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Home > Synthesis of State Space Model for Human Cardiovascular System Using Bond Graph Approach

Synthesis of State Space Model for Human Cardiovascular System Using Bond Graph Approach

Thesis Info

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Author

Chughtai, Lubna

Program

PhD

Institute

National University of Sciences & Technology

City

Islamabad

Province

Islamabad

Country

Pakistan

Thesis Completing Year

2017

Thesis Completion Status

Completed

Subject

Electrical Engineering

Language

English

Link

http://prr.hec.gov.pk/jspui/bitstream/123456789/13446/1/Lubna_Chughtai_Electrical_Enginee_HSR_2017_NUST_22.06.2017.pdf

Added

2021-02-17 19:49:13

Modified

2024-03-24 20:25:49

ARI ID

1676727844296

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Cardio Vascular System (CVS) is a closed circulatory system responsible to provide the oxygenated blood to all the parts of the body and to collect the deoxygenated blood from all the parts of the body. It mainly consists of the heart, the blood vessels and the blood. It is one of the most important systems of the body and the heart being the chief organ; pumping the blood which carry all the vital nutrients to each and every cell of the body. The pumping action of the heart is regulated by a feedback mechanism called the baroreflex mechanism. Cardio Vascular diseases have a major impact worldwide; more than 55% of the total deaths in the world are due to malfunctioning of the CVS. Cardiovascular disease includes conditions that affect the structure or function of the heart, such as, coronary artery disease, heart attack, abnormal heart rhythms arrhythmias, heart failure, heart valve disease, congenital heart disease, heart muscle disease and many others too. Depending on the different malfunction conditions of the heart, artificial pumps and other invasive surgeries are proposed. The heart is a very vital organ and is also not easily accessible as it is located inside the ribcage. Due to this fact, the experimental monitoring of the functioning of the heart assist devices is impossible and is also life threatening. Therefore for proper designing of the required assistive devices, the very first requirement is the availability of proper mathematical model of the system which can clearly portrays the hemodynamic of the heart and can serve as an important test bed against which estimation and identification algorithms can be evaluated and controlled. A significant amount of valuable research work has already been undertaken regarding the mathematical modeling of the CVS and the baroreflex system. All these models cover many of the physiological characteristics but still there is a space for new strategies and improvement. The cardiac activity includes mechanical, hydraulic, chemical and electrical events; the modeling of such a multi domain system requires a unified modeling approach. The other limitations of the existing mathematical models may include the lack of cause effect relationship, complexity due to separate feedback loops, absence of fault diagnosis at element level etc. To overcome the above stated shortcomings in the existing models, a Bond Graph modeling approach to model the CVS and the baroreflex system has been proposed in this dissertation. The Bond Graph has proved to be an effective methodology for modeling the systems having subsystems of different physical nature. The benefit of using the Bond Graph for modeling is the ability to represent the circuits using flow, effort and energy conservation elements providing cause effect relationship. The fault diagnosis at element level also became possible. Consequently, in the Bond Graph technique there is a useful distinction between the reciprocal flow of influence inherent in the dynamics of the system and the feedback that arise by the design of system and therefore eliminates the complexity due to the separate feed back loops. Bond Graph modeling approach for the CVS was also proposed and presented by some researchers and had added remarkable contributions, but none of them analyzed the whole CVS on element basis and no idea was given for finding out the state space representation of the CVS using the cause-effect relation property of the Bond Graph. In this thesis, in addition to the complete Bond Graph model of the CVS and the baroreceptors, the time varying state space is also generated for these systems. The proposed state space model from the Bond Graph provides information about the internal state variables. The internal state variables are the smallest possible subset of the system that can represent the entire state of the system at any given time. Due to the in-depth analysis on element level and the information about the internal state variable the proposed model can provide a better platform for the CVS diagnostics, therapy selection, surgery and interventions.
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اقبال شناسی کے تناظر میں فیض اور جابر علی سید کا اختصاصی مطالعہ

اقبال شناسی کےتناظر میں فیض اور جابر علی سید کا اختصاصی مطالعہ

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علم و تربیت كا باہمی ربط و تعلق

Education and practical orientation are both significantly interlinked. Education without practical training stands mere theory having no connection with life. Practical orientation without education carries no meaning. Islamic system of life seeks to espouse both education and training. The Prophet (s. a. w.) educated his people theoretically as well as trained them practically. What ever he did in this regard constitute Islamic principles for human life. Curricula of educational institutions need to be developed with a view to making students knowledgeable on the one hand and upholders ofIslamic virtues in their practical life on the other. The present paper is aimed at highlighting the co-relationship between the education and practical orientation, proving beyond doubt that isolation of one from the other is too damaging to imagine

Synthesis Characterization and Pharmacological Screening of Sulfonated Derivatives of Piroxicam

Medicinal chemistry is a discipline associated with the designing, synthesis, and development of drugs used in different pathophysiological conditions. Small organic compounds or biologics are mostly studied in medicinal chemistry but the key focus is on small molecules to develop new synthetic agents for human use. These small molecules are usually heterocyclic compounds, hold a ring in their structure along with heteroatoms in addition to the carbon. Heterocyclic compounds are abundantly present in nature and very important from the therapeutic and economic point of view. Detailed information on the pharmacological activities of each organic compound is a challenge for the medicinal chemists because a large of number of synthetic organic compounds has been prepared currently. Therefore, the idea of structure activity relationship has been used to explain the variation in biological activity of organic compounds. Structure activity relationship is used in lead optimization to improve the efficacy and minimize the toxicity of the molecules. The biology oriented synthesis "BIOS" is a starting point for the search of new therapeutic agents. It is an approach for the generation of libraries of compounds for their biological applications. Non-steroidal anti-inflammatory drugs are an important class of organic compounds, having widespread applications in different diseases and most commonly used as analgesic, antipyretic and anti-inflammatory agents. They are used for the management of various acute and chronic inflammatory conditions alone or in combination with opioid analgesics. Oxicam is comparatively a new class of drugs consists of enolic acid compounds which possess analgesic and anti-inflammatory effects. Their structure contains 1, 2-benzothiazene nucleus, substituted at position-3 with carboxamide. Piroxicam belongs to the oxicam family discovered in 1972. It is the first member of this class and has marked analgesic and antipyretic properties and therefore, has been used clinically for the treatment of persistent inflammatory disorders for the last 30 years. Chemically, piroxicam is 4-hydroxy-2-methyl-2H-1, 2-benzothiazine-1-(N-(2 pyridinyl) carboxamide)-1, 1-dioxide. It is a heterocyclic compound and consists of benzene and thiazine rings. Benzo represents benzene while thiazine represents a six-membered ring in benzothiazine. It acts by blocking the cyclooxygenase enzymes and inhibiting the synthesis of prostaglandins. Due to the existence of enolic hydroxy (OH) group, piroxicam presented fascinating structural properties which prompted the medicinal chemists and pharmacologists for further research. The present study was designed to synthesize and characterize the piroxicam derivatives and screened them for in-vivo and in-vitro biological activities. Piroxicam derivatives (1-18) were prepared by dissolving piroxicam with commercially available alkyl/aryl sulfonyl chloride and triethylamine in tetrahydrofurane as a solvent, in a round bottom flask with constant stirring at room temperature. After the completion of the reaction, the resulting products were filtered, washed with hot n-hexane and excess of solvent was removed under vacuum at reduced pressure. Different spectroscopic procedures like 1H-NMR, EIMS, IR, UV and CHN analysis were used for structural elucidation of newly synthesized piroxicam derivatives and subjected to biological screening in order to prove that changing the substituent''s modifies the inhibitory potential of the individual derivative as an evident of structure activity relationship studies. The compounds were evaluated for the antinociceptive activity at 5, 10, 20 and 30 mg/kg doses. The compounds were found to be active in acetic acid induced writhing test but inactive in hot plate test for analgesia, indicating that the compounds only possess the peripheral mechanism and no central mechanism is involved as compared with standards piroxicam and tramadol respectively. Anti-inflammatory activity was determined in the carrageenan induced paw edema model in mice. The derivatives were tested at 10, 20 and 30 mg/kg doses and most of them were found to be significantly potent as compared with standard piroxicam. The piroxicam analogues when screened for the antipyretic effect in Brewer’s yeast induced pyrexia model in mice at 10, 20 and 30 mg/kg doses, the prominent antipyretic effects were observed as compared with standard paracetamol. The results showed that the compounds exhibited significant (*P < 0.05, **P < 0.01 and ***P < 0.001.) dose dependent antinociceptive, anti-inflammatory and antipyretic activities when compared with standards. The analogues were found to be safe in acute toxicity test at the doses of 50, 100 and 150 mg/kg i.p., and no gross mortality or behavioral changes were observed during 24 hours assessment time. The piroxicam derivatives were also screened for the different in-vitro activities. In in-vitro antiglycation assay, the compounds showed varying degree of antiglycation potential when compared with standard “rutin”. Compound 2, 4, and 7 exhibited excellent antiglycation activity with better potency than the reference. In in-vitro 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium cytotoxicity assay, piroxicam derivatives exhibited varying degree of cytotoxic activity against breast cancer cell lines when compared with standard “doxorubicin”. Compound 4, 17 and 18 showed moderate anticancer activity while compound 3 showed low growth inhibitory activity. The derivatives were also screened for the in-vitro immunomodulatory activity against the standard “ibuprofen”. None of the compound was found to be active in the in-vitro immunomodulatory activity. It concludes that, changing the substituent or changing the position of substituent on aromatic ring does not impart any activity to the compounds. Results of in-vitro dipeptidyl peptidase-IV inhibitory assay showed that the substitution does not noticeably change the activity of the compounds but impart a weak inhibitory activity to the compounds 1, 4, 11, 13 and 14. Other piroxicam derivatives of this series were inactive toward in-vitro dipeptidyl peptidase-IV inhibitory assay. In case of in-vitro leishmanicidal activity, compounds 7, 8, 10, 13, 14 and 17 showed good to low leishmanicidal activity while other compounds of this series having less than 100 % inhibition values and therefore concluded them as inactive. It can be concluded that, some piroxicam derivatives possess potent, good/low in-vitro antiglycation, anticancer, dipeptidyl peptidase-IV inhibitory and leishmanicidal potential as compared with standards but inactive in in-vitro immunomodulatory activity. Findings of this research work strongly support the use of piroxicam derivatives as analgesic, antipyretic, anti-inflammatory, anti-glycating, dipeptidyl peptidase-IV inhibitors, leishmanicidal and anticancer agents. However, further comprehensive research work on piroxicam derivatives as well as their use for selective inhibition of cyclooxygenase-2 enzyme is necessary in order to minimize the gastrointestinal complications.