Alzheimer‟s disease (AD) is the most common neurodegenerative disorder, characterized by memory impairment, behavioral turbulence, cognitive dysfunction and imperfection in routine life activities. AD is the most common cause of dementia among people aged 65 years and older, with about 35 million sufferers worldwide. It is the fifth leading cause of death in people above 65 years of age and is predicted to affect 1 in 85 people globally by 2050. The most important pathological aspects of AD include deficiency of neurotransmitter acetylcholine, deposition of amyloid plaques (Aβ) and neurofibrillary tangles. Cancer is another life-threatening disease and serious health problem worldwide. More than half of the 20 million people diagnosed with cancer belong to the developing regions of the world. Due to the alarming increase in cancer incidences, it is estimated to have 10 million deaths annually by 2020. Natural products play a significant role in the drug discovery and development process. The main advantage of natural products as a source of lead compounds is the tremendous molecular diversity found in nature. Based on the folkloric uses of P. hydropiper and related species, we investigated solvent extracts, essential oils and isolated compounds for anti-Alzheimer''s and cytotoxic potentials by using in-vitro and in-vivo models. A total of seven fractions were derived from the dried whole plant of P. hydropiper using solvent-solvent extraction method. Essential oils from leaves and flowers were also isolated and subjected to Gas Chromatography-Mass Spectrometry (GC-MS) analysis. Crude methanolic extract (Ph.Cr) was subjected to qualitative phytochemical analysis, GC-MS analysis and column chromatography for isolation of bioactive compounds. Ph.Cr was tested positive for the presence of alkaloids, flavonoids, saponins, tannins, triterpenoids anthraquinones, glycosides. In GC-MS analysis of Ph.Cr, n-hexane (Ph.Hex), chloroform (Ph.Chf), butanol (Ph.Bt) and ethyl acetate (Ph.EtAc) fractions 126, 124, 181, 131 and 164 compounds were identified respectively. In acetylcholinesterase (AChE) inhibition assay, Ph.Hex , Ph.Chf and Ph.Sp were the most potent fractions that displayed IC50 values of 35, 55 and 100 μg/ml respectively. While in butyrylcholinesterase (BChE) inhibition assay, Ph.Aq and Ph.Hex were more potent with IC50 values of 3 and 40 μg/ml respectively. In DPPH free radicals scavenging assay, Ph.Bt, Ph.Chf, Ph.EtAc, Ph.Lo and Ph.Fo fractions were more potent among all samples with IC50 of 3, 10, 15, 20 and 200 μg/ml respectively. In ABTS anti-radicals assay, Ph.Bt, Ph.EtAc, Ph.Aq, Ph.Sp revealed highest ABTS scavenging effect, thus causing IC50 values91.03, 90.65, 90.56 and 90.84% inhibition of free radicals respectively. From the most active fraction including chloroform and ethyl acetate six compounds (MA1-6) were isolated , purified and their structures were confirmed by 1H NMR, 13C NMR and mass spectra. The most potent compound MA-1 and Ph.Lo were subjected to in-vivo anti-Alzheimer and cell line studies. In AChE inhibition assay, MA-1 exhibited IC50 of 55 μg/ml, whereas, in BChE inhibitory assay MA-1 showed IC50 of 50 μg/ml. Likewise Ph.Lo and Ph.Fo demonstrated IC50''s of 120 and 220 μg/ml respectively in AChE inhibition assay. In BChE inhibitory study, Ph.Lo and Ph.Fo showed IC50''s of 130 and 225 μg/ml respectively. In DPPH, ABTS, H2O2 anti-radicals assays, MA-1 exhibited IC50''s of 140, 120 and 280 μg/ml respectively. Whereas, Ph.Lo and Ph.Fo displayed IC50''s of 180 and 45 μg/ml respectively. Moreover, the IC50''s were 60 and 50 μg/ml for Ph.Lo and Ph.Fo respectively in H2O2 radicals scavenging assay. In beta amyloid cleaving enzyme (BACE1) inhibition assay, MA-1 and Ph.Lo displayed 73.00 ± 3.05 and 79.33 ± 3.17% enzyme inhibition respectively at 1 mg/ml concentration. In trasgenic animals model of Alzheimer disease MA-1 and Ph.Lo showed significant decline in cognitive dysfunctions of animals evaluated through behavioral assessment tools including Paddling water Maze (PWM), Y-Maze, open field and balance beam. Ex-vivo studies suggested that MA-1 and Ph.Lo sufficiently cross blood brain barier (BBB) and treated transgenic animals with these samples showed a significant decline in the AChE, BChE activities in the cortical and hippocampus tissues. Moreover, the cortical and hippocampus tissues of transgenic animals treated with MA-1 and Ph.Lo exhibitied a significant DPPH radicals scavenging effect. In cytotoxicity studies, Ph.Lo was less effective against all tested cell lines with LC50> 1000 μg/ml. MA-1 displayed LD50 of 440, 170, 200 μg/ml against NIH/3T3, HeLa and MCF-7 cell lines. Moreover, compound MA-3 displayed LD50 of170, 60 and 140 μg/ml against HeLA, MCF-7 and NIH/3T3 cell lines respectively. Whereas, compound MA-4 demonstrated 380, 160 and 58 140 μg/ml against HeLA, MCF-7 and NIH/3T3 cell lines respectively. Concluding the current study, it is stated that P. hydropiper crude extracts and isolated compounds possess considerable neuroprotective and selective cytotoxic potentials. Further studies are required regarding their potential use in Alzheimer disease and cancer.
موضوع 2:اسلام میں تحقیق کے اصول قرآن پاک کی روشنی میں تحقیق کی اہمیت: اسلام ایک مکمل ضابطہ حیات ہے جس کی بنیاد قرآن پاک پر قائم ہے۔اس میں قیامت تک کے انسانوں کے لیے رہنمائی موجود ہے۔ اس میں ہدایات، احکام،اصول و کلیات پر مشتمل بنیادی باتیں بیان کی گئی ہیں۔اسلام وہ واحد آفاقی مذہب ہے جو رہبانیت کی نفی کرتا ہے اور سچائی تک پہنچنے کے لیے کسی حد تک عقل کے استعمال کی اجازت دیتا ہے کیونکہ تحقیق و تجربے سے غوروفکر سے پہلو تہی کرنا حقائق تک پہنچنے کی راہ میں رکاوٹ پیدا کرتا ہے۔ ایسے موضوعات جو انسانی عقل سے مابعد طبیعاتMetaphysics مثلا اللہ تعالی کی ذات اورصفات وغیرہ سے متعلق ہیں اسلام ان کے بارے میں سوچ و بچار کی اجازت نہیں دیتا ہیے۔ ایسے سوالات ہیں جومحدود انسانی عقل میں نہیں سما سکتے ان کا علم صرف وحی کے ذریعے سے ہی حاصل ہو سکتا ہے۔ان کے علاوہ ہر وہ موضوع جس کا تعلق فلاح انسانی سے ہے۔ قرآن پاک میں جابجا غوروفکر کی دعوت دی گئی ہے۔جن میں سے چند آیات کریمہ درج ذیل ہیں۔ 1۔سورۃالنساء کی آیت نمبر 82 میں اللہ تعالی فرماتے ہیں: "تو کیا لوگ قرآن پر غور نہیں کرتے۔اگر یہ اللہ کے سوا کسی اور کی طرف سے ہوتا تو اس میں تفاوت پاتے۔" 2۔سورۃمحمد کی آیت نمبر 24 میں اللہ تعالی فرماتے ہیں: "تو کیا یہ لوگ قرآن میں غور نہیں کرتے یا دلوں پر کفر لگ گئے ہیں۔" 3۔سورۃ الانعام کی آیت نمبر50 میں اللہ تعالی فرماتے ہیں: "آپ کہیے کہ اندھا اور بینا کہیں برابر ہو سکتے ہیں؟ کیا تم غور نہیں کرتے۔" ان آیات کریمہ کے مطالعے سے معلوم ہوتا ہے کہ حق تعالی نے قرآن پاک کے ذریعے انسان کو غوروفکر یعنی تحقیق کرنے کا حکم دیا۔ اسلام میں...
Egyptian society and Indian society faced many social issues, especially during the British colonial rule in the nineteenth and twentieth centuries. The British occupation was an era of decline for the Muslims of the sub-continent. Public minds were not able to recognize this change and did not fully understand the requirements of the time. Writers and poets of that time discussed and dealt with social isues and tried to raise the almost dead community back to life. They wanted their people to be rationalized and to understand the problems of society. Two of those leading writers were Taha Hussein and Deputy Nazir Ahmed. This article will examine Taha Hussein’s role and contribution in raising of Egyptian society and enlightening the Arab minds and also throw light on the efforts of Deputy Nazir Ahmed, a leading social novelist in the sub-continent. The most important issues that were treated through their novels and their writings were the problems and issues of woman and the issue of moral decline in society.
For developing the simulation techniques applicable to engineering system, the modeling of a vertical inverted U–tube steam generator (UTSG) operating in a Nuclear Power Plant (NPP) has been carried out for finding the temperature distribution, optimum boiling length in the tube and addressing the interaction of technical and environmental factors involved in the system. Modeling of a system consists of three stages: (i) Development of computer code, (ii) Application of the model in the steam generator, (iii) Evaluation of the model in the power plant. Computer model has the ability for optimization of steam generator parameters to be used in simulation. The steam generator modeling for the temperature distributions comprises of development of a specific mathematical model considering the real engineering constraints. The modeling approach used for the simulation of a conventional boiler has to be revised, since the heat transfer regime in each tube can not be fixed by the equipment design. General equations have to be used for each tube of the boiler and the actual heat transfer conditions in the tube has to be identified. The solution of the model has been discussed analytically under steady state conditions. Empirical equations are available to predict the saturation temperature in each region of the steam generator. The computed results show the temperature distribution of the primary fluid along the whole length of the tube and the point of saturation temperature, where steam formation starts. The behaviours of important parameters involved in the process are studied by the comparison of simulated results. The analytical solution is based on certain simplifying assumptions, which to some extent limits the scope of its applicability. A numerical simulation technique has been developed by adopting Euler–Cauchy method to obtain a solution independent of the assumptions made in the analytical solution. This makes the model more realistic and flexible and enables to find the relative temperature distribution behaviours of the primary and secondary fluids in UTSG and an optimum boiling length of the tube (Lb). The main advantage of the proposed method is that it permits a better understanding of the influence of the design parameters on the cycle performance. A boundary condition needs to be prescribed along the tube to start calculations.7 The solution of the model has also been discussed under unsteady (Transient) conditions. To simulate the transients, the mathematical model is discretised in terms of time and space coordinates. The flow model in transient state is used to derive a time dependent finite difference simulation technique which gives the relative temperature distributions of the fluids and an optimum boiling length (Lb) with respect to time from 0.0% Reactor Power (RP) level to 100% RP level. For further analysis, the graphs of the temperature distributions of secondary and primary fluids are drawn at specified intervals of time. These results can be used for a multi–objective optimization of the steam generator in future. The model provides a significant analytical capabilities for the specialists working in the field of NPP safety. The purpose of the work is to predict the behaviour of steam generator working in NPP and to help correctly for defining the operator action validation and verification of Emergency Operating Instruction (EOIs). The model is practically feasible under prevailing constraints. Evaluation of the model in terms of calibration, sensitivity and verification yields a good agreement between observed and computed results (hydrograph) of the steam generator and its components. The work on unsteady (transient) heat flow in a UTSG is very scarce in the literature. Mostly, the steady flow problems have been discussed. Few attempts have been made regarding the transient flows. Keeping the above facts in view, the entire work of the present thesis is organized as follows: Chapter 1 consists of some introductory remarks, complete modeling process, explanation of computer codes, the physical model and general features of Nuclear Power Plant (NPP) and Nuclear Steam Generator (NSG). Objectives, scope of study and previous work are also mentioned in this chapter. Chapter 2 studies the basic preliminaries relevant to the laws for system analysis and energy balance equations. Parallel and counter flow heat exchangers and their temperature distributions with length are explained. Shell and tube and multipass shell and tube heat exchangers are also discussed. Heat exchangers effectiveness against the number of transfer units is described at the end of this chapter. Chapter 3 describes modeling and simulation of the steam generator in steady state – a case study. The formulation of the mathematical model and its analytical solution are given. Equation which governs the primary side incompressible fluid flow in8 a UTSG is also modeled here. Model layout and solution procedure is also discussed in this chapter. One fortunate outcome of the graphical approach works best to find percentage changes in the outlet temperature of the primary fluid corresponding to any desired changes in the mass flow rate (m) and the factor Rh. The results of this chapter are published in “Pakistan Journal of Scientific Research, Vol. 60, pp. 40–43, (2008)”. Chapter 4 is concerned with the formulation of numerical models for primary and secondary of fluids. The numerical scheme evaluates the temperature distribution of the primary fluid relative to the temperature distribution of the secondary fluid and vice– versa for the user specified input data. An iterative procedure is followed until the program converges for an optimum boiling length of the tube using relative error criteria. A reasonable agreement between experimental observations and numerical solutions is presented through graphs. These results are published in “Pakistan Journal of Engineering and Applied Sciences, Vol. 4, pp. 74–79, (2009)”. Chapter 5 deals with the solution of the model of UTSG in transient condition. The flow model in transient state is used to derive a time dependent finite difference simulation technique which gives the relative temperature distributions of the fluids and an optimum boiling length (Lb) with respect to time from 0.0% Reactor Power (RP) level to 100% RP level. The results obtained from the suggested models have been found to be in good agreement with the experimental data. The contents of this chapter are published in “Pakistan Journal of Engineering and Applied Sciences, Vol. 5, pp. 10–15, (2009)”. Some observations from chapter 5 have also been accepted for publication in “International Journal of Mathematical Modeling, Simulation and Applications, (2009)”. To upgrade the existing control system, an improved control strategy can be developed. The numerical simulation techniques show that the procedures are effective and can be used for a multi–objective optimization of the steam generator in future.