Search results for: Sharran Parkinson

Authors: Ali Bahri Lubis

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Tryptophan oxidation by Heme-dioxygenase enzyme is initial important stepTryptophan oxidation by Heme-dioxygenase enzyme is initial important step in kynurenine pathway implicating to several severe diseases such as Parkinson’s Disease, Huntington Disease, poliomyelitis and cataract. It is crucial to comprehend the oxidation mechanism with the hope to find decent treatment upon abovementioned diseases. The mechanism has been debatable since no one has been yet proved the mechanism obviously. In this research we have attempted to prove mechanistic steps of tryptophan oxidation via human indoleamine dioxygenase (h-IDO) using various substrates: L-tryptophan, L-tryptophan (indole-ring-2-13C), L-fully-labelled13C-tryptophan, L-N-methyl-tryptophan, L-tryptophan and 2-amino-3-(benzo(b)thiophene-3-yl) propanoic acid. All enzyme assay experiments were measured using a UV-Vis spectrophotometer, LC-MS, 1H-NMR, and HSQC. We also successfully synthesized enzyme products as our control in NMR measurements. The result exhibited that the distinct substrates produced N-formyl kynurenine (NFK) and hydroxypyrrolloindoleamine carboxylate acid (HPIC) in different concentrations and isomers, correlated to the proposal of considered mechanism reaction in kynurenine pathway implicating to several severe diseases such as Parkinson’s Disease, Huntington Disease, poliomyelitis and cataract. It is crucial to comprehend the oxidation mechanism with the hope to find decent treatment for the abovementioned diseases. The mechanism has been debatable since no one has yet proven the mechanism obviously. In this research we have attempted to prove mechanistic steps of tryptophan oxidation via human indoleamine dioxygenase (h-IDO) using various substrates: L-tryptophan, L-tryptophan (indole-ring-2-13C), L-fully-labelled13C-tryptophan, L-N-methyl-tryptophan, L-tryptophan and 2-amino-3-(benzo(b)thiophene-3-yl) propanoic acid. All enzyme assay experiments were measured using a UV-Vis spectrophotometer, LC-MS, 1H-NMR and HSQC. We also successfully synthesized enzyme products as our control in NMR measurements. The result exhibited that the distinct substrates produced N-formyl kynurenine (NFK) and hydroxypyrrolloindoleamine carboxylate acid (HPIC) in different concentrations and isomers, correlated to the proposal of considered mechanism reaction.

Keywords: heme-dioxygenase enzyme, tryptophan oxidation, kynurenine pathway, n-formyl kynurenine

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Authors: Abdulsallam A. Bakdash, Aiyshah M. Alshehri, Hind M. Alenzi

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Benzatropine (benztropine) is used to treat symptoms of Parkinson's disease or involuntary movements due to the side effects of certain psychiatric drugs. We report in this study, results of a procedure for the determination of benzatropine in hair using LLE, once with methanol and second with phosphate buffer (pH 6.0), followed by filtration and then re-extraction with dichloromethane. A GC/MS method was developed and validated for this determination using selected ion monitoring (SIM) detection without derivatization. Linearity established over the concentration range 0.1-20.0 ng/mg hair, and the correlation coefficients were greater than 0.99. Recoveries were 52.2% and 21.1% using methanol and phosphate buffer extraction, respectively. Detection limits of benzatropine in hair were between 0.65 and 3.0 ng/mg hair, while the accuracy were 10.4% and 18.5% (RSD), respectively. We also applied this method to the analysis of soaked hair samples and demonstrated that the LLE using methanol meets the requirement for the analysis of benzatropine in hair.

Keywords: hair analysis, benzatropine, liquid-liquid extraction, GC/MS

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Authors: Sina Saadati, Mohammadreza Razzazi

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In this article, we have tried to present an agent-based model of human muscle. A suitable model of muscle is necessary for the analysis of mankind's movements. It can be used by clinical researchers who study the influence of motion sicknesses, like Parkinson's disease. It is also useful in the development of a prosthesis that receives the electromyography signals and generates force as a reaction. Since we have focused on computational efficiency in this research, the model can compute the calculations very fast. As far as it concerns prostheses, the model can be known as a charge-efficient method. In this paper, we are about to illustrate an agent-based model. Then, we will use it to simulate the human gait cycle. This method can also be done reversely in the analysis of gait in motion sicknesses.

Keywords: agent-based modeling and simulation, human muscle, gait cycle, motion sickness

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Authors: Ardiansyah I. Ryan, Ashsholih K. R., Fathurrohman G. R., Kurniadi M. R., Huda P. A

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The burden of brain-related disease is very high. There are a lot of brain-related diseases with limited treatment result and thus raise the burden more. The Parkinson Disease (PD), Mental Health Problem, or Paralysis of extremities treatments had risen concern, as the patients for those diseases usually had a low quality of life and low chance to recover fully. There are also many other brain or related neural diseases with the similar condition, mainly the treatments for those conditions are still limited as our understanding of the brain function is insufficient. Brain Implant Technology had given hope to help in treating this condition. In this paper, we examine the current update of the brain implant technology. Neurotechnology is growing very rapidly worldwide. The United States Food and Drug Administration (FDA) has approved the use of Deep Brain Stimulation (DBS) as a brain implant in humans. As for neural implant both the cochlear implant and retinal implant are approved by FDA too. All of them had shown a promising result. DBS worked by stimulating a specific region in the brain with electricity. This device is planted surgically into a very specific region of the brain. This device consists of 3 main parts: Lead (thin wire inserted into the brain), neurostimulator (pacemaker-like device, planted surgically in the chest) and an external controller (to turn on/off the device by patient/programmer). FDA had approved DBS for the treatment of PD, Pain Management, Epilepsy and Obsessive Compulsive Disorder (OCD). The target treatment of DBS in PD is to reduce the tremor and dystonia symptoms. DBS has been showing the promising result in animal and limited human trial for other conditions such as Alzheimer, Mental Health Problem (Major Depression, Tourette Syndrome), etc. Every surgery has risks of complications, although in DBS the chance is very low. DBS itself had a very satisfying result as long as the subject criteria to be implanted this device based on indication and strictly selection. Other than DBS, there are several brain implant devices that still under development. It was included (not limited to) implant to treat paralysis (In Spinal Cord Injury/Amyotrophic Lateral Sclerosis), enhance brain memory, reduce obesity, treat mental health problem and treat epilepsy. The potential of neurotechnology is unlimited. When brain function and brain implant were fully developed, it may be one of the major breakthroughs in human history like when human find ‘fire’ for the first time. Support from every sector for further research is very needed to develop and unveil the true potential of this technology.

Keywords: brain implant, deep brain stimulation (DBS), deep brain stimulation, Parkinson

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Authors: R. Pussinen, V. Jankovic, U. Herzberg, M. Cerrada-Gimenez, T. Huhtala, A. Nurmi, T. Ahtoniemi

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Targeted over-expression of human α-synuclein using viral-vector mediated gene delivery into the substantia nigra of rats and non-human primates has been reported to lead to dopaminergic cell loss and the formation of α-synuclein aggregates reminiscent of Lewy bodies. We have previously shown how AAV-mediated expression of α-synuclein is seen in the chronic phenotype of the rats over 16 week follow-up period. In the context of these findings, we attempted to further characterize this long term PD related functional and motor deficits as well as neurochemical and neuropathological changes in AAV-mediated α-synuclein transfection model in rats during chronic follow-up period. Different titers of recombinant AAV expressing human α-synuclein (A53T) were stereotaxically injected unilaterally into substantia nigra of Wistar rats. Rats were allowed to recover for 3 weeks prior to initial baseline behavioral testing with rotational asymmetry test, stepping test and cylinder test. A similar behavioral test battery was applied again at weeks 5, 9,12 and 15. In addition to traditionally used rat PD model tests, MotoRater test system, a high speed kinematic gait performance monitoring was applied during the follow-up period. Evaluation focused on animal gait between groups. Tremor analysis was performed on weeks 9, 12 and 15. In addition to behavioral end-points, neurochemical evaluation of dopamine and its metabolites were evaluated in striatum. Furthermore, integrity of the dopamine active transport (DAT) system was evaluated by using 123I- β-CIT and SPECT/CT imaging on weeks 3, 8 and 12 after AAV- α-synuclein transfection. Histopathology was examined from end-point samples at 3 or 12 weeks after AAV- α-synuclein transfection to evaluate dopaminergic cell viability and microglial (Iba-1) activation status in substantia nigra by using stereological analysis techniques. This study focused on the characterization and validation of previously published AAV- α-synuclein transfection model in rats but with the addition of novel end-points. We present the long term phenotype of AAV- α-synuclein transfected rats with traditionally used behavioral tests but also by using novel fine motor analysis techniques and tremor analysis which provide new insight to unilateral effects of AAV α-synuclein transfection. We also present data about neurochemical and neuropathological end-points for the dopaminergic system in the model and how well they correlate with behavioral phenotype.

Keywords: adeno-associated virus, alphasynuclein, animal model, Parkinson’s disease

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Authors: Mahdi Akhbardeh

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Synchronization of neuronal firing is a hallmark of several neurological diseases. Recently, stimulation techniques have been developed which make it possible to desynchronize oscillatory neuronal activity in a mild and effective way, without suppressing the neurons' firing. As yet, these techniques are being used to establish demand-controlled deep brain stimulation (DBS) techniques for the therapy of movement disorders like severe Parkinson's disease or essential tremor. We here present a first conceptualization suggesting that the nucleus accumbens is a promising target for the standard, that is, permanent high-frequency, DBS in patients with severe and chronic obsessive-compulsive disorder (OCD). In addition, we explain how demand-controlled DBS techniques may be applied to the therapy of OCD in those cases that are refractory to behavioral therapies and pharmacological treatment.

Keywords: stereotactic neurosurgery, deep brain stimulation, obsessive-compulsive disorder, phase resetting

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Authors: Agnieszka Fryźlewicz, Jowita Kras, Mikołaj Sadowski, Agnieszka Łapczuk-Krygier, Agnieszka Kącka-Zych Radomir Jasiński

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Nicotines are a group of compounds containing conjugated pyridine and pyrrolidine molecular segments. They are widely applied in medicine, pharmacy, and agriculture. Namely as researched treatment of Alzheimer, depression, Parkinson's, Tourette syndrome, general nervous and mental disorders. Furthermore, nicotine itself is used as a stimulant, animal repellent and was widely applied as an insecticide. In our work, we obtained nicotine analogues with possible applications in agriculture. The synthesis employed [3+2] cycloaddition (32CA) reactions, occurring between pirydyl-functionalised nitrones and conjugated nitroalkenes, that allowed us to fully regio- and stereoselectively obtain product. Moreover, cycloaddition reaction realizes rapidly in mild conditions with the full atomic economy, thus fitting into “green chemistry” trends.

Keywords: nicotine, isoxazolidine, 1-3-dipolar cycloaddition, green chemistry, biological and pharmacological activity

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Authors: Dulal Bhaumik, Fei Jie, Runa Bhaumik, Bikas Sinha

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Human brain is an amazingly complex network. Aberrant activities in this network can lead to various neurological disorders such as multiple sclerosis, Parkinson’s disease, Alzheimer’s disease and autism. fMRI has emerged as an important tool to delineate the neural networks affected by such diseases, particularly autism. In this paper, we propose mixed-effects models together with an appropriate procedure for controlling false discoveries to detect disrupted connectivities in whole brain studies. Results are illustrated with a large data set known as Autism Brain Imaging Data Exchange or ABIDE which includes 361 subjects from 8 medical centers. We believe that our findings have addressed adequately the small sample inference problem, and thus are more reliable for therapeutic target for intervention. In addition, our result can be used for early detection of subjects who are at high risk of developing neurological disorders.

Keywords: ABIDE, autism spectrum disorder, fMRI, mixed-effects model

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Authors: K. Menad, A. Feddag, M. A. Hassnaoui

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We are living in a time and in a world heavily polluted. In the list of the great dangers awaiting the man can be placed on top of the list pollution by heavy metals: lead, mercury, cadmium, etc. Fatigue, Depression, Thyroid disorder, Alzheimer's, Parkinson's, Cancer, are some of the health problems caused by heavy metal pollution. The environmental protection has long since become a major political and economic issue. Among the priorities, include safeguarding water resources. All countries of the world are concerned either because they lack water or because they pollute it. There are several ways to remove these heavy metals; ion exchange by zeolites is one of these ways, which our work is based on. Zeolites were among the main clean up materials by either adsorption, ion exchange and catalysis. Lead and cadmium, heavy metals, is one of the main dangers fulminate the flora and fauna of our small planet, so many resources are deployed to remedy them. The elimination of lead and cadmium by ion exchange has been extensively studied. However, exchange capacity of more and larger formed a major challenge for researchers and industry.

Keywords: composite, ion excahnge, zeolite LTA, zeolite x

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Authors: Vinesh Janarthanan, Mohammad H. Rahman

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There are numerous neurological conditions that may result in a loss of motor function. Such conditions may include cerebral palsy, Parkinson’s disease, stroke or multiple sclerosis. Due to impaired motor function, specifically in the hand and arm, living independently becomes tremendously more difficult. Rehabilitation programs are the main method to treat these kinds of disabled individuals. However, these programs require longtime commitment from the clinicians/therapists, demand person to person caring, and typically the treatment duration is usually very long. Aside from the treatment received from the therapist, the continuation of neuroplasticity at home is essential to maximizing development and restoring the biological function. To contribute in this area, we have researched and developed a portable and comfortable hand glove for fine motor skills rehabilitation. The glove provides interactive home-based therapy to engage the patient with simple games. The key to this treatment is the repetition of moving the hand and being capable of positioning the hand in various ways.

Keywords: home based, wearable sensors, glove, rehabilitation, motor function, video games

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Authors: M. Michael Gromiha, A. Mary Thangakani, Sandeep Kumar, D. Velmurugan

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The main cause of several neurodegenerative diseases such as Alzhemier, Parkinson, and spongiform encephalopathies is formation of amyloid fibrils and plaques in proteins. We have analyzed different sets of proteins and peptides to understand the influence of sequence-based features on protein aggregation process. The comparison of 373 pairs of homologous mesophilic and thermophilic proteins showed that aggregation-prone regions (APRs) are present in both. But, the thermophilic protein monomers show greater ability to ‘stow away’ the APRs in their hydrophobic cores and protect them from solvent exposure. The comparison of amyloid forming and amorphous b-aggregating hexapeptides suggested distinct preferences for specific residues at the six positions as well as all possible combinations of nine residue pairs. The compositions of residues at different positions and residue pairs have been converted into energy potentials and utilized for distinguishing between amyloid forming and amorphous b-aggregating peptides. Our method could correctly identify the amyloid forming peptides at an accuracy of 95-100% in different datasets of peptides.

Keywords: aggregation, amyloids, thermophilic proteins, amino acid residues, machine learning techniques

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Authors: Heidi Ahonen

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Since antiquity, many cultures have seemingly known the power of low frequencies, incorporating them in healing practices through drumming, singing, humming, etc. Many music therapists recognize there is something in music that is transformative enough to make a difference in people’s lives. This paper summarizes the key findings of several low-frequency research with various client populations conducted by the author. Utilizing low-frequency sound (30 or 40 Hz) may have diverse therapeutic impacts: (1) Calming effect – decreased agitation (autism, brain injury, AD, dementia) (2) Muscle relaxation (CP & spasticity & pain/after surgery patients, MS, fibromyalgia) (3) Relaxation/stress release (anxiety, stress, PTSD, trauma, insomnia) (4) Muscular/motor functioning/ decrease of tremor (CP, MS, Parkinson) (5) Increase in alertness, cognitive awareness & short-term memory function (brain injury, severe global developmental delay, AD) (6) Increased focus (AD, PTSD, trauma). The paper will conclude by presenting ideas informing the clinical practice. Future studies need to investigate what frequencies are effective for particular client populations and why, what theories can explain the effect, and finally, something that has been long debated - is it auditive or kinaesthetic stimulation or the combination of both that is effective?

Keywords: low frequency, 40 Hz, sound, neuro disability

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Authors: Ozlem Temiz-Arpaci, Meryem Tasci, Fatma Sezer Senol, İlkay Erdogan Orhan

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Alzheimer’s disease (AD), a neurodegenerative disorder characterized by a progressive deterioration of memory and cognition, occurs more frequently in elderly people. Current treatment approaches in this disease with the major therapeutic strategy are based on the AChE and BChE inhibition. On the other hand, tyrosinase inhibition has become a target for the treatment of Parkinson’s disease (PD) since this enzyme may play a role in neuromelanin formation in the human brain and could be critical in the formation of dopamine neurotoxicity associated with neurodegeneration linked to PD. Also benzoxazoles are structural isosteres of natural nucleotides that can interact with biopolymers so that benzoxazoles showed a lot of different biological activities. In this study, a series of 2,5-disubstituted-benzoxazole derivatives were synthesized and were evaluated as possible inhibitors of acetylcholinesterase (AChE) / butyrylcholinesterase (BChE) and tyrosinase. The results demonstrated that the compounds exhibited a weak spectrum of AChE / BChE inhibitory activity ranging between 3.92% - 54.32% except compound 8 which showed no activity against AChE and compound 4 which showed no activity against BChE at the specified molar concentrations. Also, the compounds indicated lower than tyrosinase inhibitory activity of ranging between 8.14% - 22.90% to that of reference (kojic acid).

Keywords: AChE and BChE inhibition, Alzheimer’s disease, benzoxazoles, tyrosinase inhibition

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Authors: Bilal Ahmad

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Alzheimer’s disease (AD) is one of the most common neurodegenerative illnesses. However, how Gut-microbiota plays a role in the pathogenesis of AD is not well elucidated. The purpose of this literature review is to summarize and understand the current findings that may elucidate the gut microbiota's role in the development of AD. Methods: A literature review of all the relevant papers known to the author was conducted. Relevant articles, abstracts and research papers were collected from well-accepted web sources like PubMed, PMC, and Google Scholar. Results: Recent studies have shown that Gut-microbiota has an important role in the progression of AD via Gut-Microbiota-Brain Axis. The onset of AD supports the ‘Hygiene Hypothesis’, which shows that AD might begin in the Gut, causing dysbiosis, which interferes with the intestinal barrier by releasing pro-inflammatory cytokines and making its way up to the brain via the blood-brain barrier (BBB). Molecular mechanisms lipopolysaccharides and serotonin kynurenine (tryptophan) pathways have a direct association with inflammation, the immune system, neurodegeneration, and AD. Conclusion: The studies helped to analyze the molecular basis of AD, other neurological conditions like depression, autism, and Parkinson's disease and how they are linked to Gut-microbiota. Further, studies to explore the therapeutic effects of probiotics in AD and cognitive enhancement should be warranted to provide significant clinical and practical value.

Keywords: gut-microbiota, Alzheimer’s disease, second brain aging, lipopolysaccharides, short-chain fatty acids

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Authors: Barbora Chmelova, Radek Sachl

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Gangliosides are amphipathic membrane lipids. Due to the composition of bulky oligosaccharide chains containing one or more sialic acids linked to the hydrophobic ceramide base, gangliosides are classified among glycosphingolipids. This unique structure induces a high self-aggregating tendency of gangliosides and, therefore, the formation of nanoscopic clusters called nanodomains. Gangliosides are preferentially present in an extracellular membrane leaflet of all human tissues and thus have an impact on a huge number of biological processes, such as intercellular communication, cell signalling, membrane trafficking, and regulation of receptor activity. Defects in their metabolism, impairment of proper ganglioside function, or changes in their organization lead to serious health conditions such as Alzheimer´s and Parkinson´s diseases, autoimmune diseases, tumour growth, etc. This work mainly focuses on ganglioside organization into nanodomains and their dynamics within the plasma membrane. Current research investigates static ganglioside nanodomains characterization; nevertheless, the information about their diffusion is missing. In our study, fluorescence correlation spectroscopy is implemented together with stimulated emission depletion (STED-FCS), which combines the diffraction-unlimited spatial resolution with high temporal resolution. By comparison of the experiments performed on model vesicles containing 4 % of either GM1, GM2, or GM3 and Monte Carlo simulations of diffusion on the plasma membrane, the description of ganglioside clustering, diffusion of nanodomains, and even diffusion of ganglioside molecules inside investigated nanodomains are described.

Keywords: gangliosides, nanodomains, STED-FCS, flourescence microscopy, membrane diffusion

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Authors: Naso Isaiah Thanavisuth

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Medical cannabis can be used for treatment including pain, multiple sclerosis, Parkinson's disease, and cancer. However, medical cannabis leads to adverse effects (AEs), which is delta-9-tetrahydrocannabinol (THC). In previous studies, the major of THC metabolism enzymes are CYP2C9. Especially, the variation of CYP2C9 gene consist of CYP2C9*2 on exon 3 and CYP2C9*3 on exon 7 to decrease enzyme activity. Notwithstanding, there is no data describing whether the variant of CYP2C9 genes are apharmacogenetics marker for the prediction of THC-induced AEs in Thai patients. We want to investigate the association between CYP2C9 gene and THC-induced AEs in Thai patients. We enrolled 39 Thai patients with medical cannabis treatment who were classified by clinical data. The CYP2C9*2 and *3 genotyping were conducted using the TaqMan real time PCR assay. All Thai patients who received the medical cannabis consist of twenty-four (61.54%) patients were female, and fifteen (38.46%) were male, with age range 27- 87 years. Moreover, the most AEs in Thai patients who were treated with medical cannabis between cases and controls were tachycardia, arrhythmia, dry mouth, and nausea. Particularly, thirteen (72.22%) medical cannabis-induced AEs were female and age range 33 – 69 years. In this study, none of the medical cannabis groups carried CYP2C9*2 variants in Thai patients. The CYP2C9*3 variants (*1/*3, intermediate metabolizer, IM) and (*3/*3, poor metabolizer, PM) were found, three of thirty-nine (7.69%) and one of thirty-nine (2.56%), respectively. Although, our results indicate that there is no found the CYP2C9*2. However, the variation of CYP2C9 allele might serve as a pharmacogenetics marker for screening before initiating the therapy with medical cannabis for the prevention of medical cannabis-induced AEs.

Keywords: CYP2C9, medical cannabis, adverse effects, THC, P450

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Authors: Vivek Kumar

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The effects of physical activity on the human body have been well understood. It just not only keeps us healthy and away from many diseases but also helpful in delay ageing. Those who exercise every day are physically as well as mentally strong. As the age advance, we often see that there is a loss of memory in the elderly people and their retention power weaken with time. The association between physical health and mental health of elderly people nowadays is an important topic of research. Many people at their old age who all were suffering from Alzheimer or Parkinson disease or were at the stage of dementia have been benefited significantly on exercise at daily basis. We would conduct a randomized control trial, where we will select a number of old age people (65 years old or above). These selected old age people will have some sorts of mental illness and currently receiving treatment for the same. We will divide them into 3 groups. The first group of people will receive their normal treatment i.e. taking medicines. The second group of people will receive medicine as well as will do exercise for 45 minutes every day in the early morning, the 3rd group of people will do exercise everyday for 45 minutes but will be given placebo instead of medicine. All the member of these groups will be monitored carefully for 6 months of time and making this sure that all the members of the group are taking medicines or doing exercise according to the group they belong to. The mental status of all the participants will be measured; the data will be analyzed accordingly. Expected results- This research will be helpful in establishing the effect of exercise on the mental health of the old age people. Also, it will be examined that whether the medicines along with regular exercise for can months can cure the mental illness significantly.

Keywords: mental health, elderly people, physical activity, randomized control trial

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Authors: Onyedikachi Ulelu, Andrew P. Longstaff, Simon Fletcher, Simon Parkinson

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The widespread interest in 'Industry 4.0' or 'digital manufacturing' has led to significant research requiring the acquisition of data from sensors, instruments, and machine signals. In-depth research then identifies methods of analysis of the massive amounts of data generated before and during manufacture to solve a particular problem. The ultimate goal is for industrial Internet of Things (IIoT) data to be processed automatically to assist with either visualisation or autonomous system decision-making. However, the collection and processing of data in an industrial environment come with a cost. Little research has been undertaken on how to specify optimally what data to capture, transmit, process, and store at various levels of an edge-cloud network. The first step in this specification is to categorise IIoT data for efficient and effective use. This paper proposes the required attributes and classification to take manufacturing digital data from various sources to determine the most suitable location for data processing on the edge-cloud network. The proposed classification framework will minimise overhead in terms of network bandwidth/cost and processing time of machine tool data via efficient decision making on which dataset should be processed at the ‘edge’ and what to send to a remote server (cloud). A fast-and-frugal heuristic method is implemented for this decision-making. The framework is tested using case studies from industrial machine tools for machine productivity and maintenance.

Keywords: data classification, decision making, edge computing, industrial IoT, industry 4.0

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Authors: Arleta Rifati Nixha, Mustafa Arslan, Adem Ergün, Nahit Gencer

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Polyphenol oxidase (PPO), sometimes referred to as phenol oxidase, catecholase, phenolase, catechol oxidase, or even tyrosinase, is considered to be an o-dipenol. PPO (EC 1.14.18.1), a multifunctional copper containing enzyme, is widely distributed in nature. It catalyzes two distinct reactions of melanin synthesis: a hydroxylation of monophenols to o-diphenols (monophenolase activity) and an oxidation of o-diphenols to o-quinones (diphenolase activity), both using molecular oxygen. Additionaly, investigation demonstrated that various dermatological disorders, such as age spots and freckle, were caused by the accumulation of an excessive level of epidermal pigmentation. Tyrosinase has also been linked to Parkinson’s and other neurodegenerative diseases. Nitrogen heterocycles have received a great deal of attention in the literature because of biological properties. Especially, among these heterocyclic systems, pyridine containing compounds have been the subject of expanding research efforts in heteroaromatic and biological chemistry. The pyrido [2,3-d] pyrimidine heterocycles, which are those annelated to a pyrimidine ring, are important because of their wide range of biological and pharmaceutical applications (i.e., bronchodilators, vasodilators) and their anti-allergic, cardiotonic, antihypertensive, and hepatoprotective activities. In this study series of 12 new carbazole substituted pyridopyrimidine urea(thiourea) derivatives were synthesized and evaluated effect on PPO. Additionally, we presented structure-activity relationship analyses and theoretical calculations of the compounds.

Keywords: carbazole, pyridopyrimidine, urea, thiourea, tyrosinase inhibitors

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Authors: Sanjeeb Sutradhar, Archita Patnaik

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Histidine is one of the twenty-two naturally occurring essential amino acids exhibiting two conformations, L-histidine and D-histidine. D-Histidine is biologically inert, while L-histidine is bioactive because of its conversion to neurotransmitter or neuromodulator histamine in both brain as well as central nervous system. The deficiency of L-histidine causes serious diseases like Parkinson’s disease, epilepsy and the failure of normal erythropoiesis development. Gold nanocomposites are attractive materials due to their excellent biocompatibility and are easy to adsorb on the electrode surface. In the present investigation, hydrophobic fullerene-C60 was functionalized with homocysteine via nucleophilic addition reaction to make it hydrophilic and to successively make the nanocomposite with in-situ prepared gold nanoparticles with ascorbic acid as reducing agent. The electronic structure calculations of the AuNPs@Hcys-C60 nanocomposite showed a drastic reduction of HOMO-LUMO gap compared to the corresponding molecules of interest, indicating enhanced electron transportability to the electrode surface. In addition, the electrostatic potential map of the nanocomposite showed the charge was distributed over either end of the nanocomposite, evidencing faster direct electron transfer from nanocomposite to the electrode surface. This nanocomposite showed catalytic activity; the nanocomposite modified glassy carbon electrode showed a tenfold higher kₑt, the electron transfer rate constant than the bare glassy carbon electrode. Significant improvement in its sensing behavior by square wave voltammetry was noted.

Keywords: fullerene-C60, gold nanocomposites, L-Histidine, square wave voltammetry

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Authors: Chaiyawat Musikapan, Ratchatin Chancharoen, Saknan Bongsebandhu-Phubhakdi

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For many recent years, soft robotic fingers were used for supporting the patients who had survived the neurological diseases that resulted in muscular disorders and neural network damages, such as stroke and Parkinson’s disease, and inflammatory symptoms such as De Quervain and trigger finger. Generally, the major hand function is significant to manipulate objects in activities of daily living (ADL). In this work, we proposed the model of soft actuator that manufactured by full 3D printing without the molding process and one material for use. Furthermore, we designed the model with a technique of multi cavitation cells (MC-Cells). Then, we demonstrated the curvature bending, fluidic pressure and force that generated to the model for assistive finger flexor and hand grasping. Also, the soft actuators were characterized in mathematics solving by the length of chord and arc length. In addition, we used an adaptive push-button switch machine to measure the force in our experiment. Consequently, we evaluated biomechanics efficiency by the range of motion (ROM) that affected to metacarpophalangeal joint (MCP), proximal interphalangeal joint (PIP) and distal interphalangeal joint (DIP). Finally, the model achieved to exhibit the corresponding fluidic pressure with force and ROM to assist the finger flexor and hand grasping.

Keywords: biomechanics efficiency, curvature bending, hand functional assistance, multi cavitation cells (MC-Cells), range of motion (ROM)

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

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

Keywords: neurospheres, neural stem cells, papaverine, Parkinsonism

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Authors: Ali Bahri Lubis

Abstract:

Tryptophan oxidation by Heme-dioxygenase enzyme is the initial rate-limiting step in the kynurenine pathway, which leads to the formation of NADH and dangerous metabolites, implicating several severe diseases such as Parkinson’s Disease, Huntington's Disease, poliomyelitis and cataract. This oxidation, generally, allows tryptophan to convert to N-Formylkynurenine (NFK). Observing the catalytic mechanism of Heme dioxygenase in tryptophan oxidation has been a debatably scientific interest since no one has yet proven the mechanism obviously. In this research we have attempted to prove mechanistic steps of tryptophan oxidation via human indoleamine dioxygenase (h-IDO) utilising various substrates: L-tryptophan, L-tryptophan (indole-ring-2-¹³C), L-fully-labelled¹³C-tryptophan, L-N-methyl-tryptophan, L-tryptophanol and 2-amino-3-(benzo(b)thiophene-3-yl) propanoic acid. All enzyme assay experiments were measured using a UV-Vis spectrophotometer, LC-MS, 1H-NMR and HSQC. We also successfully synthesised enzyme products as our control in NMR measurements. The result exhibited that all substrates produced N-formyl kynurenine (NFK), and a side, the minor product of hydroxypyrrolloindoleamine carboxylic acid (HPIC) in cis and trans isomer, except 1-methyl tryptophan only generating cis HPIC. Interestingly, L- tryptophanol was oxidised to form HPIC derivative as a major product and 5-hydroxy tryptophan was converted to NFK derivative instead without any HPIC derivative. The bizarre result of oxidation underwent in 2-amino-3-(benzo(b)thiophene-3-yl) propanoic acid, which produced epoxide cyclic. Those phenomena have been explainable in our research based on the proposed mechanism of how tryptophan is oxidised by human indoleamine dioxygenase.

Keywords: tryptophan oxidation, heme-dioxygenases, human indoleamine dioxygenases, N-formylkynurenine, hydroxypyrroloindoleamine carboxylic acid

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Authors: B. R. O. Omidiwura, A. F. Agboola, E. A. Iyayi

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Pure form of L-Dopa is used to enhance muscular development, fat breakdown and suppress Parkinson disease in humans. However, the L-Dopa in mucuna seed, when present with other antinutritional factors, causes nutritional disorders in monogastric animals. Information on the utilisation of pure L-Dopa in monogastric animals is scanty. Therefore, effect of L-Dopa on growth performance and carcass characteristics in broiler chickens was investigated. Two hundred and forty one-day-old chicks were allotted to six treatments, which consisted of a positive control (PC) with standard energy (3100Kcal/Kg) and negative control (NC) with high energy (3500Kcal/Kg). The rest 4 diets were NC+0.1, NC+0.2, NC+0.3 and NC+0.4% L-Dopa, respectively. All treatments had 4 replicates in a completely randomized design. Body weight gain, final weight, feed intake, dressed weight and carcass characteristics were determined. Body weight gain and final weight of birds fed PC were 1791.0 and 1830.0g, NC+0.1% L-Dopa were 1827.7 and 1866.7g and NC+0.2% L-Dopa were 1871.9 and 1910.9g respectively, and the feed intake of PC (3231.5g), were better than other treatments. The dressed weight at 1375.0g and 1357.1g of birds fed NC+0.1% and NC+0.2% L-Dopa, respectively, were similar but better than other treatments. Also, the thigh (202.5g and 194.9g) and the breast meat (413.8g and 410.8g) of birds fed NC+0.1% and NC+0.2% L-Dopa, respectively, were similar but better than birds fed other treatments. The drum stick of birds fed NC+0.1% L-Dopa (220.5g) was observed to be better than birds on other diets. Meat to bone ratio and relative organ weights were not affected across treatments. L-Dopa extract, at levels tested, had no detrimental effect on broilers, rather better bird performance and carcass characteristics were observed especially at 0.1% and 0.2% L-Dopa inclusion rates. Therefore, 0.2% inclusion is recommended in diets of broiler chickens for improved performance and carcass characteristics.

Keywords: broilers, carcass characteristics, l-dopa, performance

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Authors: Peter Parkinson

Abstract:

The research investigates the effects of temperature, humidity, wind speed, and fabric composition on the drying times of blood and assesses the degree of blood transfer that can occur during the drying process. An assortment of fabrics, of different composition and thicknesses, were collected and stained using two blood volumes and exposed to varying environmental conditions. The conclusion reached was that temperature, humidity, wind speed, and fabric thickness do have an effect on drying times. An increase in temperature and wind speed results in a decrease in drying times while an increase in fabric thickness and humidity extended the drying times of blood under similar conditions. Transfer experimentation utilized three donor fabrics, 100% white cotton, 100% acrylic, and 100% cotton denim, which were bloodstained using two blood volumes. The fabrics were subjected to both full and low/light force contact from the donor fabrics onto the recipient fabric, under different environmental conditions. Transfer times onto the 100% white cotton (recipient fabric) from all donor fabrics were shorter than the drying times observed. The intensities of the bloodstains decreased from high to low with time during the drying process. The degree of transfer at high, medium, and low intensities varied significantly between different materials and is dependent on the environmental conditions, fabric compositions, blood volumes, the type of contact (full or light force), and the drying times observed for the respective donor fabrics. These factors should be considered collectively and conservatively when assessing the time frame of secondary transfer in casework.

Keywords: blood, drying time, blood stain transfer, different environmental conditions, fabrics

Procedia PDF Downloads 126

Authors: Jungkyun Im

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Nonsteroidal anti-inflammatory drugs (NSAIDs) are effective for relieving pain and reducing inflammation. They are nonselective inhibitors of two isoforms of COX, cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2), and thereby inhibiting the production of hormone-like lipid compounds such as, prostaglandins and thromboxanes which cause inflammation, pain, fever, platelet aggregation, etc. In addition, recently there are many research articles reporting the neuroprotective effect of NSAIDs in neurodegenerative diseases, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). However, the clinical use of NSAIDs in these diseases is limited by low brain distribution. Therefore, in order to assist the in-depth investigation on the pharmaceutical mechanism of flurbiprofen in neuroprotection and to make flurbiprofen a more potent drug to prevent or alleviate neurodegenerative diseases, delivery of flurbiprofen to brain should be effective and sufficient amount of flurbiprofen must penetrate the BBB thus gaining access into the patient’s brain. We have recently developed several types of guanidine-rich molecular carriers with high molecular weights and good water solubility that readily cross the blood-brain barrier (BBB) and display efficient distributions in the mouse brain. The G8 (having eight guanidine groups) molecular carrier based on D-sorbitol was found to be very effective in delivering anticancer drugs to a mouse brain. In the present study, employing the same molecular carrier, we prepared the flurbiprofen conjugate and studied its BBB permeation by mouse tissue distribution study. Flurbiprofen was attached to a molecular carrier with a fluorescein probe and multiple terminal guanidiniums. The conjugate was found to internalize into live cells and readily cross the BBB to enter the mouse brain. Our novel synthetic flurbiprofen conjugate will hopefully delivery NSAIDs into brain, and is therefore applicable to the neurodegenerative diseases treatment or prevention.

Keywords: flurbiprofen, drug delivery, molecular carrier, organic synthesis

Procedia PDF Downloads 208

Authors: Naso Isaiah Thanavisuth

Abstract:

Introduction: Medical cannabis can be used for treatment, including anorexia, pain, inflammation, multiple sclerosis, Parkinson's disease, epilepsy, cancer, and metabolic syndrome-related disorders. However, medical cannabis leads to adverse effects (AEs), which is delta-9-tetrahydrocannabinol (THC). In previous studies, the major of THC metabolism enzymes are CYP2C9. Especially, the variation of CYP2C9 gene consist of CYP2C9*2 on exon 3 (C430T) (Arg144Cys) and CYP2C9*3 on exon 7 (A1075C) (Ile359Leu) to decrease enzyme activity. Notwithstanding, there is no data describing whether the variant of CYP2C9 genes are a pharmacogenetics marker for prediction of THC-induced AEs in Thai patients. Objective: We want to investigate the association between CYP2C9 gene and THC-induced AEs in Thai patients. Method: We enrolled 39 Thai patients with medical cannabis treatment consisting of men and women who were classified by clinical data. The quality of DNA extraction was assessed by using NanoDrop ND-1000. The CYP2C9*2 and *3 genotyping were conducted using the TaqMan real time PCR assay (ABI, Foster City, CA, USA). Results: All Thai patients who received the medical cannabis consist of twenty four (61.54%) patients who were female and fifteen (38.46%) were male, with age range 27- 87 years. Moreover, the most AEs in Thai patients who were treated with medical cannabis between cases and controls were tachycardia, arrhythmia, dry mouth, and nausea. Particularly, thirteen (72.22%) medical cannabis-induced AEs were female and age range 33 – 69 years. In this study, none of the medical cannabis groups carried CYP2C9*2 variants in Thai patients. The CYP2C9*3 variants (*1/*3, intermediate metabolizer, IM) and (*3/*3, poor metabolizer, PM) were found, three of thirty nine (7.69%) and one of thirty nine (2.56%) , respectively. Conclusion: This is the first study to confirm the genetic polymorphism of CYP2C9 and medical cannabis-induced AEs in the Thai population. Although, our results indicates that there is no found the CYP2C9*2. However, the variation of CYP2C9 allele might serve as a pharmacogenetics marker for screening before initiating the therapy with medical cannabis for prevention of medical cannabis-induced AEs.

Keywords: CYP2C9, medical cannabis, adverse effects, THC, P450

Procedia PDF Downloads 79

Authors: Srishty Gulati, Anju Singh, Shrikant Kukreti

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The manifestation of structural polymorphism in DNA depends on the sequence and surrounding environment. Ample of folded DNA structures have been found in the cellular system out of which DNA hairpins are very common, however, are indispensable due to their role in the replication initiation sites, recombination, transcription regulation, and protein recognition. We enumerate this approach in our study, where the two base substitutions and change in temperature embark destabilization of DNA structure and misbalance the equilibrium between two structures of a sequence present at the overlapping region of the human COMT gene and MIR4761 gene. COMT and MIR4761 gene encodes for catechol-O-methyltransferase (COMT) enzyme and microRNAs (miRNAs), respectively. Environmental changes and errors during cell division lead to genetic abnormalities. The COMT gene entailed in dopamine regulation fosters neurological diseases like Parkinson's disease, schizophrenia, velocardiofacial syndrome, etc. A 19-mer deoxyoligonucleotide sequence 5'-AGGACAAGGTGTGCATGCC-3' (COMT19) is located at exon-4 on chromosome 22 and band q11.2 at the intersection of COMT and MIR4761 gene. Bioinformatics studies suggest that this sequence is conserved in humans and few other organisms and is involved in recognition of transcription factors in the vicinity of 3'-end. Non-denaturating gel electrophoresis and CD spectroscopy of COMT sequences indicate the formation of hairpin type DNA structures. Temperature-dependent CD studies revealed an unusual shift in the slipped DNA-Hairpin DNA equilibrium with the change in temperature. Also, UV-thermal melting techniques suggest that the two base substitutions on the complementary strand of COMT19 did not affect the structure but reduces the stability of duplex. This study gives insight about the possibility of existing structurally polymorphic transient states within DNA segments present at the intersection of COMT and MIR4761 gene.

Keywords: base-substitution, catechol-o-methyltransferase (COMT), hairpin-DNA, structural polymorphism

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Authors: Younus Mohammad, Anita B. Fallah, Ben J. Boyd, Shakila B. Rizwan

Abstract:

N-acylethanolamines (NAEs) are endogenous lipids, which have neuromodulatory properties. NAEs have shown neuroprotective properties in various neurodegenerative diseases including Alzheimer's disease, Parkinson's disease and ischemic stroke. However, NAEs are eliminated rapidly in vivo by enzymatic hydrolysis. We propose to encapsulate NAEs in liquid crystalline nanoparticles (cubosomes) to increase their biological half-life and explore their therapeutic potential. Recently, we have reported the co-formulation and nanostructural characterization of cubosomes containing the NAE, oleoylethanolamide and a synthetic cubosome forming lipid phytantriol. Here, we report on the formulation of cubosomes with the NAE, linoleoylethanolamide (LEA) as the core cubosome forming lipid. LEA-cubosomes were formulated in the presence of three different steric stabilisers: two brain targeting ligands, Tween 80 and Pluronic P188 and a control, Pluronic F127. Size, morphology and internal structure of formulations were characterized by dynamic light scattering (DLS), cryogenic transmission electron microscopy (Cryo–TEM) and small angle X–ray scattering (SAXS), respectively. Chemical stability of LEA in formulations was investigated using high-performance liquid chromatography (HPLC). Cytotoxicity of formulations towards human cerebral microvascular endothelial cell line (hCMEC/D3) was also investigated using an MTT (3-[4, 5- dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide) assay. All cubosome formulations had mean particle size of less than 250 nm and were uniformly distributed with polydispersity indices less than 0.2. Cubosomes produced had a bicontinuous cubic internal structure with an Im3m space group but different lattice parameters, indicating the different modes of interaction between the stabilisers and LEA. LEA in formulations was found to be chemically stable. At concentrations of up to 20 µg/mL LEA in the presence of all the stabilisers, greater than 80% cell viability was observed.

Keywords: blood-brain barrier, cubosomes, linoleoyl ethanolamide, N-acylethanolamines (NAEs)

Procedia PDF Downloads 178

Authors: Shay Kee Tan, Kok Haur Ng, Jennifer So-Kuen Chan

Abstract:

This paper extends the conditional autoregressive range (CARR) model to multivariate CARR (MCARR) model and further to the two-stage MCARR-return model to model and forecast volatilities, correlations and returns of multiple financial assets. The first stage model fits the scaled realised Parkinson volatility measures using individual series and their pairwise sums of indices to the MCARR model to obtain in-sample estimates and forecasts of volatilities for these individual and pairwise sum series. Then covariances are calculated to construct the fitted variance-covariance matrix of returns which are imputed into the stage-two return model to capture the heteroskedasticity of assets’ returns. We investigate different choices of mean functions to describe the volatility dynamics. Empirical applications are based on the Standard and Poor 500, Dow Jones Industrial Average and Dow Jones United States Financial Service Indices. Results show that the stage-one MCARR models using asymmetric mean functions give better in-sample model fits than those based on symmetric mean functions. They also provide better out-of-sample volatility forecasts than those using CARR models based on two robust loss functions with the scaled realised open-to-close volatility measure as the proxy for the unobserved true volatility. We also find that the stage-two return models with constant means and multivariate Student-t errors give better in-sample fits than the Baba, Engle, Kraft, and Kroner type of generalized autoregressive conditional heteroskedasticity (BEKK-GARCH) models. The estimates and forecasts of value-at-risk (VaR) and conditional VaR based on the best MCARR-return models for each asset are provided and tested using Kupiec test to confirm the accuracy of the VaR forecasts.

Keywords: range-based volatility, correlation, multivariate CARR-return model, value-at-risk, conditional value-at-risk

Procedia PDF Downloads 69