The Problem of Evil Essay Example | Topics and Well Written Essays - 1250 words

The Problem of Evil - Essay Example However, this world is filled with things beyond evil and people do feel pain and suffering, which contradicts the claims of orthodox theist that God is perfectly good. This conflict is called problem of evil. Is God willing to prevent evil, but not able? Then is He impotent. Is He able, but not willing? Then is He malevolent. Is He both able and willing? Whence then is evil? (Hume) In an attempt to unravel the complexities of this predicament, few queries must be made. Evil goes beyond what we do not want other people to do to us. According to Hick, there are two classifications of evil. First, the moral evil which includes those acts an individual or group may be responsible of such as the seven deadly sins and more. Second type is the natural evil. Pain and suffering brought by natural calamities which people has no control over. Although the line which separates the two is still blurry, since some natural evil are consequences of human actions or lack of action. Nevertheless, we cannot deny the fact that there are things beyond our control ----- accidents and natural disasters. Evil is often associated with suffering which highlights an individual’s sense of pain or loss that focuses on a particular kind of evil: one which is considered as a consequence of an act rather than a more abstract concept. Thus arise another confusion which is the existence of hell ----- a place where God put those who have failed Him to rot and suffer; because this very notion contradicts the idea of a loving God. Augustinian theodicy argues that God is wholly good, thus He’s not responsible for the existence of evil in the world. It claims that evil is not the opposite; rather it is the absence of good. According to this theodicy, evil happens as a result of people’s misuse of their free will, therefore exonerating God and putting the blame of all evil and suffering to people who abuse their free will. This particular claim of Augustinian theodicy makes the subject more baffling, for it puts all the blame to the ‘finitely perfect’ being, that is us humans, who fails to choose perfection, hence shifting the blame back to the Creator. Moreover, the term ‘privation’ is inadequate justification for the apparent effects of evil in its truest sense. Then comes the knowledge of evolution ---- a process by which humans, being the most complex creatures, learn to adapt and grow in accordance with its environment. This is the claim of Irenaean theodicy which is restated by John Hick on his Soul-making theodicy. Hick defines soul-making as the existence of evil and suffering which allows flawed creatures to outgrow their imperfections and develop to a more perfect state. It emphasizes on the development by practicing free will, people are able to overcome temptations and suffering hence bringing them closer to perfection and to God. Unlike that of the Augustinians which give much stress on the negativity of the existence of evil, Irenaean theodicy puts God in an epistemic distance from us. It explains that this distance is meant for us to learn to love God on our own free-will by prevailing over all the difficulties He places on our path as we journey through life. Evil is created by God to hone the inner values we have, for some ideals need to go through some difficulties to develop like that of courage and forgiveness amidst suffering. This theodicy believes that individuals evolve towards a higher state by

Unisys Credit Problems Essay Example | Topics and Well Written Essays - 500 words

Unisys Credit Problems - Essay Example ch Unisys has invested will contribute to a greater loss if the company were to use them to remain liquid and be able to fund its operations with the ultimate consequence being a rights issue to finance the deficit. This situation has forced the company to rethink its position on the revolving credit facility which it operates with various funding institutions to the tune of $275 million. The idea is not to renew it and avoid the escalating interests due to such. This presents the company with the challenge of how it will be able to finance its operations and come out of the financial crisis. The management theory available for use by the firm is that what has to be done for the business to remain a float must be done. The company’s management will therefore review the available options and make crucial decisions on which ones are relevant so as to implement the most effective ones. The alternatives available at the disposal of Unisys are numerous but not with serious economic consequences. It seemingly must repay the debt of $300 million by the time of expiry of the revolving credit facility. Unisys can seek funding through issuing additional shares in the market (Malz, 2011). This might not be popular with investors since the market is already volatile and most people, especially companies in the debt market such as Bloomberg realize that Unisys has the most expensive borrowing costs compared to other IT companies such as Affiliated Computer and IBM. The other possibility for Unisys is to cut down on employment expenses by laying-off employees so as to reduce operating expenses (Harvard business review on crisis management, 2000). This will only aggravate the problem as most firms would be interested to know what the situation is like to warrant such a decision. It might also result into low productivity due to reduced manpower. The uncertainty that will be accompanied by such a move would cause distrust amongst many clients, possible clients and financers

Martin Luther's Reforms Essay Example | Topics and Well Written Essays - 1250 words

Martin Luther's Reforms - Essay Example However, during the time, the Protestant Reformation created confusion and a sense of chaos among European Christians. Immediate effects of the Protestant Reformation included a division among European Christians. â€Å"The protestant reformation also generated resistance and hostility, not least from the institutions of the traditional church and its defenders† (Greengrass, 1). Prior to the Reformation, European Christians lived in a more conformed society; religion was a very large aspect of their lives and with their religion they had an understanding of their place within their communities and their world. When Martin Luther nailed his 95 Theses to the door of a church in 1517, he sparked not only a reaction from the Catholic Church but a reaction from monarchs and citizens across Europe. Some monarchies, such as in Germany, Holland, and England, eventually embraced the idea of reforming the Catholic Church and allowing for the progressive views of Protestantism to reorganize their churches and religious practices (McKay, Hill, and Buckler, 12). Other monarchies were not as accepting. Fra nce and Italy, for example, clung tightly to the history and roots of the Roman Catholic Church (McKay, Hill, and Buckler, 12). Reformists faced multiple hurdles as both the Roman Catholic Church and sympathizing monarchs worked to extinguish the Lutheran movement. Citizens were often accused of heresy or witchcraft, and they were sometimes burned or tortured for their refusal to once again accept the Papal authority of the Pope and the Catholic Church: In the sixteenth and seventeenth centuries, a frenzy spread through Europe that witches in allegiance with the Devil were combining forces to destroy the Christian faith†¦The panic of the masses, from those of the elite to the humble peasantry working together, resulted in thousands of men and women undergoing

Hamlet Essay Example for Free

Hamlet Essay Act 1- Scene 1 The first entrance of the ghost is made impressive because Marcellus and Bernardo only told Horatio about them seeing the ghost in the two nights before during their watch. Horatio did not believe them â€Å"Horatio says ‘tis but our fantasy and will not let belief take hold of him touching this sight twice seen of us;† (1.1.23-25) What makes the siting of the ghost so important is that the two guard believe it to be the ghost of the dead King Hamlet. When the ghost appears and Horatio asks it to speak the ghost suddenly disappears. In its second exit the ghost returns and again they ask it to speak but as it spreads its arms the cockcrows and the ghost disappears yet again not saying anything. A superstition that is connected with the ghost is that the guards believe that it is the ghost of the dead King that is trying to warn them of some impending misfortune for Denmark. Act 1 – Scene 2 The new King Claudius attempts to justify his marriage to the Queen by giving a speech to his courtiers, explaining his recent marriage to Queen, his brother’s widow and the mother of Prince Hamlet. Claudius says that he mourns his brother but has chosen to balance Denmark’s mourning with the delight of his marriage. â€Å"With mirth in funeral, and dirge in marriage, in equal scale weighing delight and dole, taken to wife.† (1.2.12-14) In his soliloquy Hamlet expresses that he wishes he could die. He wishes that God had not made suicide a sin. He is also thinking about how it is possible for his mother to have move on after two short month that his father has been gone. When the line â€Å"Frailty, thy name is woman† (1.3.146) is spoken he is referring of his mother because just two months ago his father and her husband died and now she has just moved on to his fathers brother because she is weak and will not make it on her own or w ithout a husband and he finds that shaming. Act 1- Scene 3 1.Laertes believes that Hamlets relationship with Ophelia is not true, because someone of his ranking can not love someone like Ophelia because he is too far above her to love her honourably. Since Hamlet is not only responsible for his feelings but also the role that he will one day play as King Laertes believe that it will be impossible for Hamlet to ever marry Ophelia. Before he leaves he tell her to make sure she does not fall in love with him. â€Å"Fear it, Ophelia, fear it, my dear sister, and keep you in the rear of your affections, out of the shot and danger of desire† (1.3.33-35) 2.Polonius has the same opinion of Laertes, and forbids Ophelia to associate with Hamlet anymore. He tells her that Hamlet has deceived her in swearing his love, and that she should see through his false vows â€Å"Affection pooh! You speak like a green girl, unsifted in such perilous circumstances. Do you believe his tenders, as you call them?† (1.3.101-03) Act 1- Scene 4 †¢Horatio, Marcellus, and Hamlet are keeping watch outside the class, while Hamlet tells the two men that the King has been spending his night drinking alcohol and how he believe that he is tarnishing the Danish people. †¢The ghost appears and calls out to Hamlet to follow him. †¢Even though Horatio and Marcellus tell him not to go and consider that the ghost could harm him Hamlet decides to follow the ghost anyways †¢Hamlet does not care if his life is in danger and follow the ghost off into the darkness †¢Horatio believes that Hamlet is now in the hands of God but Marcellus thinks that they should follow Hamlet and try to protect him, so the two set off after Hamlet and the ghost Act 1- Scene 5 In this scene King Hamlet reveals to his son that his death was cause by foul play and it was a murder. â€Å"Murder most foul, as in the best it is, but this most foul, strange and unnatural.† (1.5.27-28) The King then tells Hamlet that is was his very own brother that killed him. Now Hamlet, hear. Tis given out that, sleeping in my orchard, a serpent stung me. So the whole ear of Denmark is by a forged process of my death rankly abused. But know, thou noble youth, the serpent that did sting thy father’s life now wears his crown. (1.5.34-39 The ghost of the King tells Hamlet to â€Å"leave her to heaven† (1.5.86) which means he does not want Hamlet to do anything to his mother because the King realizes that she has been tainted by Claudius.

1,2,4-Oxadiazole Moiety Molecules Synthesis for Cancer

1,2,4-Oxadiazole Moiety Molecules Synthesis for Cancer 2.4. Synthesis of 3-(4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluorophenyl)-5-substituted-1,2,4-oxadiazole derivatives for their MTT assay using MCF-7 breast cancer cell line and degradation of DNA in EAT cells 2.4.1. INTRODUCTION In the biological and pharmacological importance, heterocycles plays a significance role. Oxadiazole molecules show biologically activity includes angiogenesis inhibitor [246] and also HIV inhibitor [247], tyrosine kinase inhibition [45], histamine H3 antagonism [48], muscarinic agonism [49], potent histamine H2 receptor antagonists [50, 51], muscarinic receptor antagonists [53, 54], interleukin-8 (IL-8) receptor antagonists [65], cytotoxic activities [68], monoamine oxidase inhibition [66], potent therapeutic agents for prostate cancer [72], anticonvulsant activity [67], tumor-selective and apoptosis-inducing agents [70, 71], antitumor [4f] and apoptosis-inducing anticancer agents [73, 74]. Breast cancer is a most terrifying disease in which cells in breast tissue grow and divide without normal control. This type of growth of cells without control forms a lump called tumor. In breast cancer, tumors are called benign or malignant. Malignant tumors will grow by eating food. They get the food by forming new blood vessels in a process called angiogenesis. These blood vessels are the main reason to promote the growth of the tumors. After this tumor growing it will spread to nearby tissue, which is called as invasion. The breakage of main tumor cells will spread into other parts of the body and it will lead to metastatic breast cancer. This happens through blood stream or lymphatic system and this process is called metastasis. The main disadvantage of the malignant breast cancer is dividing and grows out of control which leads to form number of new tumors. If those new tumors are in other parts of the body, then also we call those as breast cancer. Especially in women, breast cancer leading to the cause of cancer related death. In developing and developed countries, breast cancer is the second most common malignancy type diagnosed disease in women. In India breast cancer is the most discussing problem in the current health problem (248). By the survey conceded by the Indian Council of Medical Research (ICMR), the percentage of breast cancer patients has been nearly doubled. In the past few years nearly one lakh new patients are being detected from 1985 to 2001 (249, 250). It has been estimated that the breast cancer in 2004 is nearly 90,273 and they predicted that in 2015 the patient’s number may be nearly 1, 12,680 (251). Due to the damage in DNA, normal cells will become cancer cells. DNA is present in every cell and it directs to all its actions. When DNA gets damaged in normal cells, the cell either repairs the damage or it dies. But in the cancer cells, damaged DNA is not repaired. The damaged cell undergoes splitting. As a result cell goes on making new cells that the body doesn’t need and those cells have same damaged DNA as the first cells does. This conjecture the design and synthesis of new anticancer drugs, and drug combination and treatment modalities is still the need for effective treatment of breast cancer patients [252]. 1,2,4-Oxadiazole moiety molecules show signs of vide variety of biological activities [40, 253-255]. In connection to the above studies, our molecules are subjected to the angiogenesis using MCF-7 breast cancer cell lines and degradation of DNA studies using in EAT cells. 2.4.2. MATERIALS Melting points were recorded (uncorrected) on a Buchi Melting Point B-545 instrument. Infrared (IR) spectra were recorded using a Jasco FTIR-4100 series. All reagents and solvents used were commercially procured and used as received. 1H-NMR spectra’s were recorded on Shimadzu AMX-400-Bruker with 400 MHz with TMS as internal standard. The 13C NMR spectra were examined on a Bruker DPX-400 at 100.6 MHz. The mass spectra were recorded on a JEOL JMS-AX505HA mass spectrometer. 2.4.3. EXPERIMENTAL 2.4.3.1. Chemistry General procedure for synthesis of (Z)-4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluoro-N-hydroxybenzimidamide (2). A solution of hydroxylamine hydrochloride (1.529 g, 22.004 mmol) (2.5eq) and sodium carbonate (1.492 g, 14.082 mmol) (1.6eq) was taken in a round bottom flask. Stir for 10min to dissolve completely, then to this mixture 4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluorobenzonitrile (1) (2.0 g, 8.801 mmol) (1.0 eq) is dissolved with ethanol was added. Then the mixture is heated to 60 0C about 5-6 hr. After that the steps forward of the reaction fusion was examined by the thin layer chromatography (TLC). After reaction completion, the solvent and the product was separated in vacuum pump under reduced pressure. Then the product was poured to water and extracted with ethyl ethanoate. The organic layer was washed 2-3 times with distilled water. The organic layer was washed 2-3 times with distilled water. The extracted ethyl ethanoate layer was dried over sodium sulphate (anhydrous) and the solvent was evaporated to get (Z)-4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluoro-N-hyd roxybenzimidamide (2). 2.4.3.2. Synthesis of 3-(4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluorophenyl)-5-substituted-1,2,4-oxadiazole 4(a-f) derivatives. (Z)-4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluoro-N-hydroxybenzimidamide (2) (1.0 eq) is dissolved in dry dichloromethane and cooled to 0-5 0C in ice bath. Then N,N-diisopropylethylamine (1.1 eq) was added to cold reaction mixture and stirred for 10 minutes, then different aromatic acid chlorides (3a-e) (1 eq) were added. The reaction mixture was allowed to room temperature under stirring for 5-6 hr. After that the steps forward of the reaction fusion was examined by the thin layer chromatography (TLC). After reaction completion, the solvent and the product was separated in vacuum pump under reduced pressure. Then the product was poured to water and extracted with ethyl ethanoate. The organic layer was washed 2-3 times with distilled water. The organic layer was washed 2-3 times with distilled water. The extracted ethyl ethanoate layer was dried over sodium sulphate (anhydrous) and the product was purified with the help of column chromatography over silica gel (60-120 mesh) using hexane and ethyl acetate (1:1). Scheme 1. Reagents and conditions: (i) Sodium carbonate, water, ethanol, 60 0C, 6 h; (ii) dichloromethane, N,N-diisopropylethylamine, 0-5 0C, 6 h; 3(a-e) Where 3a = 4-chloro benzoyl chloride; 3b = 4-Fluoro benzoyl chloride; 3c = 4-(trifluoromethyl)benzoyl chloride; 3d = 4-Fluoro-3-Nitrobenzoyl chloride; 3e = 4-EthylPhenylbenzoyl chloride. 2.4.3.2.1. Synthesis of 5-(4-chlorophenyl)-3-(4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluorophenyl)-1,2,4-oxadiazole (4a) Pale yellow color from (Z)-4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluoro-N-hydroxybenzimidamide (2) (0.1 g, 0.384 mmol), 4-chlorobenzoylchloride (3a) (0.067 g, 0.384 mmol) and N,N-diisopropylethylamine (0.049 g, 0.461 mmol). 1H NMR (400 MHz, CDCl3): 8.32 (d, 1H, Ar-H), 7.75 (dd, 2H, Ar-H), 7.70, (d, 1H, imid-H), 7.55 (d, 1H, Ar-H), 7.50 (dd, 2H, Ar-H), 7.35 (d, 1H, imid-H), 7.30 (d, 1H, Ar-H), 5.05 (d, 1H, pyrrole-H), 2.56-2.30 (d, 4H, pyrrole-H); MS (ESI) m/z: 381.081 (100.0%), Anal. calcd. for C20H14ClFN4O (in %): C- 63.08, H- 3.71, N- 14.71. 2.4.3.2.2. Synthesis of 3-(4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluorophenyl)-5-(4-fluorophenyl)-1,2,4-oxadiazole (4b) Orange color from (Z)-4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluoro-N-hydroxybenzimidamide (2) (0.1 g, 0.384 mmol), 4-Fluoro benzoyl chloride (3b) (0.060 g, 0.384 mmol)and N,N-diisopropylethylamine (0.049 g, 0.461 mmol). 1H NMR (400 MHz, CDCl3): 8.31 (d, 1H, Ar-H), 7.30 (dd, 2H, Ar-H), 7.72, (d, 1H, imid-H), 7.56 (d, 1H, Ar-H), 7.34 (d, 1H, imid-H), 7.31 (d, 1H, Ar-H), 7.29 (dd, 2H, Ar-H), 5.02 (d, 1H, pyrrole-H), 2.58-2.31 (d, 4H, pyrrole-H); MS (ESI) m/z: 365.114 (100.0%), Anal. calcd. for C20H14F2N4O (in %): C- 65.93, H- 3.87, N- 15.38. 2.4.3.2.3. Synthesis of 3-(4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluorophenyl)-5-(4-(trifluoromethyl)phenyl)-1,2,4-oxadiazole (4c) Dark brown color from (Z)-4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluoro-N-hydroxybenzimidamide (2) (0.1 g, 0.384 mmol), 4-(trifluoromethyl)benzoyl chloride (3c) (0.080 g, 0.384 mmol) and N,N-diisopropylethylamine (0.049 g, 0.461 mmol). 1H NMR (400 MHz, CDCl3): 8.33 (d, 1H, Ar-H), 8.10 (dd, 2H, Ar-H), 7.74 (d, 1H, imid-H), 7.70 (dd, 2H, Ar-H), 7.58 (d, 1H, Ar-H), 7.37 (d, 1H, imid-H), 7.33 (d, 1H, Ar-H), 5.06 (d, 1H, pyrrole-H), 2.59-2.29 (d, 4H, pyrrole-H); MS (ESI) m/z: 415.110 (100.0%), Anal. calcd. for C21H14F4N4O (in %): C- 60.87, H- 3.41, N- 13.52. 2.4.3.2.4. Synthesis of 3-(4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluorophenyl)-5-(4-fluoro-3-nitrophenyl)-1,2,4-oxadiazole (4d) Pale yellow color from (Z)-4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluoro-N-hydroxybenzimidamide (2) (0.1 g, 0.384 mmol), 4-Fluoro-3-Nitrobenzoyl chloride (3d) (0.078 g, 0.384 mmol)and N,N-diisopropylethylamine (0.049 g, 0.461 mmol). 1H NMR (400 MHz, CDCl3): 8.71 (d, 1H, Ar-H), 8.65 (d, 1H, Ar-H), 8.34 (d, 1H, Ar-H), 7.74 (d, 1H, imid-H), 7.61 (dd, 1H, Ar-H), 7.58 (d, 1H, Ar-H), 7.37 (d, 1H, imid-H), 7.33 (d, 1H, Ar-H), 5.06 (d, 1H, pyrrole-H), 2.59-2.29 (d, 4H, pyrrole-H); MS (ESI) m/z: 410.099 (100.0%), Anal. calcd. for C20H13F2N5O3 (in %): C- 58.68, H- 3.20, N- 13.52. 2.4.3.2.5. Synthesis of 3-(4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluorophenyl)-5-(5-ethyl-[1,1-biphenyl]-2-yl)-1,2,4-oxadiazole (4e). White color from (Z)-4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluoro-N-hydroxybenzimidamide (2) (0.1 g, 0.384 mmol), 4-EthylPhenylbenzoyl chloride (3e) (0.094 g, 0.384 mmol) and N,N-diisopropylethylamine (0.049 g, 0.461 mmol). 1H NMR (400 MHz, CDCl3): 8.31 (d, 1H, Ar-H), 7.95 (d, 1H, Ar-H), 7.80 (dd, 2H, Ar-H), 7.75 (d, 1H, Ar-H), 7.72, (d, 1H, imid-H), 7.53 (dd, 2H, Ar-H), 7.56 (d, 1H, Ar-H), 7.45 (d, 1H, Ar-H), 7.34 (d, 1H, imid-H), 7.30 (d, 1H, Ar-H), 7.31 (d, 1H, Ar-H), 5.03 (d, 1H, pyrrole-H), 2.65 (q, 2H, -CH2), 2.58-2.31 (d, 4H, pyrrole-H), 1.27 (t, 3H, -CH3),; MS (ESI) m/z: 451.186 (100.0%), Anal. calcd. for C28H23FN4O (in %): C- 74.65, H- 5.15, N- 12.44. 2.4.4. Biology 2.4.4.1. Culture of MCF-7 cells: MCF-7 cells were cultured with minor modification in Minimal Essential medium (Invitrogen) supplemented with 10% fetal bovine serum, 100units/ml penicillin-G, 100  µg/ml streptomycin and 1% sodium bicarbonate (Invitrogen). MCF-7 cells were obtained from Cell repository unit of National Center for Cell Sciences (NCCS), Pune, India. All cell lines were maintained at 37 °C in a humidified atmosphere with 5% CO2 [256]. 2.4.4.2. Culture of EAT cells: Animals, in vivo tumor generation and imidazole derivatives treatment Six to eight weeks old female mice were acclimated for one week while caged in-group of five. Mice were housed and fed a diet of animal chow and water ad libitum throughout the experiment. All the experiments were approved by the institutional animal care and use committee of the University of Mysore, Mysore, India. Ehrlich Ascites Tumor (EAT) cells (5Ãâ€"106 cells/mouse) were injected intraperitoneally. These cells grow in mouse peritoneum forming an ascites tumor with massive abdominal swelling. The animals showed a dramatic increase in body weight over the growth period and the animals succumbed to the tumor burden 14–16 days after implantation. 2.4.4.2.1. Isolation of EAT cells from mice peritoneal cavity and compound treatment: From the peritoneal cavity of tumor-bearing mice the EAT cells were isolated (control and treated). 2-3 mm of sterile PBS was injected in to the peritoneal cavity of the mice and the peritoneal fluid containing tumor cells withdrawn, collect in sterile petri dishes and incubated at 370C for 2 h. The cells of macrophage linage adhered to the bottom of Petri dishes. The non-adherent population was aspirated out gently and washed repeatedly with PBS. Moreover, viability of these cells was assessed and was found to be >95% by trypan blue dye exclusion. The viable EAT cells were processed for further experiments. The EAT cells (5 x 106) were treated with or without compounds of 3-(4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluorophenyl)-5-substituted-1,2,4-oxadiazole series 4(a-e) and incubated at 370 C for different time interval or for known period of time. After the incubation period the cells w ere used for the further analysis [258]. 2.4.4.2.2. Cell count by Trypan blue dye exclusion assay. EAT cells were treated with different concentrations of 3-(4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluorophenyl)-5-substituted-1,2,4-oxadiazole compounds 4(a-e) at various time periods (0–4 h). Cell viability was assessed by mixing aliquots of cell suspension with 0.4% trypan blue and counted using heamocytometer. Cells that picked up the dye were considered to be dead [259(a)]. 2.4.5. Result and Discussion 2.4.5.1. Chemistry Synthesis of the key intermediate (Z)-4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluoro-N-hydroxybenzimidamide (2) is outlined in Scheme 1. Briefly, hydroxylamine hydrochloride and sodium carbonate was taken in water and stirred. 4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluorobenzonitrile (1) was dissolved in ethanol and added to the reaction mixture. The presence of –NH2 and =N-OH proton peaks NMR spectra indicates the formation of (Z)-4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluoro-N-hydroxybenzimidamide (2). The key intermediate compound (2) was taken in dry dichloromethane and cooled to 0-5 0C, and N,N-diisopropylethylamine was added. Stirred for 10 min, then different aromatic acid chlorides 3(a-e) was added drop by drop. The reaction mixture was allowed to room temperature under stirring for 5-6 h and after that the steps forward of the reaction fusion was examined by the thin layer chromatography (TLC). After reaction completion, the solvent and th e product was separated in vacuum pump under reduced pressure. Then the product was poured to water and extracted with ethyl ethanoate. The organic layer was washed 2-3 times with distilled water to get target 3-(4-(3-(1H-imidazol-5-yl)propyl)-3-fluorophenyl)-5-substituted-1,2,4-oxadiazole 4(a-e). Upon completion crude products 4(a-e) were obtained with a good yield of 81–93% and which the product was purified with the help of column chromatography over silica gel (60-120 mesh) using hexane and ethyl acetate (1:1). The absence of –CO proton peak in synthesized derivatives in 1H spectra confirmed the identity of the products. The details of chemical structures, physical data and purity of compounds are given in Table 1. Compound R1 Yield MP (oC) Purity 4a 90 277 90 4b 85 100 93 4c 81 110 89 4d 82 142 92 4e 79 95 81 Table 1. Chemical structures, physical data and purity of compounds 4(a–e) 2.4.5.2. Biology 2.4.5.2.1. MTT assay: The MTT assay was performed according to the protocol previously reported [257]. MCF-7 cells were plated at a density of 1 X 105 cells in 96-well plates. (Subsequently, the 3-(4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluorophenyl)-5-substituted-1,2,4-oxadiazole series 4(a-e) were assayed using concentrations from 0.05 to 0.5 mM). After 24 h of incubation, 10  µL of 5% 3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) (Sigma Aldrich) (0.05 mg/mL) were added to the culture medium. After 4 h at 370C the culture medium was removed and 200  µL of DMSO were added to dissolve the salts of formazan. The absorbance was measured with a 96-wells plate spectrophotometer at 570 nm. The experiments were independently performed three times and each experiment contained triple replicates. Control samples containing a complete culture medium devoid of cells or control cells with 0.1% DMSO were also included in each experiment. Figure 1. The MTT assay of compounds 4(a-e) in MCF-7 breast cancer cell lines. Sl.No. Name of the compound IC50 Value 1 Cisplatin 10ÃŽ ¼g 2 4a 100ug 3 4b 200ug 4 4c 100ug 5 4d 800ug 6 4e 200ug Table 2. Compounds 4(a-e) and their IC50 value ( µg/ml) on MCF-7 breast cancer cell lines. 2.4.5.3. DNA fragmentation assay: EAT cells were collected from mice treated with or without 3-(4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluorophenyl)-5-substituted-1,2,4-oxadiazole series 4(a-e). Thein vivo and DNA was isolated using the phenol–chloroform method. In brief, cells were lysed in a buffer containing 50mM Tris–HCl, pH 8.0, and 0.5% SDS, and incubated for 30min at 37 °C. The cell lysate was subjected to 8M potassium acetate precipitation and left for 1h at 4 °C. The supernatant was subjected to phenol/chloroform/isoamyl alcohol (25:24:1) extraction and once to chloroform extraction. DNA was precipitated by adding 1:2 volumes of ice-cold ethanol. The precipitated DNA was dissolved in 50ÃŽ ¼L TE buffer (pH 8.0). The DNA was digested with 20ÃŽ ¼g/mL RNase at 37 °C for 1h. The DNA was quantitated and equal concentration of DNA (25ÃŽ ¼g) was resolved on 1.5% agarose gel, viewed under UV light, and documented using BIORAD gel documentation system Figure 2 [259(b)]. Figure 2. The DNA degradation of compounds 4(a-e) in Ehrlich Ascites Tumor (EAT) cells. Conclusion: A series of 3-(4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluorophenyl)-5-substituted-1,2,4-oxadiazoles 4(a-e) has been synthesized by using simple synthetic procedures and were screened for their MTT assay using MCF-7 breast cancer cell line and degradation of DNA in Ehrlich Ascites Tumor (EAT) cells activity. All the final compounds exhibited good in all the in-vitro activity.

Supporting the US Patriot Act Essay -- Privacy

The US Patriot Act should stay in effect indefinitely because it helps to remove barriers to investigate terrorism, it strengthens the criminal laws against terrorism, and it gives the government the authority to intercept wire, oral and electronic communications relating to terrorism. "Originally passed after the September 11, 2001 attacks, the Patriot Act was formed in response to the terrorist attacks against the United States. This law dramatically expanded the authority of American law enforcement for the stated purpose of fighting terrorism in the United States. It is used to enhance domestic security against terrorism, and enhance surveillance procedures. It gives the government the authority to intercept wire, oral, and electronic communications relating to terrorism. It has also been used to detect and prosecute other alleged potential crimes, such as providing false information on terrorism. It was renewed on March 2, 2006 with a vote of 89 to 11 in the Senate and on M arch 7 280 to 138 in the House. The renewal was signed into law by President Bush on March 9, 2006."1 (USA Patriot Act" www.wikipedia.org on 02/08/2007). The Patriot Act has been very important to winning the War on Terror and protecting the American people. The signed legislation allows intelligence and law enforcement officials to continue sharing information and using the same tools against terrorists already employed against drug dealers and other criminals. This legislation helps to strengthen the U.S. Department of Justice (DOJ) so that it can better identify and interrupt terrorist threats. It also provides law enforcement officials new tools to combat threats, while safeguarding Americans' civil liberties. America still faces dangerous en... ... remember about government powers is not to necessarily only worry about what they do but what they allow the government to do (because eventually they likely will). These provisions in and of themselves are not a ridiculous assault on liberty but they do increase powers and reduce rights incrementally. And it is likely that any overall reduction of rights will be incremental and always driven by government 'necessity' to protect or provide. The Patriot Act is one of these measures that will allow each American life, liberty, and the pursuit happiness. Although, some laws might seem intrusive in nature; that intrusiveness provides Americans with a feeling of safety. Sources: 1. "USA Patriot Act" www.wikipedia.org. accessed on 02/08/2007 2. "USA Patriot Act" www.whitehouse.gov accessed on 02/07/2007

Everyman-a Medieval Play Review

Everyman is a play which was written to express the importance of morality, to whoever read it or experienced it being performed on stage. Some scholars say that it was written sometime in the late 1400’s, while others insist that it is a translation of a Flemish work called â€Å"Elckerlijc†, which was written by Peter van Diest in 1495. Everyman is an allegory play which is heavily based upon Christian religious perspectives; also it is resoundingly similar to the Christian belief of the resurrection of Christ, and his ascension into Heaven, after the crucifixion.The first act of Everyman, opens with a prologue which takes on the form of a messenger, telling the audience about the fate which is to come to Everyman. The messenger goes on to tell the audience that eventually God will call upon all of humanity to stand before him, and give account of their works which they had wrought in life. The next part of the play is God calling upon Death, to go and bring Everyman to stand before him. God commands Death to go and bring Everyman before him, so that he may give account of his own misdeeds that he has wrought in life. So Death goes and finds Everyman, and tells him that his time has come.Everyman then attempts to bribe Death with a thousand pounds, but Death refuses. However, he states that he will allow Everyman to bring someone with him, so that he does not have to face his judgment alone. Everyman first goes to Fellowship, whom represents friends and companions; and asks him to accompany him to go and stand before the judgment God. Fellowship, whom had promised to stand besides Everyman through whatever may come; tells Everyman that he will not go with him to the grave, because he fears Death and the judgment of God. Everyman is heartbroken, but then goes on to the next in line.Everyman then goes to Kindred and Cousin, which are supposed to represent family and kin; but they too tell him that they will not accompany him on his way to the grav e. Thirdly, Everyman turns to Goods, which represents material possessions; nonetheless she also states that she will not go with Everyman to his final judgment. Everyman is very concerned by this point, and so he turns to Good Deeds for companionship. Good Deeds states that she will go with Everyman to face his judgment with him; but unfortunately she lacks the strength for such a journey, because Everyman as neglected her throughout his life. Good Deeds tells Everyman that he must then go before her sister, Knowledge; for she will know the way in which Good Deeds may regain strength. Upon meeting Knowledge, she tells Everyman that he must go before Confession; and there Everyman confesses his sins. Afterward, Confession gives Everyman a â€Å"jewel† called Penance; which cleanses Everyman of his sins, so that he may stand before God and not be in jeopardy of damnation. With his confession behind him, Good Deeds regains his strength, and is ready to accompany Everyman to the grave.Knowledge then tells Everyman to gather together his attributes of life: Beauty, Strength, Discretion, and Five Wits; so that they too may accompany him to his reckoning with God. But when Everyman gathers them together, they tell him that they will not go with him to the grave; essentially because they are all characteristics of youth, which are all now fleeting from him, as he has the end of life. With that, Knowledge, and Good Deeds accompany Everyman to his final reckoning with God.There enters the character Angel; Knowledge then attests to Angel that Everyman was a good and just person, and in the end, he confessed his sins before God. Then Everyman and Good Deeds go down into the grave, and thus make their way to stand before God in the final judgment of Everyman. Fundamentally, this play ends with the character, Doctor, stating that all accept Good Deeds and Knowledge will all flee from a person, when they go before God for their final judgment. *** Issues in Raised in Key Resources There are several key issues which were raised by the scholars that wrote the major resources which I used to write this report.This play has received a moderate amount of popularity over the past near 500 years; and now today there are some scholars and researchers whom are exceptionally critical, both positively and negatively, of the details as to how it was written. One criticism of note would have to be one which was voiced by Thomas F van Laan. In referring to the general premise of Everyman, he contends of the writer that â€Å"His speech is essentially negative; he focuses solely on the inevitability of death and the destructiveness of sin†.Simply put, Mr. van Laan is stating that at first, the sole purpose of this work appears to emphasize specifically on death and how mankind should feel only sorrow for anything that they do, which goes against the teachings of Christianity. Another criticism of this work which Mr. van Laan refers to is the point in t he beginning when God first speaks. Mr. Van Laan states: â€Å"Gods words are wholly negative in force, implying only the difficulty to come, omitting any indication of hope for mankind†. Mr. an Laan is voicing this criticism on the opening section of the play, fundamentally about how he considers Gods words to be too negative in their approach. In expressing this condemnation, Mr. van Laan is adamant about his beliefs that God would probably not be so disconcerting in his approach to dealing with mankind. However not all that Mr. van Laan has to say about Everyman is negative in nature. He goes on to shed light on the allegory nature of the play, and how this lends credence to its being a unique, legitimate work of theater. He contends that â€Å"The first movement, is a falling action, which traces Everyman’s’ decline in fortune.This shatters the apparent serenity of his life, to the depth of his despair†¦fallowed by the second movement, a rising action, which carries him from this nadir unto his final salvation†¦which is symbolized by the words of the welcoming Angel†. It is my belief, that essentially what Mr. van Laan is stating, is that by using actual characters to personify the specific aspects of human nature; the persona of the play becomes a two-fold endeavor. Firstly, by the characters being literal representations of human qualities; they achieve a form of realism, which is normally only conveyed through the use of spoken dialog.Secondly, the movement’s themselves-transpiring from a state of utter despair, to a state of harmonious bliss; is not only characteristic of all great works of drama, but also of life itself. Throughout Mr. van Laan’s review of Everyman, he states his opinion that by the author using characters to represent the individual aspects of human identity; the play conveys a form of realism, which is distinctly unique. Next brings us to the arguments made by the researcher Roger A. Ladd. His belief is that this play was not written for the everyday person, but was in fact written to be a work which would have been performed for the â€Å"bourgeoisie†.His reasoning stems from research which had been done by scholar Dorothy Wertz; the same scholar who also believes that Everyman was probably written strictly to be performed for the elite rich. In her research, Mrs. Wertz points to the fact that â€Å"by simply examining the vocabulary and phrases used in the original piece, one can determine whom the play had been written for†. In that, she states that â€Å"the wording itself would have been too formal for ordinary citizens of the time period to ascertain†. However, unlike Mrs.Wertz, who believes that Everyman is specifically nothing more than a direct translation of Elckerlijc; Mr. Ladd assumes that it is an amalgamation of Elckerlijc and other English literary customs of the era. Mr. Ladd’s purported theory was reached in part, by investigating the traits of the character â€Å"Goods†, and comparing them with the English anti-mercantile satire traditions which were popular in the late-medieval period. An example of which being, that in the Germanic-Dutch based Elckerlijc, Goods is described as appearing as â€Å"Neglected, rusty . . heaped up, filthy†. However in Everyman as Mr. Ladd purports, Goods appears in a more English anti-mercantile manner as being â€Å"trussed and piled so high, and in chest I am locked so fast, also sacked in bags†. The Everyman description, falls in line with the late-medieval literary tradition of anti-mercantilism; which according to Mr. Ladd, comes as proof that Everyman could not have been strictly just an English translation of Elckerlijc. Another scholar whom is acquiescent in his research of Everyman is Lawrence V. Ryan. Mr.Ryan takes an approach, which seems to be more about discerning the religious implications of the play Everyman. The first point that Mr. Ryan makes is that †Without theology, the artistic merit may not be fully appreciated†¦that the theology involved is indispensable, not indefensible, and furthermore, that it gives the play its characters, structure, significance, and even its dramatic impressiveness†. One of the main points which all three scholars agree upon is that by being deserted by all those whom Everyman turns to for help; the audience develops a strong sense of pathos, for the plight of Everyman. Mr.Ryan suggests that the emergence of these false-friend characters â€Å"all appear in a climactic order, according to the increased danger of each as a distraction from one’s Maker†. Finally, Mr. Ryan gives his opinion about the reason why all the characters that abandon Everyman, as well as Everyman himself, are all men; and why the only characters that accompany him are women. In essence, the logic behind this as Mr. Ryan contends is that â€Å"All men are born into a state of sin†¦and that for dramatic suspense; the author chose to have the only redeeming characters be women†¦to show that women can counteract this dogma†.Personal Reaction to â€Å"Everyman† My personal opinion of this particular play is one of high appreciation. Unlike some of the reviews of scholars which I have read, which did not display too much positive reception for this work; I personally enjoyed reading it, and doing my report on this play. When I first tried to read the Old-English original version of this play, I found it incredibly hard to ascertain what exactly the meaning was behind what the author had written. Understandably it was difficult for me when trying to use the un-translated Everyman, as Old-English is a version of our language, which has been out-of-date for centuries.When I found the translated version of Everyman on the Fordham University website and began reading it, I almost instantly thought that it had been a work which had b een written by either someone whom was a priest, or had been another member of the Christian church in some capacity. Another notion which I had was that if the play had not been written by someone who was a church member, then it obviously had to have been written by someone whom had some form of agenda for getting people involved with the Christian church in some form or another.Perhaps the author had a legitimate reason for wanting people to become more involved with the church or to become closer to god in some fashion. On the other hand, perhaps there was a more sinister motive; like getting more people into the flock of the church, in order to acquire more money flowing into their coffers. Personally, I think that it was a combination of both motives, and that whoever had wrote this play, also had a genuine interest in using a popular mode of expression.Or perhaps the author wanted to show that by turning away from the sins of the flesh; that a person could attain a state of c onsciousness, which could bring them closer to a higher form of enlightenment. No matter what the personal objectives were for its creation, one thing remains clear; this was that the author of this particular piece was incredibly ahead of his time. From what I have examined in doing research for this report project; in reading other plays that date from the late medieval age, I can honestly say with a certainty, that I have not read anything that dates from this period, which is as unique as this.The usage of human emotions and possessions being personified into literal characters is uniquely a modern notion; and from what I have found, does not appear to have been done in a theatrical piece until sometime around 18th or 19th century. This plot construction is something which I have seen in movies and television shows; which are much more recent, than something that dates from the late medieval period. One example that immediately comes to mind is Charles Dickens’ Christmas Carol; although not entirely the same in primary foundation, the underlying principle is similar.Some of the scholars that I read about, that reviewed this work; were quick to dismiss it as being either frivolity, or simply nothing more than an act of religious propaganda. I have to disagree with both sides; I feel that this is a excellent illustration of late medieval/early modern era theatrical work, which will more than likely see its relevance come again. Summary of  key scholarship on this play The first article which I used to review for this report on the play Everyman was a modern-English translation, of the late medieval original version of the play.This particular article didn’t offer any insight into it, as in scholar reviews; but it was extremely helpful in writing my summary of the play. Without this article, I am not sure if I would have been able to do this research project on this particular play, as I would not have been able to even ascertain what it was a bout. The next article which I used to write this report was written by Roger Ladd. Mr. Ladd took a definitively scholarly approach to conducting his research.Some of the main issues which he decided to confront were how the play Everyman deals with the religious implications of how material wealth corrupts the good intentions of mankind. Ladd went into detail, comparing the details of Everyman, to other plays of similar genera that date from the period. He explains about how most everyday citizens of the late medieval period, looked at the assemblage of material wealth, as the path to avarice, which puts their immortal souls in jeopardy.Like many other scholars whom have written journals about the â€Å"morality plays†, Ladd believes that in order to find out whom the plays written for, one has to look into the wording of the work; by doing this, he states that it becomes apparent who the target was. For example Everyman, when the main character is forced to give up his worl dly possessions; it is written to appear as if this could have been the most dastardly thing which could have occurred in his life. Other key scholarship reviews of this play, comes from the scholarly works of Lawrence V. Ryan.Ryan takes an approach to his research, which is concerned with how organized religion is suspect in this play. One of his main thesis’ is about how in the play, Everyman attains salvation through his own works, and not by the salvation which comes from God. He talks about how many religious figures were quick to label Everyman as a work of unholy declarations; and that how many of these religious leaders informed members of their churches that they would be in danger of hell by going to watch a performance of Everyman. Ryan is perhaps the most non-forgiving of the three scholars that I chose to use.Mostly, he tries to make it known that he is of the opinion that Everyman was only an English translation of the Dutch work Elckerlijc. He does not make use of very much authentic information to make this claim, he simply relies on paraphrasing works which had been written by other scholars. Next, I used the research from the scholar Thomas F. vanLaan. VanLaan goes into detail describing the individual characters of Everyman. Noteworthy, is how he explains the nature of these characters, and how they relate to the human experience. Differing from the other scholars whom I referenced in this report, Mr. anLaan gives a very logical accounting of why the author chose to incorporate inanimate human natures, as the title characters for this play. The choices for the human failings and material wealth, was carefully used to make the play appeal to nearly everyone whom would have watched its production. An example being, of how Everyman had acquired material goods in his life, which would have appealed to the rich; while on the other hand, Everyman losing his material possessions would have gained the approval of the poor which might have bee n in the audience.However, I never found one scholarly review, which did not offer at least one compliment about this great play.Endnotes *** Paul Halsall, Internet Medieval Sourcebook, â€Å"Medieval Handbook: Everyman, 15th Century†, Fordham University (August 1998) (Accessed on October 20th, 2010) http://www. fordham. edu/halsall/basis/everyman. html —The entire summary which I wrote was based upon the modern-English translation of Everyman, which was available online at the Fordham University site.