Search results for: brain cells
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 4166

Search results for: brain cells

2066 Wireless Backhauling for 5G Small Cell Networks

Authors: Abdullah A. Al Orainy

Abstract:

Small cell backhaul solutions need to be cost-effective, scalable, and easy to install. This paper presents an overview of small cell backhaul technologies. Wireless solutions including TV white space, satellite, sub-6 GHz radio wave, microwave and mmWave with their backhaul characteristics are discussed. Recent research on issues like beamforming, backhaul architecture, precoding and large antenna arrays, and energy efficiency for dense small cell backhaul with mmWave communications is reviewed. Recent trials of 5G technologies are summarized.

Keywords: backhaul, small cells, wireless, 5G

Procedia PDF Downloads 489
2065 Effect of Mistranslating tRNA Alanine on Polyglutamine Aggregation

Authors: Sunidhi Syal, Rasangi Tennakoon, Patrick O'Donoghue

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Polyglutamine (polyQ) diseases are a group of diseases related to neurodegeneration caused by repeats of the amino acid glutamine (Q) in the DNA, which translates into an elongated polyQ tract in the protein. The pathological explanation is that the polyQ tract forms cytotoxic aggregates in the neurons, leading to their degeneration. There are no cures or preventative efforts established for these diseases as of today, although the symptoms of these diseases can be relieved. This study specifically focuses on Huntington's disease, which is a type of polyQ disease in which aggregation is caused by the extended cytosine, adenine, guanine (CUG) codon repeats in the huntingtin (HTT) gene, which encodes for the huntingtin protein. Using this principle, we attempted to create six models, which included mutating wildtype tRNA alanine variant tRNA-AGC-8-1 to have glutamine anticodons CUG and UUG so serine is incorporated at glutamine sites in poly Q tracts. In the process, we were successful in obtaining tAla-8-1 CUG mutant clones in the HTTexon1 plasmids with a polyQ tract of 23Q (non-pathogenic model) and 74Q (disease model). These plasmids were transfected into mouse neuroblastoma cells to characterize protein synthesis and aggregation in normal and mistranslating cells and to investigate the effects of glutamines replaced with alanines on the disease phenotype. Notably, we observed no noteworthy differences in mean fluorescence between the CUG mutants for 23Q or 74Q; however, the Triton X-100 assay revealed a significant reduction in insoluble 74Q aggregates. We were unable to create a tAla-8-1 UUG mutant clone, and determining the difference in the effects of the two glutamine anticodons may enrich our understanding of the disease phenotype. In conclusion, by generating structural disruption with the amino acid alanine, it may be possible to find ways to minimize the toxicity of Huntington's disease caused by these polyQ aggregates. Further research is needed to advance knowledge in this field by identifying the cellular and biochemical impact of specific tRNA variants found naturally in human genomes.

Keywords: Huntington's disease, polyQ, tRNA, anticodon, clone, overlap PCR

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2064 Big Brain: A Single Database System for a Federated Data Warehouse Architecture

Authors: X. Gumara Rigol, I. Martínez de Apellaniz Anzuola, A. Garcia Serrano, A. Franzi Cros, O. Vidal Calbet, A. Al Maruf

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Traditional federated architectures for data warehousing work well when corporations have existing regional data warehouses and there is a need to aggregate data at a global level. Schibsted Media Group has been maturing from a decentralised organisation into a more globalised one and needed to build both some of the regional data warehouses for some brands at the same time as the global one. In this paper, we present the architectural alternatives studied and why a custom federated approach was the notable recommendation to go further with the implementation. Although the data warehouses are logically federated, the implementation uses a single database system which presented many advantages like: cost reduction and improved data access to global users allowing consumers of the data to have a common data model for detailed analysis across different geographies and a flexible layer for local specific needs in the same place.

Keywords: data integration, data warehousing, federated architecture, Online Analytical Processing (OLAP)

Procedia PDF Downloads 223
2063 Lead-Free Inorganic Cesium Tin-Germanium Triiodide Perovskites for Photovoltaic Application

Authors: Seyedeh Mozhgan Seyed-Talebi, Javad Beheshtian

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The toxicity of lead associated with the lifecycle of perovskite solar cells (PSCs( is a serious concern which may prove to be a major hurdle in the path toward their commercialization. The current proposed lead-free PSCs including Ag(I), Bi(III), Sb(III), Ti(IV), Ge(II), and Sn(II) low-toxicity cations are still plagued with the critical issues of poor stability and low efficiency. This is mainly because of their chemical stability. In the present research, utilization of all inorganic CsSnGeI3 based materials offers the advantages to enhance resistance of device to degradation, reduce the cost of cells, and minimize the carrier recombination. The presence of inorganic halide perovskite improves the photovoltaic parameters of PCSs via improved surface coverage and stability. The inverted structure of simulated devices using a 1D simulator like solar cell capacitance simulator (SCAPS) version 3308 involves TCOHTL/Perovskite/ETL/Au contact layer. PEDOT:PSS, PCBM, and CsSnGeI3 used as hole transporting layer (HTL), electron transporting layer (ETL), and perovskite absorber layer in the inverted structure for the first time. The holes are injected from highly stable and air tolerant Sn0.5Ge0.5I3 perovskite composition to HTM and electrons from the perovskite to ETL. Simulation results revealed a great dependence of power conversion efficiency (PCE) on the thickness and defect density of perovskite layer. Here the effect of an increase in operating temperature from 300 K to 400 K on the performance of CsSnGeI3 based perovskite devices is investigated. Comparison between simulated CsSnGeI3 based PCSs and similar real testified devices with spiro-OMeTAD as HTL showed that the extraction of carriers at the interfaces of perovskite absorber depends on the energy level mismatches between perovskite and HTL/ETL. We believe that optimization results reported here represent a critical avenue for fabricating the stable, low-cost, efficient, and eco-friendly all-inorganic Cs-Sn-Ge based lead-free perovskite devices.

Keywords: hole transporting layer, lead-free, perovskite solar cell, SCAPS-1D, Sn-Ge based

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2062 Assessment of the Performance of the Sonoreactors Operated at Different Ultrasound Frequencies, to Remove Pollutants from Aqueous Media

Authors: Gabriela Rivadeneyra-Romero, Claudia del C. Gutierrez Torres, Sergio A. Martinez-Delgadillo, Victor X. Mendoza-Escamilla, Alejandro Alonzo-Garcia

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Ultrasonic degradation is currently being used in sonochemical reactors to degrade pollutant compounds from aqueous media, as emerging contaminants (e.g. pharmaceuticals, drugs and personal care products.) because they can produce possible ecological impacts on the environment. For this reason, it is important to develop appropriate water and wastewater treatments able to reduce pollution and increase reuse. Pollutants such as textile dyes, aromatic and phenolic compounds, cholorobenzene, bisphenol-A and carboxylic acid and other organic pollutants, can be removed from wastewaters by sonochemical oxidation. The effect on the removal of pollutants depends on the type of the ultrasonic frequency used; however, not much studies have been done related to the behavior of the fluid into the sonoreactors operated at different ultrasonic frequencies. Based on the above, it is necessary to study the hydrodynamic behavior of the liquid generated by the ultrasonic irradiation to design efficient sonoreactors to reduce treatment times and costs. In this work, it was studied the hydrodynamic behavior of the fluid in sonochemical reactors at different frequencies (250 kHz, 500 kHz and 1000 kHz). The performances of the sonoreactors at those frequencies were simulated using computational fluid dynamics (CFD). Due to there is great sound speed gradient between piezoelectric and fluid, k-e models were used. Piezoelectric was defined as a vibration surface, to evaluate the different frequencies effect on the fluid into sonochemical reactor. Structured hexahedral cells were used to mesh the computational liquid domain, and fine triangular cells were used to mesh the piezoelectric transducers. Unsteady state conditions were used in the solver. Estimation of the dissipation rate, flow field velocities, Reynolds stress and turbulent quantities were evaluated by CFD and 2D-PIV measurements. Test results show that there is no necessary correlation between an increase of the ultrasonic frequency and the pollutant degradation, moreover, the reactor geometry and power density are important factors that should be considered in the sonochemical reactor design.

Keywords: CFD, reactor, ultrasound, wastewater

Procedia PDF Downloads 176
2061 Statistical Wavelet Features, PCA, and SVM-Based Approach for EEG Signals Classification

Authors: R. K. Chaurasiya, N. D. Londhe, S. Ghosh

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The study of the electrical signals produced by neural activities of human brain is called Electroencephalography. In this paper, we propose an automatic and efficient EEG signal classification approach. The proposed approach is used to classify the EEG signal into two classes: epileptic seizure or not. In the proposed approach, we start with extracting the features by applying Discrete Wavelet Transform (DWT) in order to decompose the EEG signals into sub-bands. These features, extracted from details and approximation coefficients of DWT sub-bands, are used as input to Principal Component Analysis (PCA). The classification is based on reducing the feature dimension using PCA and deriving the support-vectors using Support Vector Machine (SVM). The experimental are performed on real and standard dataset. A very high level of classification accuracy is obtained in the result of classification.

Keywords: discrete wavelet transform, electroencephalogram, pattern recognition, principal component analysis, support vector machine

Procedia PDF Downloads 620
2060 Early Biological Effects in Schoolchildren Living in an Area of Salento (Italy) with High Incidence of Chronic Respiratory Diseases: The IMP.AIR. Study

Authors: Alessandra Panico, Francesco Bagordo, Tiziana Grassi, Adele Idolo, Marcello Guido, Francesca Serio, Mattia De Giorgi, Antonella De Donno

Abstract:

In the Province of Lecce (Southeastern Italy) an area with unusual high incidence of chronic respiratory diseases, including lung cancer, was recently identified. The causes of this health emergency are still not entirely clear. In order to determine the risk profile of children living in five municipalities included in this area an epidemiological-molecular study was performed in the years 2014-2016: the IMP.AIR. (Impact of air quality on health of residents in the Municipalities of Sternatia, Galatina, Cutrofiano, Sogliano Cavour and Soleto) study. 122 children aged 6-8 years attending primary school in the study area were enrolled to evaluate the frequency of micronuclei (MNs) in their buccal exfoliated cells. The samples were collected in May 2015 by rubbing the oral mucosa with a soft bristle disposable toothbrush. At the same time, a validated questionnaire was administered to parents to obtain information about health, lifestyle and eating habits of the children. In addition, information on airborne pollutants, routinely detected by the Regional Environmental Agency (ARPA Puglia) in the study area, was acquired. A multivariate analysis was performed to detect any significant association between frequency of MNs (dependent variable) and behavioral factors (independent variables). The presence of MNs was highlighted in the buccal exfoliated cells of about 42% of recruited children with a mean frequency of 0.49 MN/1000 cells, greater than in other areas of Salento. The survey on individual characteristics and lifestyles showed that one in three children was overweight and that most of them had unhealthy eating habits with frequent consumption of foods considered ‘risky’. Moreover many parents (40% of fathers and 12% of mothers) were smokers and about 20% of them admitted to smoking in the house where the children lived. Information regarding atmospheric contaminants was poor. Of the few substances routinely detected by the only one monitoring station located in the study area (PM2.5, SO2, NO2, CO, O3) only ozone showed high concentrations exceeding the limits set by the legislation for 67 times in the year 2015. The study showed that the level of early biological effect markers in children was not negligible. This critical condition could be related to some individual factors and lifestyles such as overweight, unhealthy eating habits and exposure to passive smoking. At present, no relationship with airborne pollutants can be established due to the lack of information on many substances. Therefore, it would be advisable to modify incorrect behaviors and to intensify the monitoring of airborne pollutants (e.g. including detection of PM10, heavy metals, aromatic polycyclic hydrocarbons, benzene) given the epidemiology of chronic respiratory diseases registered in this area.

Keywords: chronic respiratory diseases, environmental pollution, lifestyle, micronuclei

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2059 Improved Performance Using Adaptive Pre-Coding in the Cellular Network

Authors: Yong-Jun Kim, Jae-Hyun Ro, Chang-Bin Ha, Hyoung-Kyu Song

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This paper proposes the cooperative transmission scheme with pre-coding because the cellular communication requires high reliability. The cooperative transmission scheme uses pre-coding method with limited feedback information among small cells. Particularly, the proposed scheme has adaptive mode according to the position of mobile station. Thus, demand of recent wireless communication is resolved by this scheme. From the simulation results, the proposed scheme has better performance compared to the conventional scheme in the cellular network.

Keywords: CDD, cellular network, pre-coding, SPC

Procedia PDF Downloads 550
2058 Effects of Kolavironon Liver Oxidative Stress and Beta-Cell Damage in Streptozotocin-Induced Diabetic Rats

Authors: Omolola R. Ayepola, Nicole L. Brooks, Oluwafemi O. Oguntibeju

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The liver plays an important role in the regulation of blood glucose and is a target organ of hyperglycaemia. Hyperglycemia plays a crucial role in the onset of various liver diseases and may culminate into hepatopathy if untreated. Alteration in antioxidant defense and increase in oxidative stress that results in tissue injury is characteristic of diabetes. We evaluated the protective effects of kolaviron-a biflavonoid complex, on hepatic antioxidants, lipid peroxidation and apoptosis in the liver of diabetic rats. To induce type I diabetes, rats were injected with streptozotocin intraperitoneally at a single dose of 50 mg/kg. Oral treatment of diabetic rats with kolaviron (100 mg/kg) started on the 6th day after diabetes induction and continued for 6 weeks (5 times weekly). Diabetic rats exhibited a significant increase in the peroxidation of hepatic lipids as observed from the elevated level of malondialdehyde (MDA) estimated by High-Performance Liquid Chromatography. In addition, Oxygen Radical Absorbance Capacity (ORAC), ratio of reduced to oxidized glutathione (GSH/GSSG) and catalase (CAT) activity was decreased in the liver of diabetic rats. TUNEL assay revealed increased apoptotic cell death in the liver of diabetic rats. Examination of Pancreatic beta-cells by immunohistochemical methods revealed beta cell degeneration and reduction in beta cell/ islet area in the diabetic controls. Kolaviron-treatment increased the area of insulin immunoreactive beta-cells significantly. Kolaviron attenuated lipid peroxidation and apoptosis in the liver of diabetic rats, increased CAT activity GSH levels and the resultant GSH: GSSG. The ORAC of kolaviron-treated diabetic liver was restored to near-normal values. Kolaviron protects the liver against oxidative and apoptotic damage induced by hyperglycemia. The antidiabetic effect of kolaviron may also be related to its beneficial effects on beta-cell function.

Keywords: diabetes mellitus, kolaviron, oxidative stress, liver, apoptosis

Procedia PDF Downloads 375
2057 Role of Autophagic Lysosome Reformation for Cell Viability in an in vitro Infection Model

Authors: Muhammad Awais Afzal, Lorena Tuchscherr De Hauschopp, Christian Hübner

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Introduction: Autophagy is an evolutionarily conserved lysosome-dependent degradation pathway, which can be induced by extrinsic and intrinsic stressors in living systems to adapt to fluctuating environmental conditions. In the context of inflammatory stress, autophagy contributes to the elimination of invading pathogens, the regulation of innate and adaptive immune mechanisms, and regulation of inflammasome activity as well as tissue damage repair. Lysosomes can be recycled from autolysosomes by the process of autophagic lysosome reformation (ALR), which depends on the presence of several proteins including Spatacsin. Thus ALR contributes to the replenishment of lysosomes that are available for fusion with autophagosomes in situations of increased autophagic turnover, e.g., during bacterial infections, inflammatory stress or sepsis. Objectives: We aimed to assess whether ALR plays a role for cell survival in an in-vitro bacterial infection model. Methods: Mouse embryonic fibroblasts (MEFs) were isolated from wild-type mice and Spatacsin (Spg11-/-) knockout mice. Wild-type MEFs and Spg11-/- MEFs were infected with Staphylococcus aureus (multiplication of infection (MOI) used was 10). After 8 and 16 hours of infection, cell viability was assessed on BD flow cytometer through propidium iodide intake. Bacterial intake by cells was also calculated by plating cell lysates on blood agar plates. Results: in-vitro infection of MEFs with Staphylococcus aureus showed a marked decrease of cell viability in ALR deficient Spatacsin knockout (Spg11-/-) MEFs after 16 hours of infection as compared to wild-type MEFs (n=3 independent experiments; p < 0.0001) although no difference was observed for bacterial intake by both genotypes. Conclusion: Suggesting that ALR is important for the defense of invading pathogens e.g. S. aureus, we observed a marked increase of cell death in an in-vitro infection model in cells with compromised ALR.

Keywords: autophagy, autophagic lysosome reformation, bacterial infections, Staphylococcus aureus

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2056 Immune Modulation and Cytomegalovirus Reactivation in Sepsis-Induced Immunosuppression

Authors: G. Lambe, D. Mansukhani, A. Shetty, S. Khodaiji, C. Rodrigues, F. Kapadia

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Introduction: Sepsis is known to cause impairment of both innate and adaptive immunity and involves an early uncontrolled inflammatory response, followed by a protracting immunosuppression phase, which includes decreased expression of cell receptors, T cell anergy and exhaustion, impaired cytokine production, which may cause high risk for secondary infections due to reduced response to antigens. Although human cytomegalovirus (CMV) is widely recognized as a serious viral pathogen in sepsis and immunocompromised patients, the incidence of CMV reactivation in patients with sepsis lacking strong evidence of immunosuppression is not well defined. Therefore, it is important to determine an association between CMV reactivation and sepsis-induced immunosuppression. Aim: To determine the association between incidence of CMV reactivation and immune modulation in sepsis-induced immunosuppression with time. Material and Methods: Ten CMV-seropositive adult patients with severe sepsis were included in this study. Blood samples were collected on Day 0, and further weekly up to 21 days. CMV load was quantified by real-time PCR using plasma. The expression of immunosuppression markers, namely, HLA-DR, PD-1, and regulatory T cells, were determined by flow cytometry using whole blood. Results: At Day 0, no CMV reactivation was observed in 6/10 patients. In these patients, the median length for reactivation was 14 days (range, 7-14 days). The remaining four patients, at Day 0, had a mean viral load of 1802+2599 copies/ml, which increased with time. At Day 21, the mean viral load for all 10 patients was 60949+179700 copies/ml, indicating that viremia increased with the length of stay in the hospital. HLA-DR expression on monocytes significantly increased from Day 0 to Day 7 (p = 0.001), following which no significant change was observed until Day 21, for all patients except 3. In these three patients, HLA-DR expression on monocytes showed a decrease at elevated viral load (>5000 copies/ml), indicating immune suppression. However, the other markers, PD-1 and regulatory T cells, did not show any significant changes. Conclusion: These preliminary findings suggest that CMV reactivation can occur in patients with severe sepsis. In fact, the viral load continued to increase with the length of stay in the hospital. Immune suppression, indicated by decreased expression of HLA-DR alone, was observed in three patients with elevated viral load.

Keywords: CMV reactivation, immune suppression, sepsis immune modulation, CMV viral load

Procedia PDF Downloads 134
2055 Pt Decorated Functionalized Acetylene Black as Efficient Cathode Material for Li Air Battery and Fuel Cell Applications

Authors: Rajashekar Badam, Vedarajan Raman, Noriyoshi Matsumi

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Efficiency of energy converting and storage systems like fuel cells and Li-Air battery principally depended on oxygen reduction reaction (ORR) which occurs at cathode. As the kinetics of the ORR is very slow, it becomes the rate determining step. Exploring carbon substrates for enhancing the dispersion and activity of the metal catalyst and commercially viable simple preparation method is a very crucial area of research in the field of energy materials. Hence, many researchers made large number of carbon-based ORR materials today. But, there are hardly few studies on the effect of interaction between Pt-carbon and carbon-electrolyte on activity. In this work, we have prepared functionalized carbon-based Pt catalyst (Pt-FAB) with enhanced interfacial properties that lead to efficient ORR catalysis. The present work deals with a single-pot method to exfoliate and functionalized acetylene black with enhanced interaction with Pt as well as electrolyte. Acetylene black was functionalized and exfoliated using a facile single pot acid treatment method. The resulted FAB was further decorated with Pt-nano particles (Pt-np). The TEM images of Pt-FAB with uniformly decorated Pt-np of ~3 nm. Further, XPS studies of Pt 4f peak revealed that Pt0 peak was shifted by 0.4 eV in Pt-FAB compared to binding energy of typical Pt⁰ found in Pt/C. The shift can be ascribed to the modulation of electronic state and strong electronic interaction of Pt with carbon. Modulated electronic structure of Pt and strong electronic interaction of Pt with FAB enhances the catalytic activity and durability respectively. To understand the electrode electrolyte interface, electrochemical impedance spectroscopy was carried out. These measurements revealed that the charge transfer resistance of electrode to electrolyte for Pt-FAB is 10 times smaller than that of conventional Pt/C. The interaction with electrolyte helps reduce the interface boundaries, which in turn affects the overall catalytic performance of the electrode. Cyclic voltammetric measurements in 0.1M HClO₄ aq. at a potential scan rate of 50 mVs-1 was employed to evaluate electrochemical surface area (ECSA) of Pt. ECSA of Pt-FAB was found to be as high as 67.2 m²g⁻¹. The three-electrode system showed very high ORR catalytic activity. Mass activity at 0.9 V vs. RHE showed 460 A/g which is much higher than the DOE target values for the year 2020. Further, it showed enhanced performance by showing 723 mW/cm² of highest power density and 1006 mA/cm² of current density at 0.6 V in fuel cell single cell type configuration and 1030 mAhg⁻¹ of rechargeable capacity in Li air battery application. The higher catalytic activity can be ascribed to the improved interaction of FAB with Pt and electrolyte. The aforementioned results evince that Pt-FAB will be a promising cathode material for efficient ORR with significant cyclability for its application in fuel cells and Li-Air batteries. In conclusion, a disordered material was prepared from AB and was systematically characterized. The extremely high ORR activity and ease of preparation make it competent for replacing commercially available ORR materials.

Keywords: functionalized acetylene black, oxygen reduction reaction, fuel cells, Functionalized battery

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2054 Size and Content of the Doped Silver Affected the Pulmonary Toxicity of Silver-Doped Nano-Titanium Dioxide Photocatalysts and the Optimization of These Two Parameters

Authors: Xiaoquan Huang, Congcong Li, Tingting Wei, Changcun Bai, Na Liu, Meng Tang

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Silver is often doped on nano-titanium dioxide photocatalysts (Ag-TiO₂) by photodeposition method to improve their utilization of visible-light while increasing the toxicity of TiO₂。 However, it is not known what factors influence this toxicity and how to reduce toxicity while maintaining the maximum catalytic activity. In this study, Ag-TiO₂ photocatalysts were synthesized by the photodeposition method with different silver content (AgC) and photodeposition time (PDT). Characterization and catalytic experiments demonstrated that silver was well assembled on TiO₂ with excellent visible-light catalytic activity, and the size of silver increased with PDT. In vitro, the cell viability of lung epithelial cells A549 and BEAS-2B showed that the higher content and smaller size of silver doping caused higher toxicity. In vivo, Ag-TiO₂ catalysts with lower AgC or larger silver particle size obviously caused less pulmonary pro-inflammatory and pro-fibrosis responses. However, the visible light catalytic activity decreased with the increase in silver size. Therefore, in order to optimize the Ag-TiO₂ photocatalyst with the lowest pulmonary toxicity and highest catalytic performance, response surface methodology (RSM) was further performed to optimize the two independent variables of AgC and PDT. Visible-light catalytic activity was evaluated by the degradation rate of Rhodamine B, the antibacterial property was evaluated by killing log value for Escherichia coli, and cytotoxicity was evaluated by IC50 to BEAS-2B cells. As a result, the RSM model showed that AgC and PDT exhibited an interaction effect on catalytic activity in the quadratic model. AgC was positively correlated with antibacterial activity. Cytotoxicity was proportional to AgC while inversely proportional to PDT. Finally, the optimization values were AgC 3.08 w/w% and PDT 28 min. Under this optimal condition, the relatively high silver proportion ensured the visible-light catalytic and antibacterial activity, while the longer PDT effectively reduced the cytotoxicity. This study is of significance for the safe and efficient application of silver-doped TiO₂ photocatalysts.

Keywords: Ag-doped TiO₂, cytotoxicity, inflammtion, fibrosis, response surface methodology

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2053 N400 Investigation of Semantic Priming Effect to Symbolic Pictures in Text

Authors: Thomas Ousterhout

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The purpose of this study was to investigate if incorporating meaningful pictures of gestures and facial expressions in short sentences of text could supplement the text with enough semantic information to produce and N400 effect when probe words incongruent to the picture were subsequently presented. Event-related potentials (ERPs) were recorded from a 14-channel commercial grade EEG headset while subjects performed congruent/incongruent reaction time discrimination tasks. Since pictures of meaningful gestures have been shown to be semantically processed in the brain in a similar manner as words are, it is believed that pictures will add supplementary information to text just as the inclusion of their equivalent synonymous word would. The hypothesis is that when subjects read the text/picture mixed sentences, they will process the images and words just like in face-to-face communication and therefore probe words incongruent to the image will produce an N400.

Keywords: EEG, ERP, N400, semantics, congruency, facilitation, Emotiv

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2052 Synthesis and Characterization of Sulfonated Aromatic Hydrocarbon Polymers Containing Trifluoromethylphenyl Side Chain for Proton Exchange Membrane Fuel Cell

Authors: Yi-Chiang Huang, Hsu-Feng Lee, Yu-Chao Tseng, Wen-Yao Huang

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Proton exchange membranes as a key component in fuel cells have been widely studying over the past few decades. As proton exchange, membranes should have some main characteristics, such as good mechanical properties, low oxidative stability and high proton conductivity. In this work, trifluoromethyl groups had been introduced on polymer backbone and phenyl side chain which can provide densely located sulfonic acid group substitution and also promotes solubility, thermal and oxidative stability. Herein, a series of novel sulfonated aromatic hydrocarbon polyelectrolytes was synthesized by polycondensation of 4,4''''-difluoro-3,3''''- bis(trifluoromethyl)-2'',3''-bis(3-(trifluoromethyl)phenyl)-1,1':4',1'':4'',1''':4''',1''''-quinquephenyl with 2'',3''',5'',6''-tetraphenyl-[1,1':4',1'': 4'',1''':4''',1''''-quinquephenyl]-4,4''''-diol and post-sulfonated was through chlorosulfonic acid to given sulfonated polymers (SFC3-X) possessing ion exchange capacities ranging from 1.93, 1.91 and 2.53 mmol/g. ¹H NMR and FT-IR spectroscopy were applied to confirm the structure and composition of sulfonated polymers. The membranes exhibited considerably dimension stability (10-27.8% in length change; 24-56.5% in thickness change) and excellent oxidative stability (weight remain higher than 97%). The mechanical properties of membranes demonstrated good tensile strength on account of the high rigidity multi-phenylated backbone. Young's modulus were ranged 0.65-0.77GPa which is much larger than that of Nafion 211 (0.10GPa). Proton conductivities of membranes ranged from 130 to 240 mS/cm at 80 °C under fully humidified which were comparable or higher than that of Nafion 211 (150 mS/cm). The morphology of membranes was investigated by transmission electron microscopy which demonstrated a clear hydrophilic/hydrophobic phase separation with spherical ionic clusters in the size range of 5-20 nm. The SFC3-1.97 single fuel cell performance demonstrates the maximum power density at 1.08W/cm², and Nafion 211 was 1.24W/cm² as a reference in this work. The result indicated that SFC3-X are good candidates for proton exchange membranes in fuel cell applications. Fuel cell of other membranes is under testing.

Keywords: fuel cells, polyelectrolyte, proton exchange membrane, sulfonated polymers

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2051 Optimization of Heterojunction Solar Cell Using AMPS-1D

Authors: Benmoussa Dennai, H. Benslimane, A. Helmaoui

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Photo voltaic conversion is the direct conversion of electromagnetic energy into electrical energy continuously. This electromagnetic energy is the most solar radiation. In this work we performed a computer modelling using AMPS 1D optimization of hetero-junction solar cells GaInP/GaAs configuration for p/ n. We studied the influence of the thickness the base layer in the cell offers on the open circuit voltage, the short circuit current and efficiency.

Keywords: optimization, photovoltaic cell, GaInP / GaAs AMPS-1D, hetetro-junction

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2050 Rice Mycotoxins Fate During In vitro Digestion and Intestinal Absorption: the Effect of Individual and Combination Exposures

Authors: Carolina S. Monteiro, Eugénia Pinto, Miguel A. Faria, Sara C. Cunha

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About half of the world's population eats rice daily, making it the primary food source for billions of people. Besides its nutrition potential, rice can be a significant route of exposure to many contaminants. Mycotoxins are an example of such contaminants that can be present in rice. Among them, ochratoxin (OTA), citrinin (CIT), and zearalenone (ZEN) are frequently reported in rice. During digestion, only a fraction of mycotoxins from food can be absorbed (bioaccessible fraction), influencing their ability to cause toxic effects. Insufficient knowledge of the bioavailability of mycotoxins, alone and in combination, may hinder an accurate risk assessment of contaminants ingested by humans. In this context, two different rice (Oryza sativa) varieties, Carolino white and Carolino brown, both with and without turmeric, were boiled and individually spiked with OTA, CIT, and ZEN plus with its combination. Subsequently, samples were submitted to the INFOGEST harmonized in vitro digestion protocol to evaluate the bioaccessibility of mycotoxins. Afterward, the in vitro intestinal transport of the mycotoxins, both alone and in combination, was evaluated in digests of Carolino white rice with and without turmeric. Assays were performed with a monolayers of of Caco-2 and HT-29 cells. Bioaccessibility of OTA and ZEN, alone and in combination, were similar in Carolino white and brown rice with or without turmeric. For CIT, when Carolino white rice was used, the bioaccessibility was higher alone than in combination (62.00% vs. 25.00%, without turmeric; 87.56% vs. 53.87%, with turmeric); however, with Carolino brown rice was the opposite (66.38% vs. 75.20%, without turmeric; 43.89% vs. 59.44%, with turmeric). All the mycotoxins, isolated, reached the higher bioaccessibility in the Carolino white rice with turmeric (CIT: 87.56%; OTA: 59.24%; ZEN: 58.05%). When mycotoxins are co-present, the higher bioaccessibility of each one varies with the type of rice. In general, when turmeric is present, bioaccessibility increases, except for CIT, using Carolino brown rice. Concerning the intestinal absorption in vitro, after 3 hours of transport, all mycotoxins were detected in the basolateral compartment being thus transported through the cells monolayer. ZEN presented the highest fraction absorbed isolated and combined, followed by CIT and OTA. These findings highlight that the presence of other components in the complex dietary matrix, like turmeric, and the co-presence of mycotoxins can affect its final bioavailability with obvious implications for health risk. This work provides new insights to qualitatively and quantitatively describe mycotoxin in rice fate during human digestion and intestinal absorption and further contribute to better risk assessment.

Keywords: bioaccessibility, digestion, intestinal absorption, mycotoxins

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2049 Comparison with Two Clinical Cases of Plasma Cell Neoplasm by Using the Method of Capillary Electrophoresis

Authors: Kai Pai Huang

Abstract:

Background: There are several types of plasma cell neoplasms including multiple myeloma, plasmacytoma, lymphoplasmacytic lymphoma, and monoclonal gammopathy of undetermined significance (MGUS) are found in our lab. Today, we want to compare with two cases using the method of capillary electrophoresis. Method: Serum is prepared and electrophoresis is performed at alkaline PH in a capillary using the Sebia® Capillary 2. Albumin and globulins are detected by the detector which is located in the cathode of the capillary and the signals are transformed to peaks. Serum was treated with beta-mercaptoethanol which reducing the polymerized immunoglobulin to monomer immunoglobulin to clarify two M-protein are secreted from the same plasma cell clone in bone marrow. Result: Case 1: A 78-year-old female presenting dysuria, oliguria and leg edema for several months. Laboratory data showed proteinuria, leukocytosis, results of high serum IgA and lambda light chain. A renal biopsy found amyloid fibrils in the glomerular mesangial area. Serum protein electrophoresis shows a major monoclonal peak in the β region and minor small peak in gamma region, and the immunotyping studies for serum showed two IgA/λ type. Case 2: A 55-year-old male presenting abdominal distension and low back pain for more than one month. Laboratory data showed T12 T8 compression fracture, results of high serum IgM and kappa light chain. Bone marrow aspiration showed the cells from the bone marrow are B cells with monotypic kappa chain expression. Bone marrow biopsy found this is lymphoplasmacytic lymphoma (Waldenstrom macroglobulin). Serum protein electrophoresis shows a monoclonal peak in the β region and the immunotyping studies for serum showed IgM/κ type. Conclusion: Plasma cell neoplasm can be diagnosed by many examinations. Among them, using capillary electrophoresis by a lab can separate several types of gammopathy and the quantification of a monoclonal peak can be used to evaluate the patients’ prognosis or treatment.

Keywords: plasma cell neoplasm, capillary electrophoresis, serum protein electrophoresis, immunotyping

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2048 The Neuropsychology of Autism and ADHD

Authors: Anvikshaa Bisen, Krish Makkar

Abstract:

Professionals misdiagnose autism by ticking off symptoms on a checklist without questioning the causes of said symptoms, and without understanding the innate neurophysiology of the autistic brain. A dysfunctional cingulate gyrus (CG) hyperfocuses attention in the left frontal lobe (logical/analytical) with no ability to access the right frontal lobe (emotional/creative), which plays a central role in spontaneity, social behavior, and nonverbal abilities. Autistic people live in a specialized inner space that is entirely intellectual, free from emotional and social distractions. They have no innate biological way of emotionally connecting with other people. Autistic people process their emotions intellectually, a process that can take 24 hours, by which time it is too late to have felt anything. An inactive amygdala makes it impossible for autistic people to experience fear. Because they do not feel emotion, they have no emotional memories. All memories are of events that happened about which they felt no emotion at the time and feel no emotion when talking about it afterward.

Keywords: autism, Asperger, Asd, neuropsychology, neuroscience

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2047 Joubert Syndrome: A Rare Genetic Disorder Reported in Kurdish Family

Authors: Aran Abd Al Rahman

Abstract:

Joubert syndrome regards as a congenital cerebellar ataxia caused by autosomal recessive carried on X chromosome. The disease diagnosed by brain imaging—the so-called molar tooth sign. Neurological signs were present from the neonatal period and include hypotonia progressing to ataxia, global developmental delay, ocular motor apraxia, and breathing dysregulation. These signs are variably associated with multiorgan involvement, mainly of the retina, kidneys, skeleton, and liver. 30 causative genes have been identified so far, all of which encode for proteins of the primary cilium or its apparatus, The purpose of our project was to detect the mutant gene (INPP5E gene) which cause Joubert syndrome. There were many methods used for diagnosis such as MRI and CT- scan and molecular diagnosis by doing ARMS PCR for detection of mutant gene that we were used in this research project. In this research for individual family which reported, the two children with parents, the two children were affected and were carrier.

Keywords: Joubert syndrome, genetic disease, Kurdistan region, Sulaimani

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2046 Application of Topical Imiquimod for Treatment Cervical Intraepithelial Neoplasia in Young Women: A Preliminary Result of a Pilot Study

Authors: Phill-Seung Jung, Dae-Yeon Kim

Abstract:

Objectives: In young, especially nulliparous women, it is not easy to decide on excisional therapy for cervical intraepithelial neoplasia (CIN). We aimed to evaluate how effective topical imiquimod is in the treatment of high-grade CIN so that excisional therapy can be avoided in young women. Methods: Patients with CIN were allocated to this pilot study. They did not want excisional therapy and agreed with topical imiquimod therapy, which required once-a-week hospital visit for 8 weeks for the application of imiquimod to the cervix by a gynecologic oncologist. If the lesion got worse during treatment, it was decided to convert imiquimod therapy to excisional therapy. Results: A total of 36 patients with a median age of 29 years (range, 22–41 years) agreed to receive topical imiquimod therapy. Of these, 32 patients (88.9%) were positive for high-risk human papillomavirus (HR HPV). Twenty-five patients (69.4%) had low-grade squamous intraepithelial lesion (LSIL), and 11 (30.6%) had high-grade squamous intraepithelial lesion (HSIL) on their initial LBC. Twenty-eight patients underwent punch biopsy, which showed CIN 1 in 7 (19.4%), CIN 2 in 11 (30.6%), and CIN 3 in 10 (27.8%) patients. Twenty patients finished the 8-week imiquimod therapy. Among them, 14 patients had CIN 2 or 3, and 6 patients had CIN 1. HR HPV was positive in 12 patients. On the last examination, 14 patients (70.0%) had negative intraepithelial lesions, 3 (15.0%) had atypical squamous cells of undetermined significance, and 1 (5.0%) had LSIL. Two patients had persistent HSIL: 1 patient underwent loop electrosurgical excision procedure, resulting in CIN 3 with positive resection margin, and the other patient underwent punch biopsy, resulting in intermediate cells and restarted imiquimod therapy. Only 7 patients were negative for HR HPV. Conclusions: This study showed that topical imiquimod therapy was effective for the treatment of high-grade CIN, with a histologic regression rate of 85.7% (14/20) and HPV eradication rate of 25.0% (8/32). Based on our findings, topical imiquimod therapy might have a successful therapeutic effect in young women with CIN 2-3 so that they can avoid excisional therapy. In addition, it could be a more reassuring treatment option for CIN 1 than just follow-up after few months. To confirm its efficacy, a phase II study with larger cohort would be needed.

Keywords: Imiquimod, Cervical Intraepthelial Neoplasia, Cervical Dysplasia, Human Papillomavirus

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2045 Trigonelline: A Promising Compound for The Treatment of Alzheimer's Disease

Authors: Mai M. Farid, Ximeng Yang, Tomoharu Kuboyama, Chihiro Tohda

Abstract:

Trigonelline is a major alkaloid component derived from Trigonella foenum-graecum L. (fenugreek) and has been reported before as a potential neuroprotective agent, especially in Alzheimer’s disease (AD). However, the previous data were unclear and used model mice were not well established. In the present study, the effect of trigonelline on memory function was investigated in Alzheimer’s disease transgenic model mouse, 5XFAD which overexpresses the mutated APP and PS1 genes. Oral administration of trigonelline for 14 days significantly enhanced object recognition and object location memories. Plasma and cerebral cortex were isolated at 30 min, 1h, 3h, and 6 h after oral administration of trigonelline. LC-MS/MS analysis indicated that trigonelline was detected in both plasma and cortex from 30 min after, suggesting good penetration of trigonelline into the brain. In addition, trigonelline significantly ameliorated axonal and dendrite atrophy in Amyloid β-treated cortical neurons. These results suggest that trigonelline could be a promising therapeutic candidate for AD.

Keywords: alzheimer’s disease, cortical neurons, LC-MS/MS analysis, trigonelline

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2044 Leveraging Multimodal Neuroimaging Techniques to in vivo Address Compensatory and Disintegration Patterns in Neurodegenerative Disorders: Evidence from Cortico-Cerebellar Connections in Multiple Sclerosis

Authors: Efstratios Karavasilis, Foteini Christidi, Georgios Velonakis, Agapi Plousi, Kalliopi Platoni, Nikolaos Kelekis, Ioannis Evdokimidis, Efstathios Efstathopoulos

Abstract:

Introduction: Advanced structural and functional neuroimaging techniques contribute to the study of anatomical and functional brain connectivity and its role in the pathophysiology and symptoms’ heterogeneity in several neurodegenerative disorders, including multiple sclerosis (MS). Aim: In the present study, we applied multiparametric neuroimaging techniques to investigate the structural and functional cortico-cerebellar changes in MS patients. Material: We included 51 MS patients (28 with clinically isolated syndrome [CIS], 31 with relapsing-remitting MS [RRMS]) and 51 age- and gender-matched healthy controls (HC) who underwent MRI in a 3.0T MRI scanner. Methodology: The acquisition protocol included high-resolution 3D T1 weighted, diffusion-weighted imaging and echo planar imaging sequences for the analysis of volumetric, tractography and functional resting state data, respectively. We performed between-group comparisons (CIS, RRMS, HC) using CAT12 and CONN16 MATLAB toolboxes for the analysis of volumetric (cerebellar gray matter density) and functional (cortico-cerebellar resting-state functional connectivity) data, respectively. Brainance suite was used for the analysis of tractography data (cortico-cerebellar white matter integrity; fractional anisotropy [FA]; axial and radial diffusivity [AD; RD]) to reconstruct the cerebellum tracts. Results: Patients with CIS did not show significant gray matter (GM) density differences compared with HC. However, they showed decreased FA and increased diffusivity measures in cortico-cerebellar tracts, and increased cortico-cerebellar functional connectivity. Patients with RRMS showed decreased GM density in cerebellar regions, decreased FA and increased diffusivity measures in cortico-cerebellar WM tracts, as well as a pattern of increased and mostly decreased functional cortico-cerebellar connectivity compared to HC. The comparison between CIS and RRMS patients revealed significant GM density difference, reduced FA and increased diffusivity measures in WM cortico-cerebellar tracts and increased/decreased functional connectivity. The identification of decreased WM integrity and increased functional cortico-cerebellar connectivity without GM changes in CIS and the pattern of decreased GM density decreased WM integrity and mostly decreased functional connectivity in RRMS patients emphasizes the role of compensatory mechanisms in early disease stages and the disintegration of structural and functional networks with disease progression. Conclusions: In conclusion, our study highlights the added value of multimodal neuroimaging techniques for the in vivo investigation of cortico-cerebellar brain changes in neurodegenerative disorders. An extension and future opportunity to leverage multimodal neuroimaging data inevitably remain the integration of such data in the recently-applied mathematical approaches of machine learning algorithms to more accurately classify and predict patients’ disease course.

Keywords: advanced neuroimaging techniques, cerebellum, MRI, multiple sclerosis

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2043 Harnessing Nature's Fury: Hyptis Suaveolens Loaded Bioactive Liposome for Photothermal Therapy of Lung Cancer

Authors: Sajmina Khatun, Monika Pebam, Aravind Kumar Rengan

Abstract:

Photothermal therapy, a subset of nanomedicine, takes advantage of light-absorbing agents to generate localized heat, selectively eradicating cancer cells. This innovative approach minimizes damage to healthy tissues and offers a promising avenue for targeted cancer treatment. Unlike conventional therapies, photothermal therapy harnesses the power of light to combat malignancies precisely and effectively, showcasing its potential to revolutionize cancer treatment paradigms. The combined strengths of nanomedicine and photothermal therapy signify a transformative shift toward more effective, targeted, and tolerable cancer treatments in the medical landscape. Utilizing natural products becomes instrumental in formulating diverse bioactive medications owing to their various pharmacological properties attributed to the existence of phenolic structures, triterpenoids, and similar compounds. Hyptis suaveolens, commonly known as pignut, stands as an aromatic herb within the Lamiaceae family and represents a valuable therapeutic plant. Flourishing in swamps and alongside tropical and subtropical roadsides, these noxious weeds impede the development of adjacent plants. Hyptis suaveolens ranks among the most globally distributed alien invasive species. The present investigation revealed that a versatile, biodegradable liposome nanosystem (HIL NPs), incorporating bioactive molecules from Hyptis suaveolens, exhibits effective bioavailability to cancer cells, enabling tumor ablation upon near-infrared (NIR) laser exposure. The components within the nanosystem, specifically the bioactive molecules from Hyptis, function as anticancer agents, aiding in the photothermal ablation of highly metastatic lung cancer cells. Despite being a prolific weed impeding neighboring plant growth, Hyptis suaveolens showcases therapeutic benefits through its bioactive compounds. The obtained HIL NPs, characterized as a photothermally active liposome nanosystem, demonstrate a pronounced fluorescence absorption peak in the NIR range and achieve a high photothermal conversion efficiency under NIR laser irradiation. Transmission electron microscopy (TEM) and particle size analysis reveal that HIL NPs possess a spherical shape with a size of 141 ± 30 nm. Moreover, in vitro assessments of HIL NPs against lung cancer cell lines (A549) indicate effective anticancer activity through a combined cytotoxic effect and hyperthermia. Tumor ablation is facilitated by apoptosis induced by the overexpression of ɣ-H2AX, arresting cancer cell proliferation. Consequently, the multifunctional and biodegradable nanosystem (HIL NPs), incorporating bioactive compounds from Hyptis, provides valuable perspectives for developing an innovative therapeutic strategy originating from a challenging weed. This approach holds promise for potential applications in both bioimaging and the combined use of phyto-photothermal therapy for cancer treatment.

Keywords: bioactive liposome, hyptis suaveolens, photothermal therapy, lung cancer

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2042 Learning Environments in the Early Years: A Case Study of an Early Childhood Centre in Australia

Authors: Mingxi Xiao

Abstract:

Children’s experiences in the early years build and shape the brain. The early years learning environment plays a significantly important role in children’s development. A well-constructed environment will facilitate children’s physical and mental well-being. This case study used an early learning centre in Australia called SDN Hurstville as an example, describing the learning environment in the centre, as well as analyzing the functions of the affordances. In addition, this report talks about the sustainability of learning in the centre, and how the environment supports cultural diversity and indigenous learning. The early years for children are significant. Different elements in the early childhood centre should work together to help children develop better. This case study found that the natural environment and the artificial environment are both critical to children; only when they work together can children have better development in physical and mental well-being and have a sense of belonging when playing and learning in the centre.

Keywords: early childhood center, early childhood education, learning environment, Australia

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2041 The Budget Impact of the DISCERN™ Diagnostic Test for Alzheimer’s Disease in the United States

Authors: Frederick Huie, Lauren Fusfeld, William Burchenal, Scott Howell, Alyssa McVey, Thomas F. Goss

Abstract:

Alzheimer’s Disease (AD) is a degenerative brain disease characterized by memory loss and cognitive decline that presents a substantial economic burden for patients and health insurers in the US. This study evaluates the payer budget impact of the DISCERN™ test in the diagnosis and management of patients with symptoms of dementia evaluated for AD. DISCERN™ comprises three assays that assess critical factors related to AD that regulate memory, formation of synaptic connections among neurons, and levels of amyloid plaques and neurofibrillary tangles in the brain and can provide a quicker, more accurate diagnosis than tests in the current diagnostic pathway (CDP). An Excel-based model with a three-year horizon was developed to assess the budget impact of DISCERN™ compared with CDP in a Medicare Advantage plan with 1M beneficiaries. Model parameters were identified through a literature review and were verified through consultation with clinicians experienced in diagnosis and management of AD. The model assesses direct medical costs/savings for patients based on the following categories: •Diagnosis: costs of diagnosis using DISCERN™ and CDP. •False Negative (FN) diagnosis: incremental cost of care avoidable with a correct AD diagnosis and appropriately directed medication. •True Positive (TP) diagnosis: AD medication costs; cost from a later TP diagnosis with the CDP versus DISCERN™ in the year of diagnosis, and savings from the delay in AD progression due to appropriate AD medication in patients who are correctly diagnosed after a FN diagnosis.•False Positive (FP) diagnosis: cost of AD medication for patients who do not have AD. A one-way sensitivity analysis was conducted to assess the effect of varying key clinical and cost parameters ±10%. An additional scenario analysis was developed to evaluate the impact of individual inputs. In the base scenario, DISCERN™ is estimated to decrease costs by $4.75M over three years, equating to approximately $63.11 saved per test per year for a cohort followed over three years. While the diagnosis cost is higher with DISCERN™ than with CDP modalities, this cost is offset by the higher overall costs associated with CDP due to the longer time needed to receive a TP diagnosis and the larger number of patients who receive a FN diagnosis and progress more rapidly than if they had received appropriate AD medication. The sensitivity analysis shows that the three parameters with the greatest impact on savings are: reduced sensitivity of DISCERN™, improved sensitivity of the CDP, and a reduction in the percentage of disease progression that is avoided with appropriate AD medication. A scenario analysis in which DISCERN™ reduces the utilization for patients of computed tomography from 21% in the base case to 16%, magnetic resonance imaging from 37% to 27% and cerebrospinal fluid biomarker testing, positive emission tomography, electroencephalograms, and polysomnography testing from 4%, 5%, 10%, and 8%, respectively, in the base case to 0%, results in an overall three-year net savings of $14.5M. DISCERN™ improves the rate of accurate, definitive diagnosis of AD earlier in the disease and may generate savings for Medicare Advantage plans.

Keywords: Alzheimer’s disease, budget, dementia, diagnosis.

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2040 Tactile Cues and Spatial Navigation in Mice

Authors: Rubaiyea Uddin

Abstract:

The hippocampus, located in the limbic system, is most commonly known for its role in memory and spatial navigation (as cited in Brain Reward and Pathways). It maintains an especially important role in specifically episodic and declarative memory. The hippocampus has also recently been linked to dopamine, the reward pathway’s primary neurotransmitter. Since research has found that dopamine also contributes to memory consolidation and hippocampal plasticity, this neurotransmitter is potentially responsible for contributing to the hippocampus’s role in memory formation. In this experiment we tested to see the effect of tactile cues on spatial navigation for eight different mice. We used a radial arm that had one designated 'reward' arm containing sucrose. The presence or absence of bedding was our tactile cue. We attempted to see if the memory of that cue would enhance the mice’s memory of having received the reward in that arm. The results from our study showed there was no significant response from the use of tactile cues on spatial navigation on our 129 mice. Tactile cues therefore do not influence spatial navigation.

Keywords: mice, radial arm maze, memory, spatial navigation, tactile cues, hippocampus, reward, sensory skills, Alzheimer’s, neurodegnerative disease

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2039 Immunoliposome-Mediated Drug Delivery to Plasmodium-Infected and Non-Infected Red Blood Cells as a Dual Therapeutic/Prophylactic Antimalarial Strategy

Authors: Ernest Moles, Patricia Urbán, María Belén Jiménez-Díaz, Sara Viera-Morilla, Iñigo Angulo-Barturen, Maria Antònia Busquets, Xavier Fernàndez-Busquets

Abstract:

Bearing in mind the absence of an effective vaccine against malaria and its severe clinical manifestations causing nearly half a million deaths every year, this disease represents nowadays a major threat to life. Besides, the basic rationale followed by currently marketed antimalarial approaches is based on the administration of drugs on their own, promoting the emergence of drug-resistant parasites owing to the limitation in delivering drug payloads into the parasitized erythrocyte high enough to kill the intracellular pathogen while minimizing the risk of causing toxic side effects to the patient. Such dichotomy has been successfully addressed through the specific delivery of immunoliposome (iLP)-encapsulated antimalarials to Plasmodium falciparum-infected red blood cells (pRBCs). Unfortunately, this strategy has not progressed towards clinical applications, whereas in vitro assays rarely reach drug efficacy improvements above 10-fold. Here, we show that encapsulation efficiencies reaching >96% can be achieved for the weakly basic drugs chloroquine (CQ) and primaquine using the pH gradient active loading method in liposomes composed of neutrally charged, saturated phospholipids. Targeting antibodies are best conjugated through their primary amino groups, adjusting chemical crosslinker concentration to retain significant antigen recognition. Antigens from non-parasitized RBCs have also been considered as targets for the intracellular delivery of drugs not affecting the erythrocytic metabolism. Using this strategy, we have obtained unprecedented nanocarrier targeting to early intraerythrocytic stages of the malaria parasite for which there is a lack of specific extracellular molecular tags. Polyethylene glycol-coated liposomes conjugated with monoclonal antibodies specific for the erythrocyte surface protein glycophorin A (anti-GPA iLP) were capable of targeting 100% RBCs and pRBCs at the low concentration of 0.5 μM total lipid in the culture, with >95% of added iLPs retained into the cells. When exposed for only 15 min to P. falciparum in vitro cultures synchronized at early stages, free CQ had no significant effect over parasite viability up to 200 nM drug, whereas iLP-encapsulated 50 nM CQ completely arrested its growth. Furthermore, when assayed in vivo in P. falciparum-infected humanized mice, anti-GPA iLPs cleared the pathogen below detectable levels at a CQ dose of 0.5 mg/kg. In comparison, free CQ administered at 1.75 mg/kg was, at most, 40-fold less efficient. Our data suggest that this significant improvement in drug antimalarial efficacy is in part due to a prophylactic effect of CQ found by the pathogen in its host cell right at the very moment of invasion.

Keywords: immunoliposomal nanoparticles, malaria, prophylactic-therapeutic polyvalent activity, targeted drug delivery

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2038 Medical Advances in Diagnosing Neurological and Genetic Disorders

Authors: Simon B. N. Thompson

Abstract:

Retinoblastoma is a rare type of childhood genetic cancer that affects children worldwide. The diagnosis is often missed due to lack of education and difficulty in presentation of the tumor. Frequently, the tumor on the retina is noticed by photography when the red-eye flash, commonly seen in normal eyes, is not produced. Instead, a yellow or white colored patch is seen or the child has a noticeable strabismus. Early detection can be life-saving though often results in removal of the affected eye. Remaining functioning in the healthy eye when the child is young has resulted in super-vision and high or above-average intelligence. Technological advancement of cameras has helped in early detection. Brain imaging has also made possible early detection of neurological diseases and, together with the monitoring of cortisol levels and yawning frequency, promises to be the next new early diagnostic tool for the detection of neurological diseases where cortisol insufficiency is particularly salient, such as multiple sclerosis and Cushing’s disease.

Keywords: cortisol, neurological disease, retinoblastoma, Thompson cortisol hypothesis, yawning

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2037 Low- and High-Temperature Methods of CNTs Synthesis for Medicine

Authors: Grzegorz Raniszewski, Zbigniew Kolacinski, Lukasz Szymanski, Slawomir Wiak, Lukasz Pietrzak, Dariusz Koza

Abstract:

One of the most promising area for carbon nanotubes (CNTs) application is medicine. One of the most devastating diseases is cancer. Carbon nanotubes may be used as carriers of a slowly released drug. It is possible to use of electromagnetic waves to destroy cancer cells by the carbon nanotubes (CNTs). In our research we focused on thermal ablation by ferromagnetic carbon nanotubes (Fe-CNTs). In the cancer cell hyperthermia functionalized carbon nanotubes are exposed to radio frequency electromagnetic field. Properly functionalized Fe-CNTs join the cancer cells. Heat generated in nanoparticles connected to nanotubes warm up nanotubes and then the target tissue. When the temperature in tumor tissue exceeds 316 K the necrosis of cancer cells may be observed. Several techniques can be used for Fe-CNTs synthesis. In our work, we use high-temperature methods where arc-discharge is applied. Low-temperature systems are microwave plasma with assisted chemical vapor deposition (MPCVD) and hybrid physical-chemical vapor deposition (HPCVD). In the arc discharge system, the plasma reactor works with a pressure of He up to 0,5 atm. The electric arc burns between two graphite rods. Vapors of carbon move from the anode, through a short arc column and forms CNTs which can be collected either from the reactor walls or cathode deposit. This method is suitable for the production of multi-wall and single-wall CNTs. A disadvantage of high-temperature methods is a low purification, short length, random size and multi-directional distribution. In MPCVD system plasma is generated in waveguide connected to the microwave generator. Then containing carbon and ferromagnetic elements plasma flux go to the quartz tube. The additional resistance heating can be applied to increase the reaction effectiveness and efficiency. CNTs nucleation occurs on the quartz tube walls. It is also possible to use substrates to improve carbon nanotubes growth. HPCVD system involves both chemical decomposition of carbon containing gases and vaporization of a solid or liquid source of catalyst. In this system, a tube furnace is applied. A mixture of working and carbon-containing gases go through the quartz tube placed inside the furnace. As a catalyst ferrocene vapors can be used. Fe-CNTs may be collected then either from the quartz tube walls or on the substrates. Low-temperature methods are characterized by higher purity product. Moreover, carbon nanotubes from tested CVD systems were partially filled with the iron. Regardless of the method of Fe-CNTs synthesis the final product always needs to be purified for applications in medicine. The simplest method of purification is an oxidation of the amorphous carbon. Carbon nanotubes dedicated for cancer cell thermal ablation need to be additionally treated by acids for defects amplification on the CNTs surface what facilitates biofunctionalization. Application of ferromagnetic nanotubes for cancer treatment is a promising method of fighting with cancer for the next decade. Acknowledgment: The research work has been financed from the budget of science as a research project No. PBS2/A5/31/2013

Keywords: arc discharge, cancer, carbon nanotubes, CVD, thermal ablation

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