa before and after semen freezing and freezing cause increasing of the MDA concentration.

Keywords: MDA, semen freezing, SDS PAGE, protein profile

Procedia PDF Downloads 253

Authors: Svitlana Antonenko, Gennady Telegeev

Abstract:

Introductive statement: The development of chronic myeloid leukemia (CML) is caused by Bcr-Abl oncoprotein. Modern treatments with tyrosine kinase inhibitors are greatly complicated by the mutational variability of the Bcr-Abl oncoprotein, which causes drug resistance. Therefore, there is an urgent need to develop new approaches to the treatment of the disease, which will allow modeling the level of Bcr-Abl oncoprotein in the cell. Promising in this direction is the identification of proteases that can selectively promote cellular proteolysis of oncoproteins. The aim of the study was to study the effect of the interaction of Bcr-Abl with deubiquitinase USP1 on the level of oncoprotein in CML cells. Methodology: K562 cells were selected for the experiment. Сells were incubated with ML323 inhibitor for 24 hours. Precipitation of endogenous proteins from K562 cell lysate was performed using anti-Bcr-Abl antibodies. Cell lysates and precipitation results were studied by Western blot. Subcellular localization of proteins was studied by immunofluorescence analysis followed by confocal microscopy. The results were analyzed quantitatively and statistically. Major findings: The Bcr-Abl/USP1 protein complex was detected in CML cells, and it was found that inhibition of USP1 deubiquitinating activity by the compound ML323 leads to disruption of this protein complex and a decrease in the level of Bcr-Abl oncoprotein in cells. The interaction of Bcr-Abl with USP1 may result in deubiquitination of the oncoprotein, which disrupts its proteasomal degradation and leads to the accumulation of CML in cells. Conclusion: We believe that the interaction of oncoprotein with USP1 may be one of the prerequisites that contribute to malignant cell transformation due to the deubiquitination of oncoprotein, which leads to its accumulation and disease progression. A correlation was found between the deubiquitinating activity of USP1 and the level of oncoprotein in CML cells. Thus, we identify deubiquitinase USP1 as a promising therapeutic target for the development of a new strategy for the treatment of CML by modulating the level of Bcr-Abl in the cell.

Keywords: chronic myeloid leukemia, Bcr-Abl, USP1, deubiquitination Bcr-Abl, K562 cell

Procedia PDF Downloads 51

Authors: Madiha Liaqat, Rehan Ahmed Khan, Shahid Kamal

Abstract:

Multiple imputation with delta adjustment is a versatile and transparent technique for addressing univariate missing data in the presence of various missing mechanisms. This approach allows for the exploration of sensitivity to the missing-at-random (MAR) assumption. In this review, we outline the delta-adjustment procedure and illustrate its application for assessing the sensitivity to deviations from the MAR assumption. By examining diverse missingness scenarios and conducting sensitivity analyses, we gain valuable insights into the implications of missing data on our analyses, enhancing the reliability of our study's conclusions. In our study, we focused on assessing logPSA, a continuous biomarker in incomplete prostate cancer data, to examine the robustness of conclusions against plausible departures from the MAR assumption. We introduced several approaches for conducting sensitivity analyses, illustrating their application within the pattern mixture model (PMM) under the delta adjustment framework. This proposed approach effectively handles missing data, particularly loss to follow-up.

Keywords: loss to follow-up, incomplete response, multiple imputation, sensitivity analysis, prostate cancer

Procedia PDF Downloads 71

Authors: Rabindranath Jana, Biswajit Maity, Keka Rana

Abstract:

The most promising clean energy source is the fuel cell, since it does not generate toxic gases and other hazardous compounds. Again the direct methanol fuel cell (DMFC) is more user-friendly as it is easy to be miniaturized and suited as energy source for automobiles as well as domestic applications and portable devices. And unlike the hydrogen used for some fuel cells, methanol is a liquid that is easy to store and transport in conventional tanks. The most important part of a fuel cell is its membrane. Till now, an overall efficiency for a methanol fuel cell is reported to be about 20 ~ 25%. The lower efficiency of the cell may be due to the critical factors, e.g. slow reaction kinetics at the anode and methanol crossover. The oxidation of methanol is composed of a series of successive reactions creating formaldehyde and formic acid as intermediates that contribute to slow reaction rates and decreased cell voltage. Currently, the investigation of new anode catalysts to improve oxidation reaction rates is an active area of research as it applies to the methanol fuel cell. Surprisingly, there are very limited reports on nanostructured membranes, which are rather simple to manufacture with different tuneable compositions and are expected to allow only the proton permeation but not the methanol due to their molecular sizing effects and affinity to the membrane surface. We have developed a nanostructured fuel cell membrane from polydimethyl siloxane rubber (PDMS), ethylene methyl co-acrylate (EMA) and multi-walled carbon nanotubes (MWNTs). The effect of incorporating different proportions of f-MWNTs in polymer membrane has been studied. The introduction of f-MWNTs in polymer matrix modified the polymer structure, and therefore the properties of the device. The proton conductivity, measured by an AC impedance technique using open-frame and two-electrode cell and methanol permeability of the membranes was found to be dependent on the f-MWNTs loading. The proton conductivity of the membranes increases with increase in concentration of f-MWNTs concentration due to increased content of conductive materials. Measured methanol permeabilities at 60oC were found to be dependant on loading of f-MWNTs. The methanol permeability decreased from 1.5 x 10-6 cm²/s for pure film to 0.8 x 10-7 cm²/s for a membrane containing 0.5wt % f-MWNTs. This is due to increasing proportion of f-MWNTs, the matrix becomes more compact. From DSC melting curves it is clear that the polymer matrix with f-MWNTs is thermally stable. FT-IR studies show good interaction between EMA and f-MWNTs. XRD analysis shows good crystalline behavior of the prepared membranes. Significant cost savings can be achieved when using the blended films which contain less expensive polymers.

Keywords: fuel cell membrane, polydimethyl siloxane rubber, carbon nanotubes, proton conductivity, methanol permeability

Procedia PDF Downloads 402

Authors: Ece Çetin, İsmail Boz, Mehtap Şafak Boroğlu

Abstract:

Energy is one of the most important components of production processes, economic activities, and daily life. Non-renewable energy sources cause serious environmental problems with the increase of greenhouse gases. Obtaining energy from renewable sources is also essential for sustainable economic growth. Solar energy is also an important renewable energy source with its unlimited and clean features. In this study, the effect of 1, 2, and 3 layers of perovskite film number and antisolvent dripping on perovskite based solar cell efficiency was investigated. The yield increased as the number of perovskite films increased. In addition, the yields obtained with the antisolvent dripped in the last 5 seconds are higher than the ones dropped in the last 17 seconds. The highest efficiency was obtained with 3 perovskite films, and antisolvent dropped in the last 5 seconds.

Keywords: antisolvent, efficiency, perovskite, solar cell

Procedia PDF Downloads 96

Authors: Sibele A. F. Leite, Bernno S. Leite, José Vicente H. D´Angelo, Ana Teresa P. Dell’Isola, Julio CéSar Souza

Abstract:

The generation of bioenergy is one of the oldest and simplest biomass applications and is one of the safest options for minimizing emissions of greenhouse gasses and replace the use of fossil fuels. In addition, the increasing development of technologies for energy biomass conversion parallel to the advancement of research in biotechnology and engineering has enabled new opportunities for exploitation of biomass. Agricultural residues offer great potential for energy use, and Brazil is in a prominent position in the production and export of agricultural products such as banana and rice. Despite the economic importance of the growth prospects of these activities and the increasing of the agricultural waste, they are rarely explored for energy and production of new materials. Brazil products almost 10.5 million tons/year of rice husk and 26.8 million tons/year of banana stem. Thereby, the aim of this study was to analysis the potential of biomass residues for energy production and applications in new materials. Rice husk (specify the type) and banana stem (specify the type) were characterized by physicochemical analyses using the following parameters: organic carbon, nitrogen (NTK), proximate analyses, FT-IR spectroscopy, thermogravimetric analyses (TG), calorific values and silica content. Rice husk and banana stem presented attractive superior calorific (from 11.5 to 13.7MJ/kg), and they may be compared to vegetal coal (21.25 MJ/kg). These results are due to the high organic matter content. According to the proximate analysis, biomass has high carbon content (fixed and volatile) and low moisture and ash content. In addition, data obtained by Walkley–Black method point out that most of the carbon present in the rice husk (50.5 wt%) and in banana stalk (35.5 wt%) should be understood as organic carbon (readily oxidizable). Organic matter was also detected by Kjeldahl method which gives the values of nitrogen (especially on the organic form) for both residues: 3.8 and 4.7 g/kg of rice husk and banana stem respectively. TG and DSC analyses support the previous results, as they can provide information about the thermal stability of the samples allowing a correlation between thermal behavior and chemical composition. According to the thermogravimetric curves, there were two main stages of mass-losses. The first and smaller one occurred below 100 °C, which was suitable for water losses and the second event occurred between 200 and 500 °C which indicates decomposition of the organic matter. At this broad peak, the main loss was between 250-350 °C, and it is because of sugar decomposition (components readily oxidizable). Above 350 °C, mass loss of the biomass may be associated with lignin decomposition. Spectroscopic characterization just provided qualitative information about the organic matter, but spectra have shown absorption bands around 1030 cm-1 which may be identified as species containing silicon. This result is expected for the rice husk and deserves further investigation to the stalk of banana, as it can bring a different perspective for this biomass residue.

Keywords: rice husk, banana stem, bioenergy, renewable feedstock

Procedia PDF Downloads 260

Authors: Ponchang Apollos Wuyep, Alice Njolke Mafe, Longchi Satkat Zacheaus, Dogun Ojochogu, Dabot Ayuba Yakubu

Abstract:

Fungi causes huge losses when infections occur both in plants and animals. Synthetic Antifungal drugs are mostly very expensive and highly cytotoxic when taken. This study was aimed at determining the in vitro and in vivo antifungal activities of the leaves and stem extracts of Terminalia mantaly (Umbrella tree)H. Perrier on Aspergillus species in a bid to identify potential sources of cheap starting materials for the synthesis of new drugs to address the growing antimicrobial resistance. T. mantaly leave and stem powdered plant was extracted by fractionation using the method of solvent partition co-efficient in their graded form in the order n-hexane, Ethyl acetate, methanol and distilled water and phytochemical screening of each fraction revealed the presence of alkaloids, saponins, Tannins, flavonoids, carbohydrates, steroids, anthraquinones, cardiac glycosides and terpenoids in varying degrees. The Agar well diffusion technique was used to screen for antifungal activity of the fractions on clinical isolates of Aspergillus species (Aspergillus flavus and Aspergillus fumigatus). Minimum inhibitory concentration (MIC50) of the most active extracts was determined by the broth dilution method. The fractions test indicated a high antifungal activity with zones of inhibition ranging from 6 to 26 mm and 8 to 30mm (leave fractions) and 10mm to 34mm and 14mm to36mm (stem fractions) on A. flavus and A. fumigatus respectively. All the fractions indicated antifungal activity in a dose response relationship at concentrations of 62.5mg/ml, 125mg/ml, 250mg/ml and 500mg/ml. Better antifungal efficacy was shown by the Ethyl acetate, Hexane and Methanol fractions in the in vitro as the most potent fraction with MIC ranging from 62.5 to 125mg/ml. There was no statistically significant difference (P>0.05) in the potency of the Eight fractions from leave and stem (Hexane, Ethyl acetate, methanol and distilled water, antifungal (fluconazole), which served as positive control and 10% DMSO(Dimethyl Sulfoxide)which served as negative control. In the in vivo investigations, the ingestion technique was used for the infectious studies Female Drosophilla melanogaster(UAS-Diptericin)normal flies(positive control),infected and not treated flies (negative control) and infected flies with A. fumigatus and placed on normal diet, diet containing fractions(MSM and HSM each at concentrations of 10mg/ml 20mg/ml, 30mg/ml, 40mg/ml, 50mg/ml, 60mg/ml, 70mg/ml, 80mg/ml, 90mg/ml and 100mg/ml), diet containing control drugs(fluconazole as positive control)and infected flies on normal diet(negative control), the flies were observed for fifteen(15) days. Then the total mortality of flies was recorded each day. The results of the study reveals that the flies were susceptible to infection with A. fumigatus and responded to treatment with more effectiveness at 50mg/ml, 60mg/ml and 70mg/ml for both the Methanol and Hexane stem fractions. Therefore, the Methanol and Hexane stem fractions of T. mantaly contain therapeutically useful compounds, justifying the traditional use of this plant for the treatment of fungal infections.

Keywords: Terminalia mantaly, Aspergillus fumigatus, cytotoxic, Drosophila melanogaster, antifungal

Procedia PDF Downloads 64

Authors: Blessing Atim Aderibigbe

Abstract:

A series of amine/ester-linked hybrid compounds containing pharmacophores, such as ursolic acid, oleanolic acid, ferrocene and bisphosphonates, were synthesized in an attempt to develop potent antibacterial and anticancer agents. Their structures were analyzed and confirmed using Nuclear Magnetic Resonance, Fourier Transform Infrared Spectroscopy, and mass spectroscopy. All the synthesized hybrid compounds were evaluated for their antibacterial activities against eleven selected bacterial strains using a serial dilution method. Some of the compounds displayed significant antibacterial activity against most of the bacterial and fungal strains. In addition, the in vitro cytotoxicity of these compounds was also performed against selected cancer cell lines. Some of the compounds were also found to be more active than their parent compounds, revealing the efficacy of designing hybrid molecules using plant-based bioactive agents.

Keywords: ursolic acid, hybrid drugs, oleanolic acid, bisphosphonates

Procedia PDF Downloads 65

Authors: Dusanee Suwankhong, Pranee Liamputtong

Abstract:

Breast surgery leaves undesirable scars to all women who experienced mastectomy, despite the fact that this could be a principle approach to save one life. This paper explores how Thai women living with breast cancer perceived and experienced a scarred body after breast surgery. In-depth interviews and drawing methods were employed among 20 women diagnosed with breast cancer. The interviewed data were analysed using thematic analysis method. The results showed that all women with breast cancer who underwent breast surgery perceived and experienced scar as a persisting and visible side-effect. This disfigurement appearance presented a negative image of feminine identity and led to emotional burdens among women. They responded to being scarred in different ways relating to their perceptions of body and changes. The older group had less embarrassed feelings towards being scarred comparing to the younger one. All women tried to seek means to cope with such physical impairment and keep balance life related to their condition. For example, they relied on Buddhism practice and tried to heal the keloid using natural products. Scars appeared to be an unpleasant effect for women who underwent breast mastectomy. Nurses and health care professionals in the local health service sectors need to pay close attention to how the women see the scarred body and their experiences of living with the distorted feminine appearance, and to provide sensitive support that meets the needs of these vulnerable women. The suitable supports can reduce the sense of embarrassment and increase their sense of self-confidence about their social femininity.

Keywords: breast surgery, emotional response, qualitative study, scars, Thai women

Procedia PDF Downloads 147

Authors: Mahdiar Hosseighadiry, Farnaz Fotovatikhah, Razali Ismail, Mohsen Khaledian, Mehdi Saeidemanesh

Abstract:

In this paper, a new low-power high-performance full adder is presented based on a new design method. The proposed method relies on pass gate design and provides full-swing circuits with minimum number of transistors. The method has been applied on SUM, COUT and XOR-XNOR modules resulting on rail-to-rail intermediate and output signals with no feedback transistors. The presented full adder cell has been simulated in 45 and 32 nm CMOS technologies using HSPICE considering parasitic capacitance and compared to several well-known designs from literature. In addition, the proposed cell has been extensively evaluated with different output loads, supply voltages, temperatures, threshold voltages, and operating frequencies. Results show that it functions properly under all mentioned conditions and exhibits less PDP compared to other design styles.

Keywords: full adders, low-power, high-performance, VLSI design

Procedia PDF Downloads 374

Authors: Nura Brimo, Dilek Cokeliler Serdaroglu, Tansel Uyar, Busra Uysal, Elif Bahar Cakici, Miris Dikmen, Zerrin Canturk

Abstract:

Background: A combination of antibiotics, including metronidazole (MET), ciprofloxacin (CIP), and minocycline (MINO), has been demonstrated to disinfect bacteria in necrotic teeth before regenerative processes. It has been presented clinically that antibiotic pastes may drive to possible stem cell death and difficulties in removing from the canal system, which can limit the regenerative procedure. This study was designed to (1) synthesize nanofibrous webs containing various concentrations of different medicaments (triple, double, and calcium hydroxide,Ca(OH)2), and (2) coat thiselectrospun fibrous gutta-percha (GP) cones. Methods: Poly(vinylpyrrolidone) (PVP)-based electrospun fibrous webs were processed with low medicaments concentrations. Scanning Electron Microscopy (SEM), Energy Dispersive X-Ray Spectroscopy (EDX), and X-Ray Photoelectron Spectroscopy (XPS) were carried out to investigate fiber morphology, antibiotic incorporation, and characterized GP-coated fibrous webs, respectively. The chemical and physical properties of dentine were carried out via Fourier Transform Infrared Spectroscopy (FTIR) and Nano-SEM, respectively. The antimicrobial properties of the different fibrous webs were assessed against various bacteria by direct nanofiber/bacteria contact. Cytocompatibility was measured by applying the MTT method. Results: The mean fiber diameter of the experiment groups of medicament-containing fibers ranged in the nm scale and was significantly smaller than PVP fibers. EDX analysis confirmed the presence of medicaments in the nanofibers. XPS analysis presented a complete coating of the fibers with GPs; FTIR and Nano-SEM showed no chemical and physical configuration of intracanal medicaments on the dentine surface. Meanwhile, nanofibrous webs led to a significant reduction in the percentage of viable bacteria compared with the negative control and PVP. Conclusion: Our findings suggest that TA-NFs, DA-NFs, and Cₐ(OH)₂)-NFs coated GP cones have significant potential in eliminating intracanal bacteria, cell-friendly behavior, and clinical usage features.

Keywords: drug delivery, drug carrier, electrospinning, nano/microfibers, regenerative endodontic, morphology

Procedia PDF Downloads 100

Authors: S. Rodosik, J. P. Poirot-Crouvezier, Y. Bultel

Abstract:

With the expansion of the hydrogen economy, Proton Exchange Membrane Fuel Cell (PEMFC) systems are often presented as promising energy converters suitable for transport applications. However, reaching a durability of 5000 h recommended by the U.S. Department of Energy and decreasing system cost are still major hurdles to their development. In order to increase the system efficiency and simplify the system without affecting the fuel cell lifetime, an architecture called alternative fuel feeding has been developed. It consists in a fuel cell stack divided into two parts, alternatively fed, implemented on a 5-kW system for real scale testing. The operation strategy can be considered close to Dead End Anode (DEA) with specific modifications to avoid water and nitrogen accumulation in the cells. The two half-stacks are connected in series to enable each stack to be alternatively fed. Water and nitrogen accumulated can be shifted from one half-stack to the other one according to the alternative feeding frequency. Thanks to the homogenization of water vapor along the stack, water management was improved. The operating conditions obtained at system scale are close to recirculation without the need of a pump or an ejector. In a first part, a performance comparison with the DEA strategy has been performed. At high temperature and low pressure (80°C, 1.2 bar), performance of alternative fuel feeding was higher, and the system efficiency increased. In a second part, in order to highlight the benefits of the architecture on the fuel cell lifetime, two durability tests, lasting up to 1000h, have been conducted. A test on the 5-kW system has been compared to a reference test performed on a test bench with a shorter stack, conducted with well-controlled operating parameters and flow-through hydrogen strategy. The durability test is based upon the Fuel Cell Dynamic Load Cycle (FC-DLC) protocol but adapted to the system limitations: without OCV steps and a maximum current density of 0.4 A/cm². In situ local measurements with a segmented S++® plate performed all along the tests, showed a more homogeneous distribution of the current density with alternative fuel feeding than in flow-through strategy. Tests performed in this work enabled the understanding of this architecture advantages and drawbacks. Alternative fuel feeding architecture appeared to be a promising solution to ensure the humidification function at the anode side with a simplified fuel cell system.

Keywords: automotive conditions, durability, fuel cell system, proton exchange membrane fuel cell, stack architecture

Procedia PDF Downloads 128

Authors: Sourita Ghosh, Falguni Pati, Suhanya Duraiswamy

Abstract:

Spheroid, a simple three-dimensional cellular aggregate, allows us to simulate the in-vivo complexity of cellular signaling and interactions in greater detail than traditional 2D cell culture. It can be used as an in-vitro model for drug toxicity testing, tumor modeling and many other such applications specifically for cancer. Our work is focused on the development of an affordable, user-friendly, robust, reproducible, high throughput microfluidic device for water in oil droplet production, which can, in turn, be used for spheroids manufacturing. Here, we have investigated the droplet breakup between two non-Newtonian fluids, viz. silicone oil and decellularized liver matrix, which acts as our extra cellular matrix (ECM) for spheroids formation. We performed some biochemical assays to characterize the liver ECM, as well as rheological studies on our two fluids and observed a critical dependence of capillary number (Ca) on droplet breakup and homogeneous drop formation

Keywords: chip less, droplets, extracellular matrix, liver spheroid

Procedia PDF Downloads 70

Authors: Weili Shao, Qian Wang, Jianxin He

Abstract:

Recently, the applications of graphene oxide in fabricating scaffolds for bone tissue engineering have been received extensive concern. In this work, poly l-lactic/graphene oxide composite nanofibers were successfully fabricated by electrospinning. The morphology structure, porosity and mechanical properties of the composite nanofibers were characterized using different techniques. And mouse mesenchymal stem cells were cultured on the composite nanofiber scaffolds to assess their suitability for bone tissue engineering. The results indicated that the composite nanofiber scaffolds had finer fiber diameter and higher porosity as compared with pure poly l-lactic nanofibers. Furthermore, incorporation of graphene oxide into the poly l-lactic nanofibers increased protein adsorptivity, boosted the Young’s modulus and tensile strength by nearly 4.2-fold and 3.5-fold, respectively, and significantly enhanced adhesion, proliferation, and osteogenesis in mouse mesenchymal stem cells. The results indicate that composite nanofibers could be excellent and versatile scaffolds for bone tissue engineering.

Keywords: poly l-lactic, graphene oxide, osteogenesis, bone tissue engineering

Procedia PDF Downloads 289

Authors: Yong Zhang

Abstract:

Light has proven to be useful in a wide range of biomedical applications such as fluorescence imaging, photoacoustic imaging, optogenetics, photodynamic therapy, photothermal therapy, and light controlled drug/gene delivery. Taking photodynamic therapy (PDT) as an example, PDT has been proven clinically effective in early lung cancer, bladder cancer, head, and neck cancer and is the primary treatment for skin cancer as well. However, clinical use of PDT is severely constrained by the low penetration depth of visible light through thick tissue, limiting its use to target regions only a few millimeters deep. One way to enhance the range is to use invisible near-infrared (NIR) light within the optical window (700–1100nm) for biological tissues, extending the depth up to 1cm with no observable damage to the intervening tissue. We have demonstrated use of NIR-to-visible upconversion fluorescent nanoparticles (UCNPs), emitting visible fluorescence when excited by a NIR light at 980nm, as a nanotransducer for PDT to convert deep tissue-penetrating NIR light to visible light suitable for activating photosensitizers. The unique optical properties of UCNPs enable the upconversion wavelength to be tuned and matched to the activation absorption wavelength of the photosensitizer. At depths beyond 1cm, however, tissue remains inaccessible to light even within the NIR window, and this critical depth limitation renders existing phototherapy ineffective against most deep-seated cancers. We have demonstrated some new treatment modalities for deep-seated cancers based on UCNP hydrogel implants and miniaturized, wirelessly powered optoelectronic devices for light delivery to deep tissues.

Keywords: upconversion, fluorescent, nanoparticle, bioimaging, photodynamic therapy

Procedia PDF Downloads 143

Authors: Annisa Ulfah Pristya, Andi Setiawan

Abstract:

Electricity is the primary requirement today's world, including Indonesia. This is because electricity is a source of electrical energy that is flexible to use. Fossil energy sources are the major energy source that is used as a source of energy power plants. Unfortunately, this conversion process impacts on the depletion of fossil fuel reserves and causes an increase in the amount of CO2 in the atmosphere, disrupting health, ozone depletion, and the greenhouse effect. Solutions have been applied are solar cells, ocean wave power, the wind, water, and so forth. However, low efficiency and complicated treatment led to most people and industry in Indonesia still using fossil fuels. Referring to this Fuel Cell was developed. Fuel Cells are electrochemical technology that continuously converts chemical energy into electrical energy for the fuel and oxidizer are the efficiency is considerably higher than the previous natural source of electrical energy, which is 40-60%. However, Fuel Cells still have some weaknesses in terms of the use of an expensive platinum catalyst which is limited and not environmentally friendly. Because of it, required the simultaneous source of electrical energy and environmentally friendly. On the other hand, Indonesia is a rich country in marine sediments and organic content that is never exhausted. Stacking the organic component can be an alternative energy source continued development of fuel cell is A Microbial Fuel Cell. Microbial Fuel Cells (MFC) is a tool that uses bacteria to generate electricity from organic and non-organic compounds. MFC same tools as usual fuel cell composed of an anode, cathode and electrolyte. Its main advantage is the catalyst in the microbial fuel cell is a microorganism and working conditions carried out in neutral solution, low temperatures, and environmentally friendly than previous fuel cells (Chemistry Fuel Cell). However, when compared to Chemistry Fuel Cell, MFC only have an efficiency of 40%. Therefore, the authors provide a solution in the form of Nano-MFC (Nano Microbial Fuel Cell): Utilization of Carbon Nano Tube to Increase Efficiency of Microbial Fuel Cell Power as an Effective, Efficient and Environmentally Friendly Alternative Energy Source. Nano-MFC has the advantage of an effective, high efficiency, cheap and environmental friendly. Related stakeholders that helped are government ministers, especially Energy Minister, the Institute for Research, as well as the industry as a production executive facilitator. strategic steps undertaken to achieve that begin from conduct preliminary research, then lab scale testing, and dissemination and build cooperation with related parties (MOU), conduct last research and its applications in the field, then do the licensing and production of Nano-MFC on an industrial scale and publications to the public.

Keywords: CNT, efficiency, electric, microorganisms, sediment

Procedia PDF Downloads 391

Authors: Robin L. Rohrer

Abstract:

Introduction: Pre-natal or early childhood exposure to the medical radiation used in diagnosis or treatment is an identified risk for childhood cancers but can be difficult to document. The author developed a family questionnaire/interview form to identify possible exposures. Aims: This retrospective study examines pre-natal and early childhood medical radiation exposure in a cohort of children diagnosed with a solid tumor including brain tumors from 1985-2015 at the Children’s Hospital of Pittsburgh (CHP). The hospital is a tri-state regional referral center which treats about 150-180 new cases of cancer in children per year. About 70% are diagnosed with a solid tumor. Methods: Each consented family so far (approximately 50% of the cohort) has been interviewed in person or by the phone call. Medical staff and psycho- social staff referred patient families for the interview with the author. Results: Among the families interviewed to date at least one medical radiation exposure has been identified (pre-conception, pre-natal or early childhood) in over 70% of diagnosed children. These exposures have included pre-conception sinus or chest CT or X-ray in either parent, sinus CT or X-ray in the mother or diagnostic radiation of chest or abdomen in children. Conclusions: Exposures to medical radiation for a child later diagnosed with cancer may occur at several critical junctures. These exposures may well contribute to a ‘perfect storm’ in the still elusive causes of childhood cancer. The author plans to expand the study from 1975 to present to hopefully further document these junctures.

Keywords: pediatric, solid tumors, medical radiation, cancer

Procedia PDF Downloads 252

Authors: Itee Chowdhury, Shikha Modi

Abstract:

Introduction: Cancer is beginning to outpace cardiovascular disease as a cause of death affecting every major organ system with profound implications for perioperative management. Breast cancer is the most common cancer in women in India, accounting for 27% of all cancers. The small changes in analgesic management of cancer patients can greatly improve prognosis and reduce the risk of postsurgical cancer recurrence as opioid-based analgesia has a deleterious effect on cancer outcomes. Shortened postsurgical recovery time facilitates earlier return to intended oncological therapy maximising the chance of successful treatment. Literature reveals that the role of BIS since FDA approval has been assessed in various types of surgeries, but clinical data on its use in oncosurgical patients are scanty. Our study focuses on the role of BIS-guided anaesthesia for breast cancer surgery patients. Methods: A prospective randomized controlled study in patients aged 36-55years scheduled for modified radical mastectomy was conducted in 51 patients in each group who met the inclusion and exclusion criteria, and randomization was done by sealed envelope technique. In BIS guided anaesthesia group (B), sevoflurane was titrated to keep the BIS value 45-60, and thereafter if the patient showed hypertension/tachycardia, an opioid was given. In standard anaesthesia care (group C), sevoflurane was titrated to keep MAC in the range of 0.8-1, and fentanyl was given if the patient showed hypertension/tachycardia. Intraoperative opioid consumption was calculated. Postsurgery recovery characteristics, including Aldrete score, were assessed. Patients were questioned for pain, PONV, and recall of the intraoperative event. A comparison of age, BMI, ASA, recovery characteristics, opioid, and VAS score was made using the non-parametric Mann-Whitney U test. Categorical data like intraoperative awareness of surgery and PONV was studied using the Chi-square test. A comparison of heart rate and MAP was made by an independent sample t-test. #ggplot2 package was used to show the trend of the BIS index for all intraoperative time points for each patient. For a statistical test of significance, the cut-off p-value was set as <0.05. Conclusions: BIS monitoring led to reduced opioid consumption and early recovery from anaesthesia in breast cancer patients undergoing MRM resulting in less postoperative nausea and vomiting and less pain intensity in the immediate postoperative period without any recall of the intraoperative event. Thus, the use of a Bispectral index monitor allows for tailoring of anaesthesia administration with a good outcome.

Keywords: bispectral index, depth of anaesthesia, recovery, opioid consumption

Procedia PDF Downloads 105

Authors: Nurul Hamirah Kamsani, Mohd Hamim Rajikin, Nor Ashikin Mohamed Noor Khan, Sharaniza Abdul Rahim

Abstract:

Cytoskeletal structures, in particular actin and tubulin, provide a fundamental framework in all cells, including embryos. Under influence of nicotine, the cytoskeletal organization may be subjected to oxidative stress (OS) insult and cause alteration. Tocotrienol-rich fraction (TRF) is proven to enhance fertility better than the other sub-group of Vitamin E, tocopherols (TCPs). The objective of this study was to evaluate the effects of TRF on 1) actin and tubulin of 2- and 8-cell murine embryos and 2) the regulation of reactive oxygen species (ROS)-scavenging enzymes; induced by nicotine. Twenty four female Balb/C were subjected to either subcutaneous (sc) injection of 0.9% NaCl; sc injection of 3.0 mg/kg bw/day nicotine; sc injection of 3.0 mg/kg bw/day nicotine + oral gavage (OG) of 60 mg/kg bw/day TRF; or OG of 60 mg/kg bw/day TRF for 7 consecutive days. After superovulation and mating, animals were euthanized. 2-cell developing embryos were retrieved. 50% of the retrieved embryos were visualized under confocal laser staining microscopy (CLSM) for alterations of actin and tubulin. The remaining amount of embryos was cultured in vitro until 8-cell stage followed by CLSM visualization. Blood plasma was subjected to OS assays. Plasma malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were determined and analysed accordingly. At both 2- and 8-cell developing stages, actin intensities were significantly reduced in the nicotine group (p<0.001). After the intervention, actin intensity was significantly increased compared to that of the nicotine group (p<0.001). The same trend was seen in tubulin at both cell stages. TRF has minimized the deleterious effects of nicotine in actin and tubulin of both 2- and 8-cell developmental stages during pre-implantation embryonic development in mice in vitro. Levels of endogenous anti-oxidative enzymes were sustained close to control accompanied by decreased levels of OS biomarker.

Keywords: actin, nicotine, pre-implantation embryos, tocotrienol rich fraction, tubulin

Procedia PDF Downloads 132

Authors: Vishvas N. Patel, Mehul Chorawala

Abstract:

Currently, according to the authors best knowledge there are less effective therapeutic agents to limit intestinal mucosa damage associated with inflammatory bowel disease (IBD). Clinical studies have shown beneficial effects of several probiotics in patients of IBD. Probiotics are live organisms; confer a health benefit to the host by modulating immunoinflammation and oxidative stress. Although probiotics in murine and human improve disease severity, very little is known about the specific contribution of cell wall contents of probiotics in IBD. Herein, we investigated the ameliorative potential of cell wall contents of Lactobacillus casei (LC) in lipopolysaccharide (LPS)-induced murine colitis. Methods: Colitis was induced in LPS-sensitized rats by intracolonic instillation of LPS (50 µg/rat) for consecutive 14 days. Concurrently, cell wall contents isolated from 103, 106 and 109 CFU of LC was given subcutaneously to each rat for 21 days, considering sulfasalazine (100 mg/kg, p.o.) as standard. The severity of colitis was assessed by body weight loss, food intake, stool consistency, rectal bleeding, colon weight/length, spleen weight and histological analysis. Colonic inflammatory markers (myeloperoxidase (MPO) activity, C-reactive protein and proinflammatory cytokines) and oxidative stress markers (malondialdehyde, reduced glutathione and nitric oxide) were also assayed. Results: Cell wall contents of isolated from 106 and 109 CFU of LC significantly improved the severity of colitis by reducing body weight loss and diarrhea & bleeding incidence, improving food intake, colon weight/length, spleen weight and microscopic damage to the colonic mucosa. The treatment also reduced levels of inflammatory and oxidative stress markers and boosted antioxidant molecule. However, cell wall contents of isolated from 103 were ineffective. Conclusion: In conclusion, cell wall contents of LC attenuate LPS-induced colitis by modulating immuno-inflammation and oxidative stress.

Keywords: probiotics, Lactobacillus casei, immuno-inflammation, oxidative stress, lipopolysaccharide, colitis

Procedia PDF Downloads 69

Authors: Emily Schlebes, Christian Hundhausen, Jens W. Fischer

Abstract:

The glycosaminoglycan hyaluronan (HA) is a major component of the extracellular matrix, typically produced by fibroblasts of the connective tissue but also by immune cells. Here, we investigated the capacity of human peripheral blood CD8 T cells from healthy donors to produce HA and to express HA receptors as well as HA degrading enzymes. Further, we evaluated the effect of pharmacological HA inhibition on CD8 T cell function. Using immunocytochemistry together with quantitative PCR analysis, we found that HA synthesis is rapidly induced upon antibody-induced T cell receptor (TCR) activation and almost exclusively mediated by HA synthase 3 (HAS3). TCR activation also resulted in the upregulation of HA receptors CD44, hyaluronan-mediated motility receptor (HMMR), and layilin (LAYN), although kinetics and strength of expression varied greatly between subjects. The HA-degrading enzymes HYAL1 and HYAL2 were detected at low levels and induced by cell activation in some individuals. Interestingly, expression of HAS3, HA receptors, and hyaluronidases were modulated by the proinflammatory cytokines IL-6 and IL-1bβ in most subjects. To assess the functional role of HA in CD8 T cells, we performed carboxyfluorescein succinimidyl ester (CFSE) based proliferation assays and cytokine analysis in the presence of the HA inhibitor 4- Methylumbelliferone (4-MU). Despite significant inter-individual variation with regard to the effective dose, 4-MU resulted in the inhibition of CD8 T cell proliferation and reduced release of TNF-α and IFN-γ. Collectively, these data demonstrate that human CD8 T cells respond to TCR stimulation with a synthesis of HA and expression of HA-related genes. They further suggest that HA inhibition may be helpful in interfering with pathogenic T cell activation in human disease.

Keywords: CD8 T cells, extracellular matrix, hyaluronan, hyaluronan synthase 3

Procedia PDF Downloads 80

Authors: Samira B. R. Prado, Paulo R. Melfi, Beatriz T. Minguzzi, João P. Fabi

Abstract:

Fruit softening is the main change that occurs during papaya (Carica papaya L.) ripening. It is characterized by the depolymerization of cell wall polysaccharides, especially the pectic fractions, which causes cell wall disassembling. However, it is uncertain how the modification of the two main pectin polysaccharides fractions (water-soluble – WSF, and oxalate-soluble fractions - OSF) accounts for fruit softening. The aim of this work was to correlate molecular weight changes of WSF and OSF with the gene expression of pectin-solubilizing enzymes (pectinases) during papaya ripening. Papaya fruits obtained from a producer were harvest and storage under specific conditions. The fruits were divided in five groups according to days after harvesting. Cell walls from all groups of papaya pulp were isolated and fractionated (WSF and OSF). Expression profiles of pectinase genes were achieved according to the MIQE guidelines (Minimum Information for publication of Quantitative real-time PCR Experiments). The results showed an increased yield and a decreased molecular weight throughout ripening for WSF and OSF. Gene expression data support that papaya softening is achieved by polygalacturonases (PGs) up-regulation, in which their actions might have been facilitated by the constant action of pectinesterases (PMEs). Moreover, BGAL1 gene was up-regulated during ripening with a simultaneous galactose release, suggesting that galactosidases (GALs) could also account for pulp softening. The data suggest that a solubilization of galacturonans and a depolymerization of cell wall components were caused mainly by the action of PGs and GALs.

Keywords: carica papaya, fruit ripening, galactosidases, plant cell wall, polygalacturonases

Procedia PDF Downloads 407

Authors: Ibrahim M. Labouta, Gina N. Tageldin, Salwa M. Fahmy, Hayam M. Ashour, Mounir A. Khalil, Tamer M. Ibrahim, Nefertiti A. El-Nikhely

Abstract:

Bruton’s tyrosine kinase (BTK) is a critical effector molecule in B cell antigen receptor (BCR) signaling transduction. It regulates B cell proliferation, development and survival. Since BTK is widely expressed in many B cell leukaemias and lymphomas, targeting BTK by small molecules inhibitors became an attractive idea as new treatment modalities for B cell mediated hematologic malignancies. Ibrutinib is the 1st generation BTK inhibitor, approved by FDA for treatment of relapsed mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL). It binds irreversibly to the unique cysteine (Cys481) within the ATP-binding pocket of BTK. Besides ibrutinib, many irreversible covalent BTK inhibitors comprising pyrimidine nucleus such as spebrutinib (phase IIb) showed high selectivity and potency when compared to it. In this study, the designed compounds were based on 5-cyano-2-methylsulfanyl pyrimidine core and decorated with electrophilic warheads which are essential for the optimal activity for targeted covalent inhibition (TCI). However, modifications at pyrimidine C4 or C6 were made by introduction of substituted amines which are provided to behave differently. The synthesized derivatives were evaluated for their anticancer activity in leukemia cell lines (e.g. THP-1). Results showed that, some derivatives exhibited antiproliferative activity with IC50 ranged from 5-50 μM, The in vitro enzymatic inhibitory assay for these compounds against BTK is still under investigation. Nevertheless, we could conclude from the initial biological screening that, the synthesized 4 or 6-subsitituted aminopyrimidines represent promising and novel antileukemic agents. Meanwhile, further studies are still needed to attribute this activity through targeting BTK enzyme and inhibition of BCR signaling pathway.

Keywords: BTK inhibitors, hematologic malignancies, structure based drug design (SBDD), targeted covalent inhibitors (TCI)

Procedia PDF Downloads 137

Authors: Ella Tyuryumina, Alexey Neznanov

Abstract:

This study is an attempt to obtain reliable data on the natural history of breast cancer growth. We analyze the opportunities for using classical mathematical models (exponential and logistic tumor growth models, Gompertz and von Bertalanffy tumor growth models) to try to describe growth of the primary tumor and the secondary distant metastases of human breast cancer. The research aim is to improve predicting accuracy of breast cancer progression using an original mathematical model referred to CoMPaS and corresponding software. We are interested in: 1) modelling the whole natural history of the primary tumor and the secondary distant metastases; 2) developing adequate and precise CoMPaS which reflects relations between the primary tumor and the secondary distant metastases; 3) analyzing the CoMPaS scope of application; 4) implementing the model as a software tool. The foundation of the CoMPaS is the exponential tumor growth model, which is described by determinate nonlinear and linear equations. The CoMPaS corresponds to TNM classification. It allows to calculate different growth periods of the primary tumor and the secondary distant metastases: 1) ‘non-visible period’ for the primary tumor; 2) ‘non-visible period’ for the secondary distant metastases; 3) ‘visible period’ for the secondary distant metastases. The CoMPaS is validated on clinical data of 10-years and 15-years survival depending on the tumor stage and diameter of the primary tumor. The new predictive tool: 1) is a solid foundation to develop future studies of breast cancer growth models; 2) does not require any expensive diagnostic tests; 3) is the first predictor which makes forecast using only current patient data, the others are based on the additional statistical data. The CoMPaS model and predictive software: a) fit to clinical trials data; b) detect different growth periods of the primary tumor and the secondary distant metastases; c) make forecast of the period of the secondary distant metastases appearance; d) have higher average prediction accuracy than the other tools; e) can improve forecasts on survival of breast cancer and facilitate optimization of diagnostic tests. The following are calculated by CoMPaS: the number of doublings for ‘non-visible’ and ‘visible’ growth period of the secondary distant metastases; tumor volume doubling time (days) for ‘non-visible’ and ‘visible’ growth period of the secondary distant metastases. The CoMPaS enables, for the first time, to predict ‘whole natural history’ of the primary tumor and the secondary distant metastases growth on each stage (pT1, pT2, pT3, pT4) relying only on the primary tumor sizes. Summarizing: a) CoMPaS describes correctly the primary tumor growth of IA, IIA, IIB, IIIB (T1-4N0M0) stages without metastases in lymph nodes (N0); b) facilitates the understanding of the appearance period and inception of the secondary distant metastases.

Keywords: breast cancer, exponential growth model, mathematical model, metastases in lymph nodes, primary tumor, survival

Procedia PDF Downloads 328

Authors: Nisha Singh, Neeru Adlakha

Abstract:

Calcium signalling is one of the most important intracellular signalling mechanisms. A lot of approaches and investigators have been made in the study of calcium signalling in various cells to understand its mechanisms over recent decades. However, most of existing investigators have mainly focussed on the study of calcium signalling in various cells without paying attention to the dependence of calcium signalling on other chemical ions like inositol-1; 4; 5 triphosphate ions, etc. Some models for the independent study of calcium signalling and inositol-1; 4; 5 triphosphate signalling in various cells are present but very little attention has been paid by the researchers to study the interdependence of these two signalling processes in a cell. In this paper, we propose a coupled mathematical model to understand the interdependence of inositol-1; 4; 5 triphosphate dynamics and calcium dynamics in a myocyte cell. Such studies will provide the deeper understanding of various factors involved in calcium signalling in myocytes, which may be of great use to biomedical scientists for various medical applications.

Keywords: calcium signalling, coupling, finite difference method, inositol 1, 4, 5-triphosphate

Procedia PDF Downloads 273