Search results for: malignant mixed mullerian tumor
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 3626

Search results for: malignant mixed mullerian tumor

3146 Synthesis of Erlotinib Analogues, Conjugation of BSA to Erlotinib Alcohol and Their Anti-Cancer Activity against NSCLC

Authors: Ramalingam Boobalan, Chinpiao Chen, Jui-I. Chiao

Abstract:

A series of erlotinib analogues that have structural modification at 6,7-alkoxyl positions is efficiently synthesized. The key reactions that involved in synthesis are one-pot oxime formation-dehydration for the formation of nitrile, quinazoline ring formation reaction between aniline and o-cyanoaniline via formamidine intermediate, Fe/NH4Cl catalyzed reduction-hetereocyclization-reductive ring opening reaction for the formation of o-aminobenzamide, high yielding seal tube reactions for O-demethylation, sodium iodide substitution, ammonia substitution. The in vitro anti-tumor activity of synthesized compounds is studied in two non-small cell lung cancer (NSCLC) cell lines (A549 and H1975). Among the synthesized compounds, the iodo compound 6 (ETN-6) exhibits higher anti-cancer activity compared to erlotinib. An efficient method is developed for the conjugation of erlotinib analogue-4, alcohol compound, with protein, bovine serum albumin (BSA), via succinic acid linker. The in vitro anti-tumor activity of the protein attached erlotinib analogue, 8 (ETN-4-Suc-BSA), showed stronger inhibitory activity in both A549 and H1975 NSCLC cell lines.

Keywords: anti-cancer, BSA, EGFR, Erlotinib

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3145 PEG-b-poly(4-vinylbenzyl phosphonate) Coated Magnetic Iron Oxide Nanoparticles as Drug Carrier System: Biological and Physicochemical Characterization

Authors: Magdalena Hałupka-Bryl, Magdalena Bednarowicz, Ryszard Krzyminiewski, Yukio Nagasaki

Abstract:

Due to their unique physical properties, superparamagnetic iron oxide nanoparticles are increasingly used in medical applications. They are very useful carriers for delivering antitumor drugs in targeted cancer treatment. Magnetic nanoparticles (PEG-PIONs/DOX) with chemotherapeutic were synthesized by coprecipitation method followed by coating with biocompatible polymer PEG-derivative (poly(ethylene glycol)-block-poly(4-vinylbenzylphosphonate). Complete physicochemical characterization was carried out (ESR, HRTEM, X-ray diffraction, SQUID analysis) to evaluate the magnetic properties of obtained PEG-PIONs/DOX. Nanoparticles were investigated also in terms of their stability, drug loading efficiency, drug release and antiproliferative effect on cancer cells. PEG-PIONs/DOX have been successfully used for the efficient delivery of an anticancer drug into the tumor region. Fluorescent imaging showed the internalization of PEG-PIONs/DOX in the cytoplasm. Biodistribution studies demonstrated that PEG-PIONs/DOX preferentially accumulate in tumor region via the enhanced permeability and retention effect. The present findings show that synthesized nanosystem is promising tool for potential magnetic drug delivery.

Keywords: targeted drug delivery, magnetic properties, iron oxide nanoparticles, biodistribution

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3144 Prostatic Cyst in Suprapubic Ultrasound Examination

Authors: Angelis P. Barlampas, Ghita Bianca-Andreea

Abstract:

A case of a prostatic midline cyst is presented, which was found during a routine general ultrasound examination in an otherwise healthy young man. The incidence of prostatic cysts discovered in suprapubic ultrasound examination has constantly been rising over the previous decades. Despite the fact that the majority of them are benign, a significant amount is related to symptoms, such as pain, dysuria, infertility, and even cancer. The wide use of ultrasound examination and the increasing availability of high-resolution ultrasound systems have rendered new diagnostic challenges. Once upon a time a suprapubic ultrasound was only useful for measuring only the size and the dimensions of the prostatic gland. It did not have the ability to analyze and resolve structures such as cystic or solid nodules. The current machine equipment has managed to depict the imaging characteristics of lesions with high acuity that compares of an intrarectal ultrasound. But the last one is a specialized examination, which demands expertise and good knowledge. Maybe the time has come for the general radiologist and, especially the one who uses suprapubic ultrasound, to pay more attention to the examination of the prostate gland and to take advantage of the superb abilities and the high resolution of the new ultrasound systems. That is exactly, what this case is emphasizing. The incidental discovery of prostatic cysts, and the relatively little available literature about managing them turns them into an interesting theme for exploring and studying. The prostatic cysts are further divided into midline and paramidline cysts, with the first being usually utricle cysts. A more precise categorization is as follows: A midline cystic lesion usually regards a Mullerian duct cyst, a prostatic utricle cyst, an ejaculatory duct cyst, a prostatic cystadenoma, a ductus deferens cyst, and a TURP. On the other hand, a lateral cystic lesion usually refers to a cystic degeneration of benign prostatic hyperplasia, a prostatic retention cyst, a seminal vesicle cyst, diverticular prostatitis, a prostatic abscess, cavitatory prostatitis from chronic prostatitis, a parasitic prostatic cyst, a cystic prostatic carcinoma, e.t.c.

Keywords: prostatic cyst, radiology, benign prostatic lesions, prostatic cancer, suprapubic prostatic ultrasound

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3143 Chemopreventive Potency of Medicinal and Eatable Plant, Gromwell Seed on in Vitro and in Vivo Carcinogenesis Systems

Authors: Harukuni Tokuda, Xu FengHao, Nobutaka Suzuki

Abstract:

As part of an ongoing our projects to investigate the anti-tumor promoring properties (chemopreventive potency) of Gromwell seed, dry powder materials and its active compounds were carried out through useful test systems. Gromwell seed (Coix lachryma-jobi seed) (GS) is a grass crop that has long been used and played a role in traditional medicine as a nourishing food, and for the treatment of various aliments, paticularly cancer. The application of a new screening procedure which utilizes the synergistic effect of short-chain fatty acids and phorbol esters in enable rapid and easy detection of naturally occurring substances(anti-tumor promoters chemo-preventive agents) with inhibition of Epstein-Barr virus(EBV) activation, using human lymphblastoid cells. In addition, we have now extended these investigations to a new tumorigenesis model in which we initiated the tumors with DMBA intiation and promoted with 1.7 nmol of TPA in two-stage mouse skin test and other models. these results provide a basis for further development of these botanical supplements for human cancer chemoprevention and observations seem that this materials more extensively as one of the trials for the purpose of complementary and alternative medicine.

Keywords: chemoprevention, medicinal plant, mouse, carcinogenesis systems

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3142 An Integrated Mixed-Integer Programming Model to Address Concurrent Project Scheduling and Material Ordering

Authors: Babak H. Tabrizi, Seyed Farid Ghaderi

Abstract:

Concurrent planning of project scheduling and material ordering can provide more flexibility to the project scheduling problem, as the project execution costs can be enhanced. Hence, the issue has been taken into account in this paper. To do so, a mixed-integer mathematical model is developed which considers the aforementioned flexibility, in addition to the materials quantity discount and space availability restrictions. Moreover, the activities duration has been treated as decision variables. Finally, the efficiency of the proposed model is tested by different instances. Additionally, the influence of the aforementioned parameters is investigated on the model performance.

Keywords: material ordering, project scheduling, quantity discount, space availability

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3141 Effect of Carbon Nanotubes on Nanocomposite from Nanofibrillated Cellulose

Authors: M. Z. Shazana, R. Rosazley, M. A. Izzati, A. W. Fareezal, I. Rushdan, A. B. Suriani, S. Zakaria

Abstract:

There is an increasing interest in the development of flexible energy storage for application of Carbon Nanotubes and nanofibrillated cellulose (NFC). In this study, nanocomposite is consisting of Carbon Nanotube (CNT) mixed with suspension of nanofibrillated cellulose (NFC) from Oil Palm Empty Fruit Bunch (OPEFB). The use of Carbon Nanotube (CNT) as additive nanocomposite was improved the conductivity and mechanical properties of nanocomposite from nanofibrillated cellulose (NFC). The nanocomposite were characterized for electrical conductivity and mechanical properties in uniaxial tension, which were tensile to measure the bond of fibers in nanocomposite. The processing route is environmental friendly which leads to well-mixed structures and good results as well.

Keywords: carbon nanotube (CNT), nanofibrillated cellulose (NFC), mechanical properties, electrical conductivity

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3140 Identification of the Target Genes to Increase the Immunotherapy Response in Bladder Cancer Patients using Computational and Experimental Approach

Authors: Sahar Nasr, Lin Li, Edwin Wang

Abstract:

Bladder cancer (BLCA) is known as the 13th cause of death among cancer patients worldwide, and ~575,000 new BLCA cases are diagnosed each year. Urothelial carcinoma (UC) is the most prevalent subtype among BLCA patients, which can be categorized into muscle-invasive bladder cancer (MIBC) and non-muscle-invasive bladder cancer (NMIBC). Currently, various therapeutic options are available for UC patients, including (1) transurethral resection followed by intravesical instillation of chemotherapeutics or Bacillus Calmette-Guérin for NMIBC patients, (2) neoadjuvant platinum-based chemotherapy (NAC) plus radical cystectomy is the standard of care for localized MIBC patients, and (3) systematic chemotherapy for metastatic UC. However, conventional treatments may lead to several challenges for treating patients. As an illustration, some patients may suffer from recurrence of the disease after the first line of treatment. Recently, immune checkpoint therapy (ICT) has been introduced as an alternative treatment strategy for the first or second line of treatment in advanced or metastatic BLCA patients. Although ICT showed lucrative results for a fraction of BLCA patients, ~80% of patients were not responsive to it. Therefore, novel treatment methods are required to augment the ICI response rate within BLCA patients. It has been shown that the infiltration of T-cells into the tumor microenvironment (TME) is positively correlated with the response to ICT within cancerous patients. Therefore, the goal of this study is to enhance the infiltration of cytotoxic T-cells into TME through the identification of target genes within the tumor that are responsible for the non-T-cell inflamed TME and their inhibition. BLCA bulk RNA-sequencing data from The Cancer Genome Atlas (TCGA) and immune score for TCGA samples were used to determine the Pearson correlation score between the expression of different genes and immune score for each sample. The genes with strong negative correlations were selected (r < -0.2). Thereafter, the correlation between the expression of each gene and survival in BLCA patients was calculated using the TCGA data and Cox regression method. The genes that are common in both selected gene lists were chosen for further analysis. Afterward, BLCA bulk and single-cell RNA-sequencing data were ranked based on the expression of each selected gene and the top and bottom 25% samples were used for pathway enrichment analysis. If the pathways related to the T-cell infiltration (e.g., antigen presentation, interferon, or chemokine pathways) were enriched within the low-expression group, the gene was included for downstream analysis. Finally, the selected genes will be used to calculate the correlation between their expression and the infiltration rate of the activated CD+8 T-cells, natural killer cells and the activated dendric cells. A list of potential target genes has been identified and ranked based on the above-mentioned analysis and criteria. SUN-1 got the highest score within the gene list and other identified genes in the literature as benchmarks. In conclusion, inhibition of SUN1 may increase the tumor-infiltrating lymphocytes and the efficacy of ICI in BLCA patients. BLCA tumor cells with and without SUN-1 CRISPR/Cas9 knockout will be injected into the syngeneic mouse model to validate the predicted SUN-1 effect on increasing tumor-infiltrating lymphocytes.

Keywords: data analysis, gene expression analysis, gene identification, immunoinformatic, functional genomics, transcriptomics

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3139 Stochastic Modelling for Mixed Mode Fatigue Delamination Growth of Wind Turbine Composite Blades

Authors: Chi Zhang, Hua-Peng Chen

Abstract:

With the increasingly demanding resources in the word, renewable and clean energy has been considered as an alternative way to replace traditional ones. Thus, one of practical examples for using wind energy is wind turbine, which has gained more attentions in recent research. Like most offshore structures, the blades, which is the most critical components of the wind turbine, will be subjected to millions of loading cycles during service life. To operate safely in marine environments, the blades are typically made from fibre reinforced composite materials to resist fatigue delamination and harsh environment. The fatigue crack development of blades is uncertain because of indeterminate mechanical properties for composite and uncertainties under offshore environment like wave loads, wind loads, and humid environments. There are three main delamination failure modes for composite blades, and the most common failure type in practices is subjected to mixed mode loading, typically a range of opening (mode 1) and shear (mode 2). However, the fatigue crack development for mixed mode cannot be predicted as deterministic values because of various uncertainties in realistic practical situation. Therefore, selecting an effective stochastic model to evaluate the mixed mode behaviour of wind turbine blades is a critical issue. In previous studies, gamma process has been considered as an appropriate stochastic approach, which simulates the stochastic deterioration process to proceed in one direction such as realistic situation for fatigue damage failure of wind turbine blades. On the basis of existing studies, various Paris Law equations are discussed to simulate the propagation of the fatigue crack growth. This paper develops a Paris model with the stochastic deterioration modelling according to gamma process for predicting fatigue crack performance in design service life. A numerical example of wind turbine composite materials is investigated to predict the mixed mode crack depth by Paris law and the probability of fatigue failure by gamma process. The probability of failure curves under different situations are obtained from the stochastic deterioration model for comparisons. Compared with the results from experiments, the gamma process can take the uncertain values into consideration for crack propagation of mixed mode, and the stochastic deterioration process shows a better agree well with realistic crack process for composite blades. Finally, according to the predicted results from gamma stochastic model, assessment strategies for composite blades are developed to reduce total lifecycle costs and increase resistance for fatigue crack growth.

Keywords: Reinforced fibre composite, Wind turbine blades, Fatigue delamination, Mixed failure mode, Stochastic process.

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3138 Current Status of Ir-192 Brachytherapy in Bangladesh

Authors: M. Safiqul Islam, Md Arafat Hossain Sarkar

Abstract:

Brachytherapy is one of the most important cancer treatment management systems in radiotherapy department. Brachytherapy treatment is moved into High Dose Rate (HDR) after loader from Low Dose Rate (LDR) after loader due to radiation protection advantage. HDR Brachytherapy is a highly multipurpose system for enhancing cure and achieving palliation in many common cancers disease of developing countries. High-dose rate (HDR) Brachytherapy is a type of internal radiation therapy that delivers radiation from implants placed close to or inside, the tumor(s) in the body. This procedure is very effective at providing localized radiation to the tumor site while minimizing the patient’s whole body dose. Brachytherapy has proven to be a highly successful treatment for cancers of the prostate, cervix, endometrium, breast, skin, bronchus, esophagus, and head and neck, as well as soft tissue sarcomas and several other types of cancer. For the time being in our country we have 10 new HDR Remote after loading Brachytherapy. Right now 4 HDR Brachytherapy is already installed and running for patient’s treatment out of 10 HDR Brachytherapy. Ir-192 source is more comfortable than Co-60. In that case people or expert personnel prefer Ir-192 source for different kind of cancer patients. Ir-192 are economically, more flexible and familiar in our country.

Keywords: Ir-192, brachytherapy, cancer treatment, prostate, cervix, endometrium, breast, skin, bronchus, esophagus, soft tissue sarcomas

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3137 Diagnostic Performance of Tumor Associated Trypsin Inhibitor in Early Detection of Hepatocellular Carcinoma in Patients with Hepatitis C Virus

Authors: Aml M. El-Sharkawy, Hossam M. Darwesh

Abstract:

Abstract— Background/Aim: Hepatocellular carcinoma (HCC) is often diagnosed at advanced stage where effective therapies are lacking. Identification of new scoring system is needed to discriminate HCC patients from those with chronic liver disease. Based on the link between tumor associated trypsin inhibitor (TATI) and HCC progression, we aimed to develop a novel score based on combination of TATI and routine laboratory tests for early prediction of HCC. Methods: TATI was assayed for HCC group (123), liver cirrhosis group (210) and control group (50) by Enzyme Linked Immunosorbent Assay (ELISA). Data from all groups were retrospectively analyzed including α feto protein (AFP), international normalized ratio (INR), albumin and platelet count, transaminases, and age. Areas under ROC curve were used to develop the score. Results: A novel index named hepatocellular carcinoma-vascular endothelial growth factor score (HCC-TATI score) = 3.1 (numerical constant) + 0.09 ×AFP (U L-1) + 0.067 × TATI (ng ml-1) + 0.16 × INR – 1.17 × Albumin (g l-1) – 0.032 × Platelet count × 109 l-1 was developed. HCC-TATI score produce area under ROC curve of 0.98 for discriminating HCC patients from liver cirrhosis with sensitivity of 91% and specificity of 82% at cut-off 6.5 (ie less than 6.5 considered cirrhosis and greater than 4.4 considered HCC). Conclusion: Hepatocellular carcinoma-TATI score could replace AFP in HCC screening and follow up of cirrhotic patients.

Keywords: Hepatocellular carcinoma, cirrhosis, HCV, diagnosis, TATI

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3136 18F-Fluoro-Ethyl-Tyrosine-Positron Emission Tomography in Gliomas: Comparison with Magnetic Resonance Imaging and Computed Tomography

Authors: Habib Alah Dadgar, Nasim Norouzbeigi

Abstract:

The precise definition margin of high and low-grade gliomas is crucial for treatment. We aimed to assess the feasibility of assessment of the resection legions with post-operative positron emission tomography (PET) using [18F]O-(2-[18F]-fluoroethyl)-L-tyrosine ([18F]FET). Four patients with the suspicion of high and low-grade were enrolled. Patients underwent post-operative [18F]FET-PET, pre-operative magnetic resonance imaging (MRI) and CT for clinical evaluations. In our study, three patients had negative response to recurrence and progression and one patient indicated positive response after surgery. [18F]FET-PET revealed a legion of increased radiotracer uptake in the dura in the craniotomy site for patient 1. Corresponding to the patient history, the study was negative for recurrence of brain tumor. For patient 2, there was a lesion in the right parieto-temporal with slightly increased uptake in its posterior part with SUVmax = 3.79, so the study was negative for recurrence evaluation. In patient 3 there was no abnormal uptake with negative result for recurrence of brain tumor. Intense radiotracer uptake in the left parietal lobe where in the MRI there was a lesion with no change in enhancement in the post-contrast image is indicated in patient 4. Assessment of the resection legions in high and low-grade gliomas with [18F]FET-PET seems to be useful.

Keywords: FET-PET, CT, glioma, MRI

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3135 Supplier Selection by Considering Cost and Reliability

Authors: K. -H. Yang

Abstract:

Supplier selection problem is one of the important issues of supply chain problems. Two categories of methodologies include qualitative and quantitative approaches which can be applied to supplier selection problems. However, due to the complexities of the problem and lacking of reliable and quantitative data, qualitative approaches are more than quantitative approaches. This study considers operational cost and supplier’s reliability factor and solves the problem by using a quantitative approach. A mixed integer programming model is the primary analytic tool. Analyses of different scenarios with variable cost and reliability structures show that the effectiveness of this approach to the supplier selection problem.

Keywords: mixed integer programming, quantitative approach, supplier’s reliability, supplier selection

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3134 Structural and Magnetic Properties of Calcium Mixed Ferrites Prepared by Co-Precipitation Method

Authors: Sijo S. Thomas, S. Hridya, Manoj Mohan, Bibin Jacob, Hysen Thomas

Abstract:

Ferrites are iron based oxides with technologically significant magnetic properties and have widespread applications in medicine, technology, and industry. There has been a growing interest in the study of magnetic, electrical and structural properties of mixed ferrites. In the present work, structural and magnetic properties of Nickel and Calcium substituted Fe₃O₄ nanoparticles were investigated. NiₓCa₁₋ₓFe₂O₄ nanoparticles (x = 0, 0.1, 0.3, 0.5, 0.7, 0.9) were synthesized by chemical co-precipitation method and the samples were subsequently sintered at 900°C. The magnetic and structural properties of NiₓCa₁₋ₓFe₂O₄ were investigated using Vibrating Sample Magnetometer and X-Ray diffraction. The XRD results revealed that the synthesized particles have nanometer size and it varies from 46-72 nm as the calcium concentration diminishes. The variation is explained based on the increase in the reaction rate with Ni concentration which favors the formation of ultrafine particles of mixed ferrites. VSM results show pure CaFe₂O₄ exhibit paramagnetic behavior with low saturation value. As the concentration of Ca decreases, a transition occurs from paramagnetic state to ferromagnetic state. When the concentration of Ni becomes dominant, magnetic saturation, coercivity, and retentivity become high, indicating near ferromagnetic behavior of the compound.

Keywords: co-precipitation, ferrites, magnetic behavior, structure

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3133 A Reflection of the Contemporary Life of Urban People Through Mixed Media Art

Authors: Van Huong Mai, Kanokwan Nithiratphat, Adool Booncham

Abstract:

The Movement of Contemporary Life consisted of two purposes, which were to study the movement and development of the modern life and to create the visual arts, which were paintings expressed via the form of apartment buildings was used from mixed media (digital printing and acrylic painting on canvas) which conveyed the rapid pace of modern life leading to diverse movements in viewer’s feeling. The operation of this creation was collected field data, documentary data, and influence from creative work. The data analysis was analyzed in order to theme, form, technique, and process to satisfy of concept and special character of the pieces.

Keywords: movement, contemporary life, visual art, acrylic painting, digital art, urban space

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3132 Ameliorating Effects of Rosemary and Costus on Blood-Associated Toxicity in Ehrlich-Bearing Mice Treated with Cisplatin

Authors: Yousry El-Sayed Elbolkiny, Mohamed Labib Salem

Abstract:

Background: Rosemary (ROLE) and costus (SLRE) have been established to show antioxidant effects. Aim: This study aimed to evaluate the ameliorating effects of ROLE and SLRE on the side effects induced by cisplatin (CIS) in tumor-bearing mice. Materials and Methods: Extracts of ROLE and SLRE were examined for their phytochemical activities. To evaluate their anti-tumor effects, mice were inoculated intraperitoneally (i.p.) with 2.5x105 Ehrlich ascites carcinoma (EAC) and then treated i.p. with CIS at days 3-7 and with ROLE (dose) or SLRE (dose) at days 3-14. Mice were sacrificed on day 14 for CBC and T-cell analyses. Results: Phytochemical analysis revealed that both ROLE and SLRE showed similar antioxidant activities. Treatment of EAC-bearing mice with CIS-induced antitumor efficacy of about 90%. Treatment with CIS in combination with ROLE or SLRE did not further enhance the antitumor activity of CIS. However, co-administration of ROLE or SLRE with CIS significantly increased the antitumor efficacy of CIS. Flow cytometric analysis showed that the numbers of CD4+ and CD8+ T cells were decreased in EAC-bearing mice after treatment with CIS. Treatment with both ROLE and SLRE improved the number of these cells. Conclusion: Combinatorial treatment with rosemary and costus can enhance the antitumor activity of CIS

Keywords: CBC, cisplantin, costus, rosemary

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3131 Thermal Radiation Effect on Mixed Convection Boundary Layer Flow over a Vertical Plate with Varying Density and Volumetric Expansion Coefficient

Authors: Sadia Siddiqa, Z. Khan, M. A. Hossain

Abstract:

In this article, the effect of thermal radiation on mixed convection boundary layer flow of a viscous fluid along a highly heated vertical flat plate is considered with varying density and volumetric expansion coefficient. The density of the fluid is assumed to vary exponentially with temperature, however; volumetric expansion coefficient depends linearly on temperature. Boundary layer equations are transformed into convenient form by introducing primitive variable formulations. Solutions of transformed system of equations are obtained numerically through implicit finite difference method along with Gaussian elimination technique. Results are discussed in view of various parameters, like thermal radiation parameter, volumetric expansion parameter and density variation parameter on the wall shear stress and heat transfer rate. It is concluded from the present investigation that increase in volumetric expansion parameter decreases wall shear stress and enhances heat transfer rate.

Keywords: thermal radiation, mixed convection, variable density, variable volumetric expansion coefficient

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3130 Ruminal VFA of Beef Fed Different Protein

Authors: P. Paengkoum, S. C. Chen, S. Paengkoum

Abstract:

Six male growing Thai-indigenous beef cattle with body weight (BW) of 154±13.2 kg were randomly assigned in replicated 3×3 Latin square design, and fed with different levels of crude protein (CP) in total mixed ration (TMR) diets. CP levels in diets were 4.3%, 7.3% and 10.3% base on dry matter (DM). Ruminal ammonia nitrogen (NH3-N) and blood urea nitrogen (BUN) concentrations increased (P<0.01) with increasing CP levels. Moreover, there is a positive relationship between BUN and ruminal NH3-N. Rumen pH, total volatile fatty acid (VFA), molar proportions of acetate, propionate and butyrate were not affected by CP levels (P>0.05).

Keywords: Thai-indigenous beef cattle, crude protein, volatile fatty acid (VFA), total mixed ration (TMR) diets

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3129 The Porcine Reproductive and Respiratory Syndrome Virus Genotype 2 (PRRSV-2)-derived Oncolytic Protein Reprograms Tumor-Associated Macrophages

Authors: Farrah Putri Salmanida, Mei-Li Wu, Rika Wahyuningtyas, Wen-Bin Chung, Hso-Chi Chaung, Ko-Tung Chang

Abstract:

Within the field of immunotherapy, oncolytic virotherapy (OVT) employs dual approaches that directly eliminate tumor cells while preserving healthy ones and indirectly reprogram the tumor microenvironment (TME) to elicit antitumor responses. Within the TME, tumor associated macrophages (TAMs) manifest characteristics akin to those of anti-inflammatory M2 macrophages, thus earning the designation of M2-like TAMs. In prior research, two antigens denoted as A1 (g6Ld10T) and A3 (ORF6L5), derived from a complete sequence of ORF5 with partial sequence of ORF6 in Porcine Reproductive and Respiratory Syndrome Virus Genotype 2 (PRRSV-2), demonstrated the capacity to repolarize M2-type porcine alveolar macrophages (PAMs) into M1 phenotypes. In this study, we sought for utilizing OVT strategies by introducing A1 or A3 on TAMs to endow them with the anti-tumor traits of M1 macrophages while retaining their capacity to target cancer cells. Upon exposing human THP-1-derived M2 macrophages to a cross-species test with 2 µg/ml of either A1 or A3 for 24 hours, real time PCR revealed that A3, but not A1, treated cells exhibited upregulated gene expressions of M1 markers (CCR7, IL-1ß, CCL2, Cox2, CD80). These cells reacted to virus-derived antigen, as evidenced by increased expression of pattern-recognition receptors TLR3, TLR7, and TLR9, subsequently providing feedback in the form of type I interferon responses like IFNAR1, IFN-ß, IRF3, IRF7, OAS1, Mx1, and ISG15. Through an MTT assay, only after 15 µg/ml of A3 treatment could the cell viability decrease, with a predicted IC50 of 16.96 µg/ml. Interestingly, A3 caused dose-dependent toxicity to a rat C6 glial cancer cell line even at doses as low as 2.5 µg/ml and reached its IC50 at 9.419 µg/ml. Using Annexin V/7AAD staining and PCR test, we deduced that a significant proportion of C6 cells were undergoing the early apoptosis phase predominantly through the intrinsic apoptosis cascade involving Bcl-2 family proteins. Following this stage, we conducted a test on A3’s repolarization ability, which revealed a significant rise in M1 gene expression markers, such as TNF, CD80, and IL-1ß, in M2-like TAMs generated in vitro from murine RAW264.7 macrophages grown with conditioned medium of 4T1 breast cancer cells. This was corroborated by the results of transcriptome analysis, which revealed that the primary subset among the top 10 to top 30 significantly upregulated differentially expressed genes (DEGs) dominantly consisted of M1 macrophages profiles, including Ccl3, Ccl4, Csf3, TNF, Bcl6b, Stc1, and Dusp2. Our findings unveiled the remarkable potential of the PRRSV-derived antigen A3 to repolarize macrophages while also being capable of selectively inducing apoptosis in cancerous cells. While further in vivo study is needed for A3, it holds promise as an adjuvant by its dual effects in cancer therapy modalities.

Keywords: cancer cell apoptosis, interferon responses, macrophage repolarization, recombinant protein

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3128 Different Motor Inhibition Processes in Action Selection Stage: A Study with Spatial Stroop Paradigm

Authors: German Galvez-Garcia, Javier Albayay, Javiera Peña, Marta Lavin, George A. Michael

Abstract:

The aim of this research was to investigate whether the selection of the actions needs different inhibition processes during the response selection stage. In Experiment 1, we compared the magnitude of the Spatial Stroop effect, which occurs in response selection stage, in two motor actions (lifting vs reaching) when the participants performed both actions in the same block or in different blocks (mixed block vs. pure blocks).Within pure blocks, we obtained faster latencies when lifting actions were performed, but no differences in the magnitude of the Spatial Stroop effect were observed. Within mixed block, we obtained faster latencies as well as bigger-magnitude for Spatial Stroop effect when reaching actions were performed. We concluded that when no action selection is required (the pure blocks condition), inhibition works as a unitary system, whereas in the mixed block condition, where action selection is required, different inhibitory processes take place within a common processing stage. In Experiment 2, we investigated this common processing stage in depth by limiting participants’ available resources, requiring them to engage in a concurrent auditory task within a mixed block condition. The Spatial Stroop effect interacted with Movement as it did in Experiment 1, but it did not significantly interact with available resources (Auditory task x Spatial Stroop effect x Movement interaction). Thus, we concluded that available resources are distributed equally to both inhibition processes; this reinforces the likelihood of there being a common processing stage in which the different inhibitory processes take place.

Keywords: inhibition process, motor processes, selective inhibition, dual task

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3127 The Flexural Strength of Fiber-Reinforced Polymer Cement Mortars Using UM Resin

Authors: Min Ho Kwon, Woo Young Jung, Hyun Su Seo

Abstract:

A Polymer Cement Mortar (PCM) has been widely used as the material of repair and restoration work for concrete structure; however a PCM usually induces an environmental pollutant. Therefore, there is a need to develop PCM which is less impact to environments. Usually, UM resin is known to be harmless to the environment. Accordingly, in this paper, the properties of the PCM using UM resin were studied. The general cement mortar and UM resin was mixed in the specified ratio. A certain percentage of PVA fibers, steel fibers and mixed fibers (PVA fiber and steel fiber) were added to enhance the flexural strength. The flexural tests were performed in order to investigate the flexural strength of each PCM. Experimental results showed that the strength of proposed PCM using UM resin is improved when they are compared with general cement mortar.

Keywords: polymer cement mortar, UM resin, compressive strength, PVA fiber, steel fiber

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3126 Case Report of Left Atrial Myxoma Diagnosed by Bedside Echocardiography

Authors: Anthony S. Machi, Joseph Minardi

Abstract:

We present a case report of left atrial myxoma diagnosed by bedside transesophageal (TEE) ultrasound. Left atrial myxoma is the most common benign cardiac tumor and can obstruct blood flow and cause valvular insufficiency. Common symptoms consist of dyspnea, pulmonary edema and other features of left heart failure in addition to thrombus release in the form of tumor fragments. The availability of bedside ultrasound equipment is essential for the quick diagnosis and treatment of various emergency conditions including cardiac neoplasms. A 48-year-old Caucasian female with a four-year history of an untreated renal mass and anemia presented to the ED with two months of sharp, intermittent, bilateral flank pain radiating into the abdomen. She also reported intermittent vomiting and constipation along with generalized body aches, night sweats, and 100-pound weight loss over last year. She had a CT in 2013 showing a 3 cm left renal mass and a second CT in April 2016 showing a 3.8 cm left renal mass along with a past medical history of diverticulosis, chronic bronchitis, dyspnea on exertion, uncontrolled hypertension, and hyperlipidemia. Her maternal family history is positive for breast cancer, hypertension, and Type II Diabetes. Her paternal family history is positive for stroke. She was a current everyday smoker with an 11 pack/year history. Alcohol and drug use were denied. Physical exam was notable for a Grade II/IV systolic murmur at the right upper sternal border, dyspnea on exertion without angina, and a tender left lower quadrant. Her vitals and labs were notable for a blood pressure of 144/96, heart rate of 96 beats per minute, pulse oximetry of 96%, hemoglobin of 7.6 g/dL, hypokalemia, hypochloremia, and multiple other abnormalities. Physicians ordered a CT to evaluate her flank pain which revealed a 7.2 x 8.9 x 10.5 cm mixed cystic/solid mass in the lower pole of the left kidney and a filling defect in the left atrium. Bedside TEE was ordered to follow up on the filling defect. TEE reported an ejection fraction of 60-65% and visualized a mobile 6 x 3 cm mass in the left atrium attached to the interatrial septum extending into the mitral valve. Cardiothoracic Surgery and Urology were consulted and confirmed a diagnosis of left atrial myxoma and clear cell renal cell carcinoma. The patient returned a week later due to worsening nausea and vomiting and underwent emergent nephrectomy, lymph node dissection, and colostomy due to a necrotic colon. Her condition declined over the next four months due to lung and brain metastases, infections, and other complications until she passed away.

Keywords: bedside ultrasound, echocardiography, emergency medicine, left atrial myxoma

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3125 The impact of Breast Cancer Polymorphism on Breast Cancer

Authors: Roudabeh Vakil Monfared, Farhad Mashayekhi

Abstract:

Breast cancer is the most common malignancy type among women with about 1 million new cases each year. The immune system plays an important role in the breast cancer development. OX40L (also known as TNFSF4), a membrane protein, which is a member of the tumor necrosis factor super family binds to its receptor OX40 and this co-stimulation has a crucial role in T-cell proliferation, survival and cytokine release. Due to the importance of the T-cells in anti-tumor activities of OX40L we studied the association of rs3850641 (T→C) polymorphism of OX40L gene with breast cancer. The study included 123 women with breast cancer and 126 healthy volunteers with no signs of cancer. Genomic DNA was extracted from blood leucocytes. Genotype and allele frequencies were determined in patients and control cases with the method of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and the analysis was performed by Med Calc. The prevalence of genotype frequencies of TT, CT and CC were 60.9%, 30.08% and 8.9 % in patients with breast cancer and 74.6 %, 18.25 % and 7.14 % in healthy volunteers while the T and C allelic frequency was 76.01% and 23.98 % in patients and 83.73% and 16.26% in healthy controls. Respectively Statistical analysis has shown no significant difference from the comparison of either genotype (P=0.06). According to these results, the rs3850641 SNP has no association with the susceptibility of breast cancer in a population in northern Iran. However, further studies in larger populations including other genetic and environmental factors are required to achieve conclusion.

Keywords: OX40L, gene, polymorphism, breast cancer

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3124 Contact Phenomena in Medieval Business Texts

Authors: Carmela Perta

Abstract:

Among the studies flourished in the field of historical sociolinguistics, mainly in the strand devoted to English history, during its Medieval and early modern phases, multilingual texts had been analysed using theories and models coming from contact linguistics, thus applying synchronic models and approaches to the past. This is true also in the case of contact phenomena which would transcend the writing level involving the language systems implicated in contact processes to the point of perceiving a new variety. This is the case for medieval administrative-commercial texts in which, according to some Scholars, the degree of fusion of Anglo-Norman, Latin and middle English is so high a mixed code emerges, and there are recurrent patterns of mixed forms. Interesting is a collection of multilingual business writings by John Balmayn, an Englishman overseeing a large shipment in Tuscany, namely the Cantelowe accounts. These documents display various analogies with multilingual texts written in England in the same period; in fact, the writer seems to make use of the above-mentioned patterns, with Middle English, Latin, Anglo-Norman, and the newly added Italian. Applying an atomistic yet dynamic approach to the study of contact phenomena, we will investigate these documents, trying to explore the nature of the switching forms they contain from an intra-writer variation perspective. After analysing the accounts and the type of multilingualism in them, we will take stock of the assumed mixed code nature, comparing the characteristics found in this genre with modern assumptions. The aim is to evaluate the possibility to consider the switching forms as core elements of a mixed code, used as professional variety among merchant communities, or whether such texts should be analysed from a switching perspective.

Keywords: historical sociolinguistics, historical code switching, letters, medieval england

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3123 Malignancy in Venous Thromboembolism

Authors: Naser Shagerdi Esmaeli, Mohsen Hamidpour

Abstract:

Purposes: The activation of coagulation in patients with cancer contributes significantly to morbidity and mortality rates and may play a fundamental role in the host response to growing tumor’s. Patients with cancer are clearly at high risk for the development of venous thromboembolism (VTE), particularly during chemotherapy and surgery. This situation is aggravated by the use of venous access catheters and possibly growth factors. Methods: Data derived from large, randomized, controlled trials have been used to determine the true incidence of this complication of cancer and its treatment. The incidence based on the analyses of these randomized controlled trials varies from 1% for limited stage patients with breast cancer treated with tamoxifen to 60% for patients with any type of cancer who are subjected to orthopedic surgery and do not receive prophylactic therapy. Results: In view of the morbidity and mortality attributable to VTE in cancer, widespread utilization of prophylactic anticoagulation therapy, which has proven safe and effective in a variety of situations, should be considered. While migratory thrombophlebitis is a clear indicator of an underlying neoplasm, the risk of cancer in patients with the more typical form of VTE has been the subject of intense debate over recent years. Conclusion: Some investigators have suggested that the relative risk of being diagnosed with occult cancer within six months of an episode of VTE (particularly recurrent VTE) could be up to 10-fold. However, the cost-effectiveness of aggressive screening for cancer in patients with VTE has not yet been defined adequately.

Keywords: venous thromboembolism, malignancy, cancer, tumor, heparin

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3122 Tocilizumab Suppresses the Pro-carcinogenic Effects of Breast Cancer-associated Fibroblasts Through Inhibition of the STAT3/AUF1 Pathway

Authors: Naif Al-Jomah, Falah H Al-Mohanna, Abdelilah Aboussekhra

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Active breast cancer-associated fibroblasts (CAFs), the most influential cells in breast tumor microenvironment, express/secrete high levels of the proinvasive/metastatic interleukin-6 (IL-6). Therefore, we have tested here the effect of the IL-6 receptor (IL-6R) inhibitor tocilizumab (TCZ; Actemra) on different active breast CAFs. We have shown that TCZ potently and persistently suppresses the expression of various CAF biomarkers, namely α-SMA, SDF-1 as well as the STAT3 pathway and its downstream target AUF1. TCZ also inhibited the proliferation, migration and invasion abilities of active breast CAF cells. Additionally, TCZ repressed the ability of CAF cells in promoting epithelial-to-mesenchymal transition, and enhancing the migratory/invasive and proliferative capacities of breast cancer cells in vitro. Importantly, these findings were confirmed in orthotopic humanized breast tumors in mice. Furthermore, TCZ suppressed the expression of the pro-angiogenic factor VEGF-A and its transactivator HIF-1α in CAF cells, and consequently inhibited the angiogenic-promoting effect of active CAFs both in vitro and in orthotopic tumor xenografts. These results indicate that inhibition of the IL-6/STAT3/AUF1 pathway by TCZ can normalize active breast CAFs and suppress their paracrine pro-carcinogenic effects, which paves the way toward development of specific CAF-targeting therapy, badly needed for more efficient breast cancer treatments.

Keywords: angiogenesis, interleukin-6, paracrine, cancer-associated fibroblasts

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3121 Mixed Hydrotropic Zaleplon Oral Tablets: Formulation and Neuropharmacological Effect on Plasma GABA Level

Authors: Ghada A. Abdelbary, Maha M. Amin, Mostafa Abdelmoteleb

Abstract:

Zaleplon (ZP) is a non-benzodiazepine poorly soluble hypnotic drug indicated for the short term treatment of insomnia having a bioavailability of about 30%. The aim of the present study is to enhance the solubility and consequently the bioavailability of ZP using hydrotropic agents (HA). Phase solubility diagrams of ZP in presence of different molar concentrations of HA (Sodium benzoate, Urea, Ascorbic acid, Resorcinol, Nicotinamide, and Piperazine) were constructed. ZP/Sodium benzoate and Resorcinol microparticles were prepared adopting melt, solvent evaporation and melt-evaporation techniques followed by XRD. Directly compressed mixed hydrotropic ZP tablets of Sodium benzoate and Resorcinol in different weight ratios were prepared and evaluated compared to the commercially available tablets (Sleep aid® 5 mg). The effect of shelf and accelerated stability storage (40°C ± 2°C/75%RH ± 5%RH) on the optimum tablet formula (F5) for six months were studied. The enhancement of ZP solubility follows the order of: Resorcinol > Sodium benzoate > Ascorbic acid > Piperazine > Urea > Nicotinamide with about 350 and 2000 fold increase using 1M of Sodium benzoate and Resorcinol respectively. ZP/HA microparticles exhibit the order of: Solvent evaporation > melt-solvent evaporation > melt > physical mixture which was further confirmed by the complete conversion of ZP into amorphous form. Mixed hydrotropic tablet formula (F5) composed of ZP/(Resorcinol: Sodium benzoate 4:1w/w) microparticles prepared by solvent evaporation exhibits in-vitro dissolution of 31.7±0.11% after five minutes (Q5min) compared to 10.0±0.10% for Sleep aid® (5 mg) respectively. F5 showed significantly higher GABA concentration of 122.5±5.5mg/mL in plasma compared to 118±1.00 and 27.8±1.5 mg/mL in case of Sleep aid® (5 mg) and control taking only saline respectively suggesting a higher neuropharmacological effect of ZP following hydrotropic solubilization.

Keywords: zaleplon, hydrotropic solubilization, plasma GABA level, mixed hydrotropy

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3120 Green Materials for Hot Mixed Asphalt Production

Authors: Salisu Dahiru, Jibrin M. Kaura, Abubakar I. Jumare, Sulaiman M. Mahmood

Abstract:

Reclaimed asphalt, used automobile tires and rice husk, were regarded as waste. These materials could be used in construction of new roads and for roads rehabilitation. Investigation into the production of a Green Hot Mixed Asphalt (GHMA) pavement using Reclaimed Asphalt Pavement (RAP) as partial replacement for coarse aggregate, Crumb Rubber (CR) from waste automobile tires as modifier for bitumen binder and Rice Husk Ash (RHA) as partial replacement of ordinary portland cement (OPC) filler, for roads construction and rehabilitation was presented. 30% Reclaimed asphalt of total aggregate, 15% Crumb Rubber of total binder content, 5% Rice Husk Ash of total mix, and 5.2% Crumb Rubber Modified Bitumen content were recommended for optimum performance. Loss of marshal stability was investigated on mix with the recommended optimum CRMB. The mix revealed good performance with only about 13% loss of stability after 24 hours of immersion in hot water bath, as against about 24% marshal stability lost reported in previous studies for conventional Hot Mixed Asphalt (HMA).

Keywords: rice husk, reclaimed asphalt, filler, crumb rubber, bitumen content green hot mix asphalt

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3119 A Self-Adaptive Stimulus Artifacts Removal Approach for Electrical Stimulation Based Muscle Rehabilitation

Authors: Yinjun Tu, Qiang Fang, Glenn I. Matthews, Shuenn-Yuh Lee

Abstract:

This paper reports an efficient and rigorous self-adaptive stimulus artifacts removal approach for a mixed surface EMG (Electromyography) and stimulus signal during muscle stimulation. The recording of EMG and the stimulation of muscles were performing simultaneously. It is difficult to generate muscle fatigue feature from the mixed signal, which can be further used in closed loop system. A self-adaptive method is proposed in this paper, the stimulation frequency was calculated and verified firstly. Then, a mask was created based on this stimulation frequency to remove the undesired stimulus. 20 EMG signal recordings were analyzed, and the ANOVA (analysis of variance) approach illustrated that the decreasing trend of median power frequencies was successfully generated from the 'cleaned' EMG signal.

Keywords: EMG, FES, stimulus artefacts, self-adaptive

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3118 Introduction of Artificial Intelligence for Estimating Fractal Dimension and Its Applications in the Medical Field

Authors: Zerroug Abdelhamid, Danielle Chassoux

Abstract:

Various models are given to simulate homogeneous or heterogeneous cancerous tumors and extract in each case the boundary. The fractal dimension is then estimated by least squares method and compared to some previous methods.

Keywords: simulation, cancerous tumor, Markov fields, fractal dimension, extraction, recovering

Procedia PDF Downloads 357
3117 Photoluminescence Spectroscopy to Probe Mixed Valence State in Eu-Doped Nanocrystalline Glass-Ceramics

Authors: Ruchika Bagga, Mauro Falconieri, Venu Gopal Achanta, José M. F. Ferreira, Ashutosh Goel, Gopi Sharma

Abstract:

Mixed valence Eu-doped nanocrystalline NaAlSiO4/NaY9Si6O26 glass-ceramics have been prepared by controlled crystallization of melt quenched bulk glasses. XRD and SEM techniques were employed to characterize the crystallization process of the precursor glass and their resultant glass-ceramics. Photoluminescence spectroscopy was used to analyze the formation of divalent europium (Eu2+) from Eu3+ ions during high temperature synthesis under ambient atmosphere and is explained on the basis of optical basicity model. The observed luminescence properties of Eu: NaY9Si6O26 are compared with that of well explored Eu: β-PbF2 nanocrystals and their marked differences are discussed.

Keywords: rare earth, oxyfluoride glasses, nano-crystalline glass-ceramics, photoluminescence spectroscopy

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