Search results for: injection drug users
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 5166

Search results for: injection drug users

3516 Understanding the Top Questions Asked about Hong Kong by Travellers Worldwide through a Corpus-Based Discourse Analytic Approach

Authors: Phoenix W. Y. Lam

Abstract:

As one of the most important service-oriented industries in contemporary society, tourism has increasingly seen the influence of the Internet on all aspects of travelling. Travellers nowadays habitually research online before making travel-related decisions. One platform on which such research is conducted is destination forums. The emergence of such online destination forums in the last decade has allowed tourists to share their travel experiences quickly and easily with a large number of online users around the world. As such, these destination forums also provide invaluable data for tourism bodies to better understand travellers’ views on their destinations. Collecting posts from the Hong Kong travel forum on the world’s largest travel website TripAdvisor®, the present study identifies the top questions asked by TripAdvisor users about Hong Kong through a corpus-based discourse analytic approach. Based on questions posted on the forum and their associated meta-data gathered in a one-year period, the study examines the top questions asked by travellers around the world to identify the key geographical locations in which users have shown the greatest interest in the city. Questions raised by travellers from different geographical locations are also compared to see if traveller communities by location vary in terms of their areas of interest. This analysis involves the study of key words and concordance of frequently-occurring items and a close reading of representative examples in context. Findings from the present study show that travellers who asked the most questions about Hong Kong are from North America and Asia, and that travellers from different locations have different concerns and interests, which are clearly reflected in the language of the questions asked on the travel forum. These findings can therefore provide tourism organisations with useful information about the key markets that should be targeted for promotional purposes, and can also allow such organisations to design advertising campaigns which better address the specific needs of such markets. The present study thus demonstrates the value of applying linguistic knowledge and methodologies to the domain of tourism to address practical issues.

Keywords: corpus, hong kong, online travel forum, tourism, TripAdvisor

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3515 Dual Drug Piperine-Paclitaxel Nanoparticles Inhibit Migration and Invasion in Human Breast Cancer Cells

Authors: Monika Verma, Renuka Sharma, B. R. Gulati, Namita Singh

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In combination therapy, two chemotherapeutic agents work together in a collaborative action. It has appeared as one of the promising approaches to improve anti-cancer treatment efficacy. In the present investigation, piperine (P-NPS), paclitaxel (PTX NPS), and a combination of both, piperine-paclitaxel nanoparticle (Pip-PTX NPS), were made by the nanoprecipitation method and later characterized by PSA, DSC, SEM, TEM, and FTIR. All nanoparticles exhibited a monodispersed size distribution with a size of below 200 nm, zeta potential ranges from (-30-40mV) and a narrow polydispersity index (>0.3) of the drugs. The average encapsulation efficiency was found to be between 80 and 90%. In vitro release of drugs for nanoparticles was done spectrophotometrically. FTIR and DSC results confirmed the presence of the drug. The Pip-PTX NPS significantly inhibit cell proliferation as compared to the native drugs nanoparticles in the breast cancer cell line MCF-7. In addition, Pip-PTX NPS suppresses cells in colony formation and soft gel agar assay. Scratch migration and Transwell chamber invasion assays revealed that combined nanoparticles reduce the migration and invasion of breast cancer cells. Morphological studies showed that Pip-PTX NPS penetrates the cells and induces apoptosis, which was further confirmed by DNA fragmentation, SEM, and western blot analysis. Taken together, Pip-PTX NPS inhibits cell proliferation, anchorage dependent and anchorage independent cell growth, reduces migration and invasion, and induces apoptosis in cells. These findings support that combination therapy using Pip-PTX NPS represents a potential approach and could be helpful in the future for breast cancer therapy.

Keywords: piperine, paclitaxel, breast cancer, apoptosis

Procedia PDF Downloads 87
3514 Evaluation of Gesture-Based Password: User Behavioral Features Using Machine Learning Algorithms

Authors: Lakshmidevi Sreeramareddy, Komalpreet Kaur, Nane Pothier

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Graphical-based passwords have existed for decades. Their major advantage is that they are easier to remember than an alphanumeric password. However, their disadvantage (especially recognition-based passwords) is the smaller password space, making them more vulnerable to brute force attacks. Graphical passwords are also highly susceptible to the shoulder-surfing effect. The gesture-based password method that we developed is a grid-free, template-free method. In this study, we evaluated the gesture-based passwords for usability and vulnerability. The results of the study are significant. We developed a gesture-based password application for data collection. Two modes of data collection were used: Creation mode and Replication mode. In creation mode (Session 1), users were asked to create six different passwords and reenter each password five times. In replication mode, users saw a password image created by some other user for a fixed duration of time. Three different duration timers, such as 5 seconds (Session 2), 10 seconds (Session 3), and 15 seconds (Session 4), were used to mimic the shoulder-surfing attack. After the timer expired, the password image was removed, and users were asked to replicate the password. There were 74, 57, 50, and 44 users participated in Session 1, Session 2, Session 3, and Session 4 respectfully. In this study, the machine learning algorithms have been applied to determine whether the person is a genuine user or an imposter based on the password entered. Five different machine learning algorithms were deployed to compare the performance in user authentication: namely, Decision Trees, Linear Discriminant Analysis, Naive Bayes Classifier, Support Vector Machines (SVMs) with Gaussian Radial Basis Kernel function, and K-Nearest Neighbor. Gesture-based password features vary from one entry to the next. It is difficult to distinguish between a creator and an intruder for authentication. For each password entered by the user, four features were extracted: password score, password length, password speed, and password size. All four features were normalized before being fed to a classifier. Three different classifiers were trained using data from all four sessions. Classifiers A, B, and C were trained and tested using data from the password creation session and the password replication with a timer of 5 seconds, 10 seconds, and 15 seconds, respectively. The classification accuracies for Classifier A using five ML algorithms are 72.5%, 71.3%, 71.9%, 74.4%, and 72.9%, respectively. The classification accuracies for Classifier B using five ML algorithms are 69.7%, 67.9%, 70.2%, 73.8%, and 71.2%, respectively. The classification accuracies for Classifier C using five ML algorithms are 68.1%, 64.9%, 68.4%, 71.5%, and 69.8%, respectively. SVMs with Gaussian Radial Basis Kernel outperform other ML algorithms for gesture-based password authentication. Results confirm that the shorter the duration of the shoulder-surfing attack, the higher the authentication accuracy. In conclusion, behavioral features extracted from the gesture-based passwords lead to less vulnerable user authentication.

Keywords: authentication, gesture-based passwords, machine learning algorithms, shoulder-surfing attacks, usability

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3513 Effect of Miconazole Nitrate on Immunological Response and Its Preventive Efficacy in Labeo rohita Fingerlings against Oomycetes Saprolegnia parasitica

Authors: Mukta Singh, Ratan Kumar Saha, Himadri Saha, Paramveer Singh

Abstract:

The present study evaluated the effect of sub-lethal doses of antifungal drug miconazole nitrate (MCZ) on immunological responses including immune-related gene expression and its role as a prophylactic drug against S. parasitica in Labeo rohita fingerlings. Fish were fed with sub lethal doses of MCZ i.e., T1- 6.30 mg MCZ kgBW⁻¹, T2- 12.61 mg MCZ kgBW⁻¹ and T3- 25.22 mg MCZ kgBW⁻¹ and sampling was done at different time intervals for 240 h. Immunological parameters viz. lysozyme activity, oxygen radical production and plasma anti-protease activity showed significant enhancement (p < 0.05) in fish fed with T2 and T3 doses. Significant reduction in plasma protein content was observed in all the dietary groups as compared to control. Expression of immune-relevant genes like TLR-22 and β2-M showed significantly higher expression at six h and 24 h of sampling in both liver and head-kidney. However, these genes showed a down-regulation after 120 h of sampling in both the tissues. Preventive efficacy study showed that single dose of MCZ provides protection against oomycetes up to the fourth day of infection. Significantly higher mortality was observed in control diet-fed fish as compared to fish fed with MCZ medicated diet. Thus, from the study, it can be concluded that the MCZ can act as a potent antifungal agent for preventing oomycetes infection as well as to enhance the immune response.

Keywords: antifungal, immune gene, immunological, miconazole nitrate, prophylactic

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3512 Recent Developments in Artificial Intelligence and Information Communications Technology

Authors: Dolapo Adeyemo

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Technology can be designed specifically for geriatrics and persons with disabilities or ICT accessibility solutions. Both solutions stand to benefit from advances in Artificial intelligence, which are computer systems that perform tasks that require human intelligence. Tasks such as decision making, visual perception, speech recognition, and even language translation are useful in both situation and will provide significant benefits to people with temporarily or permanent disabilities. This research’s goal is to review innovations focused on the use of artificial intelligence that bridges the accessibility gap in technology from a user-centered perspective. A mixed method approach that utilized a comprehensive review of academic literature on the subject combined with semi structure interviews of users, developers, and technology product owners. The internet of things and artificial intelligence technology is creating new opportunities in the assistive technology space and proving accessibility to existing technology. Device now more adaptable to the needs of the user by learning the behavior of users as they interact with the internet. Accessibility to devices have witnessed significant enhancements that continue to benefit people with disabilities. Examples of other advances identified are prosthetic limbs like robotic arms supported by artificial intelligence, route planning software for the visually impaired, and decision support tools for people with disabilities and even clinicians that provide care.

Keywords: ICT, IOT, accessibility solutions, universal design

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3511 Understanding the Selectional Preferences of the Twitter Mentions Network

Authors: R. Sudhesh Solomon, P. Y. K. L. Srinivas, Abhay Narayan, Amitava Das

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Users in social networks either unicast or broadcast their messages. At mention is the popular way of unicasting for Twitter whereas general tweeting could be considered as broadcasting method. Understanding the information flow and dynamics within a Social Network and modeling the same is a promising and an open research area called Information Diffusion. This paper seeks an answer to a fundamental question - understanding if the at-mention network or the unicasting pattern in social media is purely random in nature or is there any user specific selectional preference? To answer the question we present an empirical analysis to understand the sociological aspects of Twitter mentions network within a social network community. To understand the sociological behavior we analyze the values (Schwartz model: Achievement, Benevolence, Conformity, Hedonism, Power, Security, Self-Direction, Stimulation, Traditional and Universalism) of all the users. Empirical results suggest that values traits are indeed salient cue to understand how the mention-based communication network functions. For example, we notice that individuals possessing similar values unicast among themselves more often than with other value type people. We also observe that traditional and self-directed people do not maintain very close relationship in the network with the people of different values traits.

Keywords: information diffusion, personality and values, social network analysis, twitter mentions network

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3510 Unveiling the Self-Assembly Behavior and Salt-Induced Morphological Transition of Double PEG-Tailed Unconventional Amphiphiles

Authors: Rita Ghosh, Joykrishna Dey

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PEG-based amphiphiles are of tremendous importance for its widespread applications in pharmaceutics, household purposes, and drug delivery. Previously, a number of single PEG-tailed amphiphiles having significant applications have been reported from our group. Therefore, it was of immense interest to explore the properties and application potential of PEG-based double tailed amphiphiles. Herein, for the first time, two novel double PEG-tailed amphiphiles having different PEG chain lengths have been developed. The self-assembly behavior of the newly developed amphiphiles in aqueous buffer (pH 7.0) was thoroughly investigated at 25 oC by a number of techniques including, 1H-NMR, and steady-state and time-dependent fluorescence spectroscopy, dynamic light scattering, transmission electron microscopy, atomic force microscopy, and isothermal titration calorimetry. Despite having two polar PEG chains both molecules were found to have strong tendency to self-assemble in aqueous buffered solution above a very low concentration. Surprisingly, the amphiphiles were shown to form stable vesicles spontaneously at room temperature without any external stimuli. The results of calorimetric measurements showed that the vesicle formation is driven by the hydrophobic effect (positive entropy change) of the system, which is associated with the helix-to-random coil transition of the PEG chain. The spectroscopic data confirmed that the bilayer membrane of the vesicles is constituted by the PEG chains of the amphiphilic molecule. Interestingly, the vesicles were also found to exhibit structural transitions upon addition of salts in solution. These properties of the vesicles enable them as potential candidate for drug delivery.

Keywords: double-tailed amphiphiles, fluorescence, microscopy, PEG, vesicles

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3509 The Lytic Bacteriophage VbɸAB-1 Against Drug-Resistant Acinetobacter Baumannii Isolated from Hospitalized Pressure Ulcers Patients

Authors: M. Doudi, M. H. Pazandeh, L. Rahimzadeh Torabi

Abstract:

Bedsores are pressure ulcers that occur on the skin or tissue due to being immobile and lying in bed for extended periods. Bedsores have the potential to progress into open ulcers, increasing the possibility of a variety of bacterial infections. Acinetobacter baumannii, a pathogen of considerable clinical importance, exhibited a significant correlation with Bedsores (pressure ulcers) infections, thereby manifesting a wide spectrum of antibiotic resistance. The emergence of drug resistance has led researchers to focus on alternative methods, particularly phage therapy, for tackling bacterial infections. Phage therapy has emerged as a novel therapeutic approach to regulate the activity of these agents. The management of bacterial infections greatly benefits from the clinical utilization of bacteriophages as a valuable antimicrobial intervention. The primary objective of this investigation consisted of isolating and discerning potent bacteriophage capable of targeting multi-drug-resistant (MDR) and extensively drug-resistant (XDR) bacteria obtained from pressure ulcers. The present study analyzed and isolated A. baumannii strains obtained from a cohort of patients suffering from pressure ulcers at Taleghani Hospital in Ahvaz, Iran. An approach that included biochemical and molecular identification techniques was used to determine the taxonomic classification of bacterial isolates at the genus and species levels. The molecular identification process was facilitated by using the 16S rRNA gene in combination with universal primers 27 F and 1492 R. Bacteriophage was obtained through the isolation process conducted on treatment plant sewage located in Isfahan, Iran. The main goal of this study was to evaluate different characteristics of phage, such as their appearance, the range of hosts they can infect, how quickly they can enter a host, their stability at varying temperatures and pH levels, their effectiveness in killing bacteria, the growth pattern of a single phage stage, mapping of enzymatic digestion, and identification of proteomics patterns. The findings demonstrated that an examination was conducted on a sample of 50 specimens, wherein 15 instances of A. baumannii were identified. These microorganisms are the predominant Gram-negative agents known to cause wound infections in individuals suffering from bedsores. The study's findings indicated a high prevalence of antibiotic resistance in the strains isolated from pressure ulcers, excluding the clinical strains that exhibited responsiveness to colistin. According to the findings obtained from assessments of host range and morphological characteristics of bacteriophage VbɸAB-1, it can be concluded that this phage possesses specificity towards A. Baumannii BAH_Glau1001 was classified as a member of the Podoviridae family. The bacteriophage mentioned earlier showed the strongest antibacterial effect at a temperature of 18 °C and a pH of 6.5. Through the utilization of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis on protein fragments, it was established that the bacteriophage VbɸAB-1 exhibited a size range between 50 and 75 kilodaltons (KDa). The numerous research findings on the effectiveness of phages and the safety studies conducted suggest that the phages studied in this research can be considered as a practical solution and recommended approach for controlling and treating stubborn pathogens in burn wounds among hospitalized patients. The findings of our research indicated that isolated phages could be an effective antimicrobial and an appreciate candidate for prophylaxis against pressure ulcers.

Keywords: acinetobacter baumannii, extremely drug-resistant, phage therapy, surgery wound

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3508 Occurrence of Foreign Matter in Food: Applied Identification Method - Association of Official Agricultural Chemists (AOAC) and Food and Drug Administration (FDA)

Authors: E. C. Mattos, V. S. M. G. Daros, R. Dal Col, A. L. Nascimento

Abstract:

The aim of this study is to present the results of a retrospective survey on the foreign matter found in foods analyzed at the Adolfo Lutz Institute, from July 2001 to July 2015. All the analyses were conducted according to the official methods described on Association of Official Agricultural Chemists (AOAC) for the micro analytical procedures and Food and Drug Administration (FDA) for the macro analytical procedures. The results showed flours, cereals and derivatives such as baking and pasta products were the types of food where foreign matters were found more frequently followed by condiments and teas. Fragments of stored grains insects, its larvae, nets, excrement, dead mites and rodent excrement were the most foreign matter found in food. Besides, foreign matters that can cause a physical risk to the consumer’s health such as metal, stones, glass, wood were found but rarely. Miscellaneous (shell, sand, dirt and seeds) were also reported. There are a lot of extraneous materials that are considered unavoidable since are something inherent to the product itself, such as insect fragments in grains. In contrast, there are avoidable extraneous materials that are less tolerated because it is preventable with the Good Manufacturing Practice. The conclusion of this work is that although most extraneous materials found in food are considered unavoidable it is necessary to keep the Good Manufacturing Practice throughout the food processing as well as maintaining a constant surveillance of the production process in order to avoid accidents that may lead to occurrence of these extraneous materials in food.

Keywords: extraneous materials, food contamination, foreign matter, surveillance

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3507 Political Communication in Twitter Interactions between Government, News Media and Citizens in Mexico

Authors: Jorge Cortés, Alejandra Martínez, Carlos Pérez, Anaid Simón

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The presence of government, news media, and general citizenry in social media allows considering interactions between them as a form of political communication (i.e. the public exchange of contradictory discourses about politics). Twitter’s asymmetrical following model (users can follow, mention or reply to other users that do not follow them) could foster alternative democratic practices and have an impact on Mexican political culture, which has been marked by a lack of direct communication channels between these actors. The research aim is to assess Twitter’s role in political communication practices through the analysis of interaction dynamics between government, news media, and citizens by extracting and visualizing data from Twitter’s API to observe general behavior patterns. The hypothesis is that regardless the fact that Twitter’s features enable direct and horizontal interactions between actors, users repeat traditional dynamics of interaction, without taking full advantage of the possibilities of this medium. Through an interdisciplinary team including Communication Strategies, Information Design, and Interaction Systems, the activity on Twitter generated by the controversy over the presence of Uber in Mexico City was analysed; an issue of public interest, involving aspects such as public opinion, economic interests and a legal dimension. This research includes techniques from social network analysis (SNA), a methodological approach focused on the comprehension of the relationships between actors through the visual representation and measurement of network characteristics. The analysis of the Uber event comprised data extraction, data categorization, corpus construction, corpus visualization and analysis. On the recovery stage TAGS, a Google Sheet template, was used to extract tweets that included the hashtags #UberSeQueda and #UberSeVa, posts containing the string Uber and tweets directed to @uber_mx. Using scripts written in Python, the data was filtered, discarding tweets with no interaction (replies, retweets or mentions) and locations outside of México. Considerations regarding bots and the omission of anecdotal posts were also taken into account. The utility of graphs to observe interactions of political communication in general was confirmed by the analysis of visualizations generated with programs such as Gephi and NodeXL. However, some aspects require improvements to obtain more useful visual representations for this type of research. For example, link¬crossings complicates following the direction of an interaction forcing users to manipulate the graph to see it clearly. It was concluded that some practices prevalent in political communication in Mexico are replicated in Twitter. Media actors tend to group together instead of interact with others. The political system tends to tweet as an advertising strategy rather than to generate dialogue. However, some actors were identified as bridges establishing communication between the three spheres, generating a more democratic exercise and taking advantage of Twitter’s possibilities. Although interactions in Twitter could become an alternative to political communication, this potential depends on the intentions of the participants and to what extent they are aiming for collaborative and direct communications. Further research is needed to get a deeper understanding on the political behavior of Twitter users and the possibilities of SNA for its analysis.

Keywords: interaction, political communication, social network analysis, Twitter

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3506 Antioxidant Activity of Avocado Puree on Blood Urea Nitrogen and Creatinine Level in White Rats (Rattus norvegicus) Induced with Toxic Doses of Meloxicam

Authors: Amelia R. Anshar, Dini Kurnia, Muh A. Bahar

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Nowadays, there are so many incidences had been reported in pet animals regarding drug overdose caused by incorrect doses of a non-steroidal anti-inflammatory drug (NSAID), for instance, meloxicam. As supporting treatment, the avocado is used in traditional medicine to treat or prevent some health cases. The study was aimed at providing the basis for the antioxidant activity of avocado puree in animal medicine. Experimental animals used in this study were 24 male rats that were randomly divided into 4 groups (n=6). Control Group I got 1 ml CMC 1% and control II got meloxicam 30 mg/kgBB and 1 ml CMC 1%. Treatment group I got meloxicam 30 mg/kgBB and avocado 5 g/kgBB/day and treatment II got meloxicam 30 mg/kgBB and avocado 10 g/kgBB/day. The study was conducted over 8 days, then the level of Blood Urea Nitrogen and creatinine of the white rats were examined in 1st day and 8th day. The results were analyzed by ANOVA Two Way With Replication, then followed by T-test (α = 0,05) if there were a difference. Comparison test among the four groups after treatment with avocado using Anova Two Way With Replication test showed that there were significant differences between the mean of the four groups either decreased levels of Blood Urea Nitrogen and creatinine with p < 0,05. Treatment group I and II received treatment showed remarkable (p < 0,05) decreases ini Blood Urea Nitrogen level by 27,17 mg/dl and 17,83 mg/dl respectively. There was also significant decrease in the values of creatinine in Treatment group I and treatment group II by 0,983 mg/dl and 0,713 mg/dl respectively. The conclusion of this study was that avocado decreases level of Blood Urea Nitrogen and creatinine in white rats which are exposed to toxic doses of meloxicam.

Keywords: avocado, blood urea nitrogen, creatinine, meloxicam

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3505 Convolution Neural Network Based on Hypnogram of Sleep Stages to Predict Dosages and Types of Hypnotic Drugs for Insomnia

Authors: Chi Wu, Dean Wu, Wen-Te Liu, Cheng-Yu Tsai, Shin-Mei Hsu, Yin-Tzu Lin, Ru-Yin Yang

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Background: The results of previous studies compared the benefits and risks of receiving insomnia medication. However, the effects between hypnotic drugs used and enhancement of sleep quality were still unclear. Objective: The aim of this study is to establish a prediction model for hypnotic drugs' dosage used for insomnia subjects and associated the relationship between sleep stage ratio change and drug types. Methodologies: According to American Academy of Sleep Medicine (AASM) guideline, sleep stages were classified and transformed to hypnogram via the polysomnography (PSG) in a hospital in New Taipei City (Taiwan). The subjects with diagnosis for insomnia without receiving hypnotic drugs treatment were be set as the comparison group. Conversely, hypnotic drugs dosage within the past three months was obtained from the clinical registration for each subject. Furthermore, the collecting subjects were divided into two groups for training and testing. After training convolution neuron network (CNN) to predict types of hypnotics used and dosages are taken, the test group was used to evaluate the accuracy of classification. Results: We recruited 76 subjects in this study, who had been done PSG for transforming hypnogram from their sleep stages. The accuracy of dosages obtained from confusion matrix on the test group by CNN is 81.94%, and accuracy of hypnotic drug types used is 74.22%. Moreover, the subjects with high ratio of wake stage were correctly classified as requiring medical treatment. Conclusion: CNN with hypnogram was potentially used for adjusting the dosage of hypnotic drugs and providing subjects to pre-screening the types of hypnotic drugs taken.

Keywords: convolution neuron network, hypnotic drugs, insomnia, polysomnography

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3504 DPAGT1 Inhibitors: Discovery of Anti-Metastatic Drugs

Authors: Michio Kurosu

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Alterations in glycosylation not only directly impact cell growth and survival but also facilitate tumor-induced immunomodulation and eventual metastasis. Identification of cell type-specific glycoconjugates (tumor markers) has led to the discovery of new assay systems for certain cancers via immunodetection reagents. N- and O-linked glycans are the most abundant forms of glycoproteins. Recent studies of cancer immunotherapy are based on the immunogenicity of truncated O-glycan chains (e.g., Tn, sTn, T, and sLea/x). The prevalence of N-linked glycan changes in the development of tumor cells is known; however, therapeutic antibodies against N-glycans have not yet been developed. This is due to the lack of specificity of N-linked glycans between normal/healthy and cancer cells. Abnormal branching of N-linked glycans has been observed, particularly in solid cancer cells. While the discovery of drug-like glycosyltransferase inhibitors that block the biosynthesis of specific branching has a very low likelihood of success, altered glycosylation levels can be exploited by suppressing N-glycan biosynthesis through the inhibition of dolichyl-phosphate N-acetylglucosaminephosphotransferase1 (DPAGT1) activity. Inhibition of DPAGT1 function leads to changes of O-glycosylation on proteins associated with mitochondria and zinc finger binding proteins (indirect effects). On the basis of dynamic crosstalk between DPAGT1 and Snail/Slung/ZEB1 (a family of transcription factors that promote the repression of the adhesion molecules), we have developed pharmacologically acceptable selective DPAGT1 inhibitors. Tunicamycin kills a wide range of cancer and healthy cells in a non-selective manner. In sharp contrast, our DPAGT1 inhibitors display strong cytostatic effects against 16 solid cancers, which require the overexpression of DPAGT1 in their progression but do not affect the cell viability of healthy cells. The identified DPAGT1 inhibitors possess impressive anti-metastatic ability in various solid cancer cell lines and induce their mitochondrial structural changes, resulting in apoptosis. A prototype DPAGT1 inhibitor, APPB has already been proven to shrink solid tumors (e.g., pancreatic cancers, triple-negative breast cancers) in vivo while suppressing metastases and has strong synergistic effects when combined with current cytotoxic drugs (e.g., paclitaxel). At this conference, our discovery of selective DPAGT1 inhibitors with drug-like properties and proof-of-pharmaceutical concept studies of a novel DPAGT1 inhibitor are presented.

Keywords: DPAGT1 inhibitors, anti-metastatic drugs, natural product based drug designs, cytostatic effects

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3503 Diselenide-Linked Redox Stimuli-Responsive Methoxy Poly(Ethylene Glycol)-b-Poly(Lactide-Co-Glycolide) Micelles for the Delivery of Doxorubicin in Cancer Cells

Authors: Yihenew Simegniew Birhan, Hsieh Chih Tsai

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The recent advancements in synthetic chemistry and nanotechnology fostered the development of different nanocarriers for enhanced intracellular delivery of pharmaceutical agents to tumor cells. Polymeric micelles (PMs), characterized by small size, appreciable drug loading capacity (DLC), better accumulation in tumor tissue via enhanced permeability and retention (EPR) effect, and the ability to avoid detection and subsequent clearance by the mononuclear phagocyte (MNP) system, are convenient to improve the poor solubility, slow absorption and non-selective biodistribution of payloads embedded in their hydrophobic cores and hence, enhance the therapeutic efficacy of chemotherapeutic agents. Recently, redox-responsive polymeric micelles have gained significant attention for the delivery and controlled release of anticancer drugs in tumor cells. In this study, we synthesized redox-responsive diselenide bond containing amphiphilic polymer, Bi(mPEG-PLGA)-Se₂ from mPEG-PLGA, and 3,3'-diselanediyldipropanoic acid (DSeDPA) using DCC/DMAP as coupling agents. The successful synthesis of the copolymers was verified by different spectroscopic techniques. Above the critical micelle concentration, the amphiphilic copolymer, Bi(mPEG-PLGA)-Se₂, self-assembled into stable micelles. The DLS data indicated that the hydrodynamic diameter of the micelles (123.9 ± 0.85 nm) was suitable for extravasation into the tumor cells through the EPR effect. The drug loading content (DLC) and encapsulation efficiency (EE) of DOX-loaded micelles were found to be 6.61 wt% and 54.9%, respectively. The DOX-loaded micelles showed initial burst release accompanied by sustained release trend where 73.94% and 69.54% of encapsulated DOX was released upon treatment with 6mM GSH and 0.1% H₂O₂, respectively. The biocompatible nature of Bi(mPEG-PLGA)-Se₂ copolymer was confirmed by the cell viability study. In addition, the DOX-loaded micelles exhibited significant inhibition against HeLa cells (44.46%), at a maximum dose of 7.5 µg/mL. The fluorescent microscope images of HeLa cells treated with 3 µg/mL (equivalent DOX concentration) revealed efficient internalization and accumulation of DOX-loaded Bi(mPEG-PLGA)-Se₂ micelles in the cytosol of cancer cells. In conclusion, the intelligent, biocompatible, and the redox stimuli-responsive behavior of Bi(mPEG-PLGA)-Se₂ copolymer marked the potential applications of diselenide-linked mPEG-PLGA micelles for the delivery and on-demand release of chemotherapeutic agents in cancer cells.

Keywords: anticancer drug delivery, diselenide bond, polymeric micelles, redox-responsive

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3502 Phishing Detection: Comparison between Uniform Resource Locator and Content-Based Detection

Authors: Nuur Ezaini Akmar Ismail, Norbazilah Rahim, Norul Huda Md Rasdi, Maslina Daud

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A web application is the most targeted by the attacker because the web application is accessible by the end users. It has become more advantageous to the attacker since not all the end users aware of what kind of sensitive data already leaked by them through the Internet especially via social network in shake on ‘sharing’. The attacker can use this information such as personal details, a favourite of artists, a favourite of actors or actress, music, politics, and medical records to customize phishing attack thus trick the user to click on malware-laced attachments. The Phishing attack is one of the most popular attacks for social engineering technique against web applications. There are several methods to detect phishing websites such as Blacklist/Whitelist based detection, heuristic-based, and visual similarity-based detection. This paper illustrated a comparison between the heuristic-based technique using features of a uniform resource locator (URL) and visual similarity-based detection techniques that compares the content of a suspected phishing page with the legitimate one in order to detect new phishing sites based on the paper reviewed from the past few years. The comparison focuses on three indicators which are false positive and negative, accuracy of the method, and time consumed to detect phishing website.

Keywords: heuristic-based technique, phishing detection, social engineering and visual similarity-based technique

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3501 Insight into the Binding Theme of CA-074Me to Cathepsin B: Molecular Dynamics Simulations and Scaffold Hopping to Identify Potential Analogues as Anti-Neurodegenerative Diseases

Authors: Tivani Phosa Mashamba-Thompson, Mahmoud E. S. Soliman

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To date, the cause of neurodegeneration is not well understood and diseases that stem from neurodegeneration currently have no known cures. Cathepsin B (CB) enzyme is known to be involved in the production of peptide neurotransmitters and toxic peptides in neurodegenerative diseases (NDs). CA-074Me is a membrane-permeable irreversible selective cathepsin B (CB) inhibitor as confirmed by in vivo studies. Due to the lack of the crystal structure, the binding mode of CA-074Me with the human CB at molecular level has not been previously reported. The main aim of this study is to gain an insight into the binding mode of CB CA-074Me to human CB using various computational tools. Herein, molecular dynamics simulations, binding free energy calculations and per-residue energy decomposition analysis were employed to accomplish the aim of the study. Another objective was to identify novel CB inhibitors based on the structure of CA-074Me using fragment based drug design using scaffold hoping drug design approach. Results showed that two of the designed ligands (hit 1 and hit 2) were found to have better binding affinities than the prototype inhibitor, CA-074Me, by ~2-3 kcal/mol. Per-residue energy decomposition showed that amino acid residues Cys29, Gly196, His197 and Val174 contributed the most towards the binding. The Van der Waals binding forces were found to be the major component of the binding interactions. The findings of this study should assist medicinal chemist towards the design of potential irreversible CB inhibitors.

Keywords: cathepsin B, scaffold hopping, docking, molecular dynamics, binding-free energy, neurodegerative diseases

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3500 Drug Reaction with Eosinophilia and Systemic Symptoms (Dress) Syndrome Presenting as Multi-Organ Failure

Authors: Keshari Shrestha, Philip Vatterott

Abstract:

Introduction: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare and potentially fatal drug-related syndrome. DRESS classically presents with a diffuse maculopapular rash, fevers, and eosinophilia more than three weeks after drug exposure. DRESS can present with multi-organ involvement, with liver damage being the most common and severe. Pulmonary involvement is a less common manifestation and is associated with poor clinical outcomes. Chest imaging is often nonspecific, and symptoms can range from mild cough to acute respiratory distress syndrome (ARDS) . This is a case of a 49-year-old female with a history of recent clostridium difficile colitis status post treatment with oral vancomycin who presented with rash, acute liver and kidney failure, as well as diffuse nodular alveolar lung opacities concerning for DRESS syndrome with multi-organ involvement. Clinical Course: This patient initially presented to an outside hospital with clostridium difficile colitis, acute liver injury, and acute kidney injury. She developed a desquamating maculopapular rash in the setting of recent oral vancomycin, meloxicam, and furosemide initiation. She was hospitalized on two additional occasions with worsening altered mental status, liver injury, and acute kidney injury and was initiated on intermittent hemodialysis. Notably, she was found to have systemic eosinophilia (4100 cells/microliter) several weeks prior. She was transferred to this institution for further management where she was found to have encephalopathy, jaundice, lower extremity edema, and diffuse bilateral rhonchorous breath sounds on pulmonary examination. The patient was started on methylprednisolone for suspected DRESS syndrome. She underwent an evaluation for alternative causes of her organ failure. Her workup included a negative infectious, autoimmune, metabolic, toxic, and malignant work-up. Abdominal computed tomography (CT) and ultrasound were remarkable for evidence of hepatic steatosis and possible cirrhotic morphology. Additionally, a chest CT demonstrated diffuse and symmetric nodular alveolar lung opacities with peripheral sparing not consistent with acute respiratory distress syndrome or edema. Ultimately, her condition continued to decline, and she required intubation on several occasions. On hospital day 25 she succumbed to distributive shock in the setting of probable sepsis and multi-organ failure. Discussion: DRESS syndrome occurs in 1 in 1,000 to 10,000 patients with a mortality rate of around 10%. Anti-convulsant, anti-bacterial, anti-viral, and sulfonamide drugs are the most common drugs implicated in the development of DRESS syndrome; however, the list of offending agents is extensive . The diagnosis of DRESS syndrome is made after excluding other causes of disease such as infectious and autoimmune etiologies. The RegiSCAR scoring system is used to diagnose DRESS syndrome with 2-3 points indicating possible disease, 4-5 probable disease, and >5 definite disease. This patient scored a 7 on the RegiSCAR scale for eosinophilia, rash, organ involvement, and exclusion of other causes (infectious and autoimmune). While the pharmacologic trigger in this case is unknown, it is speculated to be caused by vancomycin, meloxicam, or furosemide due to the favorable timeline of initiation. Despite aggressive treatment, DRESS syndrome can often be fatal. Because of this, early diagnosis and treatment of patients with suspected DRESS syndrome is imperative.

Keywords: drug reaction with eosinophilia and systemic symptoms, multi-organ failure, pulmonary involvement, renal failure

Procedia PDF Downloads 156
3499 Interactivity as a Predictor of Intent to Revisit Sports Apps

Authors: Young Ik Suh, Tywan G. Martin

Abstract:

Sports apps in a smartphone provide up-to-date information and fast and convenient access to live games. The market of sports apps has emerged as the second fastest growing app category worldwide. Further, many sports fans use their smartphones to know the schedule of sporting events, players’ position and bios, videos and highlights. In recent years, a growing number of scholars and practitioners alike have emphasized the importance of interactivity with sports apps, hypothesizing that interactivity plays a significant role in enticing sports apps users and that it is a key component in measuring the success of sports apps. Interactivity in sports apps focuses primarily on two functions: (1) two-way communication and (2) active user control, neither of which have been applicable through traditional mass media and communication technologies. Therefore, the purpose of this study is to examine whether the interactivity function on sports apps leads to positive outcomes such as intent to revisit. More specifically, this study investigates how three major functions of interactivity (i.e., two-way communication, active user control, and real-time information) influence the attitude of sports apps users and their intent to revisit the sports apps. The following hypothesis is proposed; interactivity functions will be positively associated with both attitudes toward sports apps and intent to revisit sports apps. The survey questionnaire includes four parts: (1) an interactivity scale, (2) an attitude scale, (3) a behavioral intention scale, and (4) demographic questions. Data are to be collected from ESPN apps users. To examine the relationships among the observed and latent variables and determine the reliability and validity of constructs, confirmatory factor analysis (CFA) is conducted. Structural equation modeling (SEM) is utilized to test hypothesized relationships among constructs. Additionally, this study compares the proposed interactivity model with a rival model to identify the role of attitude as a mediating factor. The findings of the current sports apps study provide several theoretical and practical contributions and implications by extending the research and literature associated with the important role of interactivity functions in sports apps and sports media consumption behavior. Specifically, this study may improve the theoretical understandings of whether the interactivity functions influence user attitudes and intent to revisit sports apps. Additionally, this study identifies which dimensions of interactivity are most important to sports apps users. From practitioners’ perspectives, this findings of this study provide significant implications. More entrepreneurs and investors in the sport industry need to recognize that high-resolution photos, live streams, and up-to-date stats are in the sports app, right at sports fans fingertips. The result will imply that sport practitioners may need to develop sports mobile apps that offer greater interactivity functions to attract sport fans.

Keywords: interactivity, two-way communication, active user control, real time information, sports apps, attitude, intent to revisit

Procedia PDF Downloads 135
3498 The Role of Formal and Informal Institutions in Water Governance in the Central Rift Valley of Ethiopia

Authors: Endalew Jibat, Feyera Senbeta, Tesfaye Zeleke, Fitsum Hagos

Abstract:

Institutions can play a key role in coordinating how natural resources are effectively used without over-exploitation. Institutions are the laws, policies, and organizational arrangements that permit, forbid or regulate human action. The aim of this study was to look into the roles of formal and informal institutions, as well as their interactions, in water resource governance in Ethiopia's Central Rift Valley (CRV), where water scarcity is a concern. Key informant interviews, group discussions, in depth-interview, and secondary data sources were used to generate relevant data. The study revealed that formal and informal institutions were involved in water resource governance in the study area. However, the influence of informal institutions on formal institutions or vice versa is trivial to change the action of water users. Lack of clear roles and responsibilities of actors, weak capacity and lack of meaningful decentralization and participation of key actors in policy development, lack of synergy and incongruence between formal and informal institutions, and absence of enforcement mechanisms including incentives are attributed to inefficient use of water resources in the CRV. Enhancing the interplay of formal and informal institutions in the water resource policy development and meaningful decentralization and key stakeholders' engagement is recommended for sustainable water use.

Keywords: institutions, governance, institutional interplay, water users

Procedia PDF Downloads 157
3497 Study of Biocomposites Based of Poly(Lactic Acid) and Olive Husk Flour

Authors: Samra Isadounene, Amar Boukerrou, Dalila Hammiche

Abstract:

In this work, the composites were prepared with poly(lactic acid) (PLA) and olive husk flour (OHF) with different percentages (10, 20 and 30%) using extrusion method followed by injection molding. The morphological, mechanical properties and thermal behavior of composites were investigated. Tensile strength and elongation at break of composites showed a decreasing trend with increasing fiber content. On the other hand, Young modulus and storage modulus were increased. The addition of OHF resulted in a decrease in thermal stability of composites. The presence of OHF led to an increase in percentage of crystallinity (Xc) of PLA matrix.

Keywords: biopolymers, composites, mechanical properties, poly(lactic acid)

Procedia PDF Downloads 221
3496 Generating Ideas to Improve Road Intersections Using Design with Intent Approach

Authors: Omar Faruqe Hamim, M. Shamsul Hoque, Rich C. McIlroy, Katherine L. Plant, Neville A. Stanton

Abstract:

Road safety has become an alarming issue, especially in low-middle income developing countries. The traditional approaches lack the out of the box thinking, making engineers confined to applying usual techniques in making roads safer. A socio-technical approach has recently been introduced in improving road intersections through designing with intent. This Design With Intent (DWI) approach aims to give practitioners a more nuanced approach to design and behavior, working with people, people’s understanding, and the complexities of everyday human experience. It's a collection of design patterns —and a design and research approach— for exploring the interactions between design and people’s behavior across products, services, and environments, both digital and physical. Through this approach, it can be seen that how designing with people in behavior change can be applied to social and environmental problems, as well as commercially. It has a total of 101 cards across eight different lenses, such as architectural, error-proofing, interaction, ludic, perceptual, cognitive, Machiavellian, and security lens each having its own distinct characteristics of extracting ideas from the participant of this approach. For this research purpose, a three-legged accident blackspot intersection of a national highway has been chosen to perform the DWI workshop. Participants from varying fields such as civil engineering, naval architecture and marine engineering, urban and regional planning, and sociology actively participated for a day long workshop. While going through the workshops, the participants were given a preamble of the accident scenario and a brief overview of DWI approach. Design cards of varying lenses were distributed among 10 participants and given an hour and a half for brainstorming and generating ideas to improve the safety of the selected intersection. After the brainstorming session, the participants spontaneously went through roundtable discussions regarding the ideas they have come up with. According to consensus of the forum, ideas were accepted or rejected. These generated ideas were then synthesized and agglomerated to bring about an improvement scheme for the intersection selected in our study. To summarize the improvement ideas from DWI approach, color coding of traffic lanes for separate vehicles, channelizing the existing bare intersection, providing advance warning traffic signs, cautionary signs and educational signs motivating road users to drive safe, using textured surfaces at approach with rumble strips before the approach of intersection were the most significant one. The motive of this approach is to bring about new ideas from the road users and not just depend on traditional schemes to increase the efficiency, safety of roads as well and to ensure the compliance of road users since these features are being generated from the minds of users themselves.

Keywords: design with intent, road safety, human experience, behavior

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3495 Studying the Effect of Nanoclays on the Mechanical Properties of Polypropylene/Polyamide Nanocomposites

Authors: Benalia Kouini, Aicha Serier

Abstract:

Nanocomposites based on polypropylene/polyamide 66 (PP/PA66) nanoblends containing organophilic montmorillonite (OMMT) and maleic anhydride grafted polypropylene (PP-g-MAH) were prepared by melt compounding method followed by injection molding. Two different types of nanoclays were used in this work. DELLITE LVF is the untreated nanoclay and DELLITE 67G is the treated one. The morphology of the nanocomposites was studied using the XR diffraction (XRD). The results indicate that the incorporation of treated nanoclay has a significant effect on the impact strength of PP/PA66 nanocomposites. Furthermore, it was found that XRD results revealed the intercalation, exfoliation of nanaclays of nanocomposites.

Keywords: nNanoclay, Nanocomposites, Polypropylene, Polyamide, melt processing, mechanical properties.

Procedia PDF Downloads 336
3494 A Two-Stage Adaptation towards Automatic Speech Recognition System for Malay-Speaking Children

Authors: Mumtaz Begum Mustafa, Siti Salwah Salim, Feizal Dani Rahman

Abstract:

Recently, Automatic Speech Recognition (ASR) systems were used to assist children in language acquisition as it has the ability to detect human speech signal. Despite the benefits offered by the ASR system, there is a lack of ASR systems for Malay-speaking children. One of the contributing factors for this is the lack of continuous speech database for the target users. Though cross-lingual adaptation is a common solution for developing ASR systems for under-resourced language, it is not viable for children as there are very limited speech databases as a source model. In this research, we propose a two-stage adaptation for the development of ASR system for Malay-speaking children using a very limited database. The two stage adaptation comprises the cross-lingual adaptation (first stage) and cross-age adaptation. For the first stage, a well-known speech database that is phonetically rich and balanced, is adapted to the medium-sized Malay adults using supervised MLLR. The second stage adaptation uses the speech acoustic model generated from the first adaptation, and the target database is a small-sized database of the target users. We have measured the performance of the proposed technique using word error rate, and then compare them with the conventional benchmark adaptation. The two stage adaptation proposed in this research has better recognition accuracy as compared to the benchmark adaptation in recognizing children’s speech.

Keywords: Automatic Speech Recognition System, children speech, adaptation, Malay

Procedia PDF Downloads 376
3493 Optimized Scheduling of Domestic Load Based on User Defined Constraints in a Real-Time Tariff Scenario

Authors: Madia Safdar, G. Amjad Hussain, Mashhood Ahmad

Abstract:

One of the major challenges of today’s era is peak demand which causes stress on the transmission lines and also raises the cost of energy generation and ultimately higher electricity bills to the end users, and it was used to be managed by the supply side management. However, nowadays this has been withdrawn because of existence of potential in the demand side management (DSM) having its economic and- environmental advantages. DSM in domestic load can play a vital role in reducing the peak load demand on the network provides a significant cost saving. In this paper the potential of demand response (DR) in reducing the peak load demands and electricity bills to the electric users is elaborated. For this purpose the domestic appliances are modeled in MATLAB Simulink and controlled by a module called energy management controller. The devices are categorized into controllable and uncontrollable loads and are operated according to real-time tariff pricing pattern instead of fixed time pricing or variable pricing. Energy management controller decides the switching instants of the controllable appliances based on the results from optimization algorithms. In GAMS software, the MILP (mixed integer linear programming) algorithm is used for optimization. In different cases, different constraints are used for optimization, considering the comforts, needs and priorities of the end users. Results are compared and the savings in electricity bills are discussed in this paper considering real time pricing and fixed tariff pricing, which exhibits the existence of potential to reduce electricity bills and peak loads in demand side management. It is seen that using real time pricing tariff instead of fixed tariff pricing helps to save in the electricity bills. Moreover the simulation results of the proposed energy management system show that the gained power savings lie in high range. It is anticipated that the result of this research will prove to be highly effective to the utility companies as well as in the improvement of domestic DR.

Keywords: controllable and uncontrollable domestic loads, demand response, demand side management, optimization, MILP (mixed integer linear programming)

Procedia PDF Downloads 289
3492 The Role of Online Platforms in Economic Growth and the Introduction of Local Culture in Tourist Areas

Authors: Maryam Nzari

Abstract:

Today, with the advancement of Internet technology, one of the tools used by humans is a tool that allows them to do what they need easily. Online platforms in different forms and by providing different services make it possible for users to communicate with each other and users with platforms. Audience communication with mass media is not the same as in the past. Today the conditions are different; With online platforms that provide the latest news minute by minute, he has access to all the content and can choose more quickly and easily. According to professionals Galloway, Apple, Amazon, Facebook and Google companies create a wide range. They are among the products and services that are connected with the daily life of billions of people all over the planet. Over time, platforms gain high economic value and in this way gain power that will influence the social, cultural, economic and political aspects of people’s lives. As a result of the effects of the process of platformization on all areas of individual and collective life, we now live in a platform society, which communicates It is close to “platform politics”. Nowadays, with social media platforms, users can interact with many people and people can share their data on various topics with others in this space. In this research, what will be investigated is the role of these online platforms in economic growth and the introduction of local culture areas in tourist areas. Tourism in a region is linked with various factors; One of the important factors that attract tourists to a region is its culture, and on the other hand, this culture can also affect economic growth. Without a proper understanding of the culture of these tourist areas, it is not possible to plan properly for the growth of the tourism industry and the subsequent increase in economic growth. The interaction of local people and tourists will have social and cultural effects on each other and will give them the opportunity to get to know each other. Therefore, the purpose of this research is to examine issues such as the role that online platforms play in cultural interaction in tourist areas and to understand that online platforms are only seeking to show the good aspects of a region and then generate enough extra income or that platforms can They play a role beyond what we imagine and introduce the culture of a region in a proper way so that we don’t see disagreements in the tourism planning of that region. in this article It has been tried by using library and field methods Answer the questions.

Keywords: online platforms, economic growth, culture Indigenous, tourism

Procedia PDF Downloads 44
3491 Improving Our Understanding of the in vivo Modelling of Psychotic Disorders

Authors: Zsanett Bahor, Cristina Nunes-Fonseca, Gillian L. Currie, Emily S. Sena, Lindsay D.G. Thomson, Malcolm R. Macleod

Abstract:

Psychosis is ranked as the third most disabling medical condition in the world by the World Health Organization. Despite a substantial amount of research in recent years, available treatments are not universally effective and have a wide range of adverse side effects. Since many clinical drug candidates are identified through in vivo modelling, a deeper understanding of these models, and their strengths and limitations, might help us understand reasons for difficulties in psychosis drug development. To provide an unbiased summary of the preclinical psychosis literature we performed a systematic electronic search of PubMed for publications modelling a psychotic disorder in vivo, identifying 14,721 relevant studies. Double screening of 11,000 publications from this dataset so far established 2403 animal studies of psychosis, with the most common model being schizophrenia (95%). 61% of these models are induced using pharmacological agents. For all the models only 56% of publications test a therapeutic treatment. We propose a systematic review of these studies to assess the prevalence of reporting of measures to reduce risk of bias, and a meta-analysis to assess the internal and external validity of these animal models. Our findings are likely to be relevant to future preclinical studies of psychosis as this generation of strong empirical evidence has the potential to identify weaknesses, areas for improvement and make suggestions on refinement of experimental design. Such a detailed understanding of the data which inform what we think we know will help improve the current attrition rate between bench and bedside in psychosis research.

Keywords: animal models, psychosis, systematic review, schizophrenia

Procedia PDF Downloads 275
3490 Metformin Protects Cardiac Muscle against the Pro-Apoptotic Effects of Hyperglycaemia, Elevated Fatty Acid and Nicotine

Authors: Christopher R. Triggle, Hong Ding, Khaled Machaca, Gnanapragasam Arunachalam

Abstract:

The antidiabetic drug, metformin, has been in clinical use for over 50 years and remains the first choice drug for the treatment of type two diabetes. In addition to its effectiveness as an oral anti-hyperglycaemic drug metformin also possesses vasculoprotective effects that are assumed to be secondary to its ability to reduce insulin resistance and control glycated hemoglobin levels; however, recent data from our laboratory indicate that metformin also has direct vasoprotective effects that are mediated, at least in part, via the anti-ageing gene, SIRT1. Diabetes is a major risk factor for the development of cardiovascular disease (CVD) and it is also well established that tobacco use further enhances the risk of CVD; however, it is not known whether treatment with metformin can offset the negative effects of diabetes and tobacco use on cardiac function. The current study was therefore designed to investigate 1: the effects of hyperglycaemia (HG) either alone or in the presence of elevated fatty acids (palmitate) and nicotine on the protein expression levels of the deacetylase sirtuin 1 (the protein product of SIRT1), anti-apoptotic Bcl-2, pro-apoptotic BIM and the pro-apoptotic, tumour suppressor protein, acetylated p53 in cardiomyocytes. 2: the ability of metformin to prevent the detrimental effects of HG, palmitate and nicotine on cardiomyocyte survival. Cell culture protocols were designed using a rat cardiomyocyte cell line, H9c2, either under normal glycaemic (NG) conditions of 5.5mM glucose, or hyperglycaemic conditions (HG) of 25mM glucose with, or without, added palmitate (250μM) or nicotine (1.0mM) for 24h. Immuno-blotting was used to detect the expression of sirtuin 1, Bcl-2, BIM, acetylated (Ac)-p53, p53 with β-actin used as the reference protein. Exposure to HG, palmitate, or nicotine alone significantly reduced expression of sirtuin1, Bcl-2 and raised the expression levels of acetylated p53 and BIM; however, the combination of HG, palmitate and nicotine had a synergistic effect to significantly suppress the expression levels of sirtuin 1 and Bcl-2, but further enhanced the expression of Ac-p53, and BIM. The inclusion of 1000μM, but not 50μM, metformin in the H9c2 cell culture protocol prevented the effects of HG, palmitate and nicotine on the pro-apoptotic pathways. Collectively these data indicate that metformin, in addition to its anti-hyperglycaemic and vasculoprotective properties, also has direct cardioprotective actions that offset the negative effects of hyerglycaemia, elevated free fatty acids and nicotine on cardiac cell survival. These data are of particular significance for the treatment of patients with diabetes who are also smokers as the inclusion of metformin in their therapeutic treatment plan should help reduce cardiac-related morbidity and mortality.

Keywords: apoptosis, cardiac muscle, diabetes, metformin, nicotine

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3489 Disaggregate Travel Behavior and Transit Shift Analysis for a Transit Deficient Metropolitan City

Authors: Sultan Ahmad Azizi, Gaurang J. Joshi

Abstract:

Urban transportation has come to lime light in recent times due to deteriorating travel quality. The economic growth of India has boosted significant rise in private vehicle ownership in cities, whereas public transport systems have largely been ignored in metropolitan cities. Even though there is latent demand for public transport systems like organized bus services, most of the metropolitan cities have unsustainably low share of public transport. Unfortunately, Indian metropolitan cities have failed to maintain balance in mode share of various travel modes in absence of timely introduction of mass transit system of required capacity and quality. As a result, personalized travel modes like two wheelers have become principal modes of travel, which cause significant environmental, safety and health hazard to the citizens. Of late, the policy makers have realized the need to improve public transport system in metro cities for sustaining the development. However, the challenge to the transit planning authorities is to design a transit system for cities that may attract people to switch over from their existing and rather convenient mode of travel to the transit system under the influence of household socio-economic characteristics and the given travel pattern. In this context, the fast-growing industrial city of Surat is taken up as a case for the study of likely shift to bus transit. Deterioration of public transport system of bus after 1998, has led to tremendous growth in two-wheeler traffic on city roads. The inadequate and poor service quality of present bus transit has failed to attract the riders and correct the mode use balance in the city. The disaggregate travel behavior for trip generations and the travel mode choice has been studied for the West Adajan residential sector of city. Mode specific utility functions are calibrated under multi-nominal logit environment for two-wheeler, cars and auto rickshaws with respect to bus transit using SPSS. Estimation of shift to bus transit is carried indicate an average 30% of auto rickshaw users and nearly 5% of 2W users are likely to shift to bus transit if service quality is improved. However, car users are not expected to shift to bus transit system.

Keywords: bus transit, disaggregate travel nehavior, mode choice Behavior, public transport

Procedia PDF Downloads 247
3488 Artificial Intelligence in Bioscience: The Next Frontier

Authors: Parthiban Srinivasan

Abstract:

With recent advances in computational power and access to enough data in biosciences, artificial intelligence methods are increasingly being used in drug discovery research. These methods are essentially a series of advanced statistics based exercises that review the past to indicate the likely future. Our goal is to develop a model that accurately predicts biological activity and toxicity parameters for novel compounds. We have compiled a robust library of over 150,000 chemical compounds with different pharmacological properties from literature and public domain databases. The compounds are stored in simplified molecular-input line-entry system (SMILES), a commonly used text encoding for organic molecules. We utilize an automated process to generate an array of numerical descriptors (features) for each molecule. Redundant and irrelevant descriptors are eliminated iteratively. Our prediction engine is based on a portfolio of machine learning algorithms. We found Random Forest algorithm to be a better choice for this analysis. We captured non-linear relationship in the data and formed a prediction model with reasonable accuracy by averaging across a large number of randomized decision trees. Our next step is to apply deep neural network (DNN) algorithm to predict the biological activity and toxicity properties. We expect the DNN algorithm to give better results and improve the accuracy of the prediction. This presentation will review all these prominent machine learning and deep learning methods, our implementation protocols and discuss these techniques for their usefulness in biomedical and health informatics.

Keywords: deep learning, drug discovery, health informatics, machine learning, toxicity prediction

Procedia PDF Downloads 345
3487 Increasing Solubility and Bioavailability of Fluvastatin through Transdermal Nanoemulsion Gel Delivery System for the Treatment of Osteoporosis

Authors: Ramandeep Kaur, Makula Ajitha

Abstract:

Fluvastatin has been reported for increasing bone mineral density in osteoporosis since last decade. Systemically administered drug undergoes extensive hepatic first-pass metabolism, thus very small amount of drug reaches the bone tissue which is highly insignificant. The present study aims to deliver fluvastatin in the form of nanoemulsion (NE) gel directly to the bone tissue through transdermal route thereby bypassing hepatic first pass metabolism. The NE formulation consisted of isopropyl myristate as oil, tween 80 as surfactant, transcutol as co-surfactant and water as the aqueous phase. Pseudoternary phase diagrams were constructed using aqueous titration method and NE’s obtained were subjected to thermodynamic-kinetic stability studies. The stable NE formulations were evaluated for their droplet size, zeta potential, and transmission electron microscopy (TEM). The nano-sized formulations were incorporated into 0.5% carbopol 934 gel matrix. Ex-vivo permeation behaviour of selected formulations through rat skin was investigated and compared with the conventional formulations (suspension and emulsion). Further, in-vivo pharmacokinetic study was carried using male Wistar rats. The optimized NE formulations mean droplet size was 11.66±3.2 nm with polydispersity index of 0.117. Permeation flux of NE gel formulations was found significantly higher than the conventional formulations i.e. suspension and emulsion. In vivo pharmacokinetic study showed significant increase in bioavailability (1.25 fold) of fluvastatin than oral formulation. Thus, it can be concluded that NE gel was successfully developed for transdermal delivery of fluvastatin for the treatment of osteoporosis.

Keywords: fluvastatin, nanoemulsion gel, osteoporosis, transdermal

Procedia PDF Downloads 176