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John Lockes theory of Konwledge : A critical assessment
(University of North Bengal, 2022) Basak, Mrinal Kanti; Basak, Jyotish Chandra
The present work entitled ‘JOHN LOCKE’S THEORY OF KNOWLEDGE: A CRITICAL ASSESSMENT’ is done in partial fulfilment of the work of my Ph. D. programme. It primarily deals with the British philosopher John Locke’s theory of knowledge. The theory of knowledge advocated by a philosopher, or a group of philosophers, usually gets a lot of importance as other theories of him/them are based on his/their epistemological theories. Locke was not an exception in this regard. Rather his theory of knowledge has some extra importance, to my mind. It is so as it posed a challenge to the existing traditions, prevalent at that time, such as rationalistic and idealistic tendencies and set an alternative approach to philosophizing. To put it more precisely, the empiricist fashion that he initiated left a seminal impact in the philosophical arena. It is this thing that attracted me and hence I decide to work on this topic. Initiating the first step to an alternative approach is a bit risky task. As it is quite difficult to free the thinker completely from the previously time-tested line of thinking. This is also true in the case of John Locke. He was a bit controversial figure due to a number of reasons. Hence, considerable time he had to spend abroad. This also brought an opportunity to him to engage with thinkers of different unfamiliar lines of thinking. Influences of these are palpable in his philosophy. In spite of his strong advocacy of empiricist theory of knowledge, we find rationalistic elements in his philosophy. On account of this, his theory of knowledge has been subjected to severe criticism. In spite of these criticisms, his theory brought a revolution in philosophy. This I intended to show in my present endeavour. In discussing his theory of knowledge, I divided my discussion into six chapters. In the first chapter, I have given a brief life history of him as I thought that a glimpse of his life and writings will be helpful to place him in the right context. His main book on the theory of knowledge was An Essay Concerning Human Understanding. I tried to have a cursory look of the different essays of this treatise. Then I gave a chapter plan as I thought that a blueprint will help me to do the work in a proper way. Chapter II deals with the negative aspect of Locke's theory of knowledge. At the introduction of this chapter, two different forms of the theory have been elucidated. Alongside this, two different types of innate principles have been discussed. The central theme of this chapter is to demonstrate Locke's refutation of innate principles. The negative or destructive side of his theory of knowledge concentrates on the refutation of the theory of innate knowledge. But his primary goal was to attack not conceptual but propositional innatism. On the one hand, he put forward arguments in order to nullify the hypothesis of innate principles; on the other, he attempted to establish the view that our mind is similar to a white paper at the time of birth. However, this chapter mainly focuses on Locke's refutation of innate principles. The intent behind his refutation of the theory of innate knowledge is to clear the path in order to establish his empiricism. Before and during Locke it was speculated that there are certain ideas that God has imprinted in the mind at the time of birth. Besides, the Scholastic philosophers supposed that all knowledge is based on certain innate maxims. Locke challenged this standpoint. In fact, He was seeking to adopt a new critical approach towards the acquisition of all kinds of knowledge. Moreover, he was inclined to found religion and morality on reason. During and before Locke, the doctrine of innate knowledge was considered to be necessary for religion and morality. He sought to replace the old foundation of innate ideas with suitable arguments so that religion and morality would stand stronger than earlier. Next, we have investigated the reason for his refutation of innate principles. The fundamental interest of Locke was to challenge the foundation of the doctrine of innatism. He believed that if it could be shown empirically unfounded then it would no longer be possible to use it as an epistemological instrument to support obscurity as well as intellectual oppression. Most importantly, he wanted to eradicate this obstacle in order to establish his doctrine of empiricism. In addition to that, an attempt has been made to enumerate the contestants of Locke. There is a divergence of opinion among scholars regarding the opponents of Locke. Usually, it is conceived that Descartes and the Cartesians were his principal adversaries in this epistemological debate. But his polemic was not against any particular opinion rather it was directed against a widespread view. The subsequent portion of this chapter attempted to illustrate at length Locke's arguments against innate principles and also the counterarguments put forward by different scholars from different angles. Actually, this portion sought to capture as well as present the debate between Locke and the innatists in a holistic manner. In Chapter III, my main aim is to outline Locke’s theory of knowledge, i. e. the positive side of his theory. In the first section, I mainly dealt with the development of Locke’s idea of knowledge. Here I have shown how Locke established his theory of knowledge and what are the main factors for the possibility of knowledge. In this chapter, I have illustrated some indispensable concepts that helped Locke to set his epistemological viewpoints, under the umbrella of empiricism, such as ideas, qualities, modes, substances, relations, etc. In the second section, I illustrated Locke’s theory of representationalism. Here I have also shown how Locke tries to establish his representative theory of knowledge by applying his empiricist style. The final section is my concluding section, and here I have tried to explain different shortcomings of Locke’s theory of knowledge that occur from lack of attention and insufficient explanations (of the concepts of primary and secondary qualities, and the concept of reflection), given by Locke. In the concluding remark, I have suggested that if Locke paid attention to the nature of ideas, qualities, and also to the human understanding, then he could have solved most of the shortcomings of his theory of knowledge. In chapter IV, my main aim is to outline Locke’s classification of knowledge. And in this regard, I have shown that Locke classifies his theory of knowledge based on what we can know, and how we can know. In the first section of this chapter, I mainly deal with what we can know according to Locke. Here I have illustrated the Lockean definition of knowledge. And different kinds of agreement between ideas of objects, which help us to understand what we can know. Here I also have mentioned some objections raised against the classification of the agreement of ideas. Afterward, in the second section, I have spread light on the Lockean conception of how we can know. Here I have shown the Lockean classification of knowledge based on different degrees of clarity. In this section, I also have shown some shortcomings regarding Locke’s conception of Demonstrative and Sensitive knowledge. And the final section is my concluding section, where I have discussed the deficiencies that arise in Locke’s theory of knowledge. Here I have also shown that though Locke tries his best to set his theory of knowledge based on empiricist style but at the end of the inquiry, he was unable to hold this position properly. In chapter V my main aim is to spread light on Locke’s conception of truth. Here I have mainly shown the possibility of truth in terms of Locke’s theory of knowledge. In the first section of this chapter, I have stated how Locke established his theory of truth in terms of his theory of knowledge. Afterward, in the second section, I discussed Locke’s conception of truth in detail, with classifications. After this, in the third section, I have spread light on the criteria through which Locke classifies his theory of truth. And finally, the fourth section is my concluding section where I have illustrated different shortcomings regarding the theory of truth, which mainly arises out of the weaknesses of the theory of knowledge. I proceeded as per the blueprint stated above. The concluding chapter gives a critical summary of his (Locke’s) theory of knowledge. To my mind, Locke with his espousal of empiricist epistemology did a wonderful task which we must appreciate. But it is also right that his empiricism was impure empiricism as he admitted some of the things which are not in consonance with empiricists’ tenets. Later philosophers Bishop Berkeley and David Hume tried to purge these drawbacks. Locke perhaps could not foresee the radical implications of empiricism. These implications became evident in Hume’s philosophy as we find that it leads to scepticism. There is no gainsaying the fact that Locke’s theory of knowledge in particular and his philosophy in general left seminal contributions. As we find that later philosophers drew spirit from him in some way or other. It would not be an overstatement perhaps to state that even the critical philosophy that Immanuel Kant espoused, later on, had its seed latent in Locke’s philosophy. We find a number of similarities between these two great philosophers’ viewpoints.
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Virtual screening, molecular docking studies admet properties dencity functional theory and 2D-QSar modeling to design potential inhibitors
(University of North Bengal, 2023) Sarkar, Subhajit; Das, Rajesh Kumar
Conventional drug design processes use trial and error methods for screening natural and synthetic compounds. It costs millions of dollars and very long time approximately 10-15 years. To meet these severe challenges nowadays pharmaceutical companies rely very much on computer-aided design techniques to discover potential drugs. Throughout the research work, various natural inhibitors that regulate a variety of physiochemical processes in bacteria and human beings have been studied. Derivatives of them have been designed and developed in such a way that they may be used as potent drugs producing no or minimal side effects and overcome the antibiotic resistance property. We hope, in silico drug design processes followed in different studies would save precious time and millions of dollars, leading to novel alternate therapeutics. CHAPTER I Microorganism including bacterium communicates among themselves through a unique mechanism called quorum sensing. The different QS pathways of Gram-negative and Gram-positive bacteria have been discussed elaborately in this chapter. Bacteria develop antibiotic resistance through various mechanisms among them biofilm formation is regulated by quorum sensing. Quorum sensing inhibitors (QSIs) interrupt the expression of virulence factors production and inhibit biofilm formation without killing bacteria or inhibiting bacterial growth. The QSIs are of two types natural and synthetic. It includes a details study of different types of QSIs and inhibition mechanisms. Hamamelitannin (HAM) a phytochemical has the capability to inhibit Staphylococcus aureus agr QS system. Our approach is to modify HAM by incorporating an active functional group for better efficacy. We have followed the same in silico process in another study where the target protein was chosen as heat shock protein 90 rather known as HSP90 and found in all species ranging from bacteria to humans. Over expression of this client protein may lead to several refractory diseases including cancer, inflammation, neurodegeneration, and viral infection. It discussed the various roles and functions of HSP90 in the human body. Besides, we have performed quantitative structure activity relationship (QSAR) analysis in two different cases. Phophodiesterase-4 (PDE4) and lysine-specific demethylase 1 (LSD1) are two key proteins that regulate various physiochemical processes in humans. Over expression of PDE4 may lead to severe diseases including chronic obstructive pulmonary disorder (COPD), and cardiovascular disease whereas unregulated LSD1 may result in tumorigenesis, neurodegenerative disorders, viral infection, diabetes, fibrosis, and various types of cancers including prostate, gastric, breast, lung, and leukemia. Separate studies of QSAR on these two proteins help us to identify best-fitted designed molecules as potent inhibitors of the target proteins. Detailed information on both PDE4 and LSD1 is described here. CHAPTER II The major in silico techniques that are widely popular among researchers are molecular docking, density functional theory (DFT) calculation, molecular docking, molecular dynamics (MD) simulations, and absorption, distribution, metabolism, excretion, toxicity (ADMET) prediction. Collective use of all of the mentioned computer aided techniques is necessary to predict potential QS inhibitors. It includes methodologies of all of the above mentioned techniques in detail. CHAPTER III A set of 26 derivative compounds have been designed by incorporation of different active functional groups at various positions of hamamelitannin (HAM) shown here. All structures were optimized using Gaussian software. Gaussian outputs were used to perform molecular docking with the help of Autodock Vina software. Docking results of HAM with three target proteins of PDB ID 4AE5, 4G4K, and 2FNP exhibited the binding energy value of -6.7, -6.5 and -6.6 kcal/mol respectively. Out of 26 derivatives of HAM, 14 compounds have shown higher binding affinity than that of HAM. The above in silico studies concluded that 14 ligands could be developed as effective inhibitors of S. aureus biofilm formation and considered for in vitro and in vivo analysis. CHAPTER IV It includes the natural product oroidin (ODN) considered a potent inhibitor of heat shock protein 90 (Hsp90) and its derivatives had been designed by substituting various functional groups in the various position of five membered rings. A library of thirty nine derivatives was designed by introducing various functional groups such that amide, amine, phosphate, hydroxyl, fluorine, methoxy, and carboxylic acid in the active pharmacophore of oroidin. All the analyses expressed that seven analogues possessed better chemical activity and docking capabilities than that of the source molecule ODN. These seven computationally designed derivatives may be used as novel beneficial agents in various cancer therapies including breast, ovarian, colon, pancreas, liver carcinoma, and leukemia treatments, and could be considered to develop as effective anticancer drug candidates in the future. CHAPTER V Keeping in mind the importance of PDE4 inhibitors it includes a study where a quantitative structure-activity relationship (QSAR) modeling method was performed to develop a standard model on a dataset of sixty-six significant PDE4A inhibitors encompassing common scaffolds in pyrazolo-oxazine, and imidazo-pyridazine compounds. According to QSARINS software, the model comprises three descriptors namely MoRSEM11, MoRSEP26and MoRSEC11 were found to be the best ones. The three descriptor model which was employed to predict pIC50 values as the studied response exhibited good R2 (0.8185), and F (73.658) values. Internal validation parameters Q2loo= 0.7845, Q2LMO= 0.7771and external validation parameters Q2F1= 0.8277, Q2F2= 0.8246, Q2F3= 0.8626, confirmed the stability and robustness of the developed model. On the basis of this model equation, pIC50 values of thirty-nine designed compounds were calculated. The potent lead molecules, predicted from the QSAR model, were further investigated by performing in silico approaches such as molecular docking, molecular dynamics simulation, bioavailability assessments, and toxicity prediction. The study revealed that the eight compounds possessed potent PDE4A inhibitory activity and might be considered as future drugs subject to the viability of in situ and in vivo proceedings. CHAPTER VI In this chapter quantitative structure activity relationship (QSAR) model was built from a dataset of 44 compounds as LSD1 inhibitors. The best 10 compounds have fully satisfied all the criteria of drug-like properties and these designed lead molecules would have more potency to treat LSD1 target after going through in vivo and in vitro analysis. CHAPTER VII 3D-QSAR analysis and application of ANN validation in CADD to design potential inhibitors of many critical diseases in future.
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Bhim Dahalka upanyasma paine aparadhbrittiko visleshan भिम दाहालका उपन्यासमा पाइने अपराधवृत्तिको विस्लेषण
(University of North Bengal, 2022) Sharma शर्मा, Durgaprasad दुर्गाप्रसाद; Puskar पुस्कर, Parajuli पराजुली