Cloning cdc2 Essay Example | Topics and Well Written Essays - 2000 words

Cloning cdc2 - Essay Example This was used to calculate the transformation efficiency of the experiment.The aim of carrying out this experiment was to try out carry out cloning of E. coli and to calculate how efficient the cloning was. The following are the key words that will be used in this report. To begin with is the word smid pALA2, which represents the plasmid to be used in the experiment. The other word is S. pombe. This in full is known as the Schizosaccharomycespombe. It is a species of yeast that is rod shaped and reproduces by fission. In this experiment on cloning, the yeast has been used in the determination of how the cell responds to DNA replication and destruction. The other key word in this report is cdc2, which stands for cell division control protein 2. This is also referred to by the name Cyclin-dependent kinase 1. It plays the role of encoding the fission yeast S.pombe in this experiment. This section contains a brief description of the tables and figures that will be used in the report. They are as follows; figure one represents the gels showing the purified genomic DNA from S. pombe, compared to the provided DNA sample. Figure two is of the virtual gel showing restriction digest of purified plasmids. Figure three is of plasmid CPP, lane PCR product and purified PC. The forth figure is the control made of the Marker, KpnI cut pALA2 plasmid, the fifth is KpnI cut pALA2, which is a cdc2 orientation of the first plasmid. The sixth figure is the KpnI cut pALA2 that is also a cdc2 orientation of the second plasmid. The final figure is figure seven that shows the plasmid maps. Table one in the report shows the qubit values and the student number. Cloning can be defined in many ways though all these definitions will add up to the same thing. Cloning generally refers to the process of giving rise to organisms that are alike genetically either in nature like in the asexual reproduction of certain

McDonald's Health (choose a topic regarding health in mcdonalds) Research Paper

McDonald's Health (choose a topic regarding health in mcdonalds) - Research Paper Example This is despite great criticism that the corporate was selling junk foodstuffs. It should be noted that McDonald as a corporate is part of the larger community since they operate in serving the community. Being part of the society, they have all the legal rights to carryout their business independently. However, there is caution when some of the operation is causing more harm than good. It is unfair and selfish for corporates to dwell only on profit making and discard humanity (Bakan, 2005). It is sad for everybody to hold a negative impression against a corporate due to its unsocial impacts. For example, the McDonald 40% expenditure directed to kids (Bakan, 2005). This is an ethical since the kids are underage and they have not yet developed critical thinking skills that will help them evaluate media adverts. This forced the IOM (Institute of Medicine) to urge the government to insist on adverts directed to kids should promote healthy approved food (Schlosser, 2006). This policy nearly saw McDonalds corporate being closed up until they came up with rebranding their name and marketing healthy food. The questionnaire developed was entitled to gather respective reaction among people concerning the McDonald Corporation. In this regard, a total of 120 students of different grade filled in the questionnaire during the data collection. The target population was SDSU campus. According to the correspondents, there were more females (33) than males (27). Gender contribution was necessary to attain mixed feedback among people. The large sample size was aimed at eliminating possible errors likely to emanate. Considering different grades was also aimed at acquiring mixed response based on age factor. The questionnaire my group developed was composed of both closed and open ended questions. Closed questions were specific to the point and open ended question aimed at gathering descriptive responses from people.

Direct to Consumer Advertising of Prescription drugs

Direct to Consumer Advertising of Prescription drugs Abstract In Pharmaceutical industry, promotional advertisements are mostly targeted towards physicians but in recent years trend has shifted towards consumer advertisement. In many cases of Direct to Consumer Advertisement (DTCA) the pharmaceutical marketers and manufactures creates hype among patients towards disease and ultimately towards brand. It provokes the patients to seek additional information on the brand and push for its prescription generation. Objective of this study is to determine attitude of the physicians towards DTCA, and what extent patients request for particular brand leads to actual prescription generation of the advertised drugs. This study reveals that the doctors generally have positive attitude towards DTCA and are willing to provide relevant information to the patients and in some cases even provide sample of medicines or go for direct prescribing, if found relevant, as asked by the patient. This study justifies the pharmaceutical industry manufacturers sp ending in DTCA. It is also thought provoking for health policy makers that prescription drugs are being advertised directly which may lead to increased medication cost and misuse of medicine. Key words: Direct to consumer advertising, Direct to Consumer Advertised Brand, Over the counter drugs, Prescription drug. Physicians attitude. I INTRODUCTION Companies rely heavily on product detailing to physicians, which are the customer, (Zangla, 2004). To increase overall sales figures marketers started advertising directly to consumers of disease and even drug brands, (Amaldoss He, 2009). DTCA is not allowed specially for prescription drugs, (Donohue Berndt, 2010). One argument is that DTCA is a public service message about a particular disease and only plays a role as information provider and motivates people to seek proper treatment if required (Kuhn, 2006). Many researchers found DTCA good for General public health, (Bradford, Kleit, Nietert, Ornstein, 2005) and beneficial for patient care (Murray, Lo, Pollack, Donelan, Lee, 2004). So it is considered as DTCA has both merits and demerits, (Murray, 2003) 1.1 Research Objective In recent years Pharmaceutical Companies drastically increased their spending on Direct to Consumer Advertising (DTCA) (Herzenstein, Misra Posavac, 2005). In 1997 Federal drug authority (FDA) permitted DTCA and subsequently pharmaceutical companies started increasing their expenditure on direct advertisement to provoke consumers to ask their doctors about the drug (Green, 2007). Patient is more comfortable in using drug brand which is familiar to patient, (Zuvekas, 2008). Consumers have positive attitude towards DTCA and tries to find out additional information about Directly to Consumer Advertised Brand (DTCAB). To get additional information patient consults their doctor, (Herzenstein, Misra, Posavac, 2005). Asking questions by patients has strong influence on doctors selection criteria of drugs (Iizuka Jin 2005). General attitude of physicians towards DTCA its impact on prescription generation is still unknown (Herzenstein, et al., 2005). If physicians have positive general attitude towards DTCA, it may lead to actual prescription generation. Moreover if patients shows more likelihood of searching additional information tries to inquire additional information by asking questions from physician about DTCAB also leads to prescription generation (Herzenstein, et al., 2005). Information inquired from the physician about DTCAB of medicine is taken as second independent variable, pressurizes physicians towards prescribing that specific brand of drugs. Patients adherence influenced by DTCA motivates patients to seek additional information about the drug from physicians (Amaldoss Chuan, 2009). 1.2 Rationale of study 1.2.1 Increased spending on DTCA from pharmaceutical companies. Pharmaceutical companies have increased their spending in last decade, and they are planning to do more (Atherly Rubin, Feb 2008). Physicians are considered to be the best judge to decide medicine , keeping in view the patients and drugs characteristics. Due to information flow and access through electronic and print media, consumer tries to get more information about the drug and disease. With this the pharmaceutical companies started promoting prescription drugs directly to consumers. At the end of many advertisements it is advised to consult your doctor for further information, but ultimate goal is the prescription generation. These advertisements provokes patients to visit their physicians and asking information and if it is appropriate then whether it can be used or not. It is presumed by the companies that doctor will prescribe the medicine as per patient request, but it is still unknown that what is the general attitude of doctors towards direct to consumer advertisement This study will help marketers of pharmaceutical companies in finding the answer to the question, whether they are helping people in getting medication, from physicians perspective, and are they really making returns on this investment on DTCA. 1.2.2 Health policy makers. Drugs are classified in two categories, one is Over the Counter Drugs (OTC) and other is called Prescription drugs (PD). OTC drugs are usual drugs which have comparatively lesser side effects and can be used without consultation of physicians. Conversely the PD which are of either critical use or may be associated with serious side effects, and can only be used if advised by physicians. In like manner promotion of PD were made only to the physicians through detailing. Pertaining to the severity of life and death related to use of PD, DTCA should not be done for PD. But PD are being advertised under the head of Disease Advertising (DA). It should be the major concern for health policy maker either the PD are being used appropriately as per physicians advice or not. As extensive DTCA of PD may lead to misuse of medicine, increased treatment cost and unnecessary visits to physicians. DTCA should not have that much impact to generate prescription of DTCAB, if it is then specific policies should be developed to balance the usage of DTCA with its risks. 1.2.3 Knowledge contribution. It has already been explored in many researches that DTCA has both merits and demerits. Some physicians generally perceive that DTCA is good for patient overall health but from other school of thought it is just in favor of pharmaceutical companies, only physicians can better decide which drug to be used or not. In medical sciences the selection of medicine is based on mainly three factors, kind of disease, doctors judgment, patients affordability and liking or psychological experience factor of any brand (Prosser, Almond and Walley, 2003). In previous researches the impact of both physicians and consumers have been explored. But the combined impact of both variables has not been studied before. This study for the first time explores the combined effect of the two main independent variables. My research will find out the preference of physicians towards DTCA and whether information seeking by the patients leads to prescription generation. II LITERATURE REVIEW Pharmaceutical industry is heavily driven by customers (doctors) and very marketing and selling intensive (Scherer, 1990). Primarily the focus was only on doctors (customers) but recently the trend is also shifting towards addressing consumers directly (Matthews, 2001). The medium used for accessing consumers is electronic media including the internet and television advertisements, consumers are now able to freely access information about drugs and their brands which in some cases can lead to misuse of medicine and increased cost of treatment (Matthews et al., 2001). Pharmaceutical companies are now targeting advertisements towards patients which entice patients to ask for prescription of only advertised drug, the patients behavior is also effecting and directing the health systems. Matthews (2001) quoted Dr. Reardon, ex president of American Medical Association (AMA), has insightfully noted, Patients themselves are also creating a strong impetus for change. Disillusioned by restrictions on coverage and care, they are increasingly demanding choice of physician, hospital, and even type of health plan. More than ever, patients see physicians as the essential point of trust in a changing system, and demand choice and stability in their vital relationships with their doctors. At the same time, patients themselves are becoming better educated, not only about insurance options but also about medical treatments. Today, thanks to the Internet, trends in product advertising, and the massive proliferation of medical information, patients are better equipped to take part in their care than ever before. Rather than simplifying the physicians job, however, this increased patient knowledge base is creating new challenges. The other argument that supports DTCA says that it encourages hard to reach sections of populations to seek information about diseases, but it should be balanced against the increased cost of medicine from unnecessary requests generated by DTCA (Murray Pollack Donelan and Lee, 2003). DTCA has both positive and negative effects on health behaviors, health service utilization (Murray et, al., 2003). Almost five years back ads for prescription drugs were very rare but these are becoming very common in recent years, and are being advertised like any consumer goods, direct to consumer advertising (DTCA) has grown rapidly (Scherer, 2004). On the other side consumers behavior is supportive towards DTCA and would like to get more information and ask for a particular brand from physicians (Herzenstein, 2004). Another research shows that DTCA had no statistically significant effect on the choice of antidepressant (Donohue Berndt, 2004). There are three variables involved in prescription cho ice, one is Patient characteristic, second is features of medication and third is physicians preference for medication choice, moreover detailing is found to be the most effective in physicians preference for medication choice (Donohue Berndt, 2004). Increase in pharmaceutical pricing is due to increase in expenditure incurred on DTCA. 2.1 Conceptual framework Now the question arises that whether there is an impact of DTCA on sales or not (Scherer, 2004). It is also found that DTCA encourage patients to visit physicians and use specific brand medicine (Iizuka, 2005). It is agreed that DTCA has decreased the time between diagnosis and use of medicine and promotes the patients to consult their physician. 2.1.1 Inquiry about additional information or request for prescription. It has been argued that patient may demand the product just because of the attractiveness and persuasion of the advertisement, rather than look in to the effectiveness of the drug and go for proper consultation from doctor (Bradford, 2005). This is not unusual in pharmaceutical, as is a significant change from the traditional emphasis on physicians detailing, it has been found that the traditional selling of pharmaceutical brands to physicians is changing and prescription drugs is being marketed directly to consumers, as other consumer goods, as detailing and price are found to be complementary strategies for the firms in addition to the traditional detailing, (Brekkea, 2006) 2.1.1 Actual prescription generation. Still questions arises about the impact of DTCA on welfare of patients, if allowed then will lead to More visits to physicians, and they pressurizes to get prescription of desired medicine. (Brekkea et al., 2006). It is also shown that the pharmaceutical manufacturers are also facing challenges from DTCA because they has to do extensive detailing to physicians because of DTCA is also being done, so it should be banned as to keep focus on detailing (Brekkea et al., 2006). It will induce demand for new users of antidepressant medicines and can exaggerate the usage if already that medicine is being used, and will lead to misuse of brand (Chad Meyerhoefer, 2007). Direct to consumer advertising is very important and of course controversial part, advertising in journals, detailing and distribution of samples are used along with direct to consumer advertising which may leads to induce demand and generate more sales (Pasdirtz, 2009) III RESEARCH METHODOLOGY Research methodology is a system or methods followed by particular discipline of an inquiry or investigation into a subject in order to discover or revise facts, theories, applications etc. (Oxford Dictionary, 2007). This study is an applied form of research leading to the basic knowledge contribution, and is an extension of work done by Zachry, (2003). As pharmaceutical industry is very important, it has to play an important role, on one side it claims to be for better health of patients but no doubt they are making huge profits, here comes the role of health policy makers to make it justified. Moreover it is to find out the general attitude of physicians about DTCA and information asked by patients about any particular DTCAB, and its relation with actual prescription generation if asked by patient. 3.1 Problem Statement Hypothesis Pharmaceutical companies in Pakistan are promoting their brands directly to consumers (patients), now the question is What is the attitude of physicians towards DTCA, and do they provide relevant information and prescribe medicine if asked by patient. Positive attitude of physicians and information asked by patients of advertised medicine leads to prescription generation Now the objective of study is qualitative estimation of attitude, and what physicians are most likely to do if patient inquires information after exposure of pharmaceutical advertisement. Even patient may ask for prescription of specific drug, then what is the usual response of physician. 3.2 Hypothesis H-1 : Attitude of physicians towards Direct to consumer advertisement is positive. H-2: Physicians provides information of drug which is asked by patient after exposure to pharmaceutical advertisement. H-3: If found relevant, physicians prescribe the particular drug which is requested by patient on exposure to pharmaceutical advertisement. H-4: Positive attitude of physicians towards DTCA and query about information of a particular brand of medicine leads to actual prescription generation. ATTITUDE3.3 Model Independent Variable 1 PRESCRIPTION GENERATION Attitude of Physicians towards Direct to Consumer Advertising of prescription drugs Dependent Variable Actual Prescription Generation on request from patient of DTCAB medicine INFORMATION Reaction on request of information about particular DTCAB medicine Independent Variable 2 PRESCRIPTION GENERATION Dependent Variable Actual Prescription Generation on request from patient of DTCAB medicine 3.4 Data Collection Data was collected in field setting, respondent were general practicing Doctors/Physicians in hospital setting, as per previously done by (Friedman, 2006) to know the attitude of doctors. We selected hospitals because it has been found that hospitals play an important role in direct to consumer advertising (Adeoye Bozic, 2007),. 3.5 Sample and Population we choose leading hospitals of Rawalpindi/ Islamabad which have high patient turnover, i.e Pakistan institute of medical Sciences, Rawalpindi general hospital, Nescom Hospital and Shifa International. Within these hospitals we selected doctors on judgmental basis, as doctor who is dealing with more than 50 walk-in patients as previously done by (Taneja, Arora and Kaushik, 2007) and found appropriate. Sample size was taken 250, as per sample size taken by other researchers for the same kind of purpose (Bhanji, Baron, Benjamin, Lacy, Gross, Goin, Summner, Fischer, and Slaby 2008). 3.6 Instrumentation A questionnaire was adopted from two authors. Questionnaire has three parts, in first part general attitude of physicians towards direct to consumer advertising (Donhue Berndt, 2004), and in second part the likelihood behavior of physician if patient asks for more information related to drug being advertised directly, and in last part the likelihood of physician if patient asks for prescription of certain medicine (Zachry,Dalen, and Jackson, 2003). 3.7 Data Analysis These two were independent variable and one variable of prescription generation is dependant variable. Quantitative method were used, Microsoft Excel and SPSS was used to calculate percentages and relative comparison in questions through as per previous research done by Bhanji, 2008. IV FINDING AND ANALYSIS 4.1 Data Reliability and Normality Collected data is validated from Cronbachs-Alpha value which is used by many researchers like Zachry; Dalen, and Jackson, (2001,2003). The value came up to 0.8 which is acceptable as it should beis more than 0.6. Taneja, Arora and Kaushik, (2007) used descriptive statistical data analysis, I moreover used SPSS to regress two independent variable with dependent variable. 4.2 Descriptive Statistics of Respondents 4.2.1 Independent variable 1, attitude. In first part of questionnaire it is found that 40 % agree and 20 % strongly agree that it makes patients better informed and 46% agree with 32% strongly agree that it causes them to seek medical doctor. 40% agree that it also informs about side effects, although the data shows that there is increase in medication cost. Little agreement on suggesting medicine from patients. More that half percent of people suggested that it is good trend in health care, and causes more time spent in front of doctor while discussing disease. 42% agree that this also helps in increases motivation towards treatment. 39% think that it not only provokes patients to visit doctor for better health but also encourages, 41%, patients to talk to their doctor about right concern. 41% agree that it also helps in following treatment instructions and 58% with 7% strongly agree that it improves the understanding of medical conditions and treatment.1 is for strong agreement, 2 is for agreement, 3 is neutral and 4 is for disagreement while 5 is strongly disagreement.General description and frequency analysis is given in Table 4.1 OVERALL ATTITUDE OF PHYSICIANS TOWARDS DIRECT TO CONSUMER ADVERTISING ATTITUDE Questions Asked Variance Std Deviation Make patients better informed about their medical problems 1.18 1.08 Motivate patients to seek medical care 1.21 1.1 Provide enough information on other treatments 1.41 1.18 Do a good job of informing patients of side effects 1.3 1.15 Have less or no impact on increase in medication cost 1.08 1.03 Helps doctors in suggesting medicines from patients 1.06 1.02 Are a positive trend in health care 0.94 0.97 Increase in time spent with doctor 1 1.01 Increases motivation towards treatment, overall drug consumption 0.8 0.89 Increase more doctor visit for better health 1.47 1.21 Encourages patients to talk to their doctor about their right concerns 1 1 Encourages people to follow treatment instructions or advice from their doctors 1.15 1.07 Helps patients get treatments they would not otherwise get 1.16 1.07 Have less of no impact on driveing up the cost of prescription drugs 1.17 1.08 Improves peoples understanding of medical conditions and treatments 0.89 0.94 4.2.2 Independent variable 2, information. 44% agree that they become frustrated, 37% get annoyed but 52% agree and 32% strongly agree that they answer patient question about medication if asked. Only 35% agree that they provide more information. General description and frequency analysis is given in Table 4.2 LIKELLIHOOD OF PHYSICIANS WHEN ASKED FOR SPECIFIC BRAND DUE TO DTCA INFORMATION Questions asked Variance Std. Deviation You become frustrated with patient for asking for more information about disease or medicine 1.57 1.25 You become annoyed with patient for asking for more information about disease or medicine 1.42 1.19 Answer patient questions about the medication 0.79 0.89 Provide more information to patient beyond original inquiry 1.39 1.18 Attempt to change subject rather than discuss the medication 1.4 1.18 Explains that the information is probably beyond patients comprehension 1.42 1.19 4.2.3 Dependent variable, actual prescription generation. It is revealed from data that 37% get frustrated, 36% get annoyed if asked to prescribe certain brand and 36% feel uncomfortable with this request, and even less willing to communicate to the patient 33%, mostly 41% are neutral. With this if samples are available then 61% agree and 17% strongly agree to provide samples on patient request, it is also supported by agreement of 51% and strong agreement 24% that they will prescribe medicine if no medicine is available. But if found relevant, as while asking question of simply prescribing the medicine if is anyway relevant , to satisfy the patient then the agreement was 47% and only 8% with strong agreement. General description and frequency analysis is given in Table 4.3 LIKELIHOOD OF PHYSICIANS ON REQUEST OF PATIENT FOR SPECIFIC BRAND PRESCRIPTION GENERATION Dependent Variable Questions Asked Variance Std. Deviation Become frustrated with patient for asking to try the medication 1.13 1.06 Become annoyed with patient for asking to try the medication 0.96 0.98 Feel uncomfortable with the medication request 1.34 1.16 Communicate to the patient your discomfort with the medication request 0.87 0.93 Attempt to prescribe different medication to keep from promoting patient to ask for medication, if available 0.93 0.96 Provides samples of the medication, if available 0.73 0.86 Provide prescription of the medication if no samples available 1.2 1.09 Simply prescribes the medicine if is anyway relevant, to satisfy the patient 1.11 1.06 4.3 Correlation Regression Analysis SPSS was used to show the relationship between two independent variables i.e attitude of doctors towards DTCA and behavior likelihood if information asked by the patient and its impact on dependent variable which is actual prescription generation if requested by the patient. 4.3.1 Model summary and ANOVA. R value shows 40% relationship between dependent variable and independent variables. R square shows 16.6% of the variant in dependent variable can be predicted by the combination of two independent variable. Durbin Watson value is 2.08 showing that there is very less multicollinearity. ANOVA statistics shows overall model significance, f value is 15.09, and sig value is less than 0.00 which is less than 0.05, and is the indicator of significance, so that we can go for regression analysis of independent variables on dependent variables. Durbin Watson value should be between 1.5 to 2.5 means that there is no or less multicollinearity, here the value is 2.08, it shows less chances of multicollinearity. 4.4 If two independent variables combined collectively, Information + Attitude Data results with individual variables shows very weak relationship. with model significance. So It is considered combined effect of both independent variables on dependent variables. 4.4.1 Model summary and ANOVA. Model Summary shows overall model significance, which is less than 0.05, showing overall model fit, R value shows 78% dependence of dependent variable on independent variable. R square value is 0.61 showing magnitude of relationship between independent variable with dependent variable. 1% change in independent variable with 61 % change in dependent variable. Adjusted R square is the pure magnitude of relationship which is always less than the R square, 0.60. F Change statistics is 239.45 which is more than 1 then we can go for coefficients. ANOVA shows overall model significance with less than 0.05 value, it means the regression analysis be proceeded. Additionally according to second school of thought the regression sum of square should be greater then residual sum of square for better model fit. 4.4.1 Coefficient If t value is greater then 2 means it is significant. And significance value should be less than 0.05 to make a significant relationship. Here t value is 15.47, showing significant relationship, and sig value is less than 0.000. 4.2. Discussion This is similar finding with Ryan Vaithianathan, (2009). Which shows that the attitude of consumer is positive towards information provision to patient if asked and similar with the Brekke Kuhn, 2006 study which shows that the doctors rely on the information provided to them through DTCA. I accept the hypothesis that physicians have positive attitude towards DTCA. And it is accepted that the physicians are comfortable in providing information if asked by patents about any DTCAB. According to statistics shown by Data analysis I accept the hypothesis of positive relationship between general attitude of physicians towards DTCA and behavior of physicians if patient asks information has positive relationship and are correlated with actual prescription generation. Very interestingly it is found that information asking by physician and general attitude are weakly negatively correlated, it can be the area for further research that if more information is asked by patients about any brand may lead to negative attitude of physicians towards DTCA. It is found that through DTCA and patients, it is a way of putting pressure on physicians to change their prescribing behavior, (Ryan Vaithianathan, 2009) It was major concern showed by (Morgan, Mintzes barer, 2003) that the regularities authorities should consider DTCA regulations if it has impact on prescribing behavious, and in this study it has shown that the consumer advertising is creating impact in prescription choosen. This study is providing valueable information for pharmaceutical manufacturers and marketers. If more patients would ask for further information of specific drug, it may lead to the actual prescription generation. This study is also a thought provoking study for physicians that in choosing brands they are influenced by patients which may lead to increased cost and unnecessary medicines prescription. This study can be an eye opener for regularity authorities, DTCA is considered as good by physicians but it should be clearly monitored because it also creates pressure on physicians to prescribe certain brands. VI CONCLUSION Physicians have positive attitude towards DTCA and consider it supplementary in overall health care system. It stimulates patients to visit physician and seek appropriate treatment. Physicians feel comfortable in providing relevant information about DTCAB if asked, and they do not hesitate to prescribe the medicine if it is relevant to disease and patient economic characteristics. Focus of this study was to find the combined impact of attitude and information gathering on actual prescription generation. In future it may be further extended to specific disease area. However pharmaceutical companies should be monitored by regulatory authorities to check DTCA messages. Companies should focus on disease awareness rather on brand focused advertisements. REFERANCES Adeoye S, B. K. (2007 ). Direct to consumer advertising in healthcare: history, benefits, and concerns. Clinical Orthopaedics and Related Research , Volume 457, pp 96-104. Amaldoss, W., He, C. (2009). Direct-to-Consumer Advertising of Prescription Drugs: A Strategic Analysis. MARKETING SCIENCE , Vol. 28 (No. 3), pp. 472-487. Atherly, A., Rubin, P. (Feb 2008). The cost effectiveness of direct to consumer advertising for prescription drugs. Journal of Law Economics , pp. 08-28. Berndt, J. M. (2004). Effects of Direct-to-Consumer Advertising on Medication Choice: The Case of Antidepressants. Journal of Public Policy Marketing , 23 (2), 115-127. Berndt, J. M. (2004). Effects of Direct-to-Con sumer Advertising on Medication Choice: The Case of Antidepressants. Journal of Public Policy Marketing , 23 (2), 115-127. Bradford, D., Kleit, A. N., Nietert, P., Ornstein, S. (2005, August 8). The Effect of Direct to Consumer Television Advertising on the Timing of Treatment. Working Paper Series . Kurt R. Brekkea, Kuhnb, M. (2006). Direct to consumer advertising in Pharmaceutocal markets. Journal of Health Economics , pp. 102-130. Brekke, K. R., Kuhn, M. (July 2005). Direct to consumer advertising in pharmaceutical markets . Journal of Family medicine , Vol.18 (2) pp. 238-321 Donohue, J. M., Cevasco, M., Rosenthal, a. M. (2007). A Decade of Direct-to-Consumer Advertising of Presescription drugs. The new england journal of medicine , Vol . 81 pp. 357-673. E. Murray, L. Pollack, K. Donelan (2003), Direct-to-Consumer Advertising Physicians views of its effects on quality of care and the doctor patient relationship, JABFP, Vol. 16 No. 6 Pg. 513-524 Elizabeth Murray, P. M., Donelan, K., lee, K. (2004). Direct to Consumer Advertising Public Perception of its effects on Health Behaviours, Health Care, and the Doctor-Patient Relationship. The Journal of family Medicine, Vol.17 No. 1, pp. 6-18 Gould, M. F. (2007). Physicians attitudes toward direct-to-consumer prescription drug marketing. Journal of Medical Marketing , Vol. 7 (issue 1 ), 33-44. Green, R. M. (2008). Direct to consumer advertisment and pharmaceutical ethics The case of VIOXX. Journal of Business Ethics , Vol. 15, pp.749-759. Helen Prosser, S. A. (2003). Influences on GPs decision to prescribe new drugs-the importance of who says what. Journal of Family Practice , Vol. 20, (No. 1), 61-68. Herzenstein, M., Misra, S., Posavac, S. S. (2005). How Consumers Attitudes Toward Direct-to-Consumer Advertising of Prescription Drugs Influence Ad Effectiveness, and Consumer and Physician Behavior . Marketing Letters , Vol. 15 ( Number 4), 201-212. Iizuka, T., Jin, G. Z. (2005). The Effect of Prescription Drug Advertising on Doctor Visits. Journal of Economics and Management Strategy , 22 (3). Kurt R. Brekkea, Kuhnb, M. (2006). Direct to consumer advertising in Pharmaceutocal markets. Journal of Health Economics , Vol.19 (2) , Pg.102-130. Lack of Impact of Direct-to-Consumer Advertising on the

Buried Alive! The Fiction of Premature Burial :: Argumentative Persuasive Argument

Buried Alive! The Fiction of Premature Burial Why are there claims that people are being buried alive? I will tell you why; it is an old wives tale so there is no credit to. People were never buried alive, it is all fiction. There were patents put out there but the patents were never supported. The fact that there are no signs of the patented objects ever being used makes you wonder if they ever existed. If they did exist, why are they not being used today? I will tell you why people in the present age are being embalmed. Once a person is embalmed, the body is killed in order to keep it preserved and so it does not rot. In the paper, I will discuss how if a person is buried alive it is improbable that someone would live. In addition, I will discuss the theories about Anne Hill Carter Lee's double burial. If a person were buried alive, there would be no way to tell if they were in fact buried alive. Would you not hear the person screaming to be let out of their tomb? Of course you would not be able to hear a person scream or yell for help. They are six feet under the earth. In the times of old they would supposedly find scratch marks on the lids of coffins, but how do we know if they were telling the truth. Now in the twenty first century, we are finding no evidence of this ever happening in coffins of old days or even now days. There used to be bells and pulleys to let the person on the graveyard shift know someone was there. No longer are there such bells and pulleys. When the person who was on the graveyard shift and heard the supposed bells and sirens they had to dig up the coffin. In reality, this would have taken excessively long and the person in the coffin would run out of air. The fact is there are articles being revised to fit the culture of the twenty-first century. In 1898, the Journal of the American Medical Association editorial reminds us of the peculiar fascination with "premature burial" held for people in the last century. Even if a person should be so unlucky as to be buried while unconscious, the editors pointed out that the average coffin contains so little oxygen that asphyxia would probably precede any return to full consciousness. Buried Alive! The Fiction of Premature Burial :: Argumentative Persuasive Argument Buried Alive! The Fiction of Premature Burial Why are there claims that people are being buried alive? I will tell you why; it is an old wives tale so there is no credit to. People were never buried alive, it is all fiction. There were patents put out there but the patents were never supported. The fact that there are no signs of the patented objects ever being used makes you wonder if they ever existed. If they did exist, why are they not being used today? I will tell you why people in the present age are being embalmed. Once a person is embalmed, the body is killed in order to keep it preserved and so it does not rot. In the paper, I will discuss how if a person is buried alive it is improbable that someone would live. In addition, I will discuss the theories about Anne Hill Carter Lee's double burial. If a person were buried alive, there would be no way to tell if they were in fact buried alive. Would you not hear the person screaming to be let out of their tomb? Of course you would not be able to hear a person scream or yell for help. They are six feet under the earth. In the times of old they would supposedly find scratch marks on the lids of coffins, but how do we know if they were telling the truth. Now in the twenty first century, we are finding no evidence of this ever happening in coffins of old days or even now days. There used to be bells and pulleys to let the person on the graveyard shift know someone was there. No longer are there such bells and pulleys. When the person who was on the graveyard shift and heard the supposed bells and sirens they had to dig up the coffin. In reality, this would have taken excessively long and the person in the coffin would run out of air. The fact is there are articles being revised to fit the culture of the twenty-first century. In 1898, the Journal of the American Medical Association editorial reminds us of the peculiar fascination with "premature burial" held for people in the last century. Even if a person should be so unlucky as to be buried while unconscious, the editors pointed out that the average coffin contains so little oxygen that asphyxia would probably precede any return to full consciousness.

Accident essay

It was my 13th birthday. I decided to celebrate my birthday at the Cage, a soccer pitch, with my new friends, including my best friend, Stung Grunts. His name sounds like, â€Å"strong†, which is indeed true. Once, he was able to move this big table by himself to the other end! Isn’t it amazing? The people in the soccer pitch that I had rented were filled with emotions. We knew that there are exciting hours waiting for us. However, I had different plans. Every alternate day in my school whenever my friends, including Strung Grunts, and I went to the school field to play soccer, my friends would always praise Strung Grunts saying, â€Å"Hey!Strung! You are the best soccer player! You rock! † I curled my upper lip to keep myself from speaking. My mind was whirling with thoughts that only made me assume the worst. The feeling of jealousy was slowly growing in me; filling my blood, making my eyes go dark, and my mouth become a straight line. I knew that this was the time when I could do something to Strung Grunts and make sure that he does not play soccer for the rest of his life. I decided to hurt him indirectly. However, a million of thoughts ran through my mind at that point of time. Should I really cause him pain? Isn’t he my best friend? Is it wrong?Or is it right? Shouldn’t I train myself to become a better soccer player than him? I was in a dilemma. However, my jealousy got the better of me. Rather than thinking whether my act is right or wrong, I spent the time thinking what I shall do to him. Suddenly, an idea struck my mind. There were still 10 minutes left before we planned to start playing a game of soccer. Everybody went to the washroom to get a shower before playing except me. Strung Grunts left his boots outside the washroom before entering. Within a flash, I quickly went near the washroom, tied the laces of both the shoes together and fled from the washroom. minutes passed. Everyone came out of the washroom. It was very wet and slippery outside the washroom. My heart was thumping and pounding hard. A chill ran down my spine. Strung Grunts went on to put on his shoes without realising what had happened. When he took his first step itself, he slipped and fell down with a â€Å"thud†. Three, two, one†¦ Ahhhhhhhhhh!!! , Strung Grunts shouted out loud as our ears became almost deaf. A flood of tears gushed down his ashen pale cheeks staining the floor. He tried moving both his legs but he was not able to do so. All of us came to him frantically, including me, and gathered around him.We quickly informed this news to his mother as soon as possible. Within a flash, his mother came down to the pitch, horrified and bloodcurdling. I was informed that he fractured each of his legs. Moreover, the doctor advised him not to engage in any activity that requires the use of his legs for the next six months. Till now, everyone thinks that the slippery floor was the main cause of his accident. Howeve r, only I knew the truth. The scar which I have on my heart is invisible to anyone but more painful than anything I have ever felt. I would like to tell him the truth but I think it is not the right time yet, what about you?

Discovered Biological Functions Of Rna Health And Social Care Essay

Recently, the figure of ascertained biological maps of RNA has been increasing. In add-on, the range has been expanded, and therefore RNA is non merely a inactive courier of familial information from Deoxyribonucleic acid to proteins makers as had been thought earlier. It has been found that RNA plays of import functions in all of molecular biological science such as transporting familial information ( messenger RNA ) , construing the codification ( ribosomal RNA ) , and reassigning familial codification ( transfer RNA ) . It besides performs different maps which include: catalyzing chemical reactions [ 1 ] , [ 2 ] , directing the site specific alteration of RNA bases, commanding cistron look, modulating protein look and helping in protein localisation [ 3 ] , [ 4 ] . The map of RNA molecules determine many diseases caused by RNA viruses. Identifying the secondary construction of RNA molecules is the cardinal key to understand its biological map [ 5 ] . The RNA construction anticipation methods, is tremendously affected by the quality of alignment [ 6 ] . MSA significantly improves the de novo anticipation truth of proteins or RNAs structures [ 7 ] . For illustration, current RNA secondary construction anticipation methods utilizing aligned sequences is win in deriving higher anticipation truth than those utilizing individual sequence [ 8 ] . Multiple sequence alliance ( MSA ) has become widely used in many different countries in bioinformatics. Multiple alliances are present in most of the computational method used in molecular development to assist happening sequences household, predict the secondary or third construction of new sequences, RNA folding, cistron ordinance and polymerase concatenation reaction primer design [ 9 ] , foretelling maps, predict patient ‘s diseases by comparing DNAs of patients in disease find. MSA is the most natural manner to see the relation between sequences by doing an alliance between the primary sequences so that indistinguishable or similar residues will be aligned in columns. That is why this method is so called multiple sequence alliance ( MSA ) . At kernel, all widely MSA tools used to better the alignment quality of initial alliance [ 10 ] . The sequence alliance job can be considered as an optimisation job in which the aim is to maximise a marking map [ 11 ] . One chief challenge with MSA is how to gauge the quality of computer-aligned sequences. An nonsubjective map ( OF ) is required in the optimisation processes to happen the optimum alliance. The pick of nonsubjective map is critically of import in obtaining high quality alliances [ 12 ] . In add-on, OF acts an indispensable function in optimisation algorithms whereby there is a relation between the alliance mark with the mark computed by the alignment quality. MSA optimisation job is NP-complete [ 13-15 ] , which motivates, the research for heuristics [ 16 ] . Over the last decennary, the evolutionary and meta-heuristic are the recent attacks to work out the optimisation job. Consequently, most of practical MSA algorithms are based on heuristics to obtain moderately accurate MSA within moderate computational clip and normally produce quasi-optimal alliance. Many researches solve MSA job as optimisation job by utilizing familial algorithm [ 17, 18 ] , Particle Swarm [ 11 ] , ant settlement [ 19 ] , and Simulated tempering [ 20 ] . MSA job can be resolve as optimisation job based on harmoniousness hunt algorithm [ 21 ] to maximise the nonsubjective map and happen the optimum alliance. The purpose of this paper is to analyze and examined the correlativity of different nonsubjective maps utilizing standard sets of RNA datasets. The most straightforward OF is the sum-of-pairs ( SP ) score [ 3 ] , weight sum-of-pair [ ] , java [ 22 ] , Xstate [ ] and NorMD [ 23 ] . This paper is organized as follows: Section 2 introduce the multiple sequence alliance job. Section 3 explains the different nonsubjective map from the state-of-the-art. Section 4 explains the proposed methodological analysis. The rating and analysis methodological analysis that is used to measure our comparing is explained in Section 5. Last, Section 6 provides the decision and sum-up of the paper.2.0 Multiple Sequence AllianceA sequence is an ordered list of symbols from a set of alphabet S ( 20 amino acids for protein and 4 bases for RNA/DNA ) . In bioinformatics, a RNA sequence is written as s = AUUUCUGUAA. It is a twine over the set S of bases symbols Adenine ( A ) , Cytosine ( C ) , Guanine ( G ) and Uracil ( U ) : S = [ A, C, G, U ] . Alignment is a method to set up the sequences one over the other in a manner to demo the matching and mismatching between residues. A column, which has lucifer residues, shows no mutant is go oning. Whereas, the column with mismatch symbols shows that several mutant events are go oning. To better the alliance mark, the character â€Å" – † is used to match to a infinite introduced in the sequence. This infinite is normally called a spread. The spread is viewed as interpolation in one sequence and omission in the other. A mark is used to mensurate the alliance public presentation. The highest mark one is the best alliance. For lucidity ‘s interest, the generic MSA job is expressed with the following declaration: â€Å" Insert spreads within a given set of sequences in order to maximise a similarity standard † [ 24 ] . The MSA job can be divided into three troubles, which are scalability, optimisation, and nonsubjective map. Finding an accurate MSA from sequences is really hard. It is a clip consuming and computationally NP-hard job [ 13-15 ] . In fact, that complexness comes from that all three jobs must be solved at the same time. The first job is the scalability, which is to happen the alliance of many long sequences. The 2nd job is the optimisation, which is to happen the alliance with the highest mark based on a given nonsubjective map among sequences. Optimization of even a simple nonsubjective map is an NP-hard job. The 3rd job is the nonsubjective map ( OF ) , which is to rush up the computation in order to mensurate the alliance. Most modern plans for building multiple sequence alliances ( MSAs ) consist of two constituents: an nonsubjective map for measuring the quality of a candidate alliance of a set of input sequences, and an optimisation process for placing the highest scoring alliance with regard to the chosen nonsubjective map [ 25 ] .3.0 Objective mapsAligning multiple sequences is a extremely non-trivial undertaking ( in both a biological and computational sense ) whose truth in pattern depends mostly on the pick of input sequences, the cost ( or aim ) map, and the heuristics employed [ 26 ] . An of import facet of alliance mark is to set up how meaningful a given multiple alliance is. This is to find whether the aligned sequences are in fact optimum and to gauge the mark of the alliance in which there is no anterior cognition of the mention alliance. Objective map is the psyche of iterative algorithms in the sense that it determines the campaigner move to be taken to better the solution quality. In multiple sequence alliance, nonsubjective map Acts of the Apostless as the cardinal factor to command the development of an alliance into a mature one. Using optimisation algorithm to work out any job requires delegating a fittingness map. In harmony hunt algorithm, this map evaluates and ranks harmoniousnesss in the harmoniousness memory harmonizing to their tonss. Harmonies that ain good alliance mark in the harmoniousness memory are retained. In this subdivision different nonsubjective maps are studied. The pick of nonsubjective map is strictly a biological job that lies in the definition of rightness. A mathematical map able to mensurate an alignment biological quality that defines a right alliance and its expected belongingss is called nonsubjective map ( OF ) . Given a perfect map, the mathematically optimum alliance assumes to be biologically optimum. While the map defines a mathematical optimum, it is seldom that this optimum will besides be biologically optimum [ 25 ] . There are different nonsubjective maps to hit the quality of the alliance, viz. sum-of-pairs, leaden sum-of-pairs, and NorMD [ 23 ] , MstatX, amd COFFEE [ 22 ] . They are used in optimizing and iterative alliance methods to better the alliance by seeking to maximise the nonsubjective map [ 27 ] .3.0.1 sum-of-pairsPresently sum-of-pairs nonsubjective map is most widely used [ 28 ] . Carrillo and Lipman [ 29 ] foremost introduced the sum-of-pairs ( SP ) mark map, which defines the tonss of a multiple alliance of N sequences as the amount of the tonss of the N ( N-1 ) /2 pairwise alliances [ 29 ] , [ 30 ] . Although SP mark map has been widely used to measure MSA, it does n't truly supply any biological or probabilistic justification [ 30 ] . Each sequence is scored as if it is descended from the N-1 other sequences alternatively of a individual ascendant. As a consequence, evolutionary events are frequently overestimated. The job worsens as the figure of sequences additions [ 30 ] the sum-of-pairs ( SP ) mark described in [ 31 ] , [ 32 ] , [ 29 ] , [ 33 ] is used to cipher the nonsubjective map ( OF ) where there is no anterior cognition of the mention alliance. The general signifier of OF mark of alignment n sequences consist of m columns is OF = . Where is the similarity mark of the column myocardial infarction, is the spread punishment of the column myocardial infarction and is the sequence length. The similarity mark of the column myocardial infarction can be measured by the sum-of-pairs ( SP ) . The SP-score S ( myocardial infarction ) for the i-th column myocardial infarction is calculated as follows: S ( myocardial infarction ) = , ( ) where is the j-th row in the i-th column. For alining two residues x and y, the permutation matrix s ( x, y ) is used to gives the similarity mark.3.0.2 Weighted sum-of-pairsThe leaden sum-of-pairs ( WSP ) score [ 28 ] , [ 34 ] is an extension of SP mark so that each pairwise alliance mark otherwise contributes to the whole mark. A leaden SP mark map has been proposed in the manner to reflect the relationships between the sequences. The rule is to give a cost to each brace of aligned residues in each column of the alliance ( permutation cost ) , and another cost to the spreads ( spread cost ) . These are added to give the planetary cost of the alliance. Furthermore, each brace of sequences is given a weight related to their similarity to other braces. The WSP calculates a entire mark from the leaden pairwise mark of all the sequences. The undermentioned figure shows the mathematical preparation of the leaden SP mark map. WSP ( A ) = ( ) Where N is the figure of sequences, k the length of aligned sequences, is the weight given to a brace of sequences, and is the similarity cost of two symbol sequence ( ) . The cost map included spread gap and extension punishments for gap and widening spreads. The weight of pairwise aligned sequences may be proportionately score [ 35 ] , [ 36 ] harmonizing to the sum of alone information enclosed in the sequence. These weights try to diminish the influence of excess information from strongly related sequences. A weight represents a per centum equal to a per centum individuality ( PID ) calculated over each brace of aligned sequences [ 24 ] as follows ( excepting spreads ) : PID = ( )3.0.3 Normalized Mean Distancenormalized mean distance ( NorMD ) [ 23 ] is a normalized mean distance ( MD ) mark measures the normalized mean distance between the similarities of the residue braces at each alliance column, introduce in ClustalX, between similarities of residue braces at each alignment column. A mark for each column in the alliance is calculated utilizing the construct of uninterrupted sequence infinite introduced by [ 37 ] and the column tonss are so summed over the full length of the alliance. NorMD take into history the sequence information, such as the figure, length and similarity of the sequences to be aligned. NorMD is used in RASCAL [ 38 ] and AQUA [ 39 ] .3.0.4 Consistency markConsistency-based nonsubjective maps focus on improved marking of lucifers in early alliances by integrating information from of pairwise alliance. This consistence construct was originally introduced by Gotoh [ 40 ] and subsequently refined by Vingron and Argos [ 41 ] . Kececioglu [ 42 ] reformulated this job as a maximal weight hint ( MWT ) job. It was further expanded by Morgenstern [ 43 ] who proposed the first heuristic to work out this job for big cases. Consistency-based marking is used in T-Coffee [ 44 ] , MAFFT [ 45 ] , and Align-m [ 46 ] algorithms. The COFFEE [ 22 ] is a consistency-based which step optimized the figure of aligned residues that were besides aligned in planetary pairwise alliances of the same sequences. Coffee nonsubjective map which evaluates the consistence between a multiple sequence alliance and a antecedently defined library of pair-wise alliances. COFFEE required two constituents: ( I ) a set of pairwise mention alliance by utilizing any method for doing pairwise alliances, ( two ) the OF that evaluate the consistence between a multiple alliance and the pairwise alliances contain in the library. COFFEE plants by first bring forthing the pairwise library of the sequences in the alliance and so calculates the degree of individuality between the current multiple alliance and the pairwise library. COFFEE is non using excess spread punishments so that, it is non sensitive to the permutation tonss of amino acids, the mark is normalized, and the cost of similar braces is place dependent. Coffee is reflect the deg ree of consistence between a multiple sequence alliance and a library containing pairwise alliances of the same sequences. The planetary mark mensurating the quality of the alliance is computed by the undermentioned expression. Coffee mark = ( ) where Len is the length of the MSA ; Aij is the pairwise projection of sequences Si and Sj obtained from the MSA ; Wij is the per centum individuality between the two aligned sequences Si and Sj ; is the figure of residues braces that are shared between Aij and the pairwise. In add-on, utilizing chance in consistence leads to a alleged chance consistency. This hiting map is introduced in ProbCons [ 47 ] . It assigns position-specific permutation tonss based on a step of expected truth derived from a concealed Markov theoretical account. This thought is implemented and extended in the PECAN [ 48 ] , MUMMALS [ 49 ] , PROMALS [ 50 ] , ProbAlign [ 51 ] , ProDA [ 52 ] , and PicXAA [ 53 ] plans.3.0.5 POsition-Specific and consIstency-based nonsubjective function ( POSITION )POSITION [ 54, 55 ] is based on the consistence, it calculates the degree of individuality between the current multiple alliance and the pairwise library. The hiting map for POSITION is shown as under in Eq. ( 5 ) . POSITION = ( 5 ) where N is the figure of the sequences ; Aijl is the brace of residues at index cubic decimeter of the pairwise projection of sequences Si and Sj ; and Occurrence ( Aijl ) is a 0-1 binomial map of whether brace Aijl occurs in the pairwise library. W ( Aijl ) is the weight of Aijl and is assigned to the mean similarity of residue braces around index l. This is an attempt to specify the weight harmonizing to contextual information of residue braces.3.0.6 MaxZMaxZ is a statistical alliance quality mark introduced in [ 56 ] which first quantifies the grade of preservation at each alignment place and so counts the figure of significantly conserved places over the alliance. It used Zscore for mensurating the grade of preservation that is based on profile analysis [ 57 ] Then, by utilizing the importance trying method [ Using the SIR algorithm to imitate posterior distributions. ] , the statistical significance of an observed mark value is calculated. In footings of positional significance degrees, the full alliance mark is calculated.3.0.7 MstatXMstatX calculates the trident statistic of each column in the multiple sequences alliance. Then by stipulate the statistic with the flag options. It can gives many different statistical steps on columns of a multiple alliance like Shannon information, frequence counts, spread counts, and more sophisticated marking. The default statistic is a weighted-entropy which means a Shannon information based on chances computed with the sequence burdening strategy defined by [ 58 ] . Statisticss proposed in MstatX is based on [ 59 ] and [ 60 ] .3.0.8 Maximal expected truth ( MEA )Maximal expected truth ( MEA ) [ 61 ] : The basic thought of MEA is to maximise the expected figure of â€Å" right † aligned residue braces [ 62 ] . It has been used in PRIME [ 63 ] , and ProbCons [ 47 ] algorithms.3.0.9 Segment-to-segment nonsubjective mapSegment-to-segment nonsubjective map: It is used by DIALIGN [ 64 ] to build an alliance through comparing of the whole sections of the sequences instead than the residue-to-residue comparing.3.0.10 Profile markProfile hiting map uses a marking map which is defined for a brace of profile places. In add-on to SP, MUSCLE [ 65 ] uses a new profile map which is called the log-expectation ( LE ) mark. Some of these nonsubjective maps integrated into other nonsubjective maps, each have its ain advantages and disadvantages. The nonsubjective map presently used in DIALIGN that is segment-to-segment nonsubjective map is flawed [ 66 ] . On the other manus T-Coffee is excessively memory demanding [ 12 ] . Sum-of-pairs is the most popular marking method because of its comparative velocity and hardiness. The velocity advantage is chiefly because the sum-of-pairs method does non necessitate a tree [ 67 ] . Some nonsubjective maps use permutations matrices whereas other used consistence construct by involve pairwise alliance. [ 68 ] disadvantage of these permutations matrices is that they are intended to rate the similarity between two sequences at a clip merely, and in order to widen them to multiple sequences, it is common to happen that they are scaled by adding up each pairwise similarity to obtain the mark for the multiple sequence alliance [ 5 ] .4.0 Alignment QualityQ ( Quality ) is a quality map to gauge the comparing between the alliance and the mention alliance. Q mark is the figure of right aligned residue braces in the trial alliance divided by the figure of residue braces in the mention alliance. This has been termed as the developer mark [ 69 ] and SPS [ 31 ] .5.0 MATERIALS AND METHODSHarmony hunt algorithm – which is out of range of this paper – is used to happen the optimal or a close optimum alliance harmonizing to the nonsubjective map. Given a perfect map, the mathematically optimum alliance will besides be biologically optimum. While the map defines a mathematical optimum, it is seldom have an statement that this optimum will besides be biologically optimum. two type of dataset are chosen ( I ) the subset of BRAliBase which are extremely variable and suited for local MSA ; ( two ) LocalEXtR, an extension of BRAliBase 2.1, consisting large-scale trial groups and patterned on BRAliBase 2.1 ; The series of experiments has been conducted in order to analyze the relationship of the corresponding nonsubjective map mark with the alignment quality. The experiment has been done in the term of correlativity coefficient between the nonsubjective map mark and the alignment quality mark in one side and the consuming clip in another side. First, the different nonsubjective maps are used as a fittingness map in HS algorithm and the relationship between them are studied. Second compare the quality tonss of 5 nonsubjective map utilizing database In pattern, it is hence ever recommended to utilize as many different methods. hence analysis did non curtail to merely a few of the best alignment methods but aimed to utilize as many methods as possible [ 12 ] . One of the primary challenges in sequence alliance is to happen a biologically meaningful nonsubjective map. A common pick of many alliance algorithms has been the ‘sum-of-pairs ‘ ( SP ) mark, which merely takes the amount of the tonss of all pairwise alliances in a given multiple alliance. To day of the month, there is no nonsubjective map that has been every bit good accepted for multiple alliances [ 70 ] as similarity has been for pairwise alliance. Alignment quality requires a mention alliance from database benchmark. The comparing is between the trial alliance and the mention alliance and it is called here alignment quality.Performance ratingTwo scenarios are done in different manner, The first scenarios, it uses an nonsubjective map in the HS Improvising procedure and analyze the relationship between the alliance mark with alignment quality for concluding alliance. This is repeated with all nonsubjective map. The motive for mark the alliance many times in every loop was the fact that alliances generated prior to the several iterative polish are frequently rather different from the concluding alliance [ 12 ] . Second scenarios, it measures alignment mark and alignment quality for the same alliance which is the concluding alliance by every nonsubjective maps individually. Alignment mark and its quality are compared for each alliance. This seneraio is to compare the consequence of different nonsubjective map on the same alliance These experiments to cognize how strong is the relation between them in each nonsubjective map individually. A comprehensive reappraisal of all methods will non be given here, but the common nonsubjective maps will be focus on.a. Harmony hunt algorithmHarmony hunt algorithm ( HS ) is developed by Geem [ 21 ] . HS is a meta-heuristic optimisation algorithm based on music. HS is imitating a squad of instrumentalists together seeking to seek the best province of harmoniousness. Each participant generates a sound based on one of three options ( memory consideration, pitch accommodation, and random choice ) . This is tantamount to happen the optimum solution in optimisation procedure. Geem et Al. [ 21 ] theoretical accounts HS constituents into three quantitative optimisation procedure as follows: first procedure, the Harmony memory ( HM ) : It used to maintain good harmoniousnesss. A harmoniousness from HM is selected indiscriminately based on the parametric quantity called harmony memory sing ( or accepting ) rate, HMCR ?„ [ 0,1 ] . It typically uses HMCR = 0.7 ~ 0.95. Second procedure, the pitch accommodation: it is similar to local hunt. It is used to bring forth a somewhat different solution from the HM depend on pitch-adjusting rate ( PAR ) values. PAR control the grade of the accommodation by the pitch bandwidth ( brange ) . It normally uses PAR = 0.1~0.5 in most applications. Third procedure, the random choice: a new harmoniousness is generated indiscriminately to increase the diverseness of the solutions. The chance of randomisation is Prandom = 1- HMCR, and the existent chance of the pitch accommodation is Ppitch = HMCR A- PAR. The pseudo codification of the basic HS algorithm with these three constituents is summarized in Figure 1. Harmony Search Algorithm Get down Declare the nonsubjective map degree Fahrenheit ( x ) , ten = ( x1, x2, aˆÂ ¦ , xn ) Initialize the harmoniousness memory accepting rate ( HMCR ) Initialize pitch seting rate ( PAR ) and other parametric quantities Initialize Harmony Memory with random harmoniousnesss While ( t & lt ; max figure of loops ) If ( rand & lt ; HMCR ) , Choose a value from HM If ( rand & lt ; PAR ) , Adjust the value by adding certain sum End if Else Choose a new random value End if End while Measure the solution by utilizing nonsubjective map Accept the new harmoniousness ( solution ) if better Update HM End while Find the current best solution in HM End Figure 1 Pseudo Code of the Harmony Search Algorithm [ 71 ] The HS algorithm has been applied to assorted optimisation jobs [ 72 ] that include Real-world applications, Computer scientific discipline jobs, Electrical technology jobs, Civil technology jobs, Mechanical technology jobs, and Bio & A ; medical applications.B. Benchmark DatasetThree type of dataset are chosen ( I ) the subset of BRAliBase which are extremely variable and suited for local MSA ; ( two ) LocalEXtR, an extension of BRAliBase 2.1, consisting large-scale trial groups and patterned on BRAliBase 2.1 ; ( three ) Lset, a brace of large-scale trial sets representative of current biological job. The subset of the BRAliBase 2.1 are selected from the most variable dataset within the suite. They are from THI, Glycine riboswitch and Yybp-Tkoy RNA households, and contain 232 trial datasets. LocalExtR uses the same seed alliances from Rfam that BRAliBase uses and signifiers big trial groups. BRAliBase is label a trial group qi, where I is the figure of sequences for each trial set in the group. The tabular array ( 1 ) and ( 2 ) show the inside informations of the dataset and the description information about each trial set. Table 1: Trial Dataset Number of each Test Group trial Group gcvT Family THI Family yybp-ykoy Family BRALiBase 2.1 ( 232 datasets ) k5 22 69 33 k7 12 32 18 k10 3 17 12 k15 1 5 8 LocalExtR ( 90 datasets ) k20 10 10 10 k40 10 10 5 k60 10 10 0 k80 5 10 0 Entire 73 163 86 Table 2: Sequence length of each Test Group sequence length trial Group Avg. Min. BRALiBase 2.1 ( 232 datasets ) k5 109 96 k7 110 94 k10 108 94 k15 110 88 LocalExtR ( 90 datasets ) k20 115 90 k40 114 87 k60 107 81 k80 106 775.0 RESULTS AND DISCUSSIONOne chief challenge with MSA is how to gauge the quality of computer-aligned sequences. Therefore, an nonsubjective map ( OF ) is required in the optimisation processes. The pick of nonsubjective map and heuristics is critically of import in obtaining high quality alliances [ 12 ] . In add-on, OF acts an indispensable function in optimisation algorithms whereby the alliance is optimized against a mark computed by the OF [ 2 ] . The most straightforward OF is the sum-of-pairs ( SP ) score [ 3 ] , weight sum-of-pair [ ] , java [ 22 ] , Xstate [ ] and NorMD [ 23 ] .5.1 Correlation between Objective maps Score and alignment qualityTheoretically, an OF should ever give higher tonss for alliance with better quality [ ] . In world, nevertheless, since the nonsubjective map tonss and the alliance qualities are measured utilizing different standards, incompatibility happens. Correlation between alignment quality and different nonsubjective maps score were practiced on each experimental. Correlation coefficients ( R2 ) were so computed for each nonsubjective map and Q mark of the alignment quality. Two scenarios are performed to look into the correlativity the first one where utilizing the nonsubjective map as the HS Improvising procedure, the 2nd one where mark a concluding alliance by different nonsubjective maps. ( a ) First Scenario: utilizing the nonsubjective map in the generator procedure Five experiments are carried by utilizing an nonsubjective map and compared alignment mark with alignment quality in each experiment. Each experiment has been repeated 5 times for the same dataset and the norm is calculated. In this experiment, each nonsubjective map have been used individually as a fittingness map. Then, the correlativity of the nonsubjective map mark and the alignment quality mark is calculate utilizing the Correlation coefficients ( R2 ) . Each instance has been repeated 5 tallies for same dataset and calculated the norm for each nonsubjective map theoretical accounts. The figure of loop in each tally, is fixed in all the experimental in this experiment to 10,000. 322 trials set are used and their inside informations are summarized in Mistake: Reference beginning non found HS parametric quantities and others parametric quantities are setup to default puting for all nonsubjective map. Alliance Generator OF1 Alliance Mark |qualityaˆÂ ¦Alliance Generator OF2 Alliance Mark |qualityaˆÂ ¦In this experimental BHS-MSA is used to bring forth the alliance. Within the optimisation processes the nonsubjective map theoretical accounts, sum-of-pairs, weight sum-of-pair, java, Xstate and NorMD were used individually to give the good alliance quality. The concluding alliances were measured and evaluated by comparing with the mentions utilizing the rating map Quality ( Q ) and Entire column Score ( TC ) . The mean correlativity coefficient value of all dataset is listed and the spread secret plan graphs are listed as shown in Figure 2. shows the R indicated that the java and sum-of-pairs nonsubjective map has better positive correlativity with alignment quality than others does. The relation is positive that mean when the nonsubjective map is increase the alignment quality is increase this is clear shows in the Figure 3. Table 3: Correlation coefficients ( R2 ) of option Objective maps for scenario 1 SP WSP NorMD MstatX Coffee Correlation coefficients ( R2 ) 0.9216 0.7278 0.7613 0.8259 0.9642 fig 2 copy.jpg Figure 2: Scatter secret plan of alternate nonsubjective Functions for scenario 1 ( B ) Second Scenario: step a concluding alliance by different nonsubjective maps. In this experimental, 10 experiments are transporting out and alliance are bring forthing indiscriminately. Final alliance is measured by each nonsubjective map individually. Then, the correlativity of the nonsubjective map mark and the alignment quality mark is calculate utilizing the Correlation coefficients ( R2 ) [ 12 ] . This scenario is to back up the old 1. The correlativity on different nonsubjective map on alliances is study here by another manner where the nonsubjective maps are step the same alliance together and the relationship between the alliance mark with alignment quality are studied individually for each nonsubjective map. For ocular review, matching spread secret plans for all nonsubjective maps are presented. Alliance Generator OF1 Alliance Mark |qualityaˆÂ ¦aˆÂ ¦aˆÂ ¦OF2 Mark |qualityaˆÂ ¦aˆÂ ¦aˆÂ ¦HS and MSA parametric quantity are fixed to same values in all experimental. The mean correlativity coefficient value of all dataset is listed in Table 4 and the spread secret plan graphs are shown in Figure aˆZ3 Table4 shows the R indicated that the java and sum-of-pairs nonsubjective map has better positive correlativity with alignment quality than others does. The relation is positive that mean when the nonsubjective map is increase the alignment quality is increase this is clear shows in the Figure aˆZ3 Table 4: Correlation coefficients ( R2 ) of option Objective maps for scenario two sum-of-pairs ( R ) wsop ( R ) NorMD ( R ) Xstat ( R ) Coffee ( R ) Correlation coefficients ( R2 ) 0.8319 0.7558 0.6762 0.8028 0.9494 fig 3 copy.jpg Figure aˆZ3: Scatter secret plans of alternate nonsubjective maps for scenario two5.2 Study of Coffee and SP Objective maps based on clip costObjective map is the most computationally time-consuming constituent of MSA alliance method. The clip complexness of calculating an nonsubjective mark additions linearly with length of alliance and the figure of sequences. Figure aˆZ shows that increasing the sequence figure lead to increase the clip cost for calculate the nonsubjective map for the java and SP nonsubjective maps. Table5: Time cost of each Test Group Test Group No. of Seqs. sequence length Avg. Time Avg. min soap SP BRALiBase 2.1 ( 232 datasets ) k5 5 109 96 125 0.16 k7 7 110 94 131 0.32 k10 10 108 94 129 0.66 k15 15 110 88 137 1.60 LocalExtR ( 90 datasets ) k20 20 115 90 172 3.52 k40 40 114 87 180 16.96 k60 60 107 81 189 42.72 k80 80 106 77 204 88.01 Based on the correlativity shown in 4, the correlativity between the alliances hiting and the alignment quality utilizing the COFFEE nonsubjective map and sum-of-pairs were better than those found utilizing the NorMd, MstatX, and WSP nonsubjective maps. Coffee and sum-of-pairs nonsubjective maps have the highest correlativity. Based on the clip cost shown in Table5: Time cost of each Test Group and figure 4, the cost clip used by sum-of-pairs is better than java nonsubjective map for all trial groups. Figure aˆZ4: Coffee and SPS Objective map clip6.0 DecisionThe alliance of multiple sequences remains a challenging job today. Here, we do non discourse possible schemes to better alliance quality, but alternatively concentrate on the maps used to measure the quality of completed alliances. The relationship of the alliance mark and alignment quality of different nonsubjective map is the aim of this paper. It is recommended to run several maps and compare their consequences to happen the most suitable one. The consequence shows that the correlativity between the alliances tonss and the alignment quality utilizing the COFFEE nonsubjective map and sum-of-pairs were better than those found utilizing the NorMd, MstatX, and WSP nonsubjective maps. Coffee and sum-of-pairs nonsubjective maps have the highest correlativity. It besides shows that the alliance marking by sum-of-pairs is better than java nonsubjective map for all trial groups in footings of consuming clip The tonss produced by sum-of-pairs and java are better correlated to the existent alliance truths than tonss produced by other methods.7.0 RecognitionThe writers would wish to appreciate the School of Computer Sciences every bit good as University Science Malaysia for their installations and aid. The writers are appreciative of the attempts of the referees for their helpful remarks.