Creative writing Term Paper Example | Topics and Well Written Essays - 500 words

Creative writing - Term Paper Example Now 32, he has talked to Carla about starting a family. She finds the thought appealing, but wonders what things the couple should know before having a baby. They decide to consult her family doctor for advice. Starting a family is a major life step for any couple, and understanding and having reasonable expectations can make it a very happy and joyous experience. Frankly, there are some things in our lives that are not very healthy. Think about your pregnancy like a recipe that has steps that are very important, as a matter of fact, some of the steps are critical. Those critical steps are stages during your pregnancy that directly impact your baby. If you make wise decisions and change just a few aspects of your lifestyle now, there will not be any problems during the pregnancy. Now, there are some very basic things to understand about a pregnancy that are totally out of our control. Your body is made up of over 30,000 Genes that basically determine things like eye color and hair color. They also can determine if the baby is going to have a certain disease, like Down syndrome or Cystic Fibrosis. These genes and what they do are called Heredity Factors. Both parents contribute to the genes that the baby will have, and help determine how important those Heredity Factors are. There are tests that can help determine that the baby is going to be healthy, but we cannot change the baby’s genes and how they affect their development. There are things that directly affect the baby, these are called environmental factors. The environmental factors are things that we live with every day, and unlike the Heredity Factors, we can change our environmental factors. A good example of an environmental factor that can and should change is Anthony’s chemical exposure at his work. Anytime Anthony sprays or mixes a chemical he uses, he exposes himself to small trace amounts of those chemicals that he

Green Computing Research Project Part 2 Case Study

Green Computing Research Project Part 2 - Case Study Example The company will need a well functioning network that will enable the two IT analysts to maintain and implement the system by consulting Christian at the code company. This will need them to interact and work together by testing the codes of the application and ensuring that the application will be running without any problem. Compatibility will also be needed by using the required printing software that will be installed in the computers when the customers need to scan their checks. By analyzing the best printing machines the company needs to contact DevAn Consultants for them pick out the best machines needed for the project. This will be done while looking for the best market of the printing machines and considering the kind of applications that will be used in the system. The scanning project will enable the customers in the company to have an easy time to communicate with the company by sending their information and checks to the company by scanning their documents. This has been a request that has been made by many of the customers in order for them to avoid insecurity and save time. As stated early, the customers will be scanning their checks and documents then send them to the company by filling in their personal information that will be protected by the company’s security. Each customer is required to send the information from anywhere provided he or she accesses the internet. For a customer to be able to use the service, he or she will first fill in the required information for the transaction to be successful. Before the scanning starts the company must ensure that there is a network for the customers to access the company’s website. This will also be accompanied by the security the company is to provide to the customers. This includes installation of maintenance software and the security protection system in the company’s system. Example is the anti virus which will protect the company site from any malware

Object-oriented vs traditional structured Essay Example | Topics and Well Written Essays - 500 words

Object-oriented vs traditional structured - Essay Example It is indispensable to note that object oriented programming remains as the most high-level, flexible, and reusable program compared to structured programming. Object oriented programming (OPP), is much advanced than the structured programming languages since it incorporates three important principles of software development like encapsulation for data hiding which is not common in structured system. Structured programming is the application programming method created in a top- down coding style with functions oriented structures. The structured programming employs the programming mechanisms of dividing program source codes into modules, which consist of control statements like loops, library or user defined functions. The development and implementation of structured programming happens sequentially. Object oriented programming promotes the communication of objects and functions in the main program and the classes in private or public manner. There are three characteristics of object-oriented programming which the structured programming does not have for example the encapsulation, inheritance and polymorphism (Pecinovscy, 2013). In contrast, structured programming takes the top-bottom approach in the development of its codes while OOP remains organized into classes and embedded with functions that control the data within the classes. Secondly, structured programming is based on data structures and subroutines while the object oriented has object that supports polymorphism or reusability accelerating system design hence the reduction cost in software development. Structured programming split tasks into modular forms improving the readability and the simplicity of its coding system. While in the object oriented programs each object code structure include the data and the statements controlling the data flow. There is no reusability in the structured code systems while in coding system of the OPP codes there is reusability meaning a section of codes can find use

Issue analysis - if college athletes being paid Essay

Issue analysis - if college athletes being paid - Essay Example His comments elicited mixed reactions with some arguing that college athletes receive more than their fair share through athletics scholarship while others believe schools are exploiting the student athletes and they should be paid. This provokes a controversial question should college athletes be paid like professionals? Understanding the history of college athletics, the benefits these students generate to their universities and how they possibly being exploited may help in deciding whether they should be compensated above their athletic scholarships. Many scholarships are given out to college athletes every year .Over the last two centuries, the face of college athletics has drastically changed. It started as a student organization competition, but it has turned into a sports entertainment enterprise. Nowadays some students go to college mainly for the purpose of participating in sports unlike earlier when students went to school for the purpose of education and could only partici pate in such sports during their free time. Student athletes are devoting most of their time in sport related activities than studies. As a result, they generate a lot of revenue for both their colleges and the NCCA. Whether it is basketball, hockey or football intercollegiate sports have brought in revenue to their respective institutions and have increased the popularity of the College’s reputation.  Ã‚   Miller explains that the biggest issue in the subject of paying. Generally two arguments are used to demonstrate the exploitation of college athletes. First is that the college athletes do not receive quality education yet they are making large amounts of money for their schools. Secondly, the compensation college athletes receive in the form of scholarships cannot be compared to the marginal revenue gain they generate to their colleges. (1) In my opinion college athletes should not be paid. Yes, it is true that the NCAA and colleges gain huge money from them but we must consider the effect money industry has done to professional athletes. With money and fame college athletes are likely to engage in other activities such as drug taking and gambling. It is also unfair to other programs that don’t generate much revenue as college football and basketball. College sports should be a gateway for students to be educated and choose if they want to go for a pro sports career or job career. Various arguments have been raised by those in support of paying college athletes, as well as those against this idea. Arguments for payment One argument in support of paying college athletes is that, by attending college, it does not require students to make a vow of poverty. It is not wrong for students to pursue a bachelor's degree that does not restrict their ability to make money. For example, a student can act in an orchestra and earn a salary. Similarly, student athletes should be paid when they participate in sports. Another reason is that some student ath letes leave school early for a professional career in sport because they do not have enough money to pay their bills. If these students are paid, they will remain in school and will complete their education. The truth is that athletics scholarships not always cover the whole cost of tuition and living expenses.    Others argue that the college athletes not only generate revenue for their schools, but also to the television networks, shoe companies, and conferences that these colleges belong. Therefore,

Black Madonnas Essay Example for Free

Black Madonnas Essay According to Scheer Black Madonna’s have went from majesty to mystery with the construct of race as a science toward the end of the 18th century. With this construct of race it begins to dramatically undermine the pious interpretations of the objects and images surrounding the Black Madonna. A common theme used is that the Madonna’s became black unintentional, has greatly affected the depth into which the study of the Black Madonna’s has gone. Michael P. Duricy gives three categories in which the Madonna’s can be placed: 1) Dark brown or black Madonna’s with skin pigmentation matching that of the indigenous population. 2) Those that have turn black as a result of certain physical factors such as deterioration of lead-based paints, accumulated smoke from the use of votive candles; and the accumulation of grime over the ages. The third and final category is a residual category with no ready explanation. Charles Rohault de Fleury and Stephen Beissel support the second category that the images were blackened by the surround elements. There are two strong theories that if the Madonna was indeed intentionally darkened it was because the Madonna was to illustrate a text from the Canticle of Canticles or Song of Songs that said â€Å"I am black but beautiful† Stephen Benko summarizes the other theory as relating the Black Madonna to the ancient earth-goddess and then converted to Christianity. The most fertile soil is black in color and the blacker it is the more suited it is for agriculture. Scheer mentions that the ideas of pre-Christian beliefs are preserved in the folk culture of the Black Madonna’s earth centered spirituality at the helm of the hypothesis of the color choice of the Madonna’s. Scheer says that there is no mention of color of the Madonna’s only the recurrence in motifs of a miraculous find and the refused removal of the object or painting. Lastly, Scheer mentions that the votive tablets do not speak of when the images became black but when they were perceived Black.

Discovery of a Novel Oral Antithrombotic Drug Apixaban

Discovery of a Novel Oral Antithrombotic Drug Apixaban Shuangyu Ma Background Thrombosis, which is generally defined as the formation of blood clot inside blood vessels, is a major health issue in western world. Thrombosis associated disease, such as ischemic stroke and high blood pressure, remain to be the leading causes of morbidity and mortality each year in developed countries [1]. To make things worse, thrombosis is also known as a chronic disease with episodic recurrence [2]. According the American Heart Association, thirty percent of the patients diagnosed with venous thromboembolism develop recurrence within the next 10 years [2]. The balance between thrombosis formation and bleeding is prudently regulated by the blood coagulation cascade, one of the most delicate systems in human body (figure 1, [3]). The signal transmission and amplification along the cascade was conducted by a series of trypsin-like serine proteases with high specificity, often referred as zymogens [4]. The zymogens are cleaved by the previous coagulation factor to become activated proteases, which can thereby cleave the next zymogen along the cascade and achieve the signal amplification. Blood coagulation process can be triggered by intrinsic pathway or extrinsic pathway; both are followed by the activation of common pathway. The prothrombin is then cleaved by activated factor X to generate thrombin, eventually lead to the formation of stable fibrin clot. Fig 1. Blood coagulation cascade: (figure extracted from Haematology (2nd edition) by C. J. Pallister and M. S. Watson [4]) Until now, the most well-known oral anticoagulant is warfarin, which is the current standard therapy for clinic thrombosis treatment and prevention. Despite its widely application, warfarin has a huge draw back on its dosing issue. Many of the coagulation factors, including factors II, VII, IX and X are Vitamin K dependent; the ÃŽ ³-carboxylation by Vitamin K is essential for their biological activity. Targeting on vitamin-K conversion cycle, warfarin produces an anticoagulation effect by reducing activities of the four vitamin K-dependent coagulation factors. However, the responses to warfarin can be interfered dramatically by genetic and environment factors, such as the common mutation on cytochrome P450 encoding gene, disease states variation, drug-drug interaction or even diet change [5]. Hence, warfarin treated patients need blood test regularly (often once a week or even worse) to determine a safe dosage case by case. Despite handling with great cautious, the anticoagulant-asso ciated intracerebral hemorrhage keeps increasing [2]. Thus, many efforts have been put on developing a novel antithrombotic drug with low risk and high potency. From lead to drug: the development of apixaban The drug Apixaban, approved by FDA in 2012 for thromboembolism treatment and prevention, is developed by Pfizer and Bristol-Myers Squibb to serve as an optimized risk-benefit oral anticoagulant. The mechanism of apixaban is entirely different with warfarin it specifically targets on activated coagulation factor ten (FXa), rather than vitamin K. Several clinical trial has proved its higher efficacy compared to asparin and lower risk compared to warfarin treatment [6]. Given the central position in the blood coagulation cascade, FXa evolved as an attractive drug target for developing anticoagulants. The DuPont Merck Pharmaceutical Company first launched a high throughput screening on FXa inhibitor in 1997 [7]. Because of the substrate similarity between FXa and the GPIIb/IIa receptor, they screened the compound library which was originally designed to be GPIIb/IIa receptor antagonist. A hit was found with low micromolar FXa affinity (coumpound 1, Ki= 38.5 ÃŽ ¼M). However, most of the reported FXa inhibitor in literature at that time posse the bisamindinoaryl structure, such as 2 and 3 (figure 2a). Inspired by these compounds, they modified the hit to be bisamidines and obtained the first list of leads (including compound 4), as shown in figure 2b. Aiming at a higher potency, molecular modeling studies were conducted to further optimize the lead compound, which resulted in the removal of methylene unit between the isoxazoline ring and the amidine carbonyl together with the à ¯Ã¢â‚¬Å¾Ã†â€™ substitution to the carbonyl. After the comparison of different substitution groups, they obtained compound 5 with Ki of 94 nM (Figure 3) [7]. Fig 2 a. The structure of hit compound and several known FXa inhibitor b. The bisamidine lead compounds (figure extracted from [7]). Fig 3. Effects of the amidine group position and à ¯Ã¢â‚¬Å¾Ã†â€™ substitution (figure extracted from [7]) However, as an oral drug candidate, this dibasic lead compound might not have good oral absorption due to its hydrophilicity. Therefore, the next goal is to reduce its basicity by replacing one of the amidine groups with a neutral species. The molecular modeling of compound 5 bound to FXa indicated that the p-amidine group fits in an hydrophobic aryl-binding pocket of FXa, which is consist of three aromatic residues (Trp215, Tyr99 and Phe174, figure 4a) [8]. Therefore, it is possible to replace the p-amidine with aromatic functional groups without largely interrupt the affinity. They employed a biaryl group and obtained compound 6 with only 2-fold decrease in potency. Further investigation on different substitution at the terminal phenyl ring resulted in large enhancement on potency, such as compound 7 (Ki = 6.3 nM). (Figure 4b) Fig 4 a. Effects of substitutions on terminal phenyl ring (figures extracted from [8]). b. Chemical structure of compound 6 and 7 Nevertheless, another concern emerged to be the metabolic instability, as compound 7 bears an ester side chain, which is labile to esterase once it gets inside human body. Since the corresponding acid metabolite is three-fold less potent than the original ester [9], replacing the ester side chain appears becomes the imperative next step. Again, a list of compound 7 analogs bearing different side chains were synthesized and tested. Among all the functional groups, tetrazole substitution was found to be most potent, and compound 8 (Ki= 0.52 nM) was developed with additional modification on the biaryl ring motif (figure 5a). Variation on the position of amide moiety attachment and isoxazoline aromatization resulted in compound 9 (Ki= 0.15 nM, figure 5b) [10], while further investigation on a series of five-membered heterocyclic ring gives compound 10 with equal potency (Ki= 0.15 nM, figure 5c) and lower basicity [11] . Fig 5. Chemical structure of compound 8, 9 and 10 Despite the high potency and selectivity, compound 10 is still far from perfect due to potential mutagenicity of the biarylanilines motif [12]. Therefore, the cleavage of amide bond must be prevented by either ligating or eliminating the nitrogen (figure 6). Compound 11 was developed to have the optimized pyrazole with an even higher FXa affinity (Ki = 0.03 nM). After the scaffold was settled, more compound 11 analogs with various substitution groups and terminal aromatic rings were synthesized and compared to afford the final drug candidate as compound 12 (apixaban, Ki= 0.08, figure 7a) [1]. The optimized drug selectivity towards FXa was shown in figure 7b. The therapeutic index of the final drug compared to warfarin was demonstrated in rabbit thrombosis models and shown figure 7c) [6]. The drug candidate was sent for preclinical studies followed with several clinic trials, and eventually approved by FDA for venous thromboembolism prevention after hip/knee replacement and artrial fibrillation treatment. Another clinical trial for acute venous thromboembolism is still in progress. Fig 6. Compound 11 bearing the optimized pyrazole. Fig 7 a. Apixaban (compound 12) b. In vitro Ki values of apixaban for FXa and other human enzymes with structural or functional similarities (figure extracted from [6]). c. Therapeutic index of apixaban and warfarin in rabbit models (figure extracted from [6]). Conclusion Comparing to the initial lead compound, the eventual drug changed dramatically in chemical structure, while its FXa inhibiting potency was enhanced by 107. Tracing back to each modification step, the comprehensive consideration in drug potency, selectivity, absorption, metabolism and toxicity is truly impressive and reveals the tremendous efforts embedded in a single drug. It is worth noting that molecular modeling with FXa structure played a critical role during the rational drug modification process. The discovery of apixaban also demonstrated the importance of defining new drug target in modern drug development. The success of apixaban is largely attributed to the better drug target FXa. However, the clinical trial of apixaban on acute coronary syndrome was discontinued due to increased bleeding events [6], which suggests that other anticoagulants are still in demand for treating various type of thrombosis. Reference [1] Pinto, D. J.; Orwat, M. J.; Koch, S.; Rossi, K. A.; Alexander, R. S.; Smallwood, A.; Wong, P. C.; Rendina, A. R.; Luettgen, J. M.; Knabb, R. M.; He, K.; Xin, B.; Wexler, R. R; Lam, P. Y. Discovery of 1-(4-methoxyphenyl)-7-oxo-6-(4-(2-oxopiperidin-1-yl) phenyl)-4, 5, 6, 7-tetrahydro-1 H-pyrazolo [3, 4-c] pyridine-3-carboxamide (Apixaban, BMS-562247), a highly potent, selective, efficacious, and orally bioavailable inhibitor of blood coagulation factor Xa.Journal of medicinal chemistry. 2007,50, 5339-5356. [2] Go, A. S., Mozaffarian, D., Roger, V. L., Benjamin, E. J., Berry, J. D., Borden, W. B., Turner, M. B et al. Heart Disease and Stroke Statistics: 2013 Update: A Report From the American Heart Association. Circulation. 2013, 127, 143-146. [3] Pallister, C. J.; Watson, M. S. Haematology, 2nd ed. Scion Publishing: Banbury, 2010; pp 336–347. [4] Krishnaswamy, S. Exositeà ¢Ã¢â€š ¬Ã‚ driven substrate specificity and function in coagulation. Journal of thrombosis and haemostasis. 2005, 3, 54-67. [5] Hirsh, J., Fuster, V., Ansell, J., Halperin, J. L. Foundation guide to warfarin therapy. Journal of the American College of Cardiology. 2003, 41, 1633-1652. [6] Wong, P. C.; Pinto, D. J.; Zhang, D. Preclinical discovery of apixaban, a direct and orally bioavailable factor Xa inhibitor.Journal of thrombosis and thrombolysis. 2011,31, 478-492. [7] Quan, M. L.; Pruitt, J. R.; Ellis, C. D.; Liauw, A. Y.; Galemmo, R. A., Jr.; Stouten, P. F. W.; Wityak, J.; Knabb, R. M.; Thoolen, M. J.; Wong, P. C.; Wexler, R. R. Bisbenzamidine isoxazoline derivatives as factor Xa inhibitors.Bioorganic Medicinal Chemistry Letters. 1997, 7, 2813-2818. [8] Quan, M. L.; Liauw, A. Y.; Ellis, C. D.; Pruitt, J. R.; Carini, D. J.; Bostrom, L. L.; Huang, P. P.; Harrison, K.; Knabb, R. M.; Thoolen, M. J.; Wong, P. C.; Wexler, R. R. Design and Synthesis of Isoxazoline Derivatives as Factor Xa Inhibitors 1. Journal of medicinal chemistry. 1999,42, 2752-2759. [9] Quan, M. L.; Ellis, C. D.; Liauw, A. Y.; Alexander, R. S.; Knabb, R. M.; Lam, G.; Wright, M. R.; Wong, P. C.; Wexler, R. R. Design and Synthesis of Isoxazoline Derivatives as Factor Xa Inhibitors 2. Journal of medicinal chemistry. 1999,42, 2760-2773. [10] Pruitt, J. R., Pinto, D. J., Estrella, M. J., Bostrom, L. L., Knabb, R. M., Wong, P. C. Wright, M. R., Wexler, R. R. Isoxazolines and isoxazoles as factor Xa inhibitors.Bioorganic medicinal chemistry letters,2000, 10, 685-689. [11] Pinto, D. J.; Orwat, M. J.; Wang, S.; Fevig, J. M.; Quan, M. L.; Amparo, E.; Cacciola, J.; Rossi, K. A.; Alexander, R. S.; Smallwood, A. M.; Luettgen, J. M.; Liang, L.; Aungst, B. J.; Wright, M. R.; Knabb, R. M.; Wong, P. C.; Wexler, R. R.; Lam, P. Y. Discovery of 1-[3-(Aminomethyl) phenyl]-N-[3-fluoro-2-(methylsulfonyl)-[1, 1-biphenyl]-4-yl]-3-(trifluoromethyl) -1H-pyrazole-5- carboxamide (DPC423), a Highly Potent, Selective, and Orally Bioavailable Inhibitor of Blood Coagulation Factor Xa 1.Journal of medicinal chemistry. 2001, 44, 566-578. [12] Pinto, D. J.; Orwat, M. J.; Quan, M. L.; Han, Q.; Galemmo, R. A., Jr.; Amparo, E.; Wwllsg, B.; Ellisj, C.; Hek, M. Y.; Alexanderf, R. S.; Knabbb, R. M.; Mersingerg, L.; Kettnera, C.; Baih, S.; Hed, K. Wexlera, R. R.; Lam, P. 1-[3-Aminobenzisoxazol-5†²-yl]-3-trifluoromethyl -6-[2†²-(3-(R) -hydroxy-N-pyrrolidinyl) methyl-[1, 1†²]-biphen-4-yl]-1, 4, 5, 6-tetrahydropyrazolo-[3, 4-c]-pyridin -7-one (BMS-740808) a highly potent, selective, efficacious, and orally bioavailable inhibitor of blood coagulation factor Xa.Bioorganic medicinal chemistry letters. 2006,16, 4141-4147.

Mother and Daughter Relationship Exposed in Joyce Carol Oates Short Sto

Mother and Daughter Relationship Exposed in Joyce Carol Oates' Short Story, Shopping The relationship between a mother and a daughter is one of complications, heartaches, and sweet rewards.   This is no exception between Nola and Mrs. Dietrich, characters in "Shopping" by Joyce Carol Oates.   The tribulations of their relationship are shown during their annual shopping trip.   In the time spent together, Nola is obviously trying to break free from her mother and become her own woman.   This coming-of-age path is expressed by her "private thoughts" and   "answers in monosyllables" (Oates 834).   As Nola desperately tries to acquire her own self, her Mrs. Dietrich desperately tries to hang onto the child in Nola.   She tries to stay in her daughter's life by wanting to know "why are you so quiet" and "what are you thinking?" (Oates 834).   In Oates short story, she develops Mrs. Dietrich's and Nola's relationship by showing the conflicting needs of mothers and daughters.   Ã‚  Ã‚   The shopping trip allows Mrs. Dietrich to try to penetrate her daughter's new adult life and surface the child.   She is also simple trying to be a part of her daughter's life.   As a divorced woman, Mrs. Dietrich finds Nola as her only source of love-her outlet to give and to receive love. Mrs. Dietrich even finds herself thinking "she is in love with her daughter" (Oates 834).  Ã‚   These strong emotions are most likely why Mrs. Dietrich needs Nola to such an extent.   Mrs. Dietrich wants to feel needed; she wants to be a mother.   The betrayal of Mr. Dietrich causes Mrs. Dietrich to cling even more.   However, she finds that Nola no longer needs her.  Ã‚   Nola is becoming an adult. Mrs. Dietrich's memories of Nola as a child are now replaced with the images of her dau... ...ong in her actions and her words.   At the end Nola loses strength and becomes weak.   Ã‚  Ã‚   Joyce Carol Oates short story "Shopping" gives an excellent example of the trials a mother and daughter experiences. She shows that each a mother and daughter can have wants and needs in the relationship.   These things can only be understood if the two communicate to each other.   The story also presents the problem of how a mother wants her little girl, while the daughter wants to be a young woman.   Most importantly Oates shows the human tendency to be independent at times and at others dependent.   Each character won and lost a battle, expressing the human complexity of sometimes being able to be strong but then at other times weak.   This shows that in a mother and daughter relationship each is needed for the other person because each person needs someone to be strong.