Search results for: human lung carcinoma cell lines
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 12546

Search results for: human lung carcinoma cell lines

9726 Nonparametric Truncated Spline Regression Model on the Data of Human Development Index in Indonesia

Authors: Kornelius Ronald Demu, Dewi Retno Sari Saputro, Purnami Widyaningsih

Abstract:

Human Development Index (HDI) is a standard measurement for a country's human development. Several factors may have influenced it, such as life expectancy, gross domestic product (GDP) based on the province's annual expenditure, the number of poor people, and the percentage of an illiterate people. The scatter plot between HDI and the influenced factors show that the plot does not follow a specific pattern or form. Therefore, the HDI's data in Indonesia can be applied with a nonparametric regression model. The estimation of the regression curve in the nonparametric regression model is flexible because it follows the shape of the data pattern. One of the nonparametric regression's method is a truncated spline. Truncated spline regression is one of the nonparametric approach, which is a modification of the segmented polynomial functions. The estimator of a truncated spline regression model was affected by the selection of the optimal knots point. Knot points is a focus point of spline truncated functions. The optimal knots point was determined by the minimum value of generalized cross validation (GCV). In this article were applied the data of Human Development Index with a truncated spline nonparametric regression model. The results of this research were obtained the best-truncated spline regression model to the HDI's data in Indonesia with the combination of optimal knots point 5-5-5-4. Life expectancy and the percentage of an illiterate people were the significant factors depend to the HDI in Indonesia. The coefficient of determination is 94.54%. This means the regression model is good enough to applied on the data of HDI in Indonesia.

Keywords: generalized cross validation (GCV), Human Development Index (HDI), knots point, nonparametric regression, truncated spline

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9725 1,8-Naphthalimide Substituted 4,4-Difluoroboradiaza-S-Indacene Dyads: Synthesis, Structure, Properties and Live-Cell Imaging

Authors: Madhurima Poddar, Vinay Sharma, Shaikh M. Mobin, Rajneesh Misra

Abstract:

Three 1,8-naphthalimide (NPI) substituted 4,4-difluoroboradiaza-s-indacene (BODIPY) dyads were synthesized via Pd-catalyzed Sonogashira cross-coupling reaction of ethynyl substituted NPI with the meso-, β- and α-halogenated BODIPYs, respectively. The photophysical and electrochemical data reveals considerable electronic communication between the BODIPY and NPI moieties. The electronic absorption spectrum reveals that the substitution of NPI at α position of BODIPY exhibit better electronic communication between the NPI and the BODIPY units. The electronic structures of all the dyads exhibit planar geometries which are in a good correlation with the structures obtained from single crystal X-ray diffraction. The crystal structures of the dyads exhibit interesting supramolecular interactions. The dyads show good cytocompatibility with the potential of multicolor live-cell imaging; making them excellent candidates for biological applications. The work provides an important strategy of screening the substitution pattern at different position of BODIPYs which will be useful for the design of BODIPY based organic molecules for various optoelectronic applications as well as bio-imaging.

Keywords: bio-imaging studies, cross-coupling, cyclic voltammetry, density functional calculations, fluorescence spectra, single crystal XRD, UV/Vis spectroscopy

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9724 Leakage Current Analysis of FinFET Based 7T SRAM at 32nm Technology

Authors: Chhavi Saxena

Abstract:

FinFETs can be a replacement for bulk-CMOS transistors in many different designs. Its low leakage/standby power property makes FinFETs a desirable option for memory sub-systems. Memory modules are widely used in most digital and computer systems. Leakage power is very important in memory cells since most memory applications access only one or very few memory rows at a given time. As technology scales down, the importance of leakage current and power analysis for memory design is increasing. In this paper, we discover an option for low power interconnect synthesis at the 32nm node and beyond, using Fin-type Field-Effect Transistors (FinFETs) which are a promising substitute for bulk CMOS at the considered gate lengths. We consider a mechanism for improving FinFETs efficiency, called variable supply voltage schemes. In this paper, we’ve illustrated the design and implementation of FinFET based 4x4 SRAM cell array by means of one bit 7T SRAM. FinFET based 7T SRAM has been designed and analysis have been carried out for leakage current, dynamic power and delay. For the validation of our design approach, the output of FinFET SRAM array have been compared with standard CMOS SRAM and significant improvements are obtained in proposed model.

Keywords: FinFET, 7T SRAM cell, leakage current, delay

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9723 Biofouling Control during the Wastewater Treatment in Self-Support Carbon Nanotubes Membrane: Role of Low Voltage Electric Potential

Authors: Chidambaram Thamaraiselvan, Carlos Dosoretz

Abstract:

This work will explore the influence of low voltage electric field, both alternating (AC) and direct (DC) currents, on biofouling control to highly electrically conductive self-supporting carbon nanotubes (CNT) membranes at conditions which encourage bacterial growth. A mutant strain of Pseudomonas putida S12 was used a model bacterium. The antibiofouling studies were performed with flow-through mode connecting an electric circuit in resistive mode. Major emphasis was placed on AC due to its ability of repulsing and inactivating bacteria. The observations indicate that an AC potential >1500 mV, 1 kHz frequency, 100 Ω external resistance on ground side and pulse wave above the offset (+0.45) almost completely prevented attachment of bacteria (>98.5%) and bacterial inactivation (95.3±2.5%). Findings suggest that at the conditions applied, direct electron transfer might be dominant in a decrease of cell viability. AC resulted more effective than DC, both in terms of biofouling reduction compared to cathodic DC and in terms of cell inactivation compared to anodic DC. This electrically polarized CNT membranes offer a viable antibiofouling strategy to hinder biofouling and simplify membrane care during filtration.

Keywords: bacterial attachment, biofouling control, low electric potential, water treatment

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9722 Genetic Diversity of Sugar Beet Pollinators

Authors: Ksenija Taški-Ajdukovic, Nevena Nagl, Živko Ćurčić, Dario Danojević

Abstract:

Information about genetic diversity of sugar beet parental populations is of a great importance for hybrid breeding programs. The aim of this research was to evaluate genetic diversity among and within populations and lines of diploid sugar beet pollinators, by using SSR markers. As plant material were used eight pollinators originating from three USDA-ARS breeding programs and four pollinators from Institute of Field and Vegetable Crops, Novi Sad. Depending on the presence of self-fertility gene, the pollinators were divided into three groups: autofertile (inbred lines), autosterile (open-pollinating populations), and group with partial presence of autofertility gene. A total of 40 SSR primers were screened, out of which 34 were selected for the analysis of genetic diversity. A total of 129 different alleles were obtained with mean value 3.2 alleles per SSR primer. According to the results of genetic variability assessment the number and percentage of polymorphic loci was the maximal in pollinators NS1 and tester cms2 while effective number of alleles, expected heterozygosis and Shannon’s index was highest in pollinator EL0204. Analysis of molecular variance (AMOVA) showed that 77.34% of the total genetic variation was attributed to intra-varietal variance. Correspondence analysis results were very similar to grouping by neighbor-joining algorithm. Number of groups was smaller by one, because correspondence analysis merged IFVCNS pollinators with CZ25 into one group. Pollinators FC220, FC221 and C 51 were in the next group, while self-fertile pollinators CR10 and C930-35 from USDA-Salinas were separated. On another branch were self-sterile pollinators ЕL0204 and ЕL53 from USDA-East Lansing. Sterile testers cms1 and cms2 formed separate group. The presented results confirmed that SSR analysis can be successfully used in estimation of genetic diversity within and among sugar beet populations. Since the tested pollinator differed considering the presence of self-fertility gene, their heterozygosity differed as well. It was lower in genotypes with fixed self-fertility genes. Since the most of tested populations were open-pollinated, which rarely self-pollinate, high variability within the populations was expected. Cluster analysis grouped populations according to their origin.

Keywords: auto fertility, genetic diversity, pollinator, SSR, sugar beet

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9721 Targeting Matrix Metalloprotease-9 to Reduce Coronary Artery Manifestations of Kawasaki’s Disease

Authors: Mohammadjavad Sotoudeheian, Navid Farahmandian

Abstract:

Kawasaki disease (KD) is the primary cause of acquired pediatric heart disease as an acute vasculitis. In children with prolonged fever, rash, and inflammation of the mucosa KD must be considered as a clinical diagnosis. There is a persuasive suggestion of immune-mediated damage as the pathophysiologic cascade of KD. For example, the invasion of cytotoxic T-cells supports a viral etiology and the inflammasome of the innate immune system is a critical component in the vasculitis formation in KD. Animal models of KD propose the cytokine profiles, such as increased IL-1 and GM-CSF, which cause vascular damage. CRP and IFN-γ elevated expression and the upregulation of IL-6, and IL-10 production are also described in previous studies. Untreated KD is a critical risk factor for coronary artery diseases and myocardial infarction. Vascular damage may encompass amplified T-cell activity. SMAD3 is an essential molecule in down-regulating T-cells and increasing expression of FoxP3. It has a critical effect in the differentiation of regulatory T-cells. The discrepancy of regulatory T-cells and pro-inflammatory Th17 has been studied in acute coronary syndrome during KD. However in the coronary artery damaged lymphocytes and IgA plasma cells are seen at the lesion locations, the major immune cells in the coronary lesions are monocytes/macrophages and neutrophils. These cells secrete TNF-α, and activates matrix metalloprotease (MMP)-9, reducing the integrity of vessels and prompting patients to arise aneurysm. MMPs can break down the components of the extracellular matrix and assist immune cell movement. IVIG as an effective form of treatment clarified the role of the immune system, which may target pathogenic antigens and regulate cytokine production. Several reports have revealed that in the coronary arteries, high expression of MMP-9 in monocyte/macrophage results in pathologic cascades. Curcumin is a potent antioxidant and anti-inflammatory molecule. Curcumin decreases the production of reactive oxygen and nitrogen species and inhibits transcription factors like AP-1 and NF-κB. Curcumin also contains the characteristics of inhibitory effects on MMPs, especially MMP-9. The upregulation of MMP-9 is an important cellular response. Curcumin treatment caused a reverse effect and down-regulates MMP-9 gene expression which may fund the anti-inflammatory effect. Curcumin inhibits MMP-9 expression via PKC and AMPK-dependent pathways in Human monocytes cells. Elevated expression and activity of MMP-9 are correlated with advanced vascular lesions. AMPK controls lipid metabolism and oxidation, and protein synthesis. AMPK is also necessary for the MMP-9 activity and THP-1 cell adhesion to endothelial cells. Curcumin was shown to inhibit the activation of AMPKα. Compound C (AMPK inhibitor) inhibits MMP-9 expression level. Therefore, through inactivating AMPKs and PKC, curcumin decreases the MMP-9 level, which results in inhibiting monocyte/macrophage differentiation. Compound C also suppress the phosphorylation of three major classes of MAP kinase signaling, suggesting that curcumin may suppress MMP-9 level by inactivation of MAPK pathways. MAPK cascades are activated to induce the expression of MMP-9. Curcumin inhibits MAPKs phosphorylation, which contributes to the down-regulation of MMP-9. This study demonstrated that the potential inhibitory properties of curcumin over MMP-9 lead to a therapeutic strategy to reduce the risk of coronary artery involvement during KD.

Keywords: MMP-9, coronary artery aneurysm, Kawasaki’s disease, curcumin, AMPK, immune system, NF-κB, MAPK

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9720 Robust Recognition of Locomotion Patterns via Data-Driven Machine Learning in the Cloud Environment

Authors: Shinoy Vengaramkode Bhaskaran, Kaushik Sathupadi, Sandesh Achar

Abstract:

Human locomotion recognition is important in a variety of sectors, such as robotics, security, healthcare, fitness tracking and cloud computing. With the increasing pervasiveness of peripheral devices, particularly Inertial Measurement Units (IMUs) sensors, researchers have attempted to exploit these advancements in order to precisely and efficiently identify and categorize human activities. This research paper introduces a state-of-the-art methodology for the recognition of human locomotion patterns in a cloud environment. The methodology is based on a publicly available benchmark dataset. The investigation implements a denoising and windowing strategy to deal with the unprocessed data. Next, feature extraction is adopted to abstract the main cues from the data. The SelectKBest strategy is used to abstract optimal features from the data. Furthermore, state-of-the-art ML classifiers are used to evaluate the performance of the system, including logistic regression, random forest, gradient boosting and SVM have been investigated to accomplish precise locomotion classification. Finally, a detailed comparative analysis of results is presented to reveal the performance of recognition models.

Keywords: artificial intelligence, cloud computing, IoT, human locomotion, gradient boosting, random forest, neural networks, body-worn sensors

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9719 Effect of Pomegranate (Punica granatum) Seed Oil on Keratinocytes in Patients with Atopic Dermatitis

Authors: Fardis Teifoori, Mehdi Dehghani, Idoia Postigo, Jorge Martinez

Abstract:

Introduction: Many skin disorders, such as atopic dermatitis (AD), is characterized by inflammation, infection, and hyperplasia. In this work, keratinocytes from AD patients are used to study the pomegranate seed oil properties for skin care. Material and methods: Isolated keratinocytes from patients with AD were cultured and stimulated by IL-9 (20 ng/ml) and TNF-α (50ng/ml) for 48h to induce vascular endothelial growth factor (VEGF) and Regulated upon activation, normal T cell expressed and secreted (RANTES) production, respectively, in the presence of different concentrations of pomegranate seed oil (20, 50, 100, and 200 µM). Finally, the concentrations of RANTES and VEGF in the cell culture supernatant were quantified according to the standard protocol of commercial ELISA kits. Results: The results indicated that pomegranate seed oil concentrations of 50, 100, and 200 µM could significantly inhibit the production of VEGF and RANTES by stimulating keratinocytes with IL-9 (20 ng/ml) and TNF-α (50ng/ml), respectively. The decrease in VEGF and RANTES concentration in the presence of the pomegranate seed oil concentrations of 20 and 50 uM was not significant. Conclusion: It was concluded that pomegranate seed oil (PSO) counteracts atopic dermatitis conditions dose-dependently: with the highest effect at the concentration of 200 µM. We suggest that the inexpensive and easily available pomegranate seed oil is a good candidate for cosmetics and clinical utilization for skin care.

Keywords: atopic dermatitis, pomegranate, Punica granatum, RANTES, VEGF

Procedia PDF Downloads 79
9718 Vascular Targeted Photodynamic Therapy Monitored by Real-Time Laser Speckle Imaging

Authors: Ruth Goldschmidt, Vyacheslav Kalchenko, Lilah Agemy, Rachel Elmoalem, Avigdor Scherz

Abstract:

Vascular Targeted Photodynamic therapy (VTP) is a new modality for selective cancer treatment that leads to the complete tumor ablation. A photosensitizer, a bacteriochlorophyll derivative in our case, is first administered to the patient and followed by the illumination of the tumor area, by a near-IR laser for its photoactivation. The photoactivated drug releases reactive oxygen species (ROS) in the circulation, which reacts with blood cells and the endothelium leading to the occlusion of the blood vasculature. If the blood vessels are only partially closed, the tumor may recover, and cancer cells could survive. On the other hand, excessive treatment may lead to toxicity of healthy tissues nearby. Simultaneous VTP monitoring and image processing independent of the photoexcitation laser has not yet been reported, to our knowledge. Here we present a method for blood flow monitoring, using a real-time laser speckle imaging (RTLSI) in the tumor during VTP. We have synthesized over the years a library of bacteriochlorophyll derivatives, among them WST11 and STL-6014. Both are water soluble derivatives that are retained in the blood vasculature through their partial binding to HSA. WST11 has been approved in Mexico for VTP treatment of prostate cancer at a certain drug dose, and time/intensity of illumination. Application to other bacteriochlorophyll derivatives or other cancers may require different treatment parameters (such as light/drug administration). VTP parameters for STL-6014 are still under study. This new derivative mainly differs from WST11 by its lack of the central Palladium, and its conjugation to an Arg-Gly-Asp (RGD) sequence. RGD is a tumor-specific ligand that is used for targeting the necrotic tumor domains through its affinity to αVβ3 integrin receptors. This enables the study of cell-targeted VTP. We developed a special RTLSI module, based on Labview software environment for data processing. The new module enables to acquire raw laser speckle images and calculate the values of the laser temporal statistics of time-integrated speckles in real time, without additional off-line processing. Using RTLSI, we could monitor the tumor’s blood flow following VTP in a CT26 colon carcinoma ear model. VTP with WST11 induced an immediate slow down of the blood flow within the tumor and a complete final flow arrest, after some sporadic reperfusions. If the irradiation continued further, the blood flow stopped also in the blood vessels of the surrounding healthy tissue. This emphasizes the significance of light dose control. Using our RTLSI system, we could prevent any additional healthy tissue damage by controlling the illumination time and restrict blood flow arrest within the tumor only. In addition, we found that VTP with STL-6014 was the most effective when the photoactivation was conducted 4h post-injection, in terms of tumor ablation success in-vivo and blood vessel flow arrest. In conclusion, RTSLI application should allow to optimize VTP efficacy vs. toxicity in both the preclinical and clinical arenas.

Keywords: blood vessel occlusion, cancer treatment, photodynamic therapy, real time imaging

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9717 Revolutionizing Autonomous Trucking Logistics with Customer Relationship Management Cloud

Authors: Sharda Kumari, Saiman Shetty

Abstract:

Autonomous trucking is just one of the numerous significant shifts impacting fleet management services. The Society of Automotive Engineers (SAE) has defined six levels of vehicle automation that have been adopted internationally, including by the United States Department of Transportation. On public highways in the United States, organizations are testing driverless vehicles with at least Level 4 automation which indicates that a human is present in the vehicle and can disable automation, which is usually done while the trucks are not engaged in highway driving. However, completely driverless vehicles are presently being tested in the state of California. While autonomous trucking can increase safety, decrease trucking costs, provide solutions to trucker shortages, and improve efficiencies, logistics, too, requires advancements to keep up with trucking innovations. Given that artificial intelligence, machine learning, and automated procedures enable people to do their duties in other sectors with fewer resources, CRM (Customer Relationship Management) can be applied to the autonomous trucking business to provide the same level of efficiency. In a society witnessing significant digital disruptions, fleet management is likewise being transformed by technology. Utilizing strategic alliances to enhance core services is an effective technique for capitalizing on innovations and delivering enhanced services. Utilizing analytics on CRM systems improves cost control of fuel strategy, fleet maintenance, driver behavior, route planning, road safety compliance, and capacity utilization. Integration of autonomous trucks with automated fleet management, yard/terminal management, and customer service is possible, thus having significant power to redraw the lines between the public and private spheres in autonomous trucking logistics.

Keywords: autonomous vehicles, customer relationship management, customer experience, autonomous trucking, digital transformation

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9716 A Study of Human Communication in an Internet Community

Authors: Andrew Laghos

Abstract:

The Internet is a big part of our everyday lives. People can now access the internet from a variety of places including home, college, and work. Many airports, hotels, restaurants and cafeterias, provide free wireless internet to their visitors. Using technologies like computers, tablets, and mobile phones, we spend a lot of our time online getting entertained, getting informed, and communicating with each other. This study deals with the latter part, namely, human communication through the Internet. People can communicate with each other using social media, social network sites (SNS), e-mail, messengers, chatrooms, and so on. By connecting with each other they form virtual communities. Regarding SNS, types of connections that can be studied include friendships and cliques. Analyzing these connections is important to help us understand online user behavior. The method of Social Network Analysis (SNA) was used on a case study, and results revealed the existence of some useful patterns of interactivity between the participants. The study ends with implications of the results and ideas for future research.

Keywords: human communication, internet communities, online user behavior, psychology

Procedia PDF Downloads 497
9715 Economic Analysis of Domestic Combined Heat and Power System in the UK

Authors: Thamo Sutharssan, Diogo Montalvao, Wen-Chung Wang, Yong Chen, Claudia Pisac

Abstract:

A combined heat and power (CHP) system is an efficient and clean way to generate power (electricity). Heat produced by the CHP system can be used for water and space heating. The CHP system which uses hydrogen as fuel produces zero carbon emission. Its’ efficiency can reach more than 80% whereas that of a traditional power station can only reach up to 50% because much of the thermal energy is wasted. The other advantages of CHP systems include that they can decentralize energy generation, improve energy security and sustainability, and significantly reduce the energy cost to the users. This paper presents the economic benefits of using a CHP system in the domestic environment. For this analysis, natural gas is considered as potential fuel as the hydrogen fuel cell based CHP systems are rarely used. UK government incentives for CHP systems are also considered as the added benefit. Results show that CHP requires a significant initial investment in return it can reduce the annual energy bill significantly. Results show that an investment may be paid back in 7 years. After the back period, CHP can run for about 3 years as most of the CHP manufacturers provide 10-year warranty.

Keywords: combined heat and power, clean energy, hydrogen fuel cell, economic analysis of CHP, zero emission

Procedia PDF Downloads 385
9714 MicroRNA Drivers of Resistance to Androgen Deprivation Therapy in Prostate Cancer

Authors: Philippa Saunders, Claire Fletcher

Abstract:

INTRODUCTION: Prostate cancer is the most prevalent malignancy affecting Western males. It is initially an androgen-dependent disease: androgens bind to the androgen receptor and drive the expression of genes that promote proliferation and evasion of apoptosis. Despite reduced androgen dependence in advanced prostate cancer, androgen receptor signaling remains a key driver of growth. Androgen deprivation therapy (ADT) is, therefore, a first-line treatment approach and works well initially, but resistance inevitably develops. Abiraterone and Enzalutamide are drugs widely used in ADT and are androgen synthesis and androgen receptor signaling inhibitors, respectively. The shortage of other treatment options means acquired resistance to these drugs is a major clinical problem. MicroRNAs (miRs) are important mediators of post-transcriptional gene regulation and show altered expression in cancer. Several have been linked to the development of resistance to ADT. Manipulation of such miRs may be a pathway to breakthrough treatments for advanced prostate cancer. This study aimed to validate ADT resistance-implicated miRs and their clinically relevant targets. MATERIAL AND METHOD: Small RNA-sequencing of Abiraterone- and Enzalutamide-resistant C42 prostate cancer cells identified subsets of miRs dysregulated as compared to parental cells. Real-Time Quantitative Reverse Transcription PCR (qRT-PCR) was used to validate altered expression of candidate ADT resistance-implicated miRs 195-5p, 497-5p and 29a-5p in ADT-resistant and -responsive prostate cancer cell lines, patient-derived xenografts (PDXs) and primary prostate cancer explants. RESULTS AND DISCUSSION: This study suggests a possible role for miR-497-5p in the development of ADT resistance in prostate cancer. MiR-497-5p expression was increased in ADT-resistant versus ADT-responsive prostate cancer cells. Importantly, miR-497-5p expression was also increased in Enzalutamide-treated, castrated (ADT-mimicking) PDXs versus intact PDXs. MiR-195-5p was also elevated in ADT-resistant versus -responsive prostate cancer cells, while there was a drop in miR-29a-5p expression. Candidate clinically relevant targets of miR-497-5p in prostate cancer were identified by mining AGO-PAR-CLIP-seq data sets and may include AVL9 and FZD6. CONCLUSION: In summary, this study identified microRNAs that are implicated in prostate cancer resistance to androgen deprivation therapy and could represent novel therapeutic targets for advanced disease.

Keywords: microRNA, androgen deprivation therapy, Enzalutamide, abiraterone, patient-derived xenograft

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9713 Dual Ion-Crosslinking Human Keratin Based Bioink for 3D Bioprinting

Authors: Jae Seo Lee, Il Keun Kwon

Abstract:

In the last decades, keratin-based on natural extracts has considerably increased interest as a skin tissue regeneration. However, most parts of keratin had a limitation to 3D scaffolds due to low biological affinity and general low mechanical properties. To create a 3D structure, a facile bioink was designed with a photocurable crosslinking stage system using natural polymer-based human keratin. Keratin-based bioink enables the crosslinking more quickly through two types of photo and ion crosslinking for module engineering assembly. Rheological results showed that keratin-based bioink with high concentration possessed superior mechanical rigidity for 3D bioprinting. Different 3D geometrically constructs were successfully fabricated with optimal bioprinting parameters through the 3D printer with X-Y-Z controlled UV laser system. The presented study has offered a distinct advantage for 3D printing of keratin-based hydrogel into 3D complex-shaped biomimetic constructs. Thus, keratin-based bioink opens up new avenues in bioprinting to directly substitute tissue or organs.

Keywords: human keratin, hydrogel, ion-crosslinking, 3D bioprinting

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9712 Kinematic Modelling and Task-Based Synthesis of a Passive Architecture for an Upper Limb Rehabilitation Exoskeleton

Authors: Sakshi Gupta, Anupam Agrawal, Ekta Singla

Abstract:

An exoskeleton design for rehabilitation purpose encounters many challenges, including ergonomically acceptable wearing technology, architectural design human-motion compatibility, actuation type, human-robot interaction, etc. In this paper, a passive architecture for upper limb exoskeleton is proposed for assisting in rehabilitation tasks. Kinematic modelling is detailed for task-based kinematic synthesis of the wearable exoskeleton for self-feeding tasks. The exoskeleton architecture possesses expansion and torsional springs which are able to store and redistribute energy over the human arm joints. The elastic characteristics of the springs have been optimized to minimize the mechanical work of the human arm joints. The concept of hybrid combination of a 4-bar parallelogram linkage and a serial linkage were chosen, where the 4-bar parallelogram linkage with expansion spring acts as a rigid structure which is used to provide the rotational degree-of-freedom (DOF) required for lowering and raising of the arm. The single linkage with torsional spring allows for the rotational DOF required for elbow movement. The focus of the paper is kinematic modelling, analysis and task-based synthesis framework for the proposed architecture, keeping in considerations the essential tasks of self-feeding and self-exercising during rehabilitation of partially healthy person. Rehabilitation of primary functional movements (activities of daily life, i.e., ADL) is routine activities that people tend to every day such as cleaning, dressing, feeding. We are focusing on the feeding process to make people independent in respect of the feeding tasks. The tasks are focused to post-surgery patients under rehabilitation with less than 40% weakness. The challenges addressed in work are ensuring to emulate the natural movement of the human arm. Human motion data is extracted through motion-sensors for targeted tasks of feeding and specific exercises. Task-based synthesis procedure framework will be discussed for the proposed architecture. The results include the simulation of the architectural concept for tracking the human-arm movements while displaying the kinematic and static study parameters for standard human weight. D-H parameters are used for kinematic modelling of the hybrid-mechanism, and the model is used while performing task-based optimal synthesis utilizing evolutionary algorithm.

Keywords: passive mechanism, task-based synthesis, emulating human-motion, exoskeleton

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9711 Immuno-field Effect Transistor Using Carbon Nanotubes Network – Based for Human Serum Albumin Highly Sensitive Detection

Authors: Muhamad Azuddin Hassan, Siti Shafura Karim, Ambri Mohamed, Iskandar Yahya

Abstract:

Human serum albumin plays a significant part in the physiological functions of the human body system (HSA).HSA level monitoring is critical for early detection of HSA-related illnesses. The goal of this study is to show that a field effect transistor (FET)-based immunosensor can assess HSA using high aspect ratio carbon nanotubes network (CNT) as a transducer. The CNT network were deposited using air brush technique, and the FET device was made using a shadow mask process. Field emission scanning electron microscopy and a current-voltage measurement system were used to examine the morphology and electrical properties of the CNT network, respectively. X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy were used to confirm the surface alteration of the CNT. The detection process is based on covalent binding interactions between an antibody and an HSA target, which resulted in a change in the manufactured biosensor's drain current (Id).In a linear range between 1 ng/ml and 10zg/ml, the biosensor has a high sensitivity of 0.826 mA (g/ml)-1 and a LOD value of 1.9zg/ml.HSA was also identified in a genuine serum despite interference from other biomolecules, demonstrating the CNT-FET immunosensor's ability to quantify HSA in a complex biological environment.

Keywords: carbon nanotubes network, biosensor, human serum albumin

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9710 Heterodimetallic Ferrocenyl Dithiophosphonate Complexes of Nickel(II), Zinc(II) and Cadmium(II) as High Efficiency Co-Sensitizers in Dye-Sensitized Solar Cells

Authors: Tomilola J. Ajayi, Moses Ollengo, Lukas le Roux, Michael N. Pillay, Richard J. Staples, Shannon M. Biros Werner E. van Zyl

Abstract:

The formation, characterization, and dye-sensitized solar cell application of nickel(II), zinc(II) and cadmium(II) ferrocenyl dithiophosphonate complexes were investigated. The multidentate monoanionic ligand [S₂PFc(OH)]¯ (L1) was synthesized from the reaction between ferrocenyl Lawesson’s reagent, [FcP(=S)μ-S]₂ (FcLR), (Fc = ferrocenyl) and water. Ligand L1 could potentially coordinate to metal centers through the S, S’ and O donor atoms. The reaction between metal salt precursors and L1 produced a Ni(II) complex of the type [Ni{S₂P(Fc)(OH)}₂] (1) (molar ratio 1:2), a tetranickel (II) complex of the type [Ni₂{S₂OP(Fc)}₂]₂ (2) (molar ratio (1:1), as well as a Zn(II) complex [Zn{S₂P(Fc)(OH)}₂]₂ (3), and a Cd(II) complex [Cd{S₂P(Fc)(OH)}₂]₂ (4). Complexes 1-4 were characterized by 1H and 31P NMR and FT-IR, and complexes 1 and 2 were additionally analysed by X-Ray crystallography. After co-sensitization, the DSSCs were characterized using UV-Vis, cyclic voltammetry, electrochemical impedance spectroscopy, and photovoltaic measurements (I-V curves). Overall finding shows that co-sensitization of our compounds with ruthenium dye N719 resulted in a better overall solar conversion efficiency than only pure N719 dye under the same experimental conditions. In conclusion, we report the first examples of dye-sensitized solar cells (DSSCs) co-sensitized with ferrocenyl dithiophosphonate complexes.

Keywords: dithiophosphonate, dye sensitized solar cell, co-sensitization, solar efficiency

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9709 Spatial Organization of Cells over the Process of Pellicle Formation by Pseudomonas alkylphenolica KL28

Authors: Kyoung Lee

Abstract:

Numerous aerobic bacteria have the ability to form multicellular communities on the surface layer of the air-liquid (A-L) interface as a biofilm called a pellicle. Pellicles occupied at the A-L interface will benefit from the utilization of oxygen from air and nutrient from liquid. Buoyancy of cells can be obtained by high surface tension at the A-L interface. Thus, formation of pellicles is an adaptive advantage in utilization of excess nutrients in the standing culture where oxygen depletion is easily set up due to rapid cell growth. In natural environments, pellicles are commonly observed on the surface of lake or pond contaminated with pollutants. Previously, we have shown that when cultured in standing LB media an alkylphenol-degrading bacteria Pseudomonas alkylphenolia KL28 forms pellicles in a diameter of 0.3-0.5 mm with a thickness of ca 40 µm. The pellicles have unique features for possessing flatness and unusual rigidity. In this study, the biogenesis of the circular pellicles has been investigated by observing the cell organization at early stages of pellicle formation and cell arrangements in pellicle, providing a clue for highly organized cellular arrangement to be adapted to the air-liquid niche. Here, we first monitored developmental patterns of pellicle from monolayer to multicellular organization. Pellicles were shaped by controlled growth of constituent cells which accumulate extracellular polymeric substance. The initial two-dimensional growth was transited to multilayers by a constraint force of accumulated self-produced extracellular polymeric substance. Experiments showed that pellicles are formed by clonal growth and even with knock-out of genes for flagella and pilus formation. In contrast, the mutants in the epm gene cluster for alginate-like polymer biosynthesis were incompetent in cell alignment for initial two-dimensional growth of pellicles. Electron microscopic and confocal laser scanning microscopic studies showed that the fully matured structures are highly packed by matrix-encased cells which have special arrangements. The cells on the surface of the pellicle lie relatively flat and inside longitudinally cross packed. HPLC analysis of the extrapolysaccharide (EPS) hydrolysate from the colonies from LB agar showed a composition with L-fucose, L-rhamnose, D-galactosamine, D-glucosamine, D-galactose, D-glucose, D-mannose. However, that from pellicles showed similar neutral and amino sugar profile but missing galactose. Furthermore, uronic acid analysis of EPS hydrolysates by HPLC showed that mannuronic acid was detected from pellicles not from colonies, indicating the epm-derived polymer is critical for pellicle formation as proved by the epm mutants. This study verified that for the circular pellicle architecture P. alkylphenolica KL28 cells utilized EPS building blocks different from that used for colony construction. These results indicate that P. alkylphenolica KL28 is a clever architect that dictates unique cell arrangements with selected EPS matrix material to construct sophisticated building, circular biofilm pellicles.

Keywords: biofilm, matrix, pellicle, pseudomonas

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9708 An Integrative Computational Pipeline for Detection of Tumor Epitopes in Cancer Patients

Authors: Tanushree Jaitly, Shailendra Gupta, Leila Taher, Gerold Schuler, Julio Vera

Abstract:

Genomics-based personalized medicine is a promising approach to fight aggressive tumors based on patient's specific tumor mutation and expression profiles. A remarkable case is, dendritic cell-based immunotherapy, in which tumor epitopes targeting patient's specific mutations are used to design a vaccine that helps in stimulating cytotoxic T cell mediated anticancer immunity. Here we present a computational pipeline for epitope-based personalized cancer vaccines using patient-specific haplotype and cancer mutation profiles. In the workflow proposed, we analyze Whole Exome Sequencing and RNA Sequencing patient data to detect patient-specific mutations and their expression level. Epitopes including the tumor mutations are computationally predicted using patient's haplotype and filtered based on their expression level, binding affinity, and immunogenicity. We calculate binding energy for each filtered major histocompatibility complex (MHC)-peptide complex using docking studies, and use this feature to select good epitope candidates further.

Keywords: cancer immunotherapy, epitope prediction, NGS data, personalized medicine

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9707 In vitro Effects of Viscum album on the Functionality of Rabbit Spermatozoa

Authors: Marek Halenár, Eva Tvrdá, Simona Baldovská, Ľubomír Ondruška, Peter Massányi, Adriana Kolesárová

Abstract:

This study aimed to assess the in vitro effects of different concentrations of the Viscum album extract on the motility, viability, and reactive oxygen species (ROS) production by rabbit spermatozoa during different time periods (0, 2, and 8h). Spermatozoa motility was assessed by using the CASA (Computer aided sperm analysis) system. Cell viability was evaluated by using the metabolic activity MTT assay, and the luminol-based luminometry was applied to quantify the ROS formation. The CASA analysis revealed that low Viscum concentrations were able to prevent a rapid decline of spermatozoa motility, especially in the case of concentrations ranging between 1 and 5 µg/mL (P<0.05 with respect to time 8h). At the same time, concentrations ranging between 1 and 100 µg/mL of the extract led to a significant preservation of the cell viability (P<0.05 in case of 5, 50 and 100 µg/mL; P<0.01 with respect to 1 and 10 µg/mL, time 8h). 1 and 5 µg/mL of the extract exhibited antioxidant characteristics, translated into a significant reduction of the ROS production, particularly notable at time 8h (P<0.01). The results indicate that the Viscum extract is capable of delaying the damage inflicted to the spermatozoon by the in vitro environment.

Keywords: CASA, mistletoe, mitochondrial activity, motility, reactive oxygen species, rabbits, spermatozoa, Viscum album

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9706 Human Quality Treatment and Organizational Growth: The Principle of Respect at Nestle Nigeria

Authors: Rose Ogbechie, Nicholas Anakwue

Abstract:

In recent times, research has centered, in the area of Business Ethics, on the issue of human quality treatment (HQT), regarding the way people are dealt with, in organizations, taking into cognizance, respect for the dignity of the human person, as well as, the rights and responsibilities of the corporate individual. As such, the principle of respect is an essential ethical principle that should govern professional relationships in the workplace. There is a prevailing myth in the Nigerian business space, that to drive business success, business leadership must coerce and drive people, oftentimes, beyond comfort to meet work expectations. This has, most times, necessitated abuses and insults on subordinates in the workplace, and instituted a rigid hierarchy of management in business relationships. Nestlé Nigeria, one of the largest foods and beverage companies in Africa, provides a contrast to this myth in their success heuristic. Over the years in Nigeria, the company has registered significant successes in the Nigerian Fast-Moving Consumer Goods (FMCG) Market, with stellar performances year-on-year, and a high-penetration rate of its products in the Nigerian consumer space. At the heart of the FMCG giant’s success and culture is the principle of respect—respect for stakeholders, respect for all peoples, respect for cultures, respect for the environment. Utilizing qualitative research methods, through interviews and focus group discussions with Nestlé’s stakeholders, this paper explores the ethical principle of respect, and how, through it, human quality treatment influences positively organizational growth.

Keywords: human quality treatment, respect, Nestlé Nigeria, FMCG, organizational growth

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9705 Challenges for Interface Designers in Designing Sensor Dashboards in the Context of Industry 4.0

Authors: Naveen Kumar, Shyambihari Prajapati

Abstract:

Industry 4.0 is the fourth industrial revolution that focuses on interconnectivity of machine to machine, human to machine and human to human via Internet of Things (IoT). Technologies of industry 4.0 facilitate communication between human and machine through IoT and forms Cyber-Physical Production System (CPPS). In CPPS, multiple shop floors sensor data are connected through IoT and displayed through sensor dashboard to the operator. These sensor dashboards have enormous amount of information to be presented which becomes complex for operators to perform monitoring, controlling and interpretation tasks. Designing handheld sensor dashboards for supervision task will become a challenge for the interface designers. This paper reports emerging technologies of industry 4.0, changing context of increasing information complexity in consecutive industrial revolutions and upcoming design challenges for interface designers in context of Industry 4.0. Authors conclude that information complexity of sensor dashboards design has increased with consecutive industrial revolutions and designs of sensor dashboard causes cognitive load on users. Designing such complex dashboards interfaces in Industry 4.0 context will become main challenges for the interface designers.

Keywords: Industry4.0, sensor dashboard design, cyber-physical production system, Interface designer

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9704 Transmission Line Inspection Using Drones

Authors: Jae Kyung Lee, Joon Young Park

Abstract:

Maintenance on power transmission lines requires a lot of works. Sometimes they should be maintained on live-line environment with high altitude. Therefore, there always exist risks of falling from height and electric shock. To decline those risks, drones are recently applying on the electric power industry. This paper presents new operational technology while inspecting power transmission line. This paper also describes a technique for creating a flight path of a drone for transmission line inspection and a technique for controlling the drones of different types. Its technical and economical feasibilities have confirmed through experiments.

Keywords: drones, transmission line, inspection, control system

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9703 Specialized Building Terminology of the 19th Century

Authors: Klara Kroftova, Martin Ebel

Abstract:

Human history is characterized by continuous evolution. As mankind developed, so did crafts, doctrine, and, of course, language. Each field of human activity, science, and art or architecture has its own vocabulary, terms with its specific, well-defined meaning. These are words or phrases that may have a general meaning in a certain context, but which, when used in specific contexts, are characterized by their expertise. The development of architecture in this area is, therefore, closely related to the development of architecture. People discovered new building materials, building constructions, decorating, furnishings, etc. and with each new knowledge came a new name. Architecture and construction were specific to individual nations, but throughout human history, they were also copied differently from other nations. Thus, the terminology of the Czech language was established, but also adopted from foreign languages. In this paper, we will focus on the linguistic analysis of terms that we most often encounter in the study of 19th-century architecture in the Austro-Hungarian Monarchy. The article is supplemented by a small picture dictionary.

Keywords: tenement houses, 19th century, terminology, Austro-Hungarian monarchy

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9702 Defects Analysis, Components Distribution, and Properties Simulation in the Fuel Cells and Batteries by 2D and 3D Characterization Techniques

Authors: Amir Peyman Soleymani, Jasna Jankovic

Abstract:

The augmented demand of the clean and renewable energy has necessitated the fuel cell and battery industries to produce more efficient devices at the lower prices, which can be achieved through the improvement of the electrode. Microstructural characterization, as one of the main materials development tools, plays a pivotal role in the production of better clean energy devices. In this study, methods for characterization and studying of the defects and components distribution were performed on the polymer electrolyte membrane fuel cell (PEMFC) and Li-ion battery (LIB) electrodes in 2D and 3D. The particles distribution, porosity, mechanical defects, and component distribution were studied by Scanning Electron Microscope (SEM), SEM-Focused Ion Beam (SEM-FIB), and Scanning Transmission Electron Microscope equipped with Energy Dispersive Spectroscopy (STEM-EDS). The 3D results obtained from X-ray Computed Tomography (XCT) revealed the pathways for electron and ion conductivity and defects progression maps. Computer-aided methods (Avizo) were employed to simulate the properties and performance of the microstructure in the electrodes. The suggestions were provided to improve the performance of PEMFCs and LIBs by adjusting the microstructure and the distribution of the components in the electrodes.

Keywords: PEM fuel cells, Li-ion batteries, 2D and 3D imaging, materials characterizations

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9701 PDMS-Free Microfluidic Chips Fabrication and Utilisation for Pulsed Electric Fields Applications

Authors: Arunas Stirke, Neringa Bakute, Gatis Mozolevskis

Abstract:

A technology of microfluidics is an emerging tool in the field of biology, medicine and chemistry. Microfluidic device is also known as ‘lab-on-a-chip’ technology [1]. In moving from macro- to microscale, there is unprecedented control over spatial and temporal gradients and patterns that cannot be captured in conventional Petri dishes and well plates [2]. However, there is not a single standard microfluidic chip designated for all purposes – every different field of studies needs a specific microchip with certain geometries, inlet/outlet, channel depth and other parameters to precisely regulate the required function. Since our group is studying an effect of pulsed electric field (PEF) to the cells, we have manufactured a microfluidic chip designated for high-throughput electroporation of cells. In our microchip, a cell culture chamber is divided into two parallel channels by a membrane, meanwhile electrodes for electroporation are attached to the wall of the channels. Both microchannels have their own inlet and outlet, enabling injection of transfection material separately. Our perspective is to perform electroporation of mammalian cells in two different ways: (1) plasmid and cells are injected in the same microchannel and (2) injected into separate microchannels. Moreover, oxygen and pH sensors are integrated on order to analyse cell viability parameters after PEF treatment.

Keywords: microfluidics, chip, fabrication, electroporation

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9700 Trehalose Application Increased Membrane Stability and Cell Viability to Affect Growth of Wheat Genotypes under Heat Stress

Authors: S. K. Thind, Aparjot Kaur

Abstract:

Heat stress is one of the major environmental factors drastically reducing wheat production. Crop heat tolerance can be enhanced by preconditioning of plants by exogenous application of osmoprotectants. Presently, the effect of trehalose pretreatment (at 1 mM, and 1.5 nM) under heat stress of 35±2˚C (moderate) and 40±2˚ (severe) for four and eight hour was conducted in wheat (Tricticum aestivum L.) genotypes viz. HD2967, PBW 175, PBW 343, PBW 621, and PBW 590. Heat stress affects wide spectrum of physiological processes within plants that are irreversibly damaged by stress. Membrane thermal stability (MTS) and cell viability was significantly decreased under heat stress for eight hours. Pretreatment with trehalose improved MTS and cell viability under stress and this effect was more promotory with higher concentration. Thermal stability of photosynthetic apparatus differed markedly between genotypes and Hill reaction activity was recorded more in PBW621 followed by C306 as compared with others. In all genotypes photolysis of water showed decline with increase in temperature stress. Trehalose pretreatment helped in sustaining Hill reaction activity probably by stabilizing the photosynthetic apparatus against heat-induced photo inhibition. Both plant growth and development were affected by temperature in both shoot and root under heat stress. The reduction was compensated partially by trehalose (1.5 mM) application. Adaption to heat stress is associated with the metabolic adjustment which led to accumulation of soluble sugars including non-reducing and reducing for their role in adaptive mechanism. Higher acid invertase activity in shoot of tolerant genotypes appeared to be a characteristic for stress tolerance. As sucrose synthase play central role in sink strength and in studied wheat genotype was positively related to dry matter accumulation. The duration of heat stress for eight hours had more severe effect on these parameters and trehalose application at 1.5 mM ameliorated it to certain extent.

Keywords: heat stress, Triticum aestivum, trehalose, membrane thermal stability, triphenyl tetrazolium chloride, reduction test, growth, sugar metabolism

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9699 Zero-Knowledge Proof-of-Reserve: A Confidential Approach to Cryptocurrency Asset Verification

Authors: Sam Ng, Lewis Leighton, Sam Atkinson, Carson Yan, Landan Hu, Leslie Cheung, Brian Yap, Kent Lung, Ketat Sarakune

Abstract:

This paper introduces a method for verifying cryptocurrency reserves that balances the need for both transparency and data confidentiality. Our methodology employs cryptographic techniques, including Merkle Trees, Bulletproof, and zkSnark, to verify that total assets equal or exceed total liabilities, represented by customer funds. Importantly, this verification is achieved without disclosing sensitive information such as the total asset value, customer count, or cold wallet addresses. We delve into the construction and implementation of this methodology. While the system is robust and scalable, we also identify areas for potential enhancements to improve its efficiency and versatility. As the digital asset landscape continues to evolve, our approach provides a solid foundation for ensuring continued trust and security in digital asset platforms.

Keywords: cryptocurrency, crypto-currency, proof-of-reserve, por, zero-knowledge, ZKP

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9698 The Molecular Rationale for Steroid Based Therapy of Leukemia: Diagnostic and Therapeutic Implications

Authors: Eitan Yefenof

Abstract:

Glucocorticoid (GC) hormones, e.g. Dexamethasone and Prednisone, are widely used in the therapy of leukemia and lymphoma owing to their apoptogenic effect on lymphoid cells. However, the emergence of GC resistant cells during therapy is a major cause for treatment failure, urging the need for novel strategies that maintain leukemia sensitivity to the pro-apoptotic activity of GCs. GCs act by binding to the GC receptor (GR), which, in its inactive state, is sequestered in the cytosol by a multi-subunit complex of heat shock proteins. Upon ligand binding, the complex dissociates, allowing GR activation and translocation to the nucleus, where it regulates transcription of multiple genes. We demonstrated that in addition to gene expression, GR also regulates microRNA (miR) expression. Deep-sequencing analysis revealed 14 miRs that are regulated in GC-sensitive but resistant leukemias upon treatment with GC. GC up-regulates miR-103, miR-15~16 and miR-30e/d, while down-regulates miR-17, mir-18a, miR-19a, miR-19b, miR-20a and miR-92a (members of the miR-17∼92a multi-cistron). Upon transfection, miR-103 confers GC apoptotic sensitivity to otherwise GC-resistant cell. Furthermore, knocking down miR-103 expression reduces the GC apoptotic response of sensitive cells. miR-103 abrogates c-Myc expression, an oncogenic transcription factor which is deregulated in many cancers. In addition, miR-103 up-regulates Bim, a pro-apoptotic protein crucial for GC-induced death. Activated glycogen synthase kinase 3 (GSK3) is also crucial for GC-induced apoptosis. GSK3 is active in GC-sensitive but not in GC-resistant cells. We found that GSK3 associates with the GR multi-subunit complex. Upon GC exposure, it dissociates from the GR and interacts with Bim to enable activation of the mitochondrial apoptosis pathway. miR-103 mediated c-Myc ablation is followed by down-regulation of the multi-cistron miR-17~92a, in particular miR-18a and miR-20a. miR-18a targets GR for degradation whereas miR-20a targets Bim degradation. Hence, miR-103 acts, in concert with Bim and GR, as a "tumor suppressor" that leads to reduced proliferation, cell-cycle arrest and cell death. We suggest that miR-103 can provide a diagnostic tool that predicts the sensitivity of leukemia to GC based therapy. Furthermore, exosomal delivery of miR-103 or up-regulation of the endogenous miR-103 could confer apoptotic sensitivity to resistant cells at the outset, thus becoming a useful therapeutic tool combined with GCs.

Keywords: apoptosis, leukemia, micro-RNA, steroids

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9697 Combined Treatment of Estrogen-Receptor Positive Breast Microtumors with 4-Hydroxytamoxifen and Novel Non-Steroidal Diethyl Stilbestrol-Like Analog Produces Enhanced Preclinical Treatment Response and Decreased Drug Resistance

Authors: Sarah Crawford, Gerry Lesley

Abstract:

This research is a pre-clinical assessment of anti-cancer effects of novel non-steroidal diethyl stilbestrol-like estrogen analogs in estrogen-receptor positive/ progesterone-receptor positive human breast cancer microtumors of MCF 7 cell line. Tamoxifen analog formulation (Tam A1) was used as a single agent or in combination with therapeutic concentrations of 4-hydroxytamoxifen, currently used as a long-term treatment for the prevention of breast cancer recurrence in women with estrogen receptor positive/ progesterone receptor positive malignancies. At concentrations ranging from 30-50 microM, Tam A1 induced microtumor disaggregation and cell death. Incremental cytotoxic effects correlated with increasing concentrations of Tam A1. Live tumor microscopy showed that microtumos displayed diffuse borders and substrate-attached cells were rounded-up and poorly adherent. A complete cytotoxic effect was observed using 40-50 microM Tam A1 with time course kinetics similar to 4-hydroxytamoxifen. Combined treatment with TamA1 (30-50 microM) and 4-hydroxytamoxifen (10-15 microM) induced a highly cytotoxic, synergistic combined treatment response that was more rapid and complete than using 4-hydroxytamoxifen as a single agent therapeutic. Microtumors completely dispersed or formed necrotic foci indicating a highly cytotoxic combined treatment response. Moreover, breast cancer microtumors treated with both 4-hydroxytamoxifen and Tam A1 displayed lower levels of long-term post-treatment regrowth, a critical parameter of primary drug resistance, than observed for 4-hydroxytamoxifen when used as a single agent therapeutic. Tumor regrowth at 6 weeks post-treatment with either single agent 4-hydroxy tamoxifen, Tam A1 or a combined treatment was assessed for the development of drug resistance. Breast cancer cells treated with both 4-hydroxytamoxifen and Tam A1 displayed significantly lower levels of post-treatment regrowth, indicative of decreased drug resistance, than observed for either single treatment modality. The preclinical data suggest that combined treatment involving the use of tamoxifen analogs may be a novel clinical approach for long-term maintenance therapy in patients with estrogen-receptor positive/progesterone-receptor positive breast cancer receiving hormonal therapy to prevent disease recurrence. Detailed data on time-course, IC50 and tumor regrowth assays post- treatment as well as a proposed mechanism of action to account for observed synergistic drug effects will be presented.

Keywords: 4-hydroxytamoxifen, tamoxifen analog, drug-resistance, microtumors

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