Search results for: multi drug resistance tuberculosis (MDR-TB)

Authors: Arpita Roy, Navneeta Bharadvaja

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Cancer is an uncontrolled growth of abnormal cells in the body. It is one of the most serious diseases on which extensive research work has been going on all over the world. Structure-based drug designing is a computational approach which helps in the identification of potential leads that can be used for the development of a drug. Plumbagin is a naphthoquinone derivative from Plumbago zeylanica roots and belongs to one of the largest and diverse groups of plant metabolites. Anticancer and antiproliferative activities of plumbagin have been observed in animal models as well as in cell cultures. Plumbagin shows inhibitory effects on multiple cancer-signaling proteins; however, the binding mode and the molecular interactions have not yet been elucidated for most of these protein targets. In this investigation, an attempt to provide structural insights into the binding mode of plumbagin against four cancer receptors using molecular docking was performed. Plumbagin showed minimal energy against targeted cancer receptors, therefore suggested its stability and potential towards different cancers. The least binding energies of plumbagin with COX-2, TACE, and CDK6 are -5.39, -4.93, -and 4.81 kcal/mol, respectively. Comparison studies of plumbagin with different receptors showed that it is a promising compound for cancer treatment. It was also found that plumbagin obeys the Lipinski’s Rule of 5 and computed ADMET properties which showed drug likeliness and improved bioavailability. Since plumbagin is from a natural source, it has reduced side effects, and these results would be useful for cancer treatment.

Keywords: cancer, receptor, plumbagin, docking

Procedia PDF Downloads 135

Authors: Vladimir Berezin, Aizhan Turmagambetova, Andrey Bogoyavlenskiy, Pavel Alexyuk, Madina Alexyuk, Irina Zaitceva, Nadezhda Sokolova

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Introduction: Influenza viruses could infect approximately 5% to 10% of the global human population annually, resulting in serious social and economic damage. Vaccination and etiotropic antiviral drugs are used for the prevention and treatment of influenza. Vaccination is important; however, antiviral drugs represent the second line of defense against new emerging influenza virus strains for which vaccines may be unsuccessful. However, the significant drawback of commercial synthetic anti-flu drugs is the appearance of drug-resistant influenza virus strains. Therefore, the search and development of new anti-flu drugs efficient against drug-resistant strains is an important medical problem for today. The aim of this work was a study of four phenolic acids of plant origin (Gallic, Syringic, Vanillic, and Protocatechuic acids) as a possible tool for treatment against influenza virus. Methods: Phenolic acids; gallic, syringic, vanillic, and protocatechuic have been prepared by extraction from plant tissues and purified using high-performance liquid chromatography fractionation. Avian influenza virus, strain A/Tern/South Africa/1/1961 (H5N3) and human epidemic influenza virus, strain A/Almaty/8/98 (H3N2) resistant to commercial anti-flu drugs (Rimantadine, Oseltamivir) were used for testing antiviral activity. Viruses were grown in the allantoic cavity of 10 days old chicken embryos. The chemotherapeutic index (CTI), determined as the ratio of an average toxic concentration of the tested compound (TC₅₀) to the average effective virus-inhibition concentration (EC₅₀), has been used as a criteria of specific antiviral action. Results: The results of study have shown that the structure of phenolic acids significantly affected their ability to suppress the reproduction of tested influenza virus strains. The highest antiviral activity among tested phenolic acids was detected for gallic acid, which contains three hydroxyl groups in the molecule at C3, C4, and C5 positions. Antiviral activity of gallic acid against A/H5N3 and A/H3N2 influenza virus strains was higher than antiviral activity of Oseltamivir and Rimantadine. gallic acid inhibited almost 100% of the infection activity of both tested viruses. Protocatechuic acid, which possesses 2 hydroxyl groups (C3 and C4) have shown weaker antiviral activity in comparison with gallic acid and inhibited less than 10% of virus infection activity. Syringic acid, which contains two hydroxyl groups (C3 and C5), was able to suppress up to 12% of infection activity. Substitution of two hydroxyl groups by methoxy groups resulted in the complete loss of antiviral activity. Vanillic acid, which is different from protocatechuic acid by replacing of C3 hydroxyl group to methoxy group, was able to suppress about 30% of infection activity of tested influenza viruses. Conclusion: For pronounced antiviral activity, the molecular of phenolic acid must have at least two hydroxyl groups. Replacement of hydroxyl groups to methoxy group leads to a reduction of antiviral properties. Gallic acid demonstrated high antiviral activity against influenza viruses, including Rimantadine and Oseltamivir resistant strains, and could be used as a potential candidate for the development of antiviral drug against influenza virus.

Keywords: antiviral activity, influenza virus, drug resistance, phenolic acids

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Authors: Lakmini Wijesooriya, Vicki Chalker, Jessica Day, Priyantha Perera, N. P. Sunil-Chandra

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M. pneumoniae has been identified as an etiology for exacerbation of asthma (EQA), although viruses play a major role in EOA. M. pneumoniae infection is treated empirically with macrolides, and its antibiotic sensitivity is not detected routinely. Characterization of the organism by genotyping and determination of macrolide resistance is important epidemiologically as it guides the empiric antibiotic treatment. To date, there is no such characterization of M. pneumoniae performed in Sri Lanka. The present study describes the characterization of M. pneumoniae detected from a child with EOA following a screening of 100 children with EOA. Of the hundred children with EOA, M. pneumoniae was identified only in one child by Real-Time polymerase chain reaction (PCR) test for identifying the community-acquired respiratory distress syndrome (CARDS) toxin nucleotide sequences. The M. pneumoniae identified from this patient underwent detection of macrolide resistance via conventional PCR, amplifying and sequencing the region of the 23S rDNA gene that contains single nucleotide polymorphisms that confer resistance. Genotyping of the isolate was performed via nested Multilocus Sequence Typing (MLST) in which eight (8) housekeeping genes (ppa, pgm, gyrB, gmk, glyA, atpA, arcC, and adk) were amplified via nested PCR followed by gene sequencing and analysis. As per MLST analysis, the M. pneumoniae was identified as sequence type 14 (ST14), and no mutations that confer resistance were detected. Resistance to macrolides in M. pneumoniae is an increasing problem globally. Establishing surveillance systems is the key to informing local prescriptions. In the absence of local surveillance data, antibiotics are started empirically. If the relevant microbiological samples are not obtained before antibiotic therapy, as in most occasions in children, the course of antibiotic is completed without a microbiological diagnosis. This happens more frequently in therapy for M. pneumoniae which is treated with a macrolide in most patients. Hence, it is important to understand the macrolide sensitivity of M. pneumoniae in the setting. The M. pneumoniae detected in the present study was macrolide sensitive. Further studies are needed to examine a larger dataset in Sri Lanka to determine macrolide resistance levels to inform the use of macrolides in children with EOA. The MLST type varies in different geographical settings, and it also provides a clue to the existence of macrolide resistance. The present study enhances the database of the global distribution of different genotypes of M. pneumoniae as this is the first such characterization performed with the increased number of samples to determine macrolide resistance level in Sri Lanka. M. pneumoniae detected from a child with exacerbation of asthma in Sri Lanka was characterized as ST14 by MLST and no mutations that confer resistance were detected.

Keywords: mycoplasma pneumoniae, Sri Lanka, characterization, macrolide resistance

Procedia PDF Downloads 175

Authors: Swapnila V. Vanshiv, Hemant P. Joshi, Atul B. Aware

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Current study illustrates the formulation of floating microspheres for purpose of gastroretention of Dipyridamole which shows pH dependent solubility, with the highest solubility in acidic pH. The formulation involved hollow microsphere preparation by using solvent evaporation technique. Concentrations of rate controlling polymer, hydrophilic polymer, internal phase ratio, stirring speed were optimized to get desired responses, namely release of Dipyridamole, buoyancy of microspheres, entrapment efficiency of microspheres. In the formulation, the floating microspheres were prepared by using ethyl cellulose as release retardant and HPMC as a low density hydrophilic swellable polymer. Formulated microspheres were evaluated for their physical properties such as particle size and surface morphology by optical microscopy and SEM. Entrapment efficiency, floating behavior and drug release study as well the formulation was evaluated for in vivo gastroretention in rabbits using gamma scintigraphy. Formulation showed 75% drug release up to 10 hr with entrapment efficiency of 91% and 88% buoyancy till 10 hr. Gamma scintigraphic studies revealed that the optimized system was retained in the gastric region (stomach) for a prolonged period i.e. more than 5 hr.

Keywords: Dipyridamole microspheres, gastroretention, HPMC, optimization method

Procedia PDF Downloads 377

Authors: Malleshappa Japagal, Srinivas Chitragar

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The use of waste plastic in pavement is becoming important alternative worldwide for disposal of plastic as well as to improve the stability of pavement and to meet out environmental issues. However, there are still concerns on fatigue and fracture resistance of Hot Mix Asphalt with the addition of plastic waste, (HMA-Plastic mixes) and moisture damage potential. The present study was undertaken to evaluate fracture resistance of HMA-Plastic mixes using semi-circular bending (SCB) test and moisture damage potential by Indirect Tensile strength (ITS) test using retained tensile strength (TSR). In this study, a dense graded asphalt mix with 19 mm nominal maximum aggregate size was designed in the laboratory using Marshall Mix design method. Aggregates were coated with different percentages of waste plastic (0%, 2%, 3% and 4%) by weight of aggregate and performance evaluation of fracture resistance and Moisture damage was carried out. The following parameters were estimated for the mixes: J-Integral or Jc, strain energy at failure, peak load at failure, and deformation at failure. It was found that the strain energy and peak load of all the mixes decrease with an increase in notch depth, indicating that increased percentage of plastic waste gave better fracture resistance. The moisture damage potential was evaluated by Tensile strength ratio (TSR). The experimental results shown increased TRS value up to 3% addition of waste plastic in HMA mix which gives better performance hence the use of waste plastic in road construction is favorable.

Keywords: hot mix asphalt, semi circular bending, marshall mix design, tensile strength ratio

Procedia PDF Downloads 298

Authors: Hayani Anastasia, Junus Widjaja, Anis Nur Widayati

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In Indonesia, schistosomiasis is caused by Schistosoma japonicum with Oncomelania hupensis lindoensis as the intermediate host. Schistosomiasis can infect humans and all species of mammals. In order to achieve schistosomiasis elimination by 2020, schistosomiasis control, including environmental management, has been carried out by multi-sector. A cross-sectional study was conducted in 2018 to evaluate the multi-sectoral schistosomiasis control program. Data were collected by depth interviews of stakeholders, stool surveys, snail surveys, observation, and document reviews. About 53.6% of control programs in the schistosomiasis control roadmap were not achieved. The number of foci area found in 2018 are not significantly different compared to before the control programs. Moreover, the prevalence of schistosomiasis in the human was 0-5.1% and in mammals was the range from 0 to 10%. In order to overcome the problems, a policy about schistosomiasis as a priority program in ministries and agencies other than the Ministry of Health is needed. Innovative health promotion with interactive media also needs to be applied. Also, the schistosomiasis work team needs to be more active with the Agency of Regional Development as the leading sector.

Keywords: evaluation, Indonesia, multi-sector, schistosomiasis

Procedia PDF Downloads 123

Authors: Anusha M., V. Srikanth

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Maximizing spectrum usage and numerous applications of the wireless communication networks have forced to a high interest of available spectrum. Cognitive Radio control its receiver and transmitter features exactly so that they can utilize the vacant approved spectrum without impacting the functionality of the principal licensed users. The Use of various channels assists to address interferences thereby improves the whole network efficiency. The MAC protocol in cognitive radio network explains the spectrum usage by interacting with multiple channels among the users. In this paper we studied about the architecture of cognitive wireless mesh network and traditional TDMA dependent MAC method to allocate channels dynamically. The majority of the MAC protocols suggested in the research are operated on Common-Control-Channel (CCC) to handle the services between Cognitive Radio secondary users. In this paper, an extensive study of Multi-Channel Multi-Radios or frequency range channel allotment and continually synchronized TDMA scheduling are shown in summarized way.

Keywords: TDMA, MAC, multi-channel, multi-radio, WMN’S, cognitive radios

Procedia PDF Downloads 547

Authors: Norma Binti Alias, Che Rahim Che The, Norfarizan Mohd Said, Sakinah Abdul Hanan, Akhtar Ali

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This paper discusses on the transportation of magnetic drug targeting through blood within vessels, tissues and cells. There are three integrated mathematical models to be discussed and analyze the concentration of drug and blood flow through magnetic nanoparticles. The cell therapy brought advancement in the field of nanotechnology to fight against the tumors. The systematic therapeutic effect of Single Cells can reduce the growth of cancer tissue. The process of this nanoscale phenomena system is able to measure and to model, by identifying some parameters and applying fundamental principles of mathematical modeling and simulation. The mathematical modeling of single cell growth depends on three types of cell densities such as proliferative, quiescent and necrotic cells. The aim of this paper is to enhance the simulation of three types of models. The first model represents the transport of drugs by coupled partial differential equations (PDEs) with 3D parabolic type in a cylindrical coordinate system. This model is integrated by Non-Newtonian flow equations, leading to blood liquid flow as the medium for transportation system and the magnetic force on the magnetic nanoparticles. The interaction between the magnetic force on drug with magnetic properties produces induced currents and the applied magnetic field yields forces with tend to move slowly the movement of blood and bring the drug to the cancer cells. The devices of nanoscale allow the drug to discharge the blood vessels and even spread out through the tissue and access to the cancer cells. The second model is the transport of drug nanoparticles from the vascular system to a single cell. The treatment of the vascular system encounters some parameter identification such as magnetic nanoparticle targeted delivery, blood flow, momentum transport, density and viscosity for drug and blood medium, intensity of magnetic fields and the radius of the capillary. Based on two discretization techniques, finite difference method (FDM) and finite element method (FEM), the set of integrated models are transformed into a series of grid points to get a large system of equations. The third model is a single cell density model involving the three sets of first order PDEs equations for proliferating, quiescent and necrotic cells change over time and space in Cartesian coordinate which regulates under different rates of nutrients consumptions. The model presents the proliferative and quiescent cell growth depends on some parameter changes and the necrotic cells emerged as the tumor core. Some numerical schemes for solving the system of equations are compared and analyzed. Simulation and computation of the discretized model are supported by Matlab and C programming languages on a single processing unit. Some numerical results and analysis of the algorithms are presented in terms of informative presentation of tables, multiple graph and multidimensional visualization. As a conclusion, the integrated of three types mathematical modeling and the comparison of numerical performance indicates that the superior tool and analysis for solving the complete set of magnetic drug delivery system which give significant effects on the growth of the targeted cancer cell.

Keywords: mathematical modeling, visualization, PDE models, magnetic nanoparticle drug delivery model, drug release model, single cell effects, avascular tumor growth, numerical analysis

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Authors: Stacey Herzog, Mitchell McCleary, Istvan Kovacs

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Purpose: Maximal strength and maximal power are key athletic abilities in many sports disciplines. In recent years, velocity-based training (VBT) with a relatively high 75-85% 1RM resistance has been popularized in preparation for powerlifting and various other sports. The purpose of this study was to discover differences between beginner/intermediate and advanced lifters’ push/press performances after a heavy resistance-based BP training program. Methods: A six-week, three-workouts per week program was administered to 52 young, physically active adults (age: 22.4±5.1; 12 female). The majority of the participants (84.6%) had prior experience in bench pressing. Typical workouts began with BP using 75-95% 1RM in the 1-5 repetition range. The sets in the lower part of the range (75-80% 1RM) were performed with velocity-focus as well. The BP sets were followed by seated dumbbell presses and six additional upper-body assistance exercises. Pre- and post-tests were conducted on five test exercises: one-repetition maximum BP (1RM), calculated relative strength index: BP/BW (RSI), four-repetition maximal-effort dynamic BP for peak concentric velocity with 80% 1RM (4RV), 4-repetition ballistic pushups (BPU) for height (4PU), and seated medicine ball toss for distance (MBT). For analytic purposes, the participant group was divided into two subgroups: self-indicated beginner or intermediate initial resistance training status (BITS) [n=21, age: 21.9±3.6; 10 female] and advanced initial resistance training status (ATS) [n=31, age: 22.7±5.9; 2 female]. Pre- and post-test results were compared within subgroups. Results: Paired-sample t-tests indicated significant within-group improvements in all five test exercises in both groups (p < 0.05). BITS improved 18.1 lbs. (13.0%) in 1RM, 0.099 (12.8%) in RSI, 0.133 m/s (23.3%) in 4RV, 1.55 in. (27.1%) in BPU, and 1.00 ft. (5.8%) in MBT, while the ATS group improved 13.2 lbs. (5.7%) in 1RM, 0.071 (5.8%) in RSI, 0.051 m/s (9.1%) in 4RV, 1.20 in. (13.7%) in BPU, and 1.15 ft. (5.5%) in MBT. Conclusion: While the two training groups had different initial resistance training backgrounds, both showed significant improvements in all test exercises. As expected, the beginner/intermediate group displayed better relative improvements in four of the five test exercises. However, the medicine ball toss, which had the lightest resistance among the tests, showed similar relative improvements between the two groups. These findings relate to two important training principles: specificity and transfer. The ATS group had more specific experiences with heavy-resistance BP. Therefore, fewer improvements were detected in their test performances with heavy resistances. On the other hand, while the heavy resistance-based training transferred to increased power outcomes in light-resistance power exercises, the difference in the rate of improvement between the two groups disappeared. Practical applications: Based on initial training status, S&C coaches should expect different performance gains in maximal strength training-specific test exercises. However, the transfer from maximal strength to a non-training-specific performance category along the F-v curve continuum (i.e., light resistance and high velocity) might not depend on initial training status.

Keywords: exercise, power, resistance training, strength

Procedia PDF Downloads 56

Authors: Abolghasem Yousefi-Babadi, Ali Bozorgi-Amiri, Aida Kazempour, Reza Tavakkoli-Moghaddam, Maryam Irani

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All over the world, natural disasters (e.g., earthquakes, floods, volcanoes and hurricanes) causes a lot of deaths. Earthquakes are introduced as catastrophic events, which is accident by unusual phenomena leading to much loss around the world. Such could be replaced by disasters or any other synonyms strongly demand great long-term help and relief, which can be hard to be managed. Supplies and facilities are very important challenges after any earthquake which should be prepared for the disaster regions to satisfy the people's demands who are suffering from earthquake. This paper proposed disaster response facility allocation problem for disaster relief operations as a mathematical programming model. Not only damaged people in the earthquake victims, need the consumable commodities (e.g., food and water), but also they need non-consumable commodities (e.g., clothes) to protect themselves. Therefore, it is concluded that paying attention to disaster points and people's demands are very necessary. To deal with this objective, both commodities including consumable and need non-consumable commodities are considered in the presented model. This paper presented the multi-objective multi-period mathematical programming model regarding the minimizing the average of the weighted response times and minimizing the total operational cost and penalty costs of unmet demand and unused commodities simultaneously. Furthermore, a Chebycheff multi-objective solution procedure as a powerful solution algorithm is applied to solve the proposed model. Finally, to illustrate the model applicability, a case study of the Tehran earthquake is studied, also to show model validation a sensitivity analysis is carried out.

Keywords: facility location, multi-objective model, disaster response, commodity

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Authors: Yong Pan, Li Wang, Xue Qiong Su, Dong Wen Gao

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To date, nanomaterials have received extensive attention over the years because of their wide application. Various nanomaterials such as nanoparticles, nanowire, nanoring, nanostars and other nanostructures have begun to be systematically studied. The preparation of these materials by chemical methods is not only costly, but also has a long cycle and high toxicity. At the same time, preparation of nanoparticles of multi-doped composites has been limited due to the special structure of the materials. In order to prepare multi-doped composites with the same structure as macro-materials and simplify the preparation method, the Ga_xCo_1-xZnSe_0.4 (x = 0.1, 0.3, 0.5) nanoparticles are prepared by Pulse Laser Ablation (PLA) method. The particle component and structure are systematically investigated by X-ray diffraction (XRD) and Raman spectra, which show that the success of our preparation and the same concentration between nanoparticles (NPs) and target. Morphology of the NPs characterized by Transmission Electron Microscopy (TEM) indicates the circular-shaped particles in preparation. Fluorescence properties are reflected by PL spectra, which demonstrate the best performance in concentration of Ga_0.3Co_0.3ZnSe_0.4. Therefore, all the results suggest that PLA is promising to prepare the multi-NPs since it can modulate performance of NPs.

Keywords: PLA, physics, nanoparticles, multi-doped

Procedia PDF Downloads 163

Authors: Inyeol Paik, Ah-Ryang Kim

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In this research, a statistical analysis is carried out to examine the statistical properties of the formula given in the design code for concrete structures. The design formulas of the Korea highway bridge design code - the limit state design method (KHBDC) which is the current national bridge design code and the design code for concrete structures by Korea Concrete Institute (KCI) are applied for the analysis. The safety levels provided by the strength formulas of the design codes are defined based on the probabilistic and statistical theory.KHBDC is a reliability-based design code. The load and resistance factors of this code were calibrated to attain the target reliability index. It is essential to define the statistical properties for the design formulas in this calibration process. In general, the statistical characteristics of a member strength are due to the following three factors. The first is due to the difference between the material strength of the actual construction and that used in the design calculation. The second is the difference between the actual dimensions of the constructed sections and those used in design calculation. The third is the difference between the strength of the actual member and the formula simplified for the design calculation. In this paper, the statistical study is focused on the third difference. The formulas for calculating the shear strength of concrete members are presented in different ways in KHBDC and KCI. In this study, the statistical properties of design formulas were obtained through comparison with the database which comprises the experimental results from the reference publications. The test specimen was either reinforced with the shear stirrup or not. For an applied database, the bias factor was about 1.12 and the coefficient of variation was about 0.18. By applying the statistical properties of the design formula to the reliability analysis, it is shown that the resistance factors of the current design codes satisfy the target reliability indexes of both codes. Also, the minimum resistance factors of the KHBDC which is written in the material resistance factor format and KCE which is in the member resistance format are obtained and the results are presented. A further research is underway to calibrate the resistance factors of the high strength and high-performance concrete design guide.

Keywords: concrete design code, reliability analysis, resistance factor, shear strength, statistical property

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Authors: Vishwanath Pethri Kamath, Jayantha Gowda Sarapanahalli, Vishal Mishra, Siddhesh Balwant Bandgar

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Recognition of emotional information is essential in any form of communication. Growing HCI (Human-Computer Interaction) in recent times indicates the importance of understanding of emotions expressed and becomes crucial for improving the system or the interaction itself. In this research work, textual data for emotion recognition is used. The text being the least expressive amongst the multimodal resources poses various challenges such as contextual information and also sequential nature of the language construction. In this research work, the proposal is made for a neural architecture to resolve not less than 8 emotions from textual data sources derived from multiple datasets using google pre-trained word2vec word embeddings and a Multi-head attention-based bidirectional LSTM model with a one-vs-all Multi-Level Classification. The emotions targeted in this research are Anger, Disgust, Fear, Guilt, Joy, Sadness, Shame, and Surprise. Textual data from multiple datasets were used for this research work such as ISEAR, Go Emotions, Affect datasets for creating the emotions’ dataset. Data samples overlap or conflicts were considered with careful preprocessing. Our results show a significant improvement with the modeling architecture and as good as 10 points improvement in recognizing some emotions.

Keywords: text emotion recognition, bidirectional LSTM, multi-head attention, multi-level classification, google word2vec word embeddings

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Authors: Saurabh B. Ganorkar, Atul A. Shirkhedkar

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The need for investigations protecting against toxic impurities though seems to be a primary requirement; the impurities which may prove non - toxic can be explored for their therapeutic potential if any to assist advanced drug discovery. The essential role of pharmaceutical analysis can thus be extended effectively to achieve it. The present study successfully achieved these objectives with characterization of major degradation products as impurities for Zileuton which has been used for to treat asthma since years. The forced degradation studies were performed to identify the potential degradation products using Ultra-fine Liquid-chromatography. Liquid-chromatography-Mass spectrometry (Time of Flight) and Proton Nuclear Magnetic Resonance Studies were utilized effectively to characterize the drug along with five major oxidative and hydrolytic degradation products (DP’s). The mass fragments were identified for Zileuton and path for the degradation was investigated. The characterized DP’s were subjected to In-Silico studies as XP Molecular Docking to compare the gain or loss in binding affinity with 5-Lipooxygenase enzyme. One of the impurity of was found to have the binding affinity more than the drug itself indicating for its potential to be more bioactive as better Antiasthmatic. The close structural resemblance has the ability to potentiate or reduce bioactivity and or toxicity. The chances of being active biologically at other sites cannot be denied and the same is achieved to some extent by predictions for probability of being active with Prediction of Activity Spectrum for Substances (PASS) The impurities found to be bio-active as Antineoplastic, Antiallergic, and inhibitors of Complement Factor D. The toxicological abilities as Ames-Mutagenicity, Carcinogenicity, Developmental Toxicity and Skin Irritancy were evaluated using Toxicity Prediction by Komputer Assisted Technology (TOPKAT). Two of the impurities were found to be non-toxic as compared to original drug Zileuton. As the drugs are purposed and repurposed effectively the impurities can also be; as they can have more binding affinity; less toxicity and better ability to be bio-active at other biological targets.

Keywords: UFLC, LC-MS-TOF, NMR, Zileuton, impurities, toxicity, bio-activity

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Authors: Yogeeta O. Agrawal, Hitendra S. Mahajan, Sanjay J. Surana

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Methotrexate is effective in controlling recalcitrant psoriasis when administered by the oral or parenteral route long-term. However, the systematic use of this drug may provoke any of a number of side effects, notably hepatotoxic effects. To reduce these effects, clinical studies have been done with topical MTx. It is useful in treating a number of cutaneous conditions, including psoriasis. A major problem in topical administration of MTx currently available in market is that the drug is hydrosoluble and is mostly in the dissociated form at physiological pH. Its capacity for passive diffusion is thus limited. Localization of MTx in effected layers of skin is likely to improve the role of topical dosage form of the drug as a supplementary to oral therapy for treatment of psoriasis. One of the possibilities for increasing the penetration of drugs through the skin is the use of Nanostructured lipid Carriers. The objective of the present study was to formulate and characterize Methotrexate loaded Nanostructured Lipid Carriers (MtxNLCs), to understand in vitro drug release and evaluate the role of the developed gel in the topical treatment of psoriasis. MtxNLCs were prepared by solvent diffusion technique using 3(2) full factorial design.The mean diameter and surface morphology of MtxNLC was evaluated. MtxNLCs were lyophilized and crystallinity of NLC was characterized by Differential Scanning Calorimtery (DSC) and powder X-Ray Diffraction (XRD). The NLCs were incorporated in 1% w/w Carbopol 934 P gel base and in vitro skin deposition studies in Human Cadaver Skin were conducted. The optimized MtxNLCs were spherical in shape, with average particle size of 253(±9.92)nm, zeta potential of -30.4 (±0.86) mV and EE of 53.12(±1.54)%. DSC and XRD data confirmed the formation of NLCs. Significantly higher deposition of Methotrexate was found in human cadaver skin from MtxNLC gel (71.52 ±1.23%) as compared to Mtx plain gel (54.28±1.02%). Findings of the studies suggest that there is significant improvement in therapeutic index in treatment of psoriasis by MTx-NLCs incorporated gel base developed in this investigation over plain drug gel currently available in the market.

Keywords: methotrexate, psoriasis, NLCs, hepatotoxic effects

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Authors: Mehmet Fahri Sarac, Gokcen Akgun

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Ti–6Al–4V alloys are widely used in biomedical industries because of its attractive mechanical and physicochemical properties. However, they have poor wear resistance. High velocity oxygen fuel (HVOF) coatings were investigated as a way to improve the wear resistance of this alloy. In this paper, different mass ratio of Al₂O₃-TiO₂ powders (60/40, 87/13 and 97/3) was employed to enhance the tribological properties of Ti–6Al–4V. The tribological behavior was investigated by wear tests using ball-on-disc and pin-on-disc tribometer. The microstructures of the contact surfaces were determined by a scanning electron microscopy before and after the test to study the wear mechanism. Uncoated and coated surfaces after wear test are also subjected to micro-hardness tests. The tribological test results showed that the microhardness, friction and wear resistance of coated Ti-6Al-4V alloys increases by increasing TiO₂ content in the powder composite when other experimental conditions were constant. Finally, Al₂O₃-TiO₂ powder composites for the investigated conditions, both coating samples had satisfactory values of friction and wear resistance, and they could be suitable candidates for Ti–6Al–4V material.

Keywords: HVOF (High Velocity Oxygen Fuel), Al₂O₃-TiO₂, Ti-6Al-4V, tribology

Procedia PDF Downloads 180

Authors: Mandy Wilson, Emma Vieira, Jocelyn Jones, Alice V. Brown, Lindey Andrews, Louise Southalan, Jackie Oakley, Dorothy Bagshaw, Patrick Egan, Laura Dent, Duc Dau, Lucy Spanswick

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Alcohol and drug dependency are pertinent issues for those experiencing homelessness. This includes Aboriginal and Torres Strait Islander people, Australia’s traditional owners, living in Perth, Western Australia (WA). Societal narratives around the drivers behind drug and alcohol dependency in Aboriginal communities, particularly those experiencing homelessness, have been biased and unchanging, with little regard for complexity. This can include the idea that Aboriginal people have ‘chosen’ to use alcohol or other drugs without consideration for intergenerational trauma and the trauma of homelessness that may influence their choices. These narratives have flow-on impacts on policies and services that directly impact Aboriginal people experiencing homelessness. In 2021, we commenced a project which aimed to listen to and elevate the voices of 70-90 Aboriginal people experiencing homelessness in Perth. The project is community-driven, led by an Aboriginal Community Controlled Organisation in partnership with a university research institute. A community-ownership group of Aboriginal Elders endorsed the project’s methods, chosen to ensure their suitability for the Aboriginal community. In this paper, we detail these methods, including semi-structured interviews influenced by an Aboriginal yarning approach – an important style of conversation for Aboriginal people which follows cultural protocols; and photovoice – supporting people to share their stories through photography. Through these engagements, we detail the reasons Aboriginal people in Perth shared for using alcohol or other drugs while experiencing homelessness. These included supporting their survival on the streets, managing their mental health, and coping while on the journey to finding support. We also detail why they sought to discontinue alcohol and other drug use, including wanting to reconnect with family and changing priorities. Finally, we share how Aboriginal people experiencing homelessness have said they are impacted by their family’s alcohol and other drug use, including feeling uncomfortable living with a family who is drug and alcohol-dependent and having to care for grandchildren despite their own homelessness. These findings provide a richer understanding of alcohol and drug use for Aboriginal people experiencing homelessness in Perth, shedding light on potential changes to targeted policy and service approaches.

Keywords: Aboriginal and Torres Strait Islander peoples, alcohol and other drugs, homelessness, community-led research

Procedia PDF Downloads 116

Authors: Yuanping Yang, Ruolin Zhou, Xingyu Liu, Lianbin Wu

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Based on the challenges of silanization of pharmaceutical glass packaging materials, the silicone oil high-temperature baking method consumes a lot of energy; silicone oil is generally physically adsorbed on the inner surface of the medical vials, leading to protein adsorption on the surface of the silicone oil and fall off, so that the number of particles in the drug solution increases, which brings potential risks to people. In this paper, a new silanizing method is proposed. High-efficiency silanization is achieved by grafting trimethylsilyl groups to the inner surface of medical vials by chemical bond at low temperatures. The inner wall of the vial successfully obtained stable hydrophobicity, and the water contact Angle of the surface reached 100°~110°. With the increase of silicified reagent concentration, the water resistance of corresponding treatment vials increased gradually. This treatment can effectively reduce the risk of pH value increase and sodium ion leaching.

Keywords: low-temperature silanization, medical vials, chemical bonding, hydrophobicity

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Authors: Inas S. Khayal, Weiping Zhou, Jonathan Skinner

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Healthcare delivery systems around the world are in crisis. The need to improve health outcomes while decreasing healthcare costs have led to an imminent call to action to transform the healthcare delivery system. While Bioinformatics and Biomedical Engineering have primarily focused on biological level data and biomedical technology, there is clear evidence of the importance of the delivery of care on patient outcomes. Classic singular decomposition approaches from reductionist science are not capable of explaining complex systems. Approaches and methods from systems science and systems engineering are utilized to structure healthcare delivery system data. Specifically, systems architecture is used to develop a multi-scale and multi-dimensional characterization of the healthcare delivery system, defined here as the Healthcare Delivery System Knowledge Base. This paper is the first to contribute a new method of structuring and visualizing a multi-dimensional and multi-scale healthcare delivery system using systems architecture in order to better understand healthcare delivery.

Keywords: health informatics, systems thinking, systems architecture, healthcare delivery system, data analytics

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Authors: M. O. Adeniyi, R. T. Akinnubi

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The parameterization of turbulent heat fluxes is needed for modeling land-atmosphere interactions in Global Climate Models (GCMs). However, current GCMs still have difficulties with producing reliable turbulent heat fluxes for humid tropical regions, which may be due to inadequate parameterization of the roughness lengths for momentum (z0m) and heat (z0h) transfer. These roughness lengths are usually expressed in term of excess resistance factor (κB^(-1)), and this factor is used to account for different resistances for momentum and heat transfers. In this paper, a more appropriate excess resistance factor (〖 κB〗^(-1)) suitable for low wind speed condition was developed and incorporated into the aerodynamic resistance approach (ARA) in the GCMs. Also, the performance of various standard GCMs κB^(-1) schemes developed for high wind speed conditions were assessed. Based on the in-situ surface heat fluxes and profile measurements of wind speed and temperature from Nigeria Micrometeorological Experimental site (NIMEX), new κB^(-1) was derived through application of the Monin–Obukhov similarity theory and Brutsaert theoretical model for heat transfer. Turbulent flux parameterizations with this new formula provides better estimates of heat fluxes when compared with others estimated using existing GCMs κB^(-1) schemes. The derived κB^(-1) MBE and RMSE in the parameterized QH ranged from -1.15 to – 5.10 Wm-2 and 10.01 to 23.47 Wm-2, while that of QE ranged from - 8.02 to 6.11 Wm-2 and 14.01 to 18.11 Wm-2 respectively. The derived 〖 κB〗^(-1) gave better estimates of QH than QE during daytime. The derived 〖 κB〗^(-1)=6.66〖 Re〗_*^0.02-5.47, where Re_* is the Reynolds number. The derived κB^(-1) scheme which corrects a well documented large overestimation of turbulent heat fluxes is therefore, recommended for most regional models within the tropic where low wind speed is prevalent.

Keywords: humid, tropic, excess resistance factor, overestimation, turbulent heat fluxes

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Authors: Yuekun Chen, Yousef Sardahi, Salam Hajjar, Christopher Greer

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This paper presents a multi-objective optimal design of a cascade control system for an underactuated mechanical system. Cascade control structures usually include two control algorithms (inner and outer). To design such a control system properly, the following conflicting objectives should be considered at the same time: 1) the inner closed-loop control must be faster than the outer one, 2) the inner loop should fast reject any disturbance and prevent it from propagating to the outer loop, 3) the controlled system should be insensitive to measurement noise, and 4) the controlled system should be driven by optimal energy. Such a control problem can be formulated as a multi-objective optimization problem such that the optimal trade-offs among these design goals are found. To authors best knowledge, such a problem has not been studied in multi-objective settings so far. In this work, an underactuated mechanical system consisting of a rotary servo motor and a ball and beam is used for the computer simulations, the setup parameters of the inner and outer control systems are tuned by NSGA-II (Non-dominated Sorting Genetic Algorithm), and the dominancy concept is used to find the optimal design points. The solution of this problem is not a single optimal cascade control, but rather a set of optimal cascade controllers (called Pareto set) which represent the optimal trade-offs among the selected design criteria. The function evaluation of the Pareto set is called the Pareto front. The solution set is introduced to the decision-maker who can choose any point to implement. The simulation results in terms of Pareto front and time responses to external signals show the competing nature among the design objectives. The presented study may become the basis for multi-objective optimal design of multi-loop control systems.

Keywords: cascade control, multi-Loop control systems, multiobjective optimization, optimal control

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Authors: Fatima Bouazza, Rachida Hassikou, Lamiae Amallah, Jihane Ennadir, Khadija Khedid

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This study evaluated the in vitro resistance and susceptibility of Enterobacteriaceae (Escherichia coli and Klebsiella oxytoca strains) and Staphylococci strains, isolated from sheep’s milk, against antibiotics and essential oils from Thymus satureioides and Mentha pulegium. Antibiotic resistance tests were done using disc diffusion while essential oils were extracted by steam distillation, and yields were calculated relative to plant dry matter. Gas chromatography-mass Spectrometry (GC-MS) was used to analyze each oil's chemical composition. The AMC, CTX, FOX, NA, CN, CIP, and OFX were very effective against the E. coli strains tested. Half of the strains were resistant to AMC, 60% to TIC, and 80% to TE. The K. oxytoca was resistant against AMC, FOX, and TIC (100%). Antibiotic-resistant testing on Staphylococci strains indicated Staphylococcus capitis and Staphylococcus chromogenes as the most sensitive. Staphylococcus aureus, Staphylococcus xylosus, and Staphylococcus cohnii ureal exhibited less resistance to OX, TE, PT, E, and P. The M. pulegium resulted in a higher yield of essential oil of 3.2% oil compared to T. satureioides with only 1.85% yield. Staphylococcus aureus, Staphylococcus xylosus, and Staphylococcus cohnii ureal had lower OX, TE, PT, E, and P resistance. M. pulegium yielded 3.2% essential oil compared to 1.85% for T. satureioides. The monoterpene oxygenated derivatives, monoterpene hydrocarbons, and phenols are found in essential oil extracts. T. satureioides essential oil had high antibacterial activity even at low concentrations (0.2; 0.55 g/mL). The Minimal Bactericidal Concentration (MBC) values indicate that the essential oils from the plants analyzed had bactericidal effects on all strains tested and are similar to the Minimal Inhibitory Concentration (MIC) values. The high antibacterial properties of these medicinal plants, against bacteria isolated from sheep’s milk, provide an opportunity to use these medicinal plants in the breeding sector as additives and preservatives in the dairy industry.

Keywords: antibiotic resistance, medicinal plants, essential oils, enterobacteriaceae, staphylococci, sheep milk

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Authors: Haoxue Cui, Sirui Zhang, Shanshan Gao, Weiyi Zhang, Lantian Wang, Xuanwen Zheng

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The 2020 "multi-school zoning" policy makes students ineligible for direct attendance in their district. To study whether the housing price trend of the school district is affected by the policy, This paper studies housing prices based on the school district division in Xicheng District, Beijing. In this paper, we collected housing prices and the basic situation of communities from "Anjuke", which were divided into two periods of 15 months before and after the 731 policy in the Xicheng District, Beijing. Then we used DID model and time fixed effect to investigate the DIFFERENTIAL statistics, that is, the overall net impact of the policy. The results show that the coefficient is negative at a certain statistical level. It indicates that the housing prices of school districts in the Xicheng district decreased after the "multi-school zoning" policy, which shows that the policy has effectively reduced the housing price of school districts in the Xicheng District and laid a foundation for the "double reduction" policy in 2022.

Keywords: “multi-school zoning”policy, DID, time fixed effect, housing prices

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Authors: P. Karpagam, Babu Joseph, P. Ashok Kumar

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The incidence of Candida infections is increasing worldwide. The serious nature of these infections is compounded by increasing levels of drug resistance. Pure cultures of the Candida sp. were obtained from clinical isolates and fresh garlic extracts were obtained by extraction techniques. The antifungal activity of garlic extract was investigated in an in vitro system. The extract (100%, 75% and 50%) showed significant antifungal activity against Candida, whereas, low concentration (25%) of the extract showed less antifungal activity against the test organism. Antifungal activities of honey and lemon juice were tested against the Candida; however, the growth was not inhibited by these extracts. On the other hand honey and lemon when combined with garlic exhibited a good antifungal activity. The study thus confirms the antifungal properties of garlic extract along with additives like honey and lemon have significant antifungal activity against isolates of Candida species.

Keywords: Candida, garlic extract, lemon, synergitic antifungal activity

Procedia PDF Downloads 241

Authors: Abdul Matin, Muhammad Ajmal, Uzma Yunus, Noaman-ul Haq, Hafiz M. Shohaib, Ambreen G. Muazzam

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Carbon nanoparticles (CNPs) have unique properties that are useful for the diagnosis and treatment of cancer due to their precise properties like small size (ideal for delivery within the body) stability in solvent and tunable surface chemistry for targeted delivery. Here, highly fluorescent, monodispersed and water-soluble CNPs were synthesized directly from a suitable carbohydrate source (glucose and sucrose) by one-step acid assisted ultrasonic treatment at 35 KHz for 4 hours. This method is green, simple, rapid and economical and can be used for large scale production and applications. The average particle sizes of CNPs are less than 10nm and they emit bright and colorful green-blue fluorescence under the irradiation of UV-light at 365nm. The CNPs were characterized by scanning electron microscopy, fluorescent spectrophotometry, Fourier transform infrared spectrophotometry, ultraviolet-visible spectrophotometry and TGA analysis. Fluorescent CNPs were used as fluorescent probe and nano-carriers for anticancer drug. Functionalized CNPs (with ethylene diamine) were attached with anticancer drug-Methotrexate. In vitro bioactivity and biocompatibility of CNPs-drug conjugates was evaluated by LDH assay and Sulforhodamine B assay using human lung carcinoma cell lines (H157). Our results reveled that CNPs showed biocompatibility and CNPs-anticancer drug conjugates have shown potent cytotoxic effects and high antitumor activities in lung cancer cell lines. CNPs are proved to be excellent substitute for conventional drug delivery cargo systems and anticancer therapeutics in vitro. Our future studies will be more focused on using the same nanoparticles in vivo model system.

Keywords: carbon nanoparticles, carbon nanoparticles-methotrexate conjugates, human lung carcinoma cell lines, lactate dehydrogenase, methotrexate

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Authors: T. N. Girish, B. E. Pradeep, Ravi Parkash

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Insects from tropical wet or dry seasons are likely to cope starvation stress through seasonal phenotypic plasticity in energy metabolites. Accordingly, we analyzed such plastic changes in Zaprionus indianus flies reared under wet or dry season-specific conditions; and also after adult acclimation at 32℃ for 1 to 6 days; and to low (40% RH) or high (70% RH) humidity. Both thermal or humidity acclimation revealed significant accumulation of body lipids for wet season flies but low humidity acclimation did not change the level of body lipids in dry season flies. Developmental and adult acclimation showed sex specific differences i.e., starvation resistance and body lipids were higher in the males of dry season but in females of wet season. We found seasonal and sex specific differences in the relative level for body lipids at death; and in the rates of accumulation or utilization of energy metabolites (body lipids, carbohydrates and proteins). Body lipids constitute the preferred energy source under starvation for flies of both the seasons. However, utilization of carbohydrates (~20% to 30%) and proteins (~20% to 25%) was evident only in dry season flies. Higher starvation resistance after thermal or humidity acclimation is achieved by increased accumulation of lipids. Adult acclimation of wet or dry season flies revealed plastic changes in mean daily fecundity despite reduction in fecundity under starvation. Thus, thermal or humidity induced plastic responses in body lipids support starvation resistance under wet or dry seasons.

Keywords: heat or humidity acclimation, plastic changes in body lipids and starvation resistance, tropical drosophilid, Wet- or Dry seasons, Zaprionus indianus

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Authors: Abdulaziz Alakeel, Roaa Alamri, Abdulrahman Alomair, Mohammed Fouda

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Introduction: Ibrutinib is a selective, potent, and irreversible small-molecule inhibitor of Bruton's tyrosine kinase (BTK). It forms a covalent bond with a cysteine residue (CYS-481) at the active site of Btk, leading to inhibition of Btk enzymatic activity. The drug is indicated to treat certain type of cancers such as mantle cell lymphoma (MCL), chronic lymphocytic leukaemia and Waldenström's macroglobulinaemia (WM). Cardiac failure is a condition referred to inability of heart muscle to pump adequate blood to human body organs. There are multiple types of cardiac failure including left and right-sided heart failure, systolic and diastolic heart failures. The aim of this review is to evaluate the risk of cardiac failure associated with the use of ibrutinib and to suggest regulatory recommendations if required. Methodology: Signal Detection team at the National Pharmacovigilance Center (NPC) of Saudi Food and Drug Authority (SFDA) performed a comprehensive signal review using its national database as well as the World Health Organization (WHO) database (VigiBase), to retrieve related information for assessing the causality between cardiac failure and ibrutinib. We used the WHO- Uppsala Monitoring Centre (UMC) criteria as standard for assessing the causality of the reported cases. Results: Case Review: The number of resulted cases for the combined drug/adverse drug reaction are 212 global ICSRs as of July 2020. The reviewers have selected and assessed the causality for the well-documented ICSRs with completeness scores of 0.9 and above (35 ICSRs); the value 1.0 presents the highest score for best-written ICSRs. Among the reviewed cases, more than half of them provides supportive association (four probable and 15 possible cases). Data Mining: The disproportionality of the observed and the expected reporting rate for drug/adverse drug reaction pair is estimated using information component (IC), a tool developed by WHO-UMC to measure the reporting ratio. Positive IC reflects higher statistical association while negative values indicates less statistical association, considering the null value equal to zero. The results of (IC=1.5) revealed a positive statistical association for the drug/ADR combination, which means “Ibrutinib” with “Cardiac Failure” have been observed more than expected when compared to other medications available in WHO database. Conclusion: Health regulators and health care professionals must be aware for the potential risk of cardiac failure associated with ibrutinib and the monitoring of any signs or symptoms in treated patients is essential. The weighted cumulative evidences identified from causality assessment of the reported cases and data mining are sufficient to support a causal association between ibrutinib and cardiac failure.

Keywords: cardiac failure, drug safety, ibrutinib, pharmacovigilance, signal detection

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Authors: Jillian M. Hagel, Joseph E. Tucker, Peter J. Facchini

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With the aim of establishing a holistic approach for the treatment of central nervous system (CNS) disorders, we are pursuing a drug development program rapidly progressing through discovery and characterization phases. The drug candidates identified in this program are referred to as neuroplastogens owing to their ability to mediate neuroplasticity, which can be beneficial to patients suffering from anxiety, depression, or posttraumatic stress disorder. These and other related neuropsychiatric conditions are associated with the onset of neuronal atrophy, which is defined as a reduction in the number and/or productivity of neurons. The stimulation of neuroplasticity results in an increase in the connectivity between neurons and promotes the restoration of healthy brain function. We have synthesized a substantial catalogue of proprietary indolethylamine derivatives based on the general structures of serotonin (5-hydroxytryptamine) and psychedelic molecules such as N,N-dimethyltryptamine (DMT) and psilocin (4-hydroxy-DMT) that function as neuroplastogens. A primary objective in our screening protocol is the identification of derivatives associated with a significant reduction in hallucination, which will allow administration of the drug at a dose that induces neuroplasticity and triggers other efficacious outcomes in the treatment of targeted CNS disorders but which does not cause a psychedelic response in the patient. Both neuroplasticity and hallucination are associated with engagement of the 5HT2A receptor, requiring drug candidates differentially coupled to these two outcomes at a molecular level. We use novel and proprietary artificial intelligence algorithms to predict the mode of binding to the 5HT2A receptor, which has been shown to correlate with the hallucinogenic response. Hallucination is tested using the mouse head-twitch response model, whereas mouse marble-burying and sucrose preference assays are used to evaluate anxiolytic and anti-depressive potential. Neuroplasticity is assays using dendritic outgrowth assays and cell-based ELISA analysis. Pharmacokinetics and additional receptor-binding analyses also contribute the selection of lead candidates. A summary of the program is presented.

Keywords: neuroplastogen, non-hallucinogenic, drug development, anxiety, depression, PTSD, indolethylamine derivatives, psychedelic-inspired, 5-HT2A receptor, computational chemistry, head-twitch response behavioural model, neurite outgrowth assay

Procedia PDF Downloads 124

Authors: Vishal Mahale, Jayashree Bijwe, Sujeet K. Sinha

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Nowadays extensive research is going on in the field of friction materials (FMs) for development of eco-friendly brake-materials by removing copper as it is a proven threat to the aquatic organisms. Researchers are keen to find the solution for copper-free FMs by using different metals or without metals. Steel wool is used as a reinforcement in non-asbestos organic (NAO) FMs mainly for increasing thermal conductivity, and it affects wear adversely, most of the times and also adds friction fluctuations. Copper and brass used to be the preferred choices because of superior performance in almost every aspect except cost. Since these are being phased out because of a proven threat to the aquatic life. Keeping this in view, a series of realistic multi-ingredient FMs containing stainless steel (SS) swarfs as a theme ingredient in increasing amount (0, 5, 10 and 15 wt. %- S₅, S₁₀, and S₁₅) were developed in the form of brake-pads. One more composite containing copper instead of SS swarfs (C₁₀) was developed. These composites were characterized for physical, mechanical, chemical and tribological performance. Composites were tribo-evaluated on a chase machine with various test loops as per SAE J661 standards. Various performance parameters such as normal µ, hot µ, performance µ, fade µ, recovery µ, % fade, % recovery, wear resistance, etc. were used to evaluate the role of amount of SS swarfs in FMs. It was concluded that SS swarfs proved successful in Cu replacement almost in all respects except wear resistance. With increase in amount of SS swarfs, most of the properties improved. Worn surface analysis and wear mechanism were studied using SEM and EDAX techniques.

Keywords: Chase type friction tester, copper-free, non-asbestos organic (NAO) friction materials, stainless steel swarfs

Procedia PDF Downloads 178

Authors: V. Naga Sravan Kumar Varma, H. G. Shivakumar

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The aim of the study was to develop dual sensitive poly (N-isopropylacrylamide-co-acrylic acid) (PNA) nanogels(NGs) and studying its applications for Anti-Cancer therapy. NGs were fabricated by free radical polymerization using different amount of N-isopropylacrylamide and acrylic acid. A study for polymer composition over the effect on LCST in different pH was evaluated by measuring the absorbance at 500nm using UV spectrophotometer. Further selected NG’s were evaluated for change in hydrodynamic diameters in response to pH and temperature. NGs which could sharply respond to low pH value of cancer cells at body temperature were loaded with Fluorouracil (5-FU) using equilibrium swelling method and studied for drug release behaviour in different pH. A significant influence of NGs polymer composition over pH dependent LCST was observed. NGs which were spherical with an average particle size of 268nm at room temperature, shrinked forming an irregular shape when heated above to their respective LCST. 5FU loaded NGs did not intervene any difference in pH depended LCST behaviour of NGs. The in vitro drug release of NGs exhibited a pH and thermo-dependent control release. The cytoxicity study of blank carrier to MCF7 cell line showed no cytotoxicity. The results indicated that PNA NGs could be used as a potential drug carrier for anti-cancer therapy.

Keywords: pH and thermo-sensitive, nanogels, P(NIPAM-co-AAc), anti-cancer, 5-FU

Procedia PDF Downloads 343