Search results for: human brain microvascular endothelial cells
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 11460

Search results for: human brain microvascular endothelial cells

10590 Cytotoxic Metabolites from Tagetes minuta L. Growing in Saudi Arabia

Authors: Ali A. A. Alqarni, Gamal A. Mohamed, Hossam M. Abdallah, Sabrin R. M. Ibrahim

Abstract:

Phytochemical investigation of the methanolic extract of aerial parts of Tagetes minuta L. (Family: Asteraceae) using different chromatographic techniques led to the isolation of five compounds; ecliptal (1), scopoletin (2), P-hydroxy benzoic acid (3), patuletin (4), and patuletin-7-O-β-D-glucopyranoside (5) (Figure 1). Their structures were established based on physical, chemical, and spectral data [Ultraviolet (UV), Proton ¹H, Carbon thirteen ¹³C, and Heteronuclear Multiple Bond Correlation (HMBC) NMR], as well as Electrospray Ionization Mass Spectroscopy (ESIMS) and comparison with literature data. Their cytotoxic activity was assessed towards human liver hepatocellular carcinoma (HepG2), human breast cancer (MCF-7), and human colon cancer (HCT116) cancer cell lines using sulphorhodamine B (SRB) assay. It is noteworthy that compound 1 demonstrated a significant cytotoxic potential towards HepG2, MCF7, and HCT116 cells with IC₅₀s ranging from 2.74 to 7.01 μM, compared to doxorubicin (IC₅₀ 0.18, 0.60, and 0.20 μM, respectively), whereas compounds 2, 4, and 5 showed moderate cytotoxic potential with IC50s ranging from 11.71 to 35.64 μM. However, 3 was inactive up to a concentration of 100 μM towards the three tested cancer cell lines.

Keywords: Asteraceae, cytotoxicity, metabolites, Tagetes minuta

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10589 Effects of Gamma-Tocotrienol Supplementation on T-Regulatory Cells in Syngeneic Mouse Model of Breast Cancer

Authors: S. Subramaniam, J. S. A. Rao, P. Ramdas, K. R. Selvaduray, N. M. Han, M. K. Kutty, A. K. Radhakrishnan

Abstract:

Immune system is a complex system where the immune cells have the capability to respond against a wide range of immune challenges including cancer progression. However, in the event of cancer development, tumour cells trigger immunosuppressive environment via activation of myeloid-derived suppressor cells and T regulatory (Treg) cells. The Treg cells are subset of CD4+ T lymphocytes, known to have crucial roles in regulating immune homeostasis and promoting the establishment and maintenance of peripheral tolerance. Dysregulation of these mechanisms could lead to cancer progression and immune suppression. Recently, there are many studies reporting on the effects of natural bioactive compounds on immune responses against cancer. It was known that tocotrienol-rich-fraction consisting 70% tocotrienols and 30% α-tocopherol is able to exhibit immunomodulatory as well as anti-cancer properties. Hence, this study was designed to evaluate the effects of gamma-tocotrienol (G-T3) supplementation on T-reg cells in a syngeneic mouse model of breast cancer. In this study, female BALB/c mice were divided into two groups and fed with either soy oil (vehicle) or gamma-tocotrienol (G-T3) for two weeks followed by inoculation with tumour cells. All the mice continued to receive the same supplementation until day 49. The results showed a significant reduction in tumour volume and weight in G-T3 fed mice compared to vehicle-fed mice. Lung and liver histology showed reduced evidence of metastasis in tumour-bearing G-T3 fed mice. Besides that, flow cytometry analysis revealed T-helper cell population was increased, and T-regulatory cell population was suppressed following G-T3 supplementation. Moreover, immunohistochemistry analysis showed that there was a marked decrease in the expression of FOXP3 in the G-T3 fed tumour bearing mice. In conclusion, the G-T3 supplementation showed good prognosis towards breast cancer by enhancing the immune response in tumour-bearing mice. Therefore, gamma-T3 can be used as immunotherapy agent for the treatment of breast cancer.

Keywords: breast cancer, gamma tocotrienol, immune suppression, supplement

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10588 Early Diagnosis and Treatment of Cancer Using Synthetic Cationic Peptide

Authors: D. J. Kalita

Abstract:

Cancer is one of the prime causes of early death worldwide. Mutation of the gene involve in DNA repair and damage, like BRCA2 (Breast cancer gene two) genes, can be detected efficiently by PCR-RFLP to early breast cancer diagnosis and adopt the suitable method of treatment. Host Defense Peptide can be used as blueprint for the design and synthesis of novel anticancer drugs to avoid the side effect of conventional chemotherapy and chemo resistance. The change at nucleotide position 392 of a -› c in the cancer sample of dog mammary tumour at BRCA2 (exon 7) gene lead the creation of a new restriction site for SsiI restriction enzyme. This SNP may be a marker for detection of canine mammary tumour. Support vector machine (SVM) algorithm was used to design and predict the anticancer peptide from the mature functional peptide. MTT assay of MCF-7 cell line after 48 hours of post treatment showed an increase in the number of rounded cells when compared with untreated control cells. The ability of the synthesized peptide to induce apoptosis in MCF-7 cells was further investigated by staining the cells with the fluorescent dye Hoechst stain solution, which allows the evaluation of the nuclear morphology. Numerous cells with dense, pyknotic nuclei (the brighter fluorescence) were observed in treated but not in control MCF-7 cells when viewed using an inverted phase-contrast microscope. Thus, PCR-RFLP is one of the attractive approach for early diagnosis, and synthetic cationic peptide can be used for the treatment of canine mammary tumour.

Keywords: cancer, cationic peptide, host defense peptides, Breast cancer genes

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10587 Neural Synchronization - The Brain’s Transfer of Sensory Data

Authors: David Edgar

Abstract:

To understand how the brain’s subconscious and conscious functions, we must conquer the physics of Unity, which leads to duality’s algorithm. Where the subconscious (bottom-up) and conscious (top-down) processes function together to produce and consume intelligence, we use terms like ‘time is relative,’ but we really do understand the meaning. In the brain, there are different processes and, therefore, different observers. These different processes experience time at different rates. A sensory system such as the eyes cycles measurement around 33 milliseconds, the conscious process of the frontal lobe cycles at 300 milliseconds, and the subconscious process of the thalamus cycle at 5 milliseconds. Three different observers experience time differently. To bridge observers, the thalamus, which is the fastest of the processes, maintains a synchronous state and entangles the different components of the brain’s physical process. The entanglements form a synchronous cohesion between the brain components allowing them to share the same state and execute in the same measurement cycle. The thalamus uses the shared state to control the firing sequence of the brain’s linear subconscious process. Sharing state also allows the brain to cheat on the amount of sensory data that must be exchanged between components. Only unpredictable motion is transferred through the synchronous state because predictable motion already exists in the shared framework. The brain’s synchronous subconscious process is entirely based on energy conservation, where prediction regulates energy usage. So, the eyes every 33 milliseconds dump their sensory data into the thalamus every day. The thalamus is going to perform a motion measurement to identify the unpredictable motion in the sensory data. Here is the trick. The thalamus conducts its measurement based on the original observation time of the sensory system (33 ms), not its own process time (5 ms). This creates a data payload of synchronous motion that preserves the original sensory observation. Basically, a frozen moment in time (Flat 4D). The single moment in time can then be processed through the single state maintained by the synchronous process. Other processes, such as consciousness (300 ms), can interface with the synchronous state to generate awareness of that moment. Now, synchronous data traveling through a separate faster synchronous process creates a theoretical time tunnel where observation time is tunneled through the synchronous process and is reproduced on the other side in the original time-relativity. The synchronous process eliminates time dilation by simply removing itself from the equation so that its own process time does not alter the experience. To the original observer, the measurement appears to be instantaneous, but in the thalamus, a linear subconscious process generating sensory perception and thought production is being executed. It is all just occurring in the time available because other observation times are slower than thalamic measurement time. For life to exist in the physical universe requires a linear measurement process, it just hides by operating at a faster time relativity. What’s interesting is time dilation is not the problem; it’s the solution. Einstein said there was no universal time.

Keywords: neural synchronization, natural intelligence, 99.95% IoT data transmission savings, artificial subconscious intelligence (ASI)

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10586 Dosimetric Analysis of Intensity Modulated Radiotherapy versus 3D Conformal Radiotherapy in Adult Primary Brain Tumors: Regional Cancer Centre, India

Authors: Ravi Kiran Pothamsetty, Radha Rani Ghosh, Baby Paul Thaliath

Abstract:

Radiation therapy has undergone many advancements and evloved from 2D to 3D. Recently, with rapid pace of drug discoveries, cutting edge technology, and clinical trials has made innovative advancements in computer technology and treatment planning and upgraded to intensity modulated radiotherapy (IMRT) which delivers in homogenous dose to tumor and normal tissues. The present study was a hospital-based experience comparing two different conformal radiotherapy techniques for brain tumors. This analytical study design has been conducted at Regional Cancer Centre, India from January 2014 to January 2015. Ten patients have been selected after inclusion and exclusion criteria. All the patients were treated on Artiste Siemens Linac Accelerator. The tolerance level for maximum dose was 6.0 Gyfor lenses and 54.0 Gy for brain stem, optic chiasm and optical nerves as per RTOG criteria. Mean and standard deviation values of PTV98%, PTV 95% and PTV 2% in IMRT were 93.16±2.9, 95.01±3.4 and 103.1±1.1 respectively; for 3DCRT were 91.4±4.7, 94.17±2.6 and 102.7±0.39 respectively. PTV max dose (%) in IMRT and 3D-CRT were 104.7±0.96 and 103.9±1.0 respectively. Maximum dose to the tumor can be delivered with IMRT with acceptable toxicity limits. Variables such as expertise, location of tumor, patient condition, and TPS influence the outcome of the treatment.

Keywords: brain tumors, intensity modulated radiotherapy (IMRT), three dimensional conformal radiotherapy (3D-CRT), radiation therapy oncology group (RTOG)

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10585 sing Eye Tracking to Measure the Impact of Persuasion Principles in Phishing Emails

Authors: Laura Bishop, Isabel Jones, Linn Halvorsen, Angela Smith

Abstract:

Phishing emails are a form of social engineering where attackers deceive email users into revealing sensitive information or installing malware such as ransomware. Scammers often use persuasion techniques to influence email users to interact with malicious content. This study will use eye-tracking equipment to analyze how participants respond to and process Cialdini’s persuasion principles when utilized within phishing emails. Eye tracking provides insights into what is happening on the subconscious level of the brain that the participant may not be aware of. An experiment is conducted to track participant eye movements, whilst interacting with and then filing a series of persuasive emails delivered at random. Eye tracking metrics will be analyzed in relation to whether a malicious email has been identified as phishing (filed as ‘suspicious’) or not phishing (filed in any other folder). This will help determine the most influential persuasion techniques and those 'areas of interest' within an email that require intervention. The results will aid further research on how to reduce the effects of persuasion on human decision-making when interacting with phishing emails.

Keywords: cybersecurity, human-centric, phishing, psychology

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10584 GaAs Based Solar Cells: Growth, Fabrication, and Characterization

Authors: Hülya Kuru Mutlu, Mustafa Kulakcı, Uğur Serincan

Abstract:

The sun is one of the latest developments in renewable energy sources, which has a variety of application. Solar energy is the most preferred renewable energy sources because it can be used directly, it protects the environment and it is economic. In this work, we investigated that important parameter of GaAs-based solar cells with respect to the growth temperature. The samples were grown on (100) oriented p-GaAs substrates by solid source Veeco GEN20MC MBE system equipped with Ga, In, Al, Si, Be effusion cells and an Arsenic cracker cell. The structures of the grown samples are presented. After initial oxide desorption, Sample 1 and Sample 2 were grown at about 585°C and 535°C, respectively. From the grown structures, devices were fabricated by using the standard photolithography procedure. Current-voltage measurements were performed at room temperature (RT). It is observed that Sample 1 which was grown at 585°C has higher efficiency and fill factor compared to Sample 2. Hence, it is concluded that the growth temperature of 585°C is more suitable to grow GaAs-based solar cells considering our samples used in this study.

Keywords: molecular beam epitaxy, solar cell, current-voltage measurement, Sun

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10583 The Effect Study of Meditation Music in the Elderly

Authors: Metee Pigultong

Abstract:

The research aims at 1) composition of meditation music, 2) study of the meditation time reliability. The population is the older adults who meditated practitioners in the Thepnimitra Temple, Don Mueang District, Bangkok. The sample group was the older persons who meditated practitioners from the age of 60 with five volunteers. The research methodology was time-series to conduct the research progression. The research instruments included: 1) meditation music, 2) brain wave recording form. The research results found that 1) the music combines the binaural beats suitable for the meditation of the older persons, consisting of the following features: a) The tempo rate of the meditation music is no more than 60 beats per minute. b) The musical instruments for the meditation music arrangement include only 4-5 pieces. c) The meditation music arrangement needs to consider the nature of the right instrument. d) Digital music instruments are suitable for composition. e) The pure-tone sound combined in music must generate a brain frequency at the level of 10 Hz. 2) After the researcher conducted a 3-weeks brain training procedure, the researcher performed three tests for the reliability level using Cronbach's Alpha method. The result showed that the meditation reliability had the level = .475 as a moderate concentration.

Keywords: binaural beats, music therapy, meditation, older person, the Buddhist meditated practitioners

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10582 IoT Based Approach to Healthcare System for a Quadriplegic Patient Using EEG

Authors: R. Gautam, P. Sastha Kanagasabai, G. N. Rathna

Abstract:

The proposed healthcare system enables quadriplegic patients, people with severe motor disabilities to send commands to electronic devices and monitor their vitals. The growth of Brain-Computer-Interface (BCI) has led to rapid development in 'assistive systems' for the disabled called 'assistive domotics'. Brain-Computer-Interface is capable of reading the brainwaves of an individual and analyse it to obtain some meaningful data. This processed data can be used to assist people having speech disorders and sometimes people with limited locomotion to communicate. In this Project, Emotiv EPOC Headset is used to obtain the electroencephalogram (EEG). The obtained data is processed to communicate pre-defined commands over the internet to the desired mobile phone user. Other Vital Information like the heartbeat, blood pressure, ECG and body temperature are monitored and uploaded to the server. Data analytics enables physicians to scan databases for a specific illness. The Data is processed in Intel Edison, system on chip (SoC). Patient metrics are displayed via Intel IoT Analytics cloud service.

Keywords: brain computer interface, Intel Edison, Emotiv EPOC, IoT analytics, electroencephalogram

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10581 Whole Body Cooling Hypothermia Treatment Modelling Using a Finite Element Thermoregulation Model

Authors: Ana Beatriz C. G. Silva, Luiz Carlos Wrobel, Fernando Luiz B. Ribeiro

Abstract:

This paper presents a thermoregulation model using the finite element method to perform numerical analyses of brain cooling procedures as a contribution to the investigation on the use of therapeutic hypothermia after ischemia in adults. The use of computational methods can aid clinicians to observe body temperature using different cooling methods without the need of invasive techniques, and can thus be a valuable tool to assist clinical trials simulating different cooling options that can be used for treatment. In this work, we developed a FEM package applied to the solution of the continuum bioheat Pennes equation. Blood temperature changes were considered using a blood pool approach and a lumped analysis for intravascular catheter method of blood cooling. Some analyses are performed using a three-dimensional mesh based on a complex geometry obtained from computed tomography medical images, considering a cooling blanket and a intravascular catheter. A comparison is made between the results obtained and the effects of each case in brain temperature reduction in a required time, maintenance of body temperature at moderate hypothermia levels and gradual rewarming.

Keywords: brain cooling, finite element method, hypothermia treatment, thermoregulation

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10580 Plasmablastic Lymphoma a New Entity in Patients with HIV Infections

Authors: Rojith K. Balakrishnan

Abstract:

Plasmablastic lymphoma (PBL) is an uncommon, recently described B-cell derived lymphoma that is most commonly seen in patients with Human Immunodeficiency Virus (HIV) infection. Here we report a case of PBL in a 35 year old man with HIV who presented with multiple subcutaneous swellings all over the body and oral mucosal lesions.The biopsy report was suggestive of Diffuse Large B Cell Lymphoma. Immunohistochemistry was done which showed, lymphoma cells, positive for MUM1, CD 138, and VS 38. The proliferation index (MIB) was 95%. Final report was consistent with the diagnosis of Plasmablastic Lymphoma. The lesion completely regressed after treatment with systemic chemotherapy. Up to date, only a few cases of plasmablastic lymphoma have been reported from India. Increased frequency of this lymphoma in HIV patients and rarity of the tumour, along with rapid response of the same to chemotherapy, make this case a unique one. Hence the knowledge about this new entity is important for clinicians who deal with HIV patients.

Keywords: human immunodeficiency virus (HIV), oral cavity lesion, plasmablastic lymphoma, subcutaneous swelling

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10579 Attenuation of Amyloid beta (Aβ) (1-42)-Induced Neurotoxicity by Luteolin

Authors: Dona Pamoda W. Jayatunga, Veer Bala Gupta, Eugene Hone, Ralph N. Martins

Abstract:

Being a neurodegenerative disorder, Alzheimer’s disease (AD) affects a majority of the elderly demented worldwide. The key risk factors for AD are age, metabolic syndrome, allele status of APOE gene, head injuries and lifestyle. The progressive nature of AD is characterized by symptoms of multiple cognitive deficits exacerbated over time, leading to death within a decade from clinical diagnosis. However, it is revealed that AD originates via a prodromal phase that spans from one to few decades before symptoms first manifest. The key pathological hallmarks of AD brains are deposition of amyloid beta (Aβ) plaques and neurofibrillary tangles (NFT). However, the yet unknown etiology of the disease fails to distinguish mitochondrial dysfunction between a cause or an outcome. The absence of early diagnosis tools and definite therapies for AD have permitted recruits of nutraceutical-based approaches aimed at reducing the risk of AD by modulating lifestyle or be used as preventive tools during AD prodromal state before widespread neurodegeneration begins. The objective of the present study was to investigate beneficial effects of luteolin, a plant-based flavone compound, against AD. The neuroprotective effects of luteolin on amyloid beta (Aβ) (1-42)-induced neurotoxicity was measured using cultured human neuroblastoma BE(2)-M17 cells. After exposure to 20μM Aβ (1-42) for 48 h, the neuroblastoma cells exhibited marked apoptotic death. Co-treatment of 20μM Aβ (1-42) with luteolin (0.5-5μM) significantly protected the cells against Aβ (1-42)-induced toxicity, as assessed by the MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2(4sulfophenyl)-2H-tetrazolium, inner salt; MTS] reduction assay and the lactate dehydrogenase (LDH) cell death assay. The results suggest that luteolin prevents Aβ (1-42)-induced apoptotic neuronal death. However, further studies are underway to determine its protective mechanisms in AD including the activity against tau hyperphosphorylation and mitochondrial dysfunction.

Keywords: Aβ (1-42)-induced toxicity, Alzheimer’s disease, luteolin, neuroblastoma cells

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10578 The MicroRNA-2110 Suppressed Cell Proliferation and Migration Capacity in Hepatocellular Carcinoma Cells

Authors: Pelin Balcik Ercin

Abstract:

Introduction: ZEB transcription factor family member ZEB2, has a role in epithelial to mesenchymal transition during development and metastasis. The altered circulating extracellular miRNAs expression is observed in diseases, and extracellular miRNAs have an important role in cancer cell microenvironment. In ChIP-Seq study, the expression of miR-2110 was found to be regulated by ZEB2. In this study, the effects of miR2110 on cell proliferation and migration of hepatocellular carcinoma (HCC) cells were examined. Material and Methods: SNU398 cells transfected with mimic miR2110 (20nM) (HMI0375, Sigma-Aldrich) and negative control miR (HMC0002, Sigma-Aldrich). MicroRNA isolation was accomplished with miRVANA isolation kit according to manufacturer instructions. cDNA synthesis was performed expression, respectively, and calibrated with Ct of controls. The real-time quantitative PCR (RT-qPCR) reaction was performed using the TaqMan Fast Advanced Master Mix (Thermo Sci.). Ct values of miR2110 were normalized to miR-186-5p and miR16-5p for the intracellular gene. Cell proliferation analysis was analyzed with the xCELLigence RTCA System. Wound healing assay was analyzed with the ImageJ program and relative fold change calculated. Results: The mimic-miR-2110 transfected SNU398 cells nearly nine-fold (log2) more miR-2110 expressed compared to negative control transfected cells. The mimic-miR-2110 transfected HCC cell proliferation significantly inhibited compared to the negative control cells. Furthermore, miR-2110-SNU398 cell migration capacity was relatively four-fold decreased compared to negative control-miR-SNU398 cells. Conclusion: Our results suggest the miR-2110 inhibited cell proliferation and also miR-2110 negatively affect cell migration compared to control groups in HCC cells. These data suggest the complexity of microRNA EMT transcription factors regulation. These initial results are pointed out the predictive biomarker capacity of miR-2110 in HCC.

Keywords: epithelial to mesenchymal transition, EMT, hepatocellular carcinoma cells, micro-RNA-2110, ZEB2

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10577 Development of Electroencephalograph Collection System in Language-Learning Self-Study System That Can Detect Learning State of the Learner

Authors: Katsuyuki Umezawa, Makoto Nakazawa, Manabu Kobayashi, Yutaka Ishii, Michiko Nakano, Shigeichi Hirasawa

Abstract:

This research aims to develop a self-study system equipped with an artificial teacher who gives advice to students by detecting the learners and to evaluate language learning in a unified framework. 'Detecting the learners' means that the system understands the learners' learning conditions, such as each learner’s degree of understanding, the difference in each learner’s thinking process, the degree of concentration or boredom in learning, and problem solving for each learner, which can be interpreted from learning behavior. In this paper, we propose a system to efficiently collect brain waves from learners by focusing on only the brain waves among the biological information for 'detecting the learners'. The conventional Electroencephalograph (EEG) measurement method during learning using a simple EEG has the following disadvantages. (1) The start and end of EEG measurement must be done manually by the experiment participant or staff. (2) Even when the EEG signal is weak, it may not be noticed, and the data may not be obtained. (3) Since the acquired EEG data is stored in each PC, there is a possibility that the time of data acquisition will be different in each PC. This time, we developed a system to collect brain wave data on the server side. This system overcame the above disadvantages.

Keywords: artificial teacher, e-learning, self-study system, simple EEG

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10576 Landfill Leachate: A Promising Substrate for Microbial Fuel Cells

Authors: Jayesh M. Sonawane, Prakash C. Ghosh

Abstract:

Landfill leachate emerges as a promising feedstock for microbial fuel cells (MFCs). In the present investigation, direct air-breathing cathode-based MFCs are fabricated to investigate the potential of landfill leachate. Three MFCs that have different cathode areas are fabricated and investigated for 17 days under open circuit conditions. The maximum open circuit voltage (OCV) is observed to be as high as 1.29 V. The maximum cathode area specific power density achieved in the reactor is 1513 mW m-2. Further studies are under progress to understand the origin of high OCV obtained from landfill leachate-based MFCs.

Keywords: microbial fuel cells, landfill leachate, air-breathing cathode, performance study

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10575 Sensitivity Studies for a Pin Homojunction a-Si:H Solar Cell

Authors: Leila Ayat, Afak Meftah

Abstract:

Amorphous-silicon alloys have great promise as low cost solar cell materials. They have excellent photo-conductivity and high optical absorption to sunlight. Now PIN a-Si:H based solar cells are widely used in power generation modules. However, to improve the performance of these cells further, a better fundamental under-standing of the factors limiting cell performance in the homo junction PIN structure is necessary. In this paper we discuss the sensitivity of light J-V characteristics to various device and material parameters in PIN homo junction solar cells. This work is a numerical simulation of the output parameters of a PIN a-Si:H solar cell under AM1.5 spectrum. These parameters are the short circuit current (Jsc), the open circuit voltage (Voc), the fill factor (FF), the conversion efficiency. The simulation was performed with SCAPS-1D software version 3.3 developed at ELIS in Belgium by Marc Burgelman et al. The obtained results are in agreement with experiment. In addition, the effect of the thickness, doping density, capture cross sections of the gap states and the band microscopic mobilities on the output parameters of the cell are also presented.

Keywords: amorphous silicon p-i-n junctions, thin film, solar cells, sensitivity

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10574 Inhibitory Effect of P2Y1R Agonist 1-Indolinoalkyl 2-Phenolic Derivative on Prostate Cancer Cell Proliferation via the MAPK Signalling

Authors: Hien Thi Thu Le, Nuno Rafael Candeias, Olli Yli-Harja, Meenakshisundaram Kandhavelu

Abstract:

Purinergic receptor 1 (P2Y1R) is the potential therapeutic target for inducing prostate cancer (PCa) cell death. Recently, 1-indolinoalkyl 2-phenolic derivative, HIC, was identified as a P2Y1R agonist that increases apoptosis and inhibits cell proliferation of PCa. However, the biological effects of HIC have not been extensively studied at the molecular level. In the present study, we have investigated the anticancer effects of HIC and the molecular mechanisms underlying in PCa cells. Half maximal inhibitory concentration (IC₅₀) of HIC was measured as 15.98 μM and 15.64 μM for DU145 and PC3 cells, respectively. In addition, we found that HIC inhibited cell growth and metastasis of PC3 and DU145 cells colonies, spheroid areas, and migrated cells. RNA seq analysis revealed significant changes of over 3000 genes (p value < 0.05) upon HIC treatment in PC3 and DU145 cells. Genes involved in DNA damage, apoptosis, cell cycle arrest at G1/S phase were modulated by HIC treatment. MAPK and NF-κB protein array revealed the increased expression of ERK1/2, JNK1/2, p53 phosphorylation, and p53 protein. ERK1/2 and JNK1/2 activations are known to increase the stabilization of p53, a tumor suppressor protein, which is required to arrest the cell cycle at G1/S phase and cause cell death of PCa cells. Overall, our results suggest that HIC can serve as a multi-dimensional chemotherapeutic agent possessing strong cytotoxic, anti-cancer, and anti-metastasis against PCa growth.

Keywords: prostate cancer, P2Y1 receptor, apoptosis, metastasis

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10573 Effect of Papaverine on Neurospheres

Authors: Noura Shehab-Eldeen, Mohamed Elsherbeeny, Hossam Elmetwally, Mohamed Salama, Ahmed Lotfy, Mohamed Elgamal, Hussein Sheashaa, Mohamed Sobh

Abstract:

Mitochondrial toxins including papaverine may be implicated in the etiology and pathogenesis of Parkinson's disease. The aim was to detect the effect of papaverine on the proliferation and viability of neural stem cells. Rat neural progenitor cells were isolated from embryos (E14) brains. The dispersed tissues were allowed to settle, then, The supernatant was centrifuged at 1,000 g for 5 min. The pellet was placed in Hank’s solution cultured as free-floating neurospheres Dulbecco’s modified Eagle medium (DMEM) and Hams F12 (3:1) supplemented with B27 (Invitrogen GmBH, Karlsruhe, Germany), 20 ng/mL epidermal growth factor (EGF; Biosource, Karlsruhe, Germany), 20 ng/mL recombinant human fibroblast growth factor (rhFGF; R&D Systems, Wiesbaden-Nordenstadt, Germany), and penicillin and streptomycin (1:100; Invitrogen) at 37°C with 7.5% CO2 . Differentiation was initiated by growth factor withdrawal and plating onto a poly-d-lysine/ laminin matrix. The neurospheres were fed every 2-3 days by replacing 50% of the culture media with fresh media. The culture suspension was transferred to a dish containing 16 wells. The wells were divided as follows: 4 wells received no papaverine (control), 4 wells 1 u, 4 wells 5 u and 4 wells 10 u of papaverine solution. In the next 2 weeks, photography (0,4,5,11days) and viability test were done. The photographs were analysed. Results : papaverine didn't affect proliferation of neurospheres, while it affected viability compared to control , this was dose related. Conclusion: This indicates the harmful effect of papaverine suggesting it to be a candidate neurotoxin causing Parkinsonism.

Keywords: neurospheres, neural stem cells, papaverine, Parkinsonism

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10572 Taraxacum Officinale (Dandelion) and Its Phytochemical Approach to Malignant Diseases

Authors: Angel Champion

Abstract:

Chemotherapy and radiation use an acidified approach to induce apoptosis, which only kills mature cancer cells while resulting in gene and cell damage with significant levels of toxicity in tumor-affected tissues and organs. The acid approach, where the cells exterminated are not differentiated, induces the disappearance of white blood cells from the blood. This increases susceptibility to infection in severe forms of cancer spread. However, chemotherapy and radiation cannot kill cancer stem cells that metastasize, being the leading cause of 98% of cancer fatalities. With over 12 million new cancer cases symptomatic each year, including common malignancies such as Hepatocellular Carcinoma (HCC), this study aims to assess the bioactive constituents and phytochemical composition of Taraxacum Officinale (Dandelion). This analysis enables pharmaceutical quality and potency to be applied to studies on cancer cell proliferation and apoptosis. A phytochemical screening is carried out to identify the antioxidant components of Dandelion root, stem, and flower extract. The constituents tested for are phlorotannins, carbohydrates, glycosides, saponins, flavonoids, alkaloids, sterols, triterpenes, and anthraquinone glycosides. To conserve the existing phenolic compounds, a portion of the constituent tests will be examined with an acid, alcohol, or aqueous solvent. As a result, the qualitative and quantitative variations within the Dandelion extract that measure uniform effective potency are vital to the conformity for producing medicinal products. These medicines will be constructed with a consistent, uniform composition that physicians can use to control and effectively eradicate malignant diseases safely. Taraxacum Officinale's phytochemical composition comprises a highly-graded potency due to present bioactive contents that will essentially drive out malignant disease within the human body. Its high potency rate is powerful enough to eliminate both mature cancer cells and cancer stem cells without the cell and gene damage induced by chemotherapy and radiation. Correspondingly, the high margins of cancer mortality on a global scale are mitigated. This remarkable contribution to modern therapeutics will essentially optimize the margins of natural products and their derivatives, which account for 50% of pharmaceuticals in modern therapeutics, while preventing the adverse effects of radiation and chemotherapy drugs.

Keywords: antioxidant, apoptosis, metastasize, phytochemical, proliferation, potency

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10571 Defining New Limits in Hybrid Perovskites: Single-Crystal Solar Cells with Exceptional Electron Diffusion Length Reaching Half Millimeters

Authors: Bekir Turedi

Abstract:

Exploiting the potential of perovskite single-crystal solar cells in optoelectronic applications necessitates overcoming a significant challenge: the low charge collection efficiency at increased thickness, which has restricted their deployment in radiation detectors and nuclear batteries. Our research details a promising approach to this problem, wherein we have successfully fabricated single-crystal MAPbI3 solar cells employing a space-limited inverse temperature crystallization (ITC) methodology. Remarkably, these cells, up to 400-fold thicker than current-generation perovskite polycrystalline films, maintain a high charge collection efficiency even without external bias. The crux of this achievement lies in the long electron diffusion length within these cells, estimated to be around 0.45 mm. This extended diffusion length ensures the conservation of high charge collection and power conversion efficiencies, even as the thickness of the cells increases. Fabricated cells at 110, 214, and 290 µm thickness manifested power conversion efficiencies (PCEs) of 20.0, 18.4, and 14.7% respectively. The single crystals demonstrated nearly optimal charge collection, even when their thickness exceeded 200 µm. Devices of thickness 108, 214, and 290 µm maintained 98.6, 94.3, and 80.4% of charge collection efficiency relative to their maximum theoretical short-circuit current value, respectively. Additionally, we have proposed an innovative, self-consistent technique for ascertaining the electron-diffusion length in perovskite single crystals under operational conditions. The computed electron-diffusion length approximated 446 µm, significantly surpassing previously reported values for this material. In conclusion, our findings underscore the feasibility of fabricating halide perovskite single-crystal solar cells of hundreds of micrometers in thickness while preserving high charge extraction efficiency and PCE. This advancement paves the way for developing perovskite-based optoelectronics necessitating thicker active layers, such as X-ray detectors and nuclear batteries.

Keywords: perovskite, solar cell, single crystal, diffusion length

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10570 Mycophenolate Mofetil Increases Mucin Expression in Primary Cultures of Oral Mucosal Epithelial Cells for Application in Limbal Stem Cell Deficiency

Authors: Sandeep Kumar Agrawal, Aditi Bhattacharya, Janvie Manhas, Krushna Bhatt, Yatin Kholakiya, Nupur Khera, Ajoy Roychoudhury, Sudip Sen

Abstract:

Autologous cultured explants of human oral mucosal epithelial cells (OMEC) are a potential therapeutic modality for limbal stem cell deficiency (LSCD). Injury or inflammation of the ocular surface in the form of burns, chemicals, Stevens Johnson syndrome, ocular cicatricial pemphigoid etc. can lead to destruction and deficiency of limbal stem cells. LSCD manifests in the form of severe ocular surface diseases (OSD) characterized by persistent and recurrent epithelial defects, conjuntivalisation and neovascularisation of the corneal surface, scarring and ultimately opacity and blindness. Most of the cases of OSD are associated with severe dry eye pertaining to diminished mucin and aqueous secretion. Mycophenolate mofetil (MMF) has been shown to upregulate the mucin expression in conjunctival goblet cells in vitro. The aim of this study was to evaluate the effects of MMF on mucin expression in primary cultures of oral mucosal epithelial cells. With institutional ethics committee approval and written informed consent, thirty oral mucosal epithelial tissue samples were obtained from patients undergoing oral surgery for non-malignant conditions. OMEC were grown on human amniotic membrane (HAM, obtained from expecting mothers undergoing elective caesarean section) scaffold for 2 weeks in growth media containing DMEM & Ham’s F12 (1:1) with 10% FBS and growth factors. In vitro dosage of MMF was standardised by MTT assay. Analysis of stem cell markers was done using RT-PCR while mucin mRNA expression was quantified using RT-PCR and q-PCR before and after treating cultured OMEC with graded concentrations of MMF for 24 hours. Protein expression was validated using immunocytochemistry. Morphological studies revealed a confluent sheet of proliferating, stratified oral mucosal epithelial cells growing over the surface of HAM scaffold. The presence of progenitor stem cell markers (p63, p75, β1-Integrin and ABCG2) and cell surface associated mucins (MUC1, MUC15 and MUC16) were elucidated by RT-PCR. The mucin mRNA expression was found to be upregulated in MMF treated primary cultures of OMEC, compared to untreated controls as quantified by q-PCR with β-actin as internal reference gene. Increased MUC1 protein expression was validated by immunocytochemistry on representative samples. Our findings conclude that OMEC have the ability to form a multi-layered confluent sheet on the surface of HAM similar to a cornea, which is important for the reconstruction of the damaged ocular surface. Cultured OMEC has stem cell properties as demonstrated by stem cell markers. MMF can be a novel enhancer of mucin production in OMEC. It has the potential to improve dry eye in patients undergoing OMEC transplantation for bilateral OSD. Further clinical trials are required to establish the role of MMF in patients undergoing OMEC transplantation.

Keywords: limbal stem cell deficiency, mycophenolate mofetil, mucin, ocular surface disease

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10569 Insight2OSC: Using Electroencephalography (EEG) Rhythms from the Emotiv Insight for Musical Composition via Open Sound Control (OSC)

Authors: Constanza Levicán, Andrés Aparicio, Rodrigo F. Cádiz

Abstract:

The artistic usage of Brain-computer interfaces (BCI), initially intended for medical purposes, has increased in the past few years as they become more affordable and available for the general population. One interesting question that arises from this practice is whether it is possible to compose or perform music by using only the brain as a musical instrument. In order to approach this question, we propose a BCI for musical composition, based on the representation of some mental states as the musician thinks about sounds. We developed software, called Insight2OSC, that allows the usage of the Emotiv Insight device as a musical instrument, by sending the EEG data to audio processing software such as MaxMSP through the OSC protocol. We provide two compositional applications bundled with the software, which we call Mapping your Mental State and Thinking On. The signals produced by the brain have different frequencies (or rhythms) depending on the level of activity, and they are classified as one of the following waves: delta (0.5-4 Hz), theta (4-8 Hz), alpha (8-13 Hz), beta (13-30 Hz), gamma (30-50 Hz). These rhythms have been found to be related to some recognizable mental states. For example, the delta rhythm is predominant in a deep sleep, while beta and gamma rhythms have higher amplitudes when the person is awake and very concentrated. Our first application (Mapping your Mental State) produces different sounds representing the mental state of the person: focused, active, relaxed or in a state similar to a deep sleep by the selection of the dominants rhythms provided by the EEG device. The second application relies on the physiology of the brain, which is divided into several lobes: frontal, temporal, parietal and occipital. The frontal lobe is related to abstract thinking and high-level functions, the parietal lobe conveys the stimulus of the body senses, the occipital lobe contains the primary visual cortex and processes visual stimulus, the temporal lobe processes auditory information and it is important for memory tasks. In consequence, our second application (Thinking On) processes the audio output depending on the users’ brain activity as it activates a specific area of the brain that can be measured using the Insight device.

Keywords: BCI, music composition, emotiv insight, OSC

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10568 Brain-Computer Interfaces That Use Electroencephalography

Authors: Arda Ozkurt, Ozlem Bozkurt

Abstract:

Brain-computer interfaces (BCIs) are devices that output commands by interpreting the data collected from the brain. Electroencephalography (EEG) is a non-invasive method to measure the brain's electrical activity. Since it was invented by Hans Berger in 1929, it has led to many neurological discoveries and has become one of the essential components of non-invasive measuring methods. Despite the fact that it has a low spatial resolution -meaning it is able to detect when a group of neurons fires at the same time-, it is a non-invasive method, making it easy to use without possessing any risks. In EEG, electrodes are placed on the scalp, and the voltage difference between a minimum of two electrodes is recorded, which is then used to accomplish the intended task. The recordings of EEGs include, but are not limited to, the currents along dendrites from synapses to the soma, the action potentials along the axons connecting neurons, and the currents through the synaptic clefts connecting axons with dendrites. However, there are some sources of noise that may affect the reliability of the EEG signals as it is a non-invasive method. For instance, the noise from the EEG equipment, the leads, and the signals coming from the subject -such as the activity of the heart or muscle movements- affect the signals detected by the electrodes of the EEG. However, new techniques have been developed to differentiate between those signals and the intended ones. Furthermore, an EEG device is not enough to analyze the data from the brain to be used by the BCI implication. Because the EEG signal is very complex, to analyze it, artificial intelligence algorithms are required. These algorithms convert complex data into meaningful and useful information for neuroscientists to use the data to design BCI devices. Even though for neurological diseases which require highly precise data, invasive BCIs are needed; non-invasive BCIs - such as EEGs - are used in many cases to help disabled people's lives or even to ease people's lives by helping them with basic tasks. For example, EEG is used to detect before a seizure occurs in epilepsy patients, which can then prevent the seizure with the help of a BCI device. Overall, EEG is a commonly used non-invasive BCI technique that has helped develop BCIs and will continue to be used to detect data to ease people's lives as more BCI techniques will be developed in the future.

Keywords: BCI, EEG, non-invasive, spatial resolution

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10567 The Effect of Human Relation on Employee Performance at Faculty of Economics of Syiah Kuala University

Authors: Yurnalis Usman

Abstract:

In an organization, institution or enterprise, human resource is very important aspect since many human skills cannot be replaced by technology tools even though technology has advanced rapidly now. The relationship among people is very necessary to create a subordinate and leader relation in the assumption that human beings are creatures who have feeling, desires, needs, aspirations and ideas differing from one another. This study on human relation was conducted at the Faculty of Economics of UNSYIAH, Darussalam, Banda Aceh, while the research object is associated with human relations and employee performance in Faculty of Economics of UNSYIAH. To determine the extent of employee relations in Faculty of Economics with fellow employees or superiors, the employees are given some questions. The result shows that human relations influence the employee performance at Faculty of Economics UNSYIAH strongly.

Keywords: human relation, employee performance, communication, Syiah Kuala

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10566 Field Prognostic Factors on Discharge Prediction of Traumatic Brain Injuries

Authors: Mohammad Javad Behzadnia, Amir Bahador Boroumand

Abstract:

Introduction: Limited facility situations require allocating the most available resources for most casualties. Accordingly, Traumatic Brain Injury (TBI) is the one that may need to transport the patient as soon as possible. In a mass casualty event, deciding when the facilities are restricted is hard. The Extended Glasgow Outcome Score (GOSE) has been introduced to assess the global outcome after brain injuries. Therefore, we aimed to evaluate the prognostic factors associated with GOSE. Materials and Methods: In a multicenter cross-sectional study conducted on 144 patients with TBI admitted to trauma emergency centers. All the patients with isolated TBI who were mentally and physically healthy before the trauma entered the study. The patient’s information was evaluated, including demographic characteristics, duration of hospital stays, mechanical ventilation on admission laboratory measurements, and on-admission vital signs. We recorded the patients’ TBI-related symptoms and brain computed tomography (CT) scan findings. Results: GOSE assessments showed an increasing trend by the comparison of on-discharge (7.47 ± 1.30), within a month (7.51 ± 1.30), and within three months (7.58 ± 1.21) evaluations (P < 0.001). On discharge, GOSE was positively correlated with Glasgow Coma Scale (GCS) (r = 0.729, P < 0.001) and motor GCS (r = 0.812, P < 0.001), and inversely with age (r = −0.261, P = 0.002), hospitalization period (r = −0.678, P < 0.001), pulse rate (r = −0.256, P = 0.002) and white blood cell (WBC). Among imaging signs and trauma-related symptoms in univariate analysis, intracranial hemorrhage (ICH), interventricular hemorrhage (IVH) (P = 0.006), subarachnoid hemorrhage (SAH) (P = 0.06; marginally at P < 0.1), subdural hemorrhage (SDH) (P = 0.032), and epidural hemorrhage (EDH) (P = 0.037) were significantly associated with GOSE at discharge in multivariable analysis. Conclusion: Our study showed some predictive factors that could help to decide which casualty should transport earlier to a trauma center. According to the current study findings, GCS, pulse rate, WBC, and among imaging signs and trauma-related symptoms, ICH, IVH, SAH, SDH, and EDH are significant independent predictors of GOSE at discharge in TBI patients.

Keywords: field, Glasgow outcome score, prediction, traumatic brain injury.

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10565 Therapeutic Potential of GSTM2-2 C-Terminal Domain and Its Mutants, F157A and Y160A on the Treatment of Cardiac Arrhythmias: Effect on Ca2+ Transients in Neonatal Ventricular Cardiomyocytes

Authors: R. P. Hewawasam, A. F. Dulhunty

Abstract:

The ryanodine receptor (RyR) is an intracellular ion channel that releases Ca2+ from the sarcoplasmic reticulum and is essential for the excitation-contraction coupling and contraction in striated muscle. Human muscle specific glutathione transferase M2-2 (GSTM2-2) is a highly specific inhibitor of cardiac ryanodine receptor (RyR2) activity. Single channel-lipid bilayer studies and Ca2+ release assays performed using the C-terminal half of the GSTM2-2 and its mutants F157A and Y160A confirmed the ability of the C terminal domain of GSTM2-2 to specifically inhibit the cardiac ryanodine receptor activity. Objective of the present study is to determine the effect of C terminal domain of GSTM2-2 (GSTM2-2C) and the mutants, F157A and Y160A on the Ca2+ transients of neonatal ventricular cardiomyocytes. Primary cardiomyocytes were cultured from neonatal rats. They were treated with GSTM2-2C and the two mutants F157A and Y160A at 15µM and incubated for 2 hours. Then the cells were led with Fluo-4AM, fluorescent Ca2+ indicator, and the field stimulated (1 Hz, 3V and 2ms) cells were excited using the 488 nm argon laser. Contractility of the cells were measured and the Ca2+ transients in the stained cells were imaged using Leica SP5 confocal microscope. Peak amplitude of the Ca2+ transient, rise time and decay time from the peak were measured for each transient. In contrast to GSTM2C which significantly reduced the % shortening (42.8%) in the field stimulated cells, F157A and Y160A failed to reduce the % shortening.Analysis revealed that the average amplitude of the Ca2+ transient was significantly reduced (P<0.001) in cells treated with the wild type GSTM2-2C compared to that of untreated cells. Cells treated with the mutants F157A and Y160A didn’t change the Ca2+ transient significantly compared to the control. A significant increase in the rise time (P< 0.001) and a significant reduction in the decay time (P< 0.001) were observed in cardiomyocytes treated with GSTM2-2C compared to the control but not with F157A and Y160A. These results are consistent with the observation that GSTM2-2C reduced the Ca2+ release from the cardiac SR significantly whereas the mutants, F157A and Y160A didn’t show any effect compared to the control. GSTM2-2C has an isoform-specific effect on the cardiac ryanodine receptor activity and also it inhibits RyR2 channel activity only during diastole. Selective inhibition of RyR2 by GSTM2-2C has significant clinical potential in the treatment of cardiac arrhythmias and heart failure. Since GSTM2-2C-terminal construct has no GST enzyme activity, its introduction to the cardiomyocyte would not exert any unwanted side effects that may alter its enzymatic action. The present study further confirms that GSTM2-2C is capable of decreasing the Ca2+ release from the cardiac SR during diastole. These results raise the future possibility of using GSTM2-2C as a template for therapeutics that can depress RyR2 function when the channel is hyperactive in cardiac arrhythmias and heart failure.

Keywords: arrhythmia, cardiac muscle, cardiac ryanodine receptor, GSTM2-2

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10564 Specific Colon Cancer Prophylaxis Using Dendritic Stem Cells and Gold Nanoparticles Functionalized with Colon Cancer Epitopes

Authors: Teodora Mocan, Matea Cristian, Cornel Iancu, Flaviu A. Tabaran, Florin Zaharie, Bartos Dana, Lucian Mocan

Abstract:

Colon cancer (CC) a lethal human malignancy, is one of the most commonly diagnosed cancer. With its high increased mortality rate, as well as low survival rate combined with high resistance to chemotherapy CC, represents one of the most important global health issues. In the presented research, we have developed a distinct nanostructured colon carcinoma vaccine model based on a nano-biosystem composed of 39 nm gold nanoparticles conjugated to colon cancer epitopes. We prove by means of proteomic analysis, immunocytochemistry, flow cytometry and hyperspectral microscopy that our developed nanobioconjugate was able to contribute to an optimal prophylactic effect against CC by promoting major histocompatibility complex mediated (MHC) antigen presentation by dendritic cells. We may conclude that the proposed immunoprophylactic approach could be more effective than the current treatments of CC because it promotes recognition of the tumoral antigens by the immune system.

Keywords: anticancer vaccine, colon cancer, gold nanoparticles, tumor antigen

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10563 All Types of Base Pair Substitutions Induced by γ-Rays in Haploid and Diploid Yeast Cells

Authors: Natalia Koltovaya, Nadezhda Zhuchkina, Ksenia Lyubimova

Abstract:

We study the biological effects induced by ionizing radiation in view of therapeutic exposure and the idea of space flights beyond Earth's magnetosphere. In particular, we examine the differences between base pair substitution induction by ionizing radiation in model haploid and diploid yeast Saccharomyces cerevisiae cells. Such mutations are difficult to study in higher eukaryotic systems. In our research, we have used a collection of six isogenic trp5-strains and 14 isogenic haploid and diploid cyc1-strains that are specific markers of all possible base-pair substitutions. These strains differ from each other only in single base substitutions within codon-50 of the trp5 gene or codon-22 of the cyc1 gene. Different mutation spectra for two different haploid genetic trp5- and cyc1-assays and different mutation spectra for the same genetic cyc1-system in cells with different ploidy — haploid and diploid — have been obtained. It was linear function for dose-dependence in haploid and exponential in diploid cells. We suggest that the differences between haploid yeast strains reflect the dependence on the sequence context, while the differences between haploid and diploid strains reflect the different molecular mechanisms of mutations.

Keywords: base pair substitutions, γ-rays, haploid and diploid cells, yeast Saccharomyces cerevisiae

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10562 Association of Vascular Endothelial Growth Factor Gene +405 C>G and -460 T>C Polymorphism with Type 2 Diabetic Foot Ulcer Patient in Cipto Mangunkusumo National Hospital Jakarta

Authors: Dedy Pratama, Akhmadu Muradi, Hilman Ibrahim, Raden Suhartono, Alexander Jayadi Utama, Patrianef Darwis, S. Dwi Anita, Luluk Yunaini, Kemas Dahlan

Abstract:

Introduction: Vascular endothelial growth factor (VEGF) gene shows association with various angiogenesis conditions including Diabetic Foot Ulcer (DFU) disease. In this study, we performed this study to examine VEGF gene polymorphism associated with DFU. Methods: Case-control study of polymorphism of VEGF gene +405 C>G and -460 T>C, of diabetes mellitus (DM) type 2 with Diabetic Foot Ulcer (DFU) in Cipto Mangunkusumo National Hospital (RSCM) Jakarta from June to December 2016. Results: There were 203 patients, 102 patients with DFU and 101 patients without DFU. Forty-nine point 8 percent of total samples is male and 50,2% female with mean age 56,06 years. Distribution of the wild-type genotype VEGF +405 C>G wild type CC was found in 6,9% of respondents, the number of mutant heterozygote CG was 69,5% and mutant homozygote GG was 19,7%. Cumulatively, there were 6,9% wild-type and 85,2% mutant and 3,9% of total blood samples could not be detected on PCR-RFLP. Distribution of VEGF allele +405 C>G C alleles were 43% and G alleles were 57%. Distribution of genotype from VEGF gene -460 T>C is wild type TT 42,9%, mutant heterozygote TC 37,9% and mutant homozygote CC 13,3%. Cumulatively, there were 42,9% wild-type and 51% mutant type. Distribution of VEGF -460 T>C were 62% T allele and 38% C allele. Conclusion: In this study we found the distribution of alleles from VEGF +405 C>G is C 43% and G 57% and from VEGF -460 T>C; T 62% and C 38%. We propose that G allele in VEGF +405 C>G can act as a protective allele and on the other hands T allele in VEGF -460 T>C could be acted as a risk factor for DFU in diabetic patients.

Keywords: diabetic foot ulcer, diabetes mellitus, polymorphism, VEGF

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10561 Hydrophobically Modified Glycol Chitosan Nanoparticles as a Carrier for Etoposide

Authors: Akhtar Aman, Abida Raza, Shumaila Bashir, Javaid Irfan, Andreas G. Schätzlein, Ijeoma F Uchegbeu

Abstract:

Development of efficient delivery system for hydrophobic drugs remains a major concern in chemotherapy. The objective of the current study was to develop polymeric drug-delivery system for etoposide from amphiphilic derivatives of glycol chitosan, capable to improve the pharmacokinetics and to reduce the adverse effects of etoposide due to various organic solvents used in commercial formulations for solubilisation of etoposide. As a promising carrier, amphiphilic derivatives of glycol chitosan were synthesized by chemical grafting of palmitic acid N-hydroxy succinimide and quaternisation to glycol chitosan backbone. To this end a 7.9 kDa glycol chitosan was modified by palmitoylation and quaternisation into 13 kDa. Nano sized micelles prepared from this amphiphilic polymer had the capability to encapsulate up to 3 mg/ml etoposide. The pharmacokinetic results indicated that GCPQ based etoposide formulation transformed the biodistribution pattern. AUC 0.5-24 hr showed statistically significant difference in ETP-GCPQ vs. commercial preparation in liver (25 vs 70, p<0.001), spleen (27 vs. 36, P<0.05), lungs (42 vs. 136, p<0.001), kidneys (25 vs. 30, p<0.05) and brain (19 vs. 9,p<0.001). Using the hydrophobic fluorescent dye Nile red, we showed that micelles efficiently delivered their payload to MCF7 and A2780 cancer cells in-vitro and to A431 xenograft tumor in-vivo, suggesting these systems could deliver hydrophobic anti- cancer drugs such as etoposide to tumors. The pharmacokinetic results indicated that the GCPQ micelles transformed the biodistribution pattern and increased etoposide concentration in the brain significantly compared to free drug after intravenous administration. GCPQ based formulations not only reduced side effects associated with current available formulations but also increased their transport through the biological barriers, thus making it a good delivery system.

Keywords: glycol chitosan, Nile red, micelles, etoposide, A431 xenografts

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