Friday, June 7, 2019

Notes on Religious Views on Life After Death Essay Example for Free

Notes on Religious Views on Life After Death EssayQuestion is What are we make of and what survives after death of the torso. If anything survives how much of the original identity of that person survives and in what form? People try to answer this byBelieving in a superior being who has communicated a promise Gathering data about LAD near death experiences, past life memories that suggest reincarnation, the para-normal Accepting no life after death we are matter and return to matter and become part of the wider world again Exploring ideas about the nature of body and soulSome saviourians believe death is the event that makes sense of our previous lives and the meaning of death itself is changed in the promise of eternal life. John Hick, it should non evoke the foul fear with which we incline what we know to be evil It is a fuller stage in the outworking of the Creators loving purpose for his children.SOURCES Revealed Knowledge The Bible, Quran, Torah etc which tell u s of the events others stand experienced and what they claim and to those who accept them as revealed knowledge this gives certainty. Christians believe that Jesus was and is God Incarnate, so if he promises eternal life to his followers, he must be trusted. Similarly Muslims trust the Prophet Mohammed as Allahs chosen messenger and as he has spoken of paradise, then at that transport must be much(prenominal) a place. Inferential Knowledge Reasoning that the ideas expressed explain so much that they must be true even if in that respects no proof = a belief. Hindus do not have any promise in scripture, but they trust their God loves them and so will e god to them upon death.In neither crusade is there absolute proof the believer trusts that it is true.Religious views Christian Old Testament good and bad alike to go to Sheol as ghostlike individuals parentage 14.7-12 Theres hope is a tree is cut down as buds can grow from the trunk but man lies down and does not rise agai n. withal he also believes that if he has a personal relationship with God which is beyond the trials of this life he will be with God at the end. newfound Testament the crucifixion and resurrection of Christ is at the heart of the belief in LAD,. Jesuss promise to the good thief crucified with him This day you will be with me in paradise only appears in the Gospel of Luke indicates that he believes in the possibility of paradise for the righteous and the repentant. However the translation of paradise could also hint to a winning place. Jesus referred to heaven as the place where God lived Our Father which art in heavenBook of Revelations contains visions of Saints whose bloody robes have been washed clean in the blood of the lamb (Christ) in a heavenly city, the new Jerusalem. It is slang there is a heaven after death, which is separate from the last judgment, also cognise as the second coming, which will happen at the end of time.The term eschatalogical gap refers to the g ap between whats in the bible and the precise details of the future Purgatory Roman Catholics only people have to atone for sin before they can enter heaven no scriptural evidence for this idea obliviousness not in current use, but Catholics used to believe the unbaptised or good people whod never heard of Jesus would go here. Protestants believed such people would go straight to hell on earth as God would have called those to be saved. One reference in Peters letters The spirits who are in prison Reincarnation some Christians have accepted this in the past but not currently in use.Catholics in particular value appearances by Mary (Lourdes, Fatima etc) and other saints after their death as confirming an after life.Quakers religious body without creeds and so base beliefs on experience, life experience varies and therefore so do views on LAD. Three main views bit these are not fixed, all beliefs are personal. 1. The good we have done (and possibly the evil) lives on after we have gone in the lives of those affected this might be as memories or as the impact of deeds 2. Survival of the Human life story as a continuation of this life in a spiritual body (St Pauls term). Some also believe in reincarnation 3. Acceptance of heaven and hell as destinations after death but belief in a Loving God and redemption through Christ means hell cannot be eternal Personal conclusions about LAD are based on individual experiences of the Love of God in this life in ill will of the experience of suffering.Therevada Buddists Nirvana achieved in this life, without substrate and so continuing to live in bodily form is described as a set of qualities in The Questions of King Milinda. He asks Nagasena whether he can compare it to anything in this world to help him understand. Nagasena says it cant be compared to anything, but its qualities can. E.g As a lotus is unsustained by water, so Nirvana is unsustained by all the defilementsIslam God has a plan for the firm univer se and all human beings At the day of judgement to whole universe will be destroyed and the dead raised to stand before him That day will be the beginning of an unending life on which every individual will be judged and rewarded by God according to their deeds. The Quran argues that life after death is vital of make sense of morality. If there is no afterlife then a belief in God is irrelevant.Hindus believe in certain heavenly states, notably Goloka, Krishnas heaven for devotees, but there is little justification in scripture. Hindus believe as a God loves his people he must be good to them when they die.The Resurrection of the Body Key Christian belief is that the individual survives as an individual. Also that the individual is judged as a individual Jesuss resurrection and ascension is the model we will follow as he was direct to show us the way, the truth and the light.. The Apostles and Nicene Creed twain affirm belief in the resurrection of the dead and the life of the worl d to come Tey also refer to the communion of saints which refers to the Church as one body uniting those in heaven and those on earth. The point of the Creed is to reinforce belief in the face of challengesChristians believe that man can be saved as a whole, body and soul man can glorify God through his body as he is made in the image of God, the body can become a sacrifice to God and also a dwelling place of the Holy Spirit, (Corinthians 6.19-20,Do you not know that your bodies are temples of the Holy Spirit, who is in you, whom you have received from God?). Also Christ at the Last Supper gave his Body and personal credit line as a means of salvation, so the human body is important On the same day as jesuss resurrection Matthews gospel reports dead prophets rising from their sculpt indicating a bodily resurrection.Paul speaks of us dying and rising with Christ in Baptism as a spiritual experience (Romans 6.5-11) but he is clear that the body will be resurrected after death howev er in 1 Corinthians 15-50 he also says flesh and blood cannot inherit the kingdom of God. Irenaeus and Tertullian both interpret this to mean that flesh is resurrected for judgment and that the Spirit must be present in the flesh to enter heaven. The Creed also affirms belief in the Holy Spirit.1 Corinthains 15.35-50 Paul is asked How are the dead raised? He uses the analogy of a seed and a bulb to show that something completely antithetical can arise from a source. At h time there was a commonly held belief that the flesh would be resurrected the corpse Paul move to make it clear that the body refers to the whole personality and person, both inner and outer. Through Adam we are part of the physical sphere and through Christ we are part of the spiritual sphere Christ was man and God together we are physical body and spiritual body together. Paul does not describe the spiritual body.

Thursday, June 6, 2019

Research Paper Taxation Essay Example for Free

Research Paper Taxation EssayWage is the quick-frozen amount of compensation for attend rendered covering a stubborn period of date, usually hours, or fixed amount of seduce. It is usually a compensation given to skilled and unskilled labor. Commission is usually a hire given to skilled and unskilled labor. Commission is usually a wage given to a salesperson based on the amount of his sales. This amount is usually added to basic salary.Bonus is given to simulate employees to work more efficiently and effectively (Valencia Roxas, 2009) To make sure that employees comply with BIR regulation and local government laws, companies moldiness include crucial employee and keep company information in their paysheet department placements. Setting up and running the different components that comprise a paysheet department system requires delinquent diligence and adequate knowledge of tax legislation. Employees benefits In Philippine Accounting Standards (PAS) 19, paragraph 7 states that employees benefits argon all forms of consideration given by an entity in exchange of services rendered by employees.These benefits may be paid railly to the employees or to their dependents, such as their children or spouses. These eject be settled by payment in cash in form goods and services. Paragraph 4 of PSAS 19 enumerates the following four classes (a) short term employee benefits (b) post-employment benefits (c) different term employee benefits and, (d) termination. Employee information During the new hire process, companies must collect information such as medical insurance and W-2 forms to determine what should be deducted from an employees paycheck.These forms in like manner provide employers which crucial information, such as the employees companionable Security number and their refuse amount for government tax purposes. The systems must also data track and process changes make to the employees tax exemption status, pensions, insurance plans or retirem ent funds. Salary information As part of the new hire process, payroll systems include a component that designates which employees argon full epoch, part time and contractors. Classifying worker in a payroll system is important since the government levies high penalties on companies that categorize employees incorrectly.Applicable taxes and deductions The National internal Revenue Code (R. A 8424) requires the employer to withhold portion of the salaries earned by employees that willing at to the lowest degree approximate an income tax due of the earner relative to the income earned. The monthly or semi-monthly withholding s taxable could be obtained from the BIR to serve as guide as to what amount to be withheld from the salary of the employee (http//www. ehow. com/list_6725482_components-payroll-system. html, 17 July 2010). In preparing a payroll, certain government mandated contributions expected to be deducted from the gross play of each employee.These include withholding t axes, PAG-IBIG, SSS (Social Security System) and PhilHealth contributions. Withholding taxes is remitted to BIR while PAG-IBIG is remitted to Home Development and Mutual Fund (HDMF) (Cabrera, Ledesma Lupisan, 2009). early(a) payroll withholdings include employee contributions to benefits, retirement accounts, and charities, these are determined by the employee during the fringe benefits selection process offered by their employer and must be taken into account as well as any employer matches when reporting payroll .Methods of payroll Computation A payroll system involves every(prenominal)thing that has to do with the payment of employees and the filing of employment taxes. This includes keeping track of hours, calculating wages, withholding taxes and other deductions, thus allot methods must be applied in the computation to achieve a desirable output. More and more aspects of payroll are being handled electronically.Methods include direct paycheck deposit, debit cards, payroll a nd non-payroll, use Web-based information system to allow employees access, with a secure password, to their individual payroll records including pay stubs, an stipend record and in some cases, employer information, such as the company manual or health insurance plan overview (Banning, 2008) Giove (1993) stated the seven methods for computing payroll Hourly order Plan Employees paid on an hourly rate plan receive a fixed amount for each hour they work.An employees regular earnings are equal to the employees hourly rate multiplied by the number of hours worked during the payroll period. Salary Plan Salaried employees receive a fixed amount for each payroll period, whether weekly, biweekly, semimonthly, or monthly. If an employee on the salary plan works less than the regular hours during a payroll period, the employer may deduct for the time lost, although in most cases the employer does not make such a deduction. Regular earnings would be determined by multiplying that hourly rate by the genuine number of hours the employee worked during the payroll period.Overtime Pay All employees in all establishments and undertakings whether for profit or not are entitled to overtime pay for work rendered beyond eight (8) hours. But this does not apply to managerial employees, field personnel, and members of the family of the employer who are dependent on him for support, domestic helpers, person in the personal service of another, and workers who are paid by results. Employees in the government are also entitled to overtime pay but they are governed by Civil do laws and rules. Only employees in the private sector are covered by the Labor Code.Guaranteed Wage It is a written agreement to pay an employee a guaranteed borderline amount regardless of the hours worked, with an extra half-hour premium for hours over 40. Piece Rate Plan It is a compensation plan whereby employee earnings depend on the units produced. Commission Plan Sales delegation plans vary greatly from company to company but are worldwidely based on the sales made during payroll period. Combination Plan This is a compensation method whereby employees receive a fixed amount of salary for each payroll period nonnegative an extra amount for production (piece-work) or sales (commission).Timekeeping Records Accurate timekeeping is an essential part of an efficient payroll system. Every business must have an bang-up method of recording the hours employees worked during the payroll period. The time records show the date and the time the workweek starts, the number of hours worked each day, and the total hours worked during the week. Time records are filed after the payroll is prepared and, in accordance with the requirements of the law, retained up to three years. The most common methods of timekeeping use a time clock with timecards or a time sheet.There are two primary reasons to maintain accurate payroll records. First, is the collection of the data necessary to visualize the com pensation for each employee for each payroll period. Second, provision of information needed to complete the various government report-federal and state- required of all employees. All business enterprise both large and small are required by law to withhold certain amounts from employees pay for taxes, to make payment to government agencies by specific deadlines, and submit reports on official forms. (McQuaig Bille, 2008). Other Aspects of Payroll Accounting SystemPayroll Register The payroll register summarizes employee earnings and deduction information in a journal entry that is inserted into the general ledger for accounting and general research purposes. Payroll registers are also used to create tax report. These documents are prepared by payroll lag or generated using payroll computer system. Payroll Services The meteoric success of payroll services is not accidental, but rather a reproval of the business communitys willingness to outsource the tedious and complex task of p ayroll accounting to outside specialists.The upside of outsourcing payroll is that payroll services secure that the company complies with laws pertaining to payroll. That is a big deal considering the time investment it would take the payroll officer to stay current on payroll-related legislation. Another big summing up is that payroll services are responsible for keeping track of each employees accumulated earning, tax withholding, and other information needed to issue W-2 forms at the end of the year.They also stay on top of things like direct deposits, salary adjustment, quarterly tax payments and all of the other details that can be distraction from the important chew over of leading the company (http//Gaebler. com/payroll-services, 8 Aug, 2010). In-house Payroll If contracting a payroll service does not sound like a good fit for a business, the management also has the option of doing it in-house. But if the management plans on saving money by personally administering the pay roll, having more alternatives will be a better idea. Even if the company only has a few employees, dealing with payroll-related details can be a waste of time.Instead, designating the job to an employee who can give it the time it requires so precious time can be dedicated to other things (http//Gaebler. com/in-house-payroll, 8 Aug, 2010). Whoever ends up doing payroll in the company will be happy to know that there is a lot of parcel out there to help them. In fact, most accounting software solutions have payroll modules. Start by assessing the capability of their current accounting software broadcast. If it does not have a built-in payroll function, chances are it is getable from the manufacturer as an add-on.If it is not, then the company needed to decide whether to change accounting to one that does or attempt to find a payroll program that is compatible with the current system. Either way, it is worth the time to find a computerized system that meets the companys needs rathe r than trying to do it the unfashionable way. Internal Control A regularises accounting and payroll functions are critical for the maintenance of a solid financial foundation. Accurate and punctual financial reports are crucial to administration and board decision-making.Payroll must be accurate, as it represents the districts largest budgeted expenditure. Internal controls must safeguard the districts assets from misappropriation. Payroll processing is an error prone activity. If organizations have just one or two employees it may seem relatively easy to compute salaries outstanding, taxes etc, but as small business starts adding employees they find spending more and more time in computation of salaries including variable pay. Errors are common in the full and final settlement and increases when employees join in the middle of a term as the processes are manual (http//ezinearticles. om/? expert=Mikael Anderson, 4 Aug, 2010).Waterhouse (2010) said in one of his studies that the o bjective of internal controls for payroll is to ensure that payroll disbursements are properly recorded and that related legal requirements (such as payroll tax deposits) are complied with. Segregation of duties is an effective internal control. The bank reconciliation clerk reconciles the bank accounts and is not involved in processing or approving items for payment. A payroll administrator, supervisor, specialist and six clerks perform the payroll function.The Human Resources Department (HRD) enters employee data into a database share by Personnel and Payroll and sets the rate of pay. The software system controls the ability of individuals to change information based on their access to the system. This prevents unauthorized individuals from changing this information (http//window. state. tx. us, 6 Aug, 2010). Gelinas, Sutton and Hunton (2005) included in their study some of the procedures that can be used to prevent or detect schemes. First is the direct deposit of payroll to elim inate alteration, forgery and theft of paper check.Second, is checking for duplicate names, addresses, and Social Security number in the employee data, finally is comparing actual to budgeted payroll. Expense Accounts are often an area of fraud and abuse. This include (a) using legitimate bread and butter from personal expense for the business expenses (b) overstating expenses by altering receipts (c) submitting fictitious expenses by submitting copies of invoices. Such abuses can be minimized by formulating reasonable policies that even employees for their out-of-pocket expenses.Copies of invoices should only be accepted in extreme circumstances. Finally, expense account activities should be monitored on a regular basis to detect unmatched patterns (Gelinas, Sutton Hunton, 2005). Payroll Fraud Connection Payroll, similar to cash disbursements, is an area ripe with fraud potential. After all, large organizations will make thousands of payments to employees for payroll and expens es account reimbursement every payroll period. Firth (2006) expresses that Payroll Fraud is an important issue that needs to be addressed by both Finance and Payroll professionals.Some of the key activities need to be considered include improving the quality of master file data, reviewing the end to end payroll process, and reviewing the people that are performing each step in the payroll function. It is worth remembering that improving each of these areas will not only reduce the risk of payroll fraud, it will also result in many other business improvements right across the organization. Here are some of the types of payroll frauds, along with the median loss for each to an employer (a) Ghost Employee, employees do not actually work for the company but receives paychecks.These can be recently departed employees or made-up persons (b) Falsified hours and salary, employees exaggerate the time that they work or are able to increase the salary in their employee date (c) Commission Sche mes, employees falsify the sales on which commissions are based or increase the commission rate in their employee date and, (d) False workers compensation claims, employees fake injuries to collect disability payments (Gelinas, Sutton Hunton 2005).

Wednesday, June 5, 2019

Tumour Supressor Genes and Retinoblastoma

Tumour Supressor Genes and RetinoblastomaThrough turn up our life time growth is constant. Barring a a few(prenominal) cadres, most mobile phones continue to grow, divide and replace themselves. Such processes require a strict command and this is brought about by cellular phone cycle processes. These processes ar carried out by proteins which control the growth and development. Proteins ar coded by the divisors and when the transmitted in get upation is altered or is mutated, it leads to a protein which is dys serve upal and the cell might pull back its prohibition on growth processes. This in turn leads to an uncontrolled growth of the cells which then causes squirtcer.Cancer is a disorder of the brokers. At a molecular train, there ar devil major reasons which build been attri nonwithstandinged for provokecer induction. The first star is the gain of function in brokers and the other one is harm of function of genes. The genes which gain function, that is, upri se activated after certain limited events ar known as proto-oncogenes. They be typically activated in croupecer cells conferring new properties, such as hyperactive growth and division, protection against programmed cell death, loss of contact inhibition between cells, and the ability to become established in diverse and adverse environments. Those genes which lose their functions due to specific events are termed tumor stamp outor genes (Eeles et al 2004). Tumor suppressor genes are inactivated in cancer cells, resulting in loss of normal functions, such as accurate deoxyribonucleic acid replication, cell cycle control, adhesion in spite of appearance tissues.Tumor suppressor genes are named such because when they are expressed in a normal cell they maintain the cell in a dissimilariated state and do non allow unchecked proliferation of cells. Therefore, at least one functional copy is take to prevent tumor initiation. That there are tumor suppressor genes was proposed w hen it was experimentally found by Harris et al. (1969) in cell spinal fusion experiments wherein a fusion between a normal and a tumor cell rendered the cell non-cancerous and therefore, it was proposed there must be tumor suppressor genes which suppress cell growth in a dominant fashion (Skapek et al, 1997). As long as the normal copy is functional, the protein expressed maintains normal functioning of the cells. umpteen tumor suppressors have been identified and extensively characterized. TP53, WT1, NF1, BRCA, VHL, APC, MEN1 are a few examples of tumor suppressor genes.Tumor suppressor genes are shared out into three categories- the gatekeepers, the caretakers and the landscapers. Gatekeepers are genes that directly regulate the growth of tumors by inhibiting their growth or by promoting apoptosis. In contrast, inactivation of caretakers does not directly promote growth of tumors. Rather, inactivation of caretakers leads to genetic instability that only indirectly promotes gro wth by causing an increased variety rate. Landscaper genes do not directly affect cancer cell growth but set up to an abnormal stromal environment that contributes to neoplastic transformation of the overlying epithelium.This project deals with one gatekeeper gene, known as retinoblastoma susceptibility gene (RB1). RB1 is the first tumor suppressor gene to be identified and cloned (Lee at al., Eeles et al, 2004 Andrade et al, 2006). It is the gene which when mutated predisposes a person to a harsh malignancy of the eye, retinoblastoma.Retinoblastoma is the most familiar intraocular cancer in children. It generally manifests in children before the age of five years with a majority of the tumors blow overring by the age of 2 years (Lee et al., Eeles et al, 2004).clinical features of retinoblastomaAs the name imp stays, retinoblastoma is one of the rare embryonic neoplasms originating in the retina. It is the most common intraocular tumor in children (Valverde et al, 2005). It wa s first described as a specific entity by James Wardrop. In majority of cases, the first sign at presentation is the characteristic cats eye reflex, which is usually noted by direct visualization. This white, pink-white, or yellow-white pupillary reflex, termed leukocoria, results from replacement of vitreous by the tumor or by a tumor growing in the macula.Another common symptom, strabismus or squint (exotropia or esotropia) can occur alone when small macular tumors interfere with the vision, or can be associated with leukocoria.Uncommon presenting signs for retinoblastoma are red, painful eye with alternate glaucoma, orbital cellulitis (infection of the soft tissues of the eyelids), unilateral mydriasis (excessive dilation of the pupil due to disease or due to trauma), and heterochromia (the iris of the cardinal eyes show different color).In rare cases, presenting symptoms include hypopyon (pus in the anterior chamber of eye), hyphema (blood in the anterior eye chamber), keratit is, and vitreous hemorrhage (Vogelstein and Kinzler, 2002).A complete rating for retinoblastoma includes ophthalmologic examination, radiographic evaluation (skull X-ray, CT scan, MRI), and more recently, genetic testing. Fundus examination of first degree relatives is overly done to look for the presence of retinoma or a regressed tumor which may place a patrimonial component of the disease.Retinoblastoma can be exophytic or endophytic. It is exophytic when tumor occurs between the choroid and the retina and it is endophytic when it extends from retina towards the vitreous chamber.Therapy depends on the stage at which it is discovered. Based on that, treatment is given which includes enucleation, external beam radiotherapy, cryotherapy, episcleral plaques, xenon and argon laser photocoagulation, and chemotherapy. The choice of treatment depends on the factors such asMultifocal or unifocal disease,Site and dimensions of the tumor, fan out or focal vitreous seeding,Age of the in dividual,Histopathological finding.Therefore, staging and grouping of the disease is very important.Retinoblastoma can manifest in one of the eyes, both eyes and / or pineal body of the brain. When it is observed in one eye, it is referred to as unilateral retinoblastoma. When it is present in both the eyes, it is referred to as bilateral retinoblastoma. It is called trilateral retinoblastoma when the pineal secretory organ is too involved.Why should retinoblastoma occur in one eye in some individuals and both the eyes in others? One more observation was that most of the individuals who came with retinoblastoma in both the eyes were diagnosed at an age earlier than those who presented with unilateral retinoblastoma. What is different in the genotypes of these two types of individuals that warrant a delayed onset of disease in the unilateral retinoblastoma cases? This was explicateed by Knudson in his study.Genetics in retinoblastomaRetinoblastoma occurs with a frequency of 1 in 1 3,500 (Mateu et al., 1997) to1 in 20,000 (Di Commo et al., 2000). It is seen in both hereditary and nontransmissible forms (Knudson, Lee et al.) and shows no significant variation between races, countries, or level of industrialization (Mateu et al., 1997). However, contradictory views have been expressed by Mastrangelo as he questions the believability of the data. Previous studies indicated that a gene predisposing to retinoblastoma manifests in young children was localized to chromosome 13. The gene was probably at band q14, since several retinoblastoma patients had shown to carry constitutional deletions of this constituent of chromosome 13.Retinoblastoma can be hereditary as puff up as sporadic. Those who have a mutation at one of the alleles of RB1 in germline cells are said to be predisposed to the disease. Such cases are categorized under hereditary retinoblastoma. Both hereditary as well as non-hereditary forms of retinoblastoma may show tumors in one or both the eyes. In the hereditary form of retinoblastoma, a germline mutation is transmitted as high penetrance (90%) autosomal dominant trait (Martinez et al). Most inform cases are sporadic (Knudson, 1971 Mateu et al, 1997).Retinoblastoma is caused by two mutational events at the retinoblastoma (RB1) locus (Knudson, 1971). That is, biallelic inactivation of RB1 due to mutations is a crucial event in the development of retinoblastoma (Andrade et al, 2006).Knudsons hypothesisAlfred Knudson realize the implications of the fact that individuals with hereditary bilateral retinoblastoma were diagnosed at a younger age than those children with non-heritable disease, mostly unilateral retinoblastoma. The mean age of individuals on diagnosis was found to be 19 months in unilateral retinoblastoma cases whereas it was found to be 5 months in bilateral retinoblastoma cases. Also, in most cases of familial retinoblastoma, tumor develops in both the eyes. To excuse these two important phenomena, age of onset and tumor development (unifocal or multifocal) in one or both eyes, Knudson proposed the two hit hypothesis.The hypothesis seeks to explain the occurrence of hereditary and nonhereditary retinoblastoma and its correlation with the age of onset of the disease. According to Knudson, the first mutational hit can be inherited through the germline or can be incarnateally acquired, whereas the sulfur occurs somatically in both cases and leads to tumor in cells that is double defective at the RB1 locus (Knudson, 1971 Mateu et al., 1997).Thus in case of hereditary retinoblastoma, the individual must have inherited the mutation through the germline and hence, during the course of development may show the second mutational hit leading to tumorigenesis. As this individual already has a mutation in germline, it shows the second hit early in the life time. Statistical analyses indicated that as few as two mutational hits were rate limiting for the development of retinoblastoma tumors. The occu rrence of the first mutation (M1) in the germline and all developing retinal cells gives retinoblastoma tumor a head deviate in hereditary cases (only M2 must arise in a retinal cell), compared to non-hereditary tumors where both M1 and M2 must arise in a single retinal cell.On the other hand, in unilateral retinoblastoma cases, the individual has not inherited a germline mutation at the RB1 locus. During the course of development, the cells of such patients gather both the mutations in somatic cells with some exceptions. Thus these tumors arise later than the hereditary forms of retinoblastoma.Knudson performed a statistical analysis of some patients presenting with retinoblastoma. The number of tumors in each eye was calculated and he devised a distribution keeping number of tumors in one eye, m= 3. Each tumor which is seen originates from a single cell. Thus, a mutation rate can be roughly calculated. If the total number retinal cells are n, m/n is the probability of a cell unde rgoing mutation at one of the alleles.Now, retinoblastoma is derived from the national and outer neuroblastic layer. The order of magnitude of retinoblasts is reflected by the magnitude of the number of ganglion cells which are derived from the early differentiated inner nuclear layer of the retina. The estimated number of ganglion cells has been put at 2 x 106 per retina. Thus, using this as an approximation for the total number of cells, the probability that a cell give inherit one mutation is 0.75 x 10-6. Since a majority of hereditary cases occur in the first two years of life, the probability expressed per year at either member of the autosomal gene pair would be one fourth of this value, or approximately 2x 10-7 per year. This estimates the rate of second mutation in mutated cells (Knudson, 1971). It is seen that the rate at which the second mutation occurs is relatively lower than the first mutational hit.Retinoblastoma in hereditary cases which present themselves as bilate ral retinoblastoma show high penetrance. In such cases, the vast majority of high penetrance mutations are null alleles where the mutations abrogates which destabilizes RB mRNA, presumably due to pre mature truncation of translation, so that no pRb is detected. However, some mutations show low penetrance. The low penetrance phenotype can result from several different types of RB alleles.Germline deletion of the whole RB gene often results in unilateral retinoblastoma, presumably because an unknown adjacent vituperative gene is also deleted, without which the RB-/- cell cannot survive. Only cells in which M2 is a different intragenic RB mutation on an allele with the adjacent critical gene liquid intact can survive to form retinoblastoma.Some mutations reduce view of wild type pRB by targeting the promoter or splice orders.In-frame mutations result in a stable pRB with some aberrant functions.THE RB1 GENEThe RB gene family includes at least three members- RB1, RBL1, and p130. The RBL1 and p130 also show similar protein vexing characteristics as RB1 and therefore they come under one gene family (Mulligan and Jacks, 1998). All three genes code for pocket proteins because their main taking over similarity resides in the pocket domain, which mediates actions with the cellular and viral proteins to exert biological functions of this family (Pogoriler et al., 2006). The RB1 gene has been localized on chromosome 13 of pityings on the long arm with locus 14.2 (Cavenee et al, 1971). The RB1 gene codes for a protein which is 928 amino group acids long. There are 27 exons in RB1 and occupies nearly 200 kb of the genome. The gene transcribes a 4.7 kb mRNA. The exon size varies across the gene. The largest is exon 27 which is 1892bp long while exon 24 has only 30bp in its exonic region (NCBI database www.ncbi.nlm.nih.gov/).Comings et al. suggested that RB1 is a tumor suppressor gene which is recessive at cellular level (Comings, 1971 Di Commo et al., 2000). The R B1 promoter present upstream of the exons does not show the typical TATA box binding domain. The promoter sequence of RB1 reveals that the sequence between -300 and +400 is GC fecund (Hong et al, 1989). As the promoter lacks a TATA element, it might explain the presence of three transcriptional initiation sites. Deletion analysis of the promoter by Hong et al demonstrated that the sequence stretching from +13 to +83 suffices the promoter activity. Another characteristic of the promoter region is that the G+C rich region shows similarity with many housekeeping genes (Hong et al, 1989). This outlines the fact that the RB1 gene is expressed constitutively in almost all tissues of our body.The Leiden Open source Variation Database (LOVD) maintains the reported mutations in the RB1 gene. Almost 940 mutations and polymorphisms have been reported in RB1 by many scientists (www.rb1-lsdb.d-lohmann.de/). Single base pair mutations are the most frequent M1 mutations and account for nearly 40% of the confirmed mutations, followed by short and large mutations. The second hit might be associated with loss of heterozygosity (LOH) mutations, promoter hypermethylation, or even a second independent base substitution (Andrade et al, 2006 Lohmann et al., 1996). The most common point mutation found in the studies is the change from CT at the CGA sites which codes for amino acid arginine. This change leads to premature termination of the protein (Lohmann et al., 1996).Expression of Rb proteinInitially, RB gene was considered to be expressed ubiquitously in all tissues of the body considering its role in maintaining cell differentiation (Karantza et al, 1993). However, later studies revealed differential expression of Rb protein.In situ intersection studies done with Rb expression during embryogenesis show, that the Rb family of proteins is differentially expressed in only certain specific cell lineages. According to studies, Rb1 mRNA transcripts were detected not only during in t he ganglionic cell layer of retina but also during neurogenesis, hematopoiesis, myogenesis, lens development prior to and during differentiation. In the liver and the CNS, RB1 is co-expressed along with p107 protein. Consequently, RB-/-, p107-/- cells undergo cell apoptosis. RB1 transcripts were also detected throughout myogenesis. pRB has also been found to be expressed during spermatogenesis (Yan et al, 2001).Since RB1 mutations specifically arise in the human eye, analysis has been performed for the developing eye. The results suggested that RB1 transcripts were detected in the ganglion cell layer of the developing retina from embryonic day 14 through 18 (Jiang et al, 1997). Preliminary studies had indicated that Rb expression in developing retina initiates as the cells commit to differentiation, but pRb has been detected only in certain subsets of retinal cells (Di Commo et al, 2000).In conclusion, pRb expression is important for final mitosis in peripheral nervous system, kera tinocytes, and skeletal muscles (Di Commo et al, 2000).THE RETINOBLASTOMA SUSCEPTIBILITY PROTEINThe RB1 gene transcribes a 4.7 kb mRNA which encodes a phosphoprotein which is 928 amino acids long. It is an example of a pocket protein as there are sites or pockets which interact with other proteins. The protein is a negative regulator of the cell cycle. The pRb migrates in SDS PAGE as a multiple, closely spaced bands with molecular weights between 110 and 114 kDa (Skapek et al, 1997).The pRb can be divided into three domains protease resistant, protease soluble and structural domains comprising of the N terminal figure, R motif, and A/B pocket (Di Commo et al, 2000).The N TerminalThe N terminal region extends from amino acid 1-379. Although the N terminal is well conserved among Rb orthologs and paralogs, it has been studied far less. However, a significant number of mutations in this region occur in retinoblastomas, strongly implicating it in tumor suppression. Another study by Goo drich et al, 2003, suggested that integrity of the domain is necessary for rescue from both developmental defects as well as tumor susceptibility. The crystal structure of the domain reveals a globular entity formed by two rigidly connected cyclin folds similar to the pocket domains which suggests that Rb evolved through domain duplication. A coherent conformation of the Rb holoprotein has been suggested in which the N terminal domain and the pocket domains interact directly (Hassler et al).The A/B domainThe pocket domain consists of two non consecutive stretches of amino acids, A (amino acids 380-577) and B (amino acids 645-785) (Xiao et al, 2003). It is coded by the exons 12 through 22 of the RB1 gene (Brichard et al, 2006). This region has been shown to interact with many proteins. This domain has been shown to be critical for many fundamental interactions of pRb including interaction with a variety of cellular proteins handle E2F transcription factor (extensively characterized) , tethering of pRb to nuclear structures (Skapek et al., 1997), phosphorylation during the G1 descriptor of cell cycle. Between the A and B domain is a small stretch of 75 amino acids, the spacer region. A small deletion within the spacer region or replacement of the spacer region with a random sequence has no effect on the function of pRb. However, deletion of entire spacer affects the physical interaction between the two domains.There is another pocket referred to as the C pocket domain in the large A/B domain of the pRb protein. This C pocket lies within the minimal functional domain of RB (Rb amino acids 395 to 876) (Whitaker et al, 1998).The C terminalThe C terminal stretches from amino acid 786 to 928. Of the sixteen sites for phosphorylation by cdks identified, six lie in the C terminal. It has been demonstrated that phosphorylation of S788 and S795 destabilizes the E2F complex interaction directly while phosphorylation of T821 and T826 induces an intramolecular interaction with Rb pocket that destabilizes the remaining interactions indirectly (Rubin et al.). The C terminal also contains a Nuclear Localization Signal (NLS) as well as cyclin binding motif R/KXL that are important for Rb phosphorylation (Di Commo et al, 2000).RB AND cellular telephone CYCLEpRB is a negative regulator of the cell cycle. The cell cycle consists of DNA synthesis (S phase) and mitosis (M phase) separated by two gap intervals, G1 and G2. When they are not cycling, cells are in a quiescent phase, G0, and extra- and intracellular signals are required to re-enter the cell cycle. Serum-starved cells in G0 will enter G1upon growth factor stimulation, and will return to G0 if mitogens are removed prior to a point in late G1. Beyond this restriction point (R) cells traverse through S, G2 and M, and will not stop even if serum is removed. There are two checkpoint controls which ensure proper cell cycle progression. The first one is referred to as the G1S checkpoint that ensures tha t there are proper environmental conditions for cell division. Importantly, many of the extracellular and intracellular signals that regulate passage through R point converge on the pRB pathway (Di Commo et al.) The second one is called as the G2M checkpoint which ensures that all the requirements for cell division are fulfilled.Fig Schematic diagram showing RB phosphorylation pathway. (1) E2F activity repressed in G0 phase imparting cell cycle inhibition. (2) Mitogens trigger a signaling pathway leading to activation of cdk 4/6- cyclin D, cdk 2-cyclin E complexes which in turn phosphorylate RB consecutive rendering it inactive. (3) E2F mediated gene expression allows progression through S phase. (4) During transition to mitosis, the action of mitosis reactivates RB to hypophosphorylated form.The regulation of pRB is by phosphorylation. Hypophosphorylated pRb is in its active form whereas on phosphorylation it loses its activity. The protein contains 16 CDK recognition motifs (S/TP ) for phosphorylation, six of which are located in the C-terminus (Rubin et al, 2005). Hypophosphorylated pRB binds target proteins and arrests cells in G1. This block is relieved by a crescendo of CDK-mediated phosphorylation that begins as cells in G1 approach R, and is abruptly reversed at the end of M phase.The major targets for hypophosphorylated pRB are E2F and co repressors such as Histone Deacetylases (HDACs). E2F belongs to a family of transcription factors who have evolutionarily conserved domains including the one for DNA binding and a dimerization domain. E2F is found as a heterodimer with another class of proteins- Differentiation Regulated Transcription Factors (DRTF-b). E2F-pRB co repressor complexes maintain the gene repression (Lees et al, 1993) that is required for progression through R, such as cyclin E. To pass this checkpoint, these repressor complexes are disrupted in two stages by the serial action of cyclin D and cyclin E activated CDKs.As cells exit G0, cyc lin D levels rise, causing activation of CDK4/6 and phosphorylation of multiple C-terminal sites on pRB (Gorges et al, 2008). The C-terminal region of pRB contains a serial of (R/K)XL cyclin docking motifs. Ser 795 is the first site to be phosphorylated, and is critical for inactivating growth suppression by pRB. Following D-CDK4/6 phosphorylation, the increase in negative charge promotes an intramolecular interaction between the C-terminus and a series of positively charged lysine residues (the lysine patch) that surround the LXCXE binding groove in the B domain of the pocket. Associated LXCXE proteins, such as HDACs, are also dislodged. However, E2F which does not use LXCXE motif to interact with the pRB does not dislodge. Removing HDACs is thought to relieve active repression of certain target genes such as cyclin E.The genes which are required for DNA replication like gene for thymidine kinase, DNA polymerase and dihydrofolate synthase are also activated as a result of phosphor ylation of RB1 and subsequent loss of interaction with E2F protein which now recruits other transcription factors. The cell thus enters the S phase. In the S phase of cell cycle, DNA gets replicated and synthesized. Histone synthesis also occurs during the S phase. erst DNA replication is complete, the cell enters another gap, G2 where the cell continues to grow till the cell enters the M phase or mitosis phase. Significant protein synthesis takes place during the G2 phase. Proteins like microtubules involved in mitosis stage are synthesized. At the end of the G2 is the G2/M checkpoint. Once it overcomes the second checkpoint, the cell enters actual cell division- mitosis.RB1 PROTEIN INTERACTIONS IN CELL prison cell cycle control at the G1 S checkpoint and growth suppression as well as differentiation into a particular subset of cell is considered the major function of RB1 protein. Transcription regulation is a control mechanism that is critical for fundamental processes such as cel l growth and differentiation. Proteins involved in transcription regulation either bind to DNA sequences or act as co-activators or co-repressors. pRb is one such transcription regulator.In accordance with its role as a tumor suppressor, introduction of Rb into Rb-/- cells diminishes their capacity for malignant transformation which underlines the fact that pRb plays a critical role in DNA replication, cellular senescence, differentiation, and apoptosis, placing pRb at the mettle of cellular proliferation and tumorigenesis through its interaction with various proteins.At least three lucid protein binding activities have been identified and extensively studied the large A/B pocket binds E2F (Benevolenskaya et al, 2005), the A/B pocket binds the LXCXE peptide motif, and the C pocket binds the nuclear c-Abl tyrosine kinase (Whitaker et al, 1998). Also, the protein also stabilizes the heterochromatin to maintain the overall chromatin structure. The C pocket is distinct from the A/B po cket domain as pRb can simultaneously bind to c-Abl as well as E2F (Whitaker et al, 1998).The A/B domains are adapted for E2F subunit binding to Rb. However, the E2F-DP1 heterodimer requires the presence of C terminal. The retinoblastoma protein inhibits E2F mediated transcription via two distinct mechanisms- 1.) pRb binds to E2F transactivation membrane and inhibits E2Fs ability to promote transcriptional activation of E2F dependent genes. 2.) pRb actively represses expression of certain genes by recruiting HDACs and other chromatin remodeling factors (Gorges et al, 2008). The C terminal has also been shown to bind to MDM2. MDM2 interaction with the extreme C terminal region has therefore been shown to contribute towards regulation of apoptosis (Janicke et al., 1996 Sdek et al, 2004). MDM 2 has been known to stimulate E2F transactivation activity and promote S phase entry of cells, independent of p53 (Sdek et al., 2004).The retinoblastoma tumor suppressor protein has been known to bind directly and inhibit a transcriptionally important amino terminal kinase domain of TATA- binding protein associated factor TAFII250 (Siegert et al., 2000). TAF II250 is the largest of approximately 10 TAF subunits of Pol II specific human TFIID. It directly binds to TBP and is believed to be a central scaffold for assembly of TAFs and TBP into a stable TFIID complex (Siegert et al., 2000).The retinoblastoma protein interacts even with transcription factors ATF2. ATF2 enhances the activity of TGF promoter. The retinoblastoma protein also enhances the stimulatory effects of ATF 2. The site on Rb required for its effect alone and in combination with ATFs has been mapped mainly to A/B products and the C pocket (Li and Wicks, 2001).It has been also reported that the amino terminal of BRCA 1 can efficiently bind to the ABC region (from amino acids 379-928) of the Rb protein. It has been shown that growth suppressor activity of BRCA1 takes place only in presence of a functional Rb p rotein (Aprelikova et al., 1999).pRb has been known to interact with proto-oncogene c-jun. One of the transcriptional modulator target sites of pRB is the AP-1 binding site within the c-jun and collagenase promoters. c-Jun also physical interacts with pRb where the C terminal site of leucine zipper interacts with pRb (Nishitani et al., 1998). pRb also represses the expression of c-Fos gene the gene product of which , Fos, is one component of the heterodimeric transcription factor, AP-1. Thus, pRb can be functionally linked to c-jun for transcriptional regulation.pRB when recruited to DNA via E2F is a potent transcriptional repressor due to its ability to recruit HDACs (Kennedy et al., 2001) and histone methylases. Again, one pRB binding protein, EID1 is a potent inhibitor of histone acetylases, p300 and CBP and blocks differentiation (Benevolenskaya et al.). HDACs interact directly with pRB by gist of a LXCXE motif (Kennedy et al., 2001 Gorges et al., 2008).p53 controls phosphoryla tion of pRB in a cell indirectly. On DNA damage induces the transcription of its target gene p21WAF1/CIP1. The p21 protein thus formed binds to two different proteins. First, it inhibits the activity of CDKs in cell which in turn keeps pRB in active state. Thus, p53 helps in negative regulationof cell cycle. Second, the p21 protein interacts with the PCNA which then leads to inhibition of cell cycle (Hsieh et al, 1999).androgenic hormone receptors show a unique interaction with pRb at the N terminal. Over expression of pRb leads to increased transcription activity of androgen receptor, AR. pRb also potentiates the activity of glucocorticoid recptors, GR. However, loss of pRb activity inhibits AR but not GR activity (Lu and Danielsen, 1998).MUTATIONS IN RB GENEAfter RB1 gene was first cloned by Friend et al in 1986, mutations have been identified in the gene ranging from single base pair deletions, to small length insertions and deletions (Lohmann et al. 1996, Andrade et al. 2006). T he mutations do not show any hotspots and they are widely distributed over the 27 exons of RB1 as well as the promoter region (Dalamon et al. 2003).The most common mutation found to result in predisposition to retinoblastoma is the point mutation from CT. At times the mutation at this point changes the codon from CGA to TGA, from Arginine to stop codon. This premature truncation of protein leads to abrogated expression of pRb in cells.Hypermethylation of RB1 promoter has been also observed as a common epigenetic event in certain tumors (Gonzalez- Gomez et al., 2003).Retinoblastoma Gene Mutation database (RBGMdb) maintains a comprehensive list of all mutations in the RB1 gene. Till now, 932 mutations have been reported in the RBGMdb. Most of the mutations are nonsense mutations (42%).However, if recurrent nonsense mutations are not considered, the percentage comes down to 18%. RB1 mutations are illogical all along the genomic sequence. However, there are a few hotspots which show h igh recurrence. Most of the recurrences correspond to CT changes in the sequence. Out of 351 nonsense mutations 271 (79%) are CT transitions in eleven CGA (arginine) codons, in exon 8, 10, 11, 14, 17, 18, and 23. No mutations have been found in the three other CGA codons in exon 1 and 27.In four of the mutated CGA codons, R251and R255 in exon 8, R451 and R455 of exon 14, a high frequency of constitutive hypermethylation has been demonstrated. In addition to hot spots, frameshift and point mutations leading to translational changes or splice site mutations are scattered along the retinoblastoma coding region and non-coding adjacent splicing sites. With the exception of exons 5, 14, 15, 24, 25 and the non-mutated exons 26 and 27, frameshift mutations are randomly distributed through the RB1 coding sequence.Splicing mutations are also evenly distributed, but show preference for intronic sequences adjacent to exons 6, 12, 16, 17, 19 and 24. It is worth to mention that most missense subs titutions (60 %) are located in cyclin box B, underlined by exons 19 to 21.

Tuesday, June 4, 2019

Semi-structured interviews | Analysis

Semi-structured consultations AnalysisAn exploratory use of semi-structured interviewsIntroductionThis essay reports my understandings of interview as a qualitative enquiry method acting and the experience of an exploratory use of it. Considering the broad research atomic number 18a of my PhD study, learning and assessment, the key knowledge I am going to reveal bequeath be learners witness perceptions of their learning. Some data could credibly be excavated from the products of their learning, such(prenominal) as learning logs, workbooks, or teachers feedbacks, that indicate their experiences and evaluations of their learn. If the data are insufficient, however, I have to carried pop interviews to gather the data needed. As a result, I chose semi-structured interview as the method I would try out for this assignment. The usability of semi-structured interviewsThere are m each types of interviews which are differentiated by how much the interviews are structured and how many tellicipants are involved in one interview (Fontana Frey, 2000 Punch, 2005). Although interviews are basically affecting questions and receiving answers take the media of language, different types of interview are based on different assumptions (Punch, 2005, p. 169). Mason (2002, pp. 63-66) points out that the choice of semi-structured interviews is probably an indicator to the following beliefs and reasonsPeoples understandings, feelings, perceptions and other inner thoughts as well as the interactions with other plurality are parts of the social naive realism.This reality could be revealed by representations and interpretations through language.What has been revealed is situational knowledge which will be to a greater extent likely to be reconstructed under its due background. In appropriate design, the desired context could be brought into the interview conversations.Qualitative interviews do non condition to standardise however to achieve more in terms of depth, nuanc e, complexity, and roundedness of what is to be unders to a faultd.Interviewing is a process of data generation and the interviewer plays an active and reflexive billet in it.Interviewees should have more controls and freedoms throughout the interview interactions. Taking Masons view, if a research shares part or all of the above descriptions, it would find appropriate to employ semi-structured interviews as a data generation method. The exploratory inquiry I have carried out is just now one of these cases.Conducting the interviewAfter listening to me public lecture about my teaching experiences in and viewpoint on Taiwanese schools, a British fellow student, George (name changed) said he believes that there should be different types of schools. This solution kindled my curiosity because he was the third British the great unwashed who concluded our conversation in such idea that quickly transcends the dichotomy of faithful or bad. This rarely happened while I was involving in similar conversations in Taiwan. I wonder how his belief on education was formed. So I invited him to participant my interview, and he agreed.The themes and the participantsI chose this theme and this participants to interview based on a pragmatic consideration. There are limited people conveniently available to be interviewed by me and there are also a few themes related to my research, but it will be a important inquiry only if any of these people has roughthing to say about any of those themes. When they are matched, the interview is more likely to be made enjoyable to the participant and, thus, will be more ethical, too (Mason, 2002). My invitations of interview had been refused twice until I luckily identified the current participant matched with the current theme.Questions for the interviewI then made a plan of interviewing consisting with leash parts. At the beginning, I would remind George of our previous conversation by recapitulating it. After confirming that he remembe red it, too, I would raise my initial question what did you mean exactly by I believe there should be different kinds of schools in our previous conversation? I expected this question to bring back the context of our previous talk, and clarify his own interpretation of that expression.Secondly, I would explain that the key question of this interview is how do you cogitate this belief was form? And I would ask go on questions according to Georges responses explore more deeply until the answer satisfies me or noting a scent of Georges having nothing or not willing to go further on this topic.Finally, I would invite him to comment on one the Summerhill School, as well as to estimate how many British share similar beliefs with him by his own perception. I expected his commenting on one of the most extreme cases of schooling in England and self-positioning among others could help me revealing more of his stance of educational philosophy. arrangementI have also considered the technique used to record the interview. The choice of recording method was subject to both the availability of equipment and the purpose which the interview would be analysed for. Considering that the interviewee would be reflecting on his comment on my previous talk from the aspects affected by my questions, the content of the interview conversation would probably not exist nonetheless and I would be involved in the process of its generation. The value I hold prior to the interview would oblige my aspect to perceive the conversation and. Therefore, I need the spoken words and their sequences in the conversation to be recorded independently from my judgement. I thought a voice recorder would do the furrow well. Voice recording, like other recording method, could only partially record the interview (Mason, 2002 Silverman, 2001), nevertheless, the voice record could be replayed as many times as I need and it also relieves the original sequences of conversation which set each single sentence into the context (Silverman, 2001). That would enable me to analyse the conversation with perspectives that I was scarce to have while interviewing.InterviewingThe interview was taken place in the ground floor at 35 Berkeley Squire with coffee and snacks during lunch time and lasted about 30 minutes.After some small talk, a common start of interviewing (Bogdan Biklen, 2003), I turned on the voice recorder, shifted the topic to the conversation we had had and asked him to explain more about what he meant by I believe there should be different types of schools?His answers are firstly that no child is the same some children will do better in one sort of schools and secondly that if you got lots of schools, you got lots of experimentsassuming you can compare them then you can get some evoke findings. In the UK we have lots of different schools within our education, and that difference will not be necessarily a bad thing, that could be a good thing. Then, when I asked about how his belief was formed? He give me a general, rational description of the advantages of having various types of school. This though provided a deeper explain of his thought but still not sufficed what I was seeking for, so I asked him in another counselling that in what age you began to see education in this way?Instead of answering my question, George wondered whether I wanted to put his thoughts in the very personal context. After my affirmation, he then continued to tell me that he has followed his own way since quite early age. He chose to teach, which most graduate and also his family wont considered as a good job, in the UK and soon went to teach in a developing country.How early do you mean by quite early age? I asked.Probably sort of I went to secondary school, he said, its your education environment encourages sorts of ways of thinking.Are there any one else told you about this sort of ideas? I followed.I was in a boarding school and we had what we call house master I have qui te lot of contact with this person, he told us not to accept what the state or other people said without questionsthis has the impact on me and other people he answered.Since he mentioned the boarding school, I then jump and ask him about his opinions on Summerhill school which was in the third part of my original plan.Though he made it clear that I am not saying that Summerhill should be closed or any thing like that and I have not been to the Summerhill school so I cant comment on it, he maintained that I think children need to be systematically taught if children just be left too do what they want to do for children who have certain personality that could be in the main quite good thing, for other children it could be absolutely disaster there is sort of children need quite lot of structure.I have sensed that George was qualification the judgement based on some tacit value which was slightly different from the articulated beliefs. This added more tense into our conversatio n and made it more meaningful to me. So I pointed this difference out and shared my experience of similar discussions in Taiwan.Responding to my comment, George raised a new topic. Despite many developing countries, probably including Taiwan, blindly copy the western education into theirs, there must be some good in theirs that worth the western educations to learn. We talked about this topic for a while ( that was very interesting, too) then I ask him the final question about his estimation of how many British share similar views with him.Experience of this interviewMy question has been answered satisfactorily by this interview in most extent, and there are several things I can learn from it. My experiences superpower be arrange into the following two aspects.PreparationsCarefully preparations in advance are helpful and essential. I order that to acquaint my self with the theme, including the plan of asking questions, the relevant cases such as the Summerhill school and my exper iences in Taiwan, have indeed facilitated the management of the conversation to involve the participants as much as possible but still keep it focused. Voice recorder also need to be tested in advance. I found my voice recorder set in a amiss(p) mode which ruined the first ten minutes of my recording and I had to interrupt to conversation and corrected it.Interviewing as a conversationSemi-structured interviews are not just data collection tools but data generation events. I assumed that my experiences in Taiwan and perhaps my attitude toward these experiences triggered our discussion on copy education from other countries. If I did not share these experiences, I would probably get different interview data.Apart from the interviewer, the interviewee has his own intention in the interview conversation. George wanted to know what these questions for (thus he confirmed my research context before answering) and he also has assumptions about how I might interpret his words (thus he main tained his scepticism over the uncritical appreciation of western education).In this point, I would agree what Bogdan and Biklen (2003) suggest on an effective and comfortable approach to do interviewing explain to the interviewee all necessary information about myself and my inquiry like we might do to an expert. This will facilitate the understanding to the others of both participants, which is the centre part of interviews. and give the interviewee more control over how his view was understood, which could be seen clearly in my case. Conclusions From the exploratory interview and several interview related chapters (Bogdan Biklen, 2003 Fontana Frey, 2000 Mason, 2002 Punch, 2005 Silverman, 2001) , I found semi-structured interviews as a qualitative research method is good ata) revealing peoples knowledge, views, understandings, interpretations, and experiences (Mason, 2002, p. 63) , especially their situational aspectsb) giving interviewees opportunities to actively participate i n and have some control over the interviews. However, when involving interviews, it is worth being cautious that a) the power (or other kinds of) relationship(s) between interviewer and interviewee have to be counted as part of the context which the interviews has been set in, otherwise, it might turn up with unexpected or even distorted resultb) one to one interviewing has some but limited ability to create a desirable context, particularly, in researches looking at peoples interactions or how people respond in social context, where group interviewing might be a more in good order approach.c) interviewees might just say what they want to let us know rather than what we intent to know d) the represent-ability of any reality might be constrain by the capability of language of both interviewers and interviewees and, when looking at those past things, affected by the accuracy of interviewees memory. The complexity of the connection between language and reality is itself also an issue needs further inspections.e) method of interview has little validity over peoples behaviour which might more appropriately be self-contained by observations or document analyses.REFERENCESBogdan, R. C., Biklen, S. K. (2003). Qualitative research for education An introduction to theories and methods. Boston Allyn and Bacon, Inc.Fontana, A., Frey, J. H. (2000). The interview From structured questions to negotiated text. In N. K. Denzin Y. S. Lincoln (Eds.), Handbook of qualitative research (2nd ed., pp. 645-672).Mason, J. (2002). Qualitative researching. London Sage.Punch, K. (2005). Introduction to social research Quantitative and qualitative approaches. London Sage.Silverman, D. (2001). Interpreting qualitative data methods for analysing talk, text and interaction. London Sage.

Monday, June 3, 2019

Study of Impact Shocks in Fencing

Study of conflict Shocks in FencingAbstractFencing is a superior in gosity sport involving participating movements which expose the musculoskeletal system to high uphold indexs that may lead to overuse injuries. One of the most frequently utilize high mend movements is the lunge. With many diametrical types of sports footwear available providing different levels of midsole cushion, selecting the most worthy for a sport may be a promoter in preventing the onset of injury. The aim of this study was to investigate the magnitudes of the passing(a) axial match break experienced at the tibia amid traditional enclose garment and standard athletic footwear during the impact phase of the shut in lunge. Peak tibial electrical shock absorber was measured in 19 male fencers in 4 different footwear conditions using an accelerometer placed on the distal aspect of the tibia. The standard footwear resulted in significant reductions in peak impact shock in comparison to the tr aditional inclose shoes. Thus the reduction in impact shock found suggests that running or squash specific footwear may lessen overuse injury occurrence. However, despite this, the majority of thespians indicated that they preferred close in specific footwear for fencing. The results of this study suggest that at that place is acknowledgment for a re-design of fencing shoes.IntroductionCompetitive fencing (foil, sabre and epee) has experienced a rapid increase in participation rates during the past ex (Harmer, 2008). The sport places unique demands on the athlete and is characterised by asymmetry and the incidence of rapid motions which have the potency to generate large forces (Geil, 2002). In particular, the frequently utilise lunge which is the basis of most struggle motions is a high impact movement (Kopetka Stewart, 2005).The expansion in participation combined with the biomechanical demands of the sport has led to deepen awareness of the incidence of injuries ass ociated with fencing. Nonetheless, prospective, epidemiological studies of the incidence of repetitive strain and overuse injuries in fencing are scarce. As a result, it is difficult to draw unafraid conclusions regarding the etiology of fencing injuries and their prevention based on impartial discipline (Roi Bianchedi, 2008). However existing studies indicate that overuse injuries account for approximately 30% of injuries that intermeddle with training (Carter et al., 1993). The majority of injuries are confined to the pooh-pooh extremities (e.g., stress fractures, impingement enthesopathies of the patellar tendon and tibia and plantar fascia) associated with fencing (Harmer, 2008, Wild et al., 2001 Zemper Harmer, 1996) characteristic of dynamic activities involving high f number change in momentum actions (Harmer, 2008).No apparent selective information has been published providing information regarding the total number of lunges executed during a free-enterprise(a) bout. However, Roi and Bianchedi (2008) suggest that there are anywhere mingled with 66 and 210 attacks (depending on the weapon) during a competition, which given the lunges function as the most common attacking mechanism, it appears that fencers leave behind be regularly subjected to the impact forces imposed by the lunge.One of the characteristics of the foot impacting the surface during a lunge is a rapid change in amphetamine of the foot and this velocity r apiecees zero upon foot placement in a short period of time (Whittle, 1999). This impact leads to the transmission of an axial transient shock wave through the body and carries with it the potency for injury. It is important to recognise that loading is indispensable for maintenance of cartilage, bone, and muscle health (Stone, 1988). An optimal loading window for waver strength can be characterized by frequent impacts of certain magnitude, duration, and frequency. Movements beyond the optimal loading window can lead to the breakdown of body create from raw material and overuse injuries (Hardin et al., 2003).The magnitude of the impact shock is commonly measured using accelerometers. Accelerometers are traditionally placed onto the skin superimposed the tibia to quantify the transient impact shockwave during motion. Despite the consensus that soft tissue interferes with the acceleration recording of underlying bone, the utilization of skin mounted tresss is considered appropriate provided they are lightweight and rigidly accustomed to the overlying skin (Shorten and Windslow, 1992). This method has been used to examine the cushioning properties of athletic footwear (Lake Greenhalgh, 2005) and better differentiates between impact conditions compared to data acquired using a force platform (Lafortune Hennig, 1992). The high impact constitution of the lunge implies that the lower extremities may be at risk from overuse injuries.To date there is no information available regarding the potentially de trimental aftermath of the impact accelerations experienced during this movement. However, epidemiological studies suggest that a relationship exists between the magnitude of the transient shockwave and the etiology of a number of lower extremity overuse injuries (Nigg Segesser, 1992). Therefore with a significant number of lunges being undertaken by a fencer and the potential connection between the magnitude of the impact shockwave and the incidence of overuse injuries makes it important to investigate the shock attenuation properties of fencing footwear.The 1992 U.S Fencing Association review of the factors that may contribute to fencing injuries indicates that of the three primary areas for prevention, deficient equipment and facilities may be responsible for as many as 28% of the injuries associated with fencing, with ineffective footwear forming a significant grammatical constituent (Carter et al., 1993). The review noted problems with fencing shoes citing in able cushioning as well as the lack of footwear designs that could shield against the high impact nature of the sport, particularly lunging. To reduce injury, Zemper and Harmer (1996) have suggested a redesign of fencing shoes.The primary function of athletic footwear as described by Stacoff et al., (1988) is to provide shock attenuation. The properties of athletic footwear have been linked to the prevention of overuse injuries. With many different types of sports footwear available providing different levels of midsole cushioning, selecting the most suitable for a sport can be vital in preventing the onset of injury. Fencing equipment retailers in the UK offer very few options for specific footwear, with only 2 major brands on offer (Adidas and Hi Tec). It also appears that the fencing shoe has been more than(prenominal) specifically designed for the function of the trail foot to enable good grip on the piste as well as maximising the life span of the shoe if dragging the back foot, which is com mon in fencing.The limited availability of specific shock attenuating footwear to the fencer may predispose fencers to overuse injuries. The majority of studies analyzing the enamour of different footwear conditions on impact kinetics have focused on running.Therefore, the aim of the present study was twofold. First, to assess the magnitude of the peak axial tibial transient accelerations associated with the lunge in fencing to provide practitioners with information regarding the potential examples of injury. Secondly, to compare two specific fencing shoes with two standard sports shoes (running and squash) with regards to their shock attenuating properties during the lunge movement.In particular, it was predicted that peak axial transient accelerations were lower in shoes which have been particularly developed for shock absorbing qualities (running and squash shoes) in comparison to fencing shoes during the stance phase of the fencing lunge.MethodsParticipantsNineteen male (17 ri ght handed and 2 left handed) competitive fencers with a minimum of 2 years experience (Age 25.6 + 8.3 years Height 1.78 + 0.5 m Weight 76.8 + 9.0 kg) comprising a mixture of the foil (n=2), epee (n=15) and sabre (n=1) disciplines, volunteered to take part in this study. All were injury free at the time of data ingathering and completed an informed consent form. The procedure was approved by a university ethical board.MaterialsEach participant was fitted with four pairs of shoes for the study. The shoes were the same for each participant they differed in size only (sizes 9 and 10 mens UK sizes) and consisted of a conventional running shoe (Saucony Grid forum), squash shoe (Hi-Tec squash indoor) and fencing shoes (Hi-Tec blade) and (Adidas en guard). A tri-axial (Biometircs ACL 300) accelerometer sampling at 1000Hz was utilized to measure axial accelerations at the tibia. The device was mounted on a piece of lightweight carbon-fibre material. The combined weight of the accelerometer and mounting instrument was 9g. The voltage sensitivity of the signal was set to 100mV/g, allowing adequate sensitivity with a measurement range of 100 g.The device was attached securely to leading pin on the distal anterio-medial aspect of the shank 8 cm above the medial maleolus in alignment with its longitudinal axis.This location was selected as the boniest prominence of the distal tibia in accordance with the Nokes et al., (1984) conclusions to improve the mechanical coupling of the accelerometer mounting to the tibia and reduce artefact over callable to interposing soft-tissue. The accelerometer was positioned so that acceleration was measured in the direction up the tibia (Figure 1). Strong adhesive tape was placed over the device and the lower leg to avoid overestimating the peak positive acceleration due to tissue artefact. The device was attached as close to the tibia as possible, the skin on overlying the bone itself was stretched thus ensuring a more rigid coupling b etween accelerometer and tibia. Furthermore, adhesive tape was positioned over the device itself to ensure it was maintained in a fixed position along the longitudinal axis of the tibia. The acceleration signal was sent to a Biometrics data logger with a 2 GB memory card. The data logger was fastened securely to a lightweight backpack to reduce movement of the device during trials.ProcedureThe fencers completed a suitable warm-up and were allowed two minutes to familiarize themselves with the experimental protocol and footwear condition prior to the commencement of data collection. They were then required to complete ten lunges hitting a dummy with their weapon in each footwear condition whilst returning to a starting point (pre-determined by each participant prior to the commencement of data capture) following each trial to control lunge distance. Each trial was comprised of a lunge where contact between the brand name and dummy defined a successful outcome. The starting point for the movement was adjusted and maintained. The order in which the different footwear conditions were worn was randomized. Upon conclusion of the data collection participants were asked to subjectively indicate which shoe they preferred for fencing.Kinetic data was quantified/processed using Biometrics data-log software. The stance phase of each trial was acquired from each accelerometer signal for epitome. Peak positive axial tibial acceleration was defined as the highest positive acceleration peak measured during the stance phase after(prenominal) a 60Hz 1st order low pass filter had been implemented in accordance with the Lake and Greenhalgh (2005) recommendations.The mean values of the footfalls per participant/condition for the axial part of the acceleration signal was quantified and used for statistical analysis. Descriptive statistics were calculated for each variable including means and standard deviations. Differences between footwear conditions were examined via a within subjects iterate measures analysis of variance with significance accepted at the pResultsA statistical power analysis of pilot data was conducted in order to reduce the similarlihood of a type II error and determine the minimum number of participants needed for this investigation. It was found that the sample size was sufficient to provide more than 80% of statistical power in the experimental measure. Figure 2 provides the mean and standard deviations for the peak tibial accelerations for the four different shoe types. The Mauchlys globularness assumption was violated and as such the degrees of freedom of the F statistic was adjusted via the Greenhouse Geisser chastisement. The Shapiro-Wilk statistic for each footwear condition confirmed that the data was normally distributed. The analysis of variance was significant (F (1.97, 35.52) = 16.31 P DiscussionThe aim of this study was to determine the differences in the magnitude of the transient acceleration between traditional fenc ing shoes and standard athletic footwear during the impact phase of the fencing lunge. The results of this study support our hypothesis, in that the magnitudes of the axial impact shockwaves were significantly lower in two the running and squash shoes compared to the traditional fencing footwear.The transient shockwave is linked to the development of a variety of overuse injuries (Whittle, 1999). It is essential to acknowledge the link between the magnitude of these forces and overuse injuries, as the frequency of these conditions can be reduced by attenuating the impact magnitude (Whittle, 1999). Therefore the significant reduction in impact shock found would suggest that running/squash footwear may assist in the reduction of overuse injury occurrence.Interestingly, despite the higher impact magnitude and concerns regarding the potential development of overuse injuries, the majority of participants indicated that they preferred fencing specific footwear for fencing. This finding a grees with those of Geil (2002) who hypothesized that this finding centred on plantar sensory proprioceptive mechanisms, whereby the feel of the fencing piste underneath the foot is reduced in shoes that offer a high degree of midsole cushioning. Geil (2002) suggested that footwear may influence fencing performance. They noted that increased midsole cushioning and travel of the foot during compression may lead to slower motion of the feet, which in turn could contribute to diminished velocity of the weapon hand, reducing the overall execution quality of the movement itself.Based on these findings it appears that midsole cushioning properties should play only a partial role in the design characteristics of an effective fencing shoe. Fencing involves a number of movement strategies in addition to the lunge, and as such shoe designs must cater to this. Fencers like most athletes require sure footing during competition as such footwear designs must deliver adequate traction to provide s tability during lunging, attacking and retreating motions. Furthermore, the medial forefoot of the trail shoe is an area traditionally subjected to high abrasion forces and thus heavy wear. Manufacturers should therefore focus attention on developing more resistant materials for this purpose to prolong the lifespan of the shoe. Whilst shock attenuation is the primary function of midsole cushioning, the elastic energy stored and recovered by cushioning systems has been proposed as a mechanism by which the oxygen cost of movement can be reduced. Given the aerobic demands the sport of fencing places on the athlete (Roi Bianchedi, 2008) additional research should focus on this factor as it may serve to slow the onset of fatigue and improve performance.The results of this study however, suggest that there is some justification for the Zemper and Harmer (1996) recommendations regarding the re-design of fencing shoes due to the demonstrated high transient impact forces on the front foot during the lunge. The primary design dilemma facing footwear manufacturers is to include features that would serve to attenuate the large impact forces and help reduce overuse injuries. At the same time, the design characteristics should also provide the fencer with an adequate feel for the fencing piste beneath the foot.The severe angle between foot-segment and ground on initial contact is also significant when designing the shoe. The shoe cushioning system must therefore provide protection in the extreme rear of the heel, an area not normally associated with consistent high impact forces in other sports. The obvious asymmetry of the sport presents a challenge to footwear manufacturers and arguments can be made for the development of asymmetrical footwear designs.Several different surfaces in fencing are used. Surface stiffness can have a significant influence on the magnitude of the impact shock during landing (Kim et al., 1994). This study was conducted during training session s on a training surface as opposed to a traditional piste used during competition thus the results obtained may not adequately represent actual competition. During competition a hard floor can be used, as well as a metallic piste (either a cloth placed over the hard floor or a hard metallic piste). Future research should therefore concentrate on the magnitude of the impact shock during competition on a true fencing piste.LimitationsAccelerometry is a complicated approach and methodological problems can affect the efficacy of tranquil data (Lake and Greenhalgh 2005). The magnitude of the signal obtained from the accelerometer is dependent on the mounting interaction, making cross study comparisons difficult. Soft tissue artefact can also influence the acceleration recording of underlying bone (Light et al., 1980). Attaching the device directly to bone represents the most accurate method of measuring impact shock and further break is necessary to determine the efficacy of the less t raumatic skin mounting technique.The device signal is also reliant on the centripetal acceleration due to angular motion of the shank in the sagittal plane during ground contact (Lafortune and Hennig 1991). Lake and Greenhalgh (2005) noted that despite the application of a distally mounted device, correction for angular motion may still be necessary. Further research should be conducted to investigate the necessary signal corrections for angular motion.Another potential limitation/restriction of this study is that the results obtained are entirely specific to the footwear and ground surface conditions, any variation in these parameters would most likely cause changes to the participants fencing kinetics/kinematics. In addition this study analyzed the lunge motion only. The lunge represents a high impact motion however there are other movements of lower intensity which may still be important in terms of the development of overuse injuries. Therefore, additional research is necessary regarding the influence of footwear on the magnitude of the transient shockwave during different fencing movements before appropriate prescriptions of fencing footwear can be made.ReferencesCarter, C., Heil, J., and Zemper E. (1993). What hurts and why information from the 1992 USFA Fencing Injury Survey shows some common culprits. American Fencing. 43, p 16-17.Geil, M.D. (2002). The Role of Footwear on Kinematics and Plantar Foot Pressure in Fencing. ledger of Applied Biomechanics, 18, p 155-162.Harmer, P.A. (2008). Getting to the point injury patterns and medical care in competitive fencing. Current Sports Medicine Reports. 7, 303-307.Kim, W., Voloshin, A.S., and Johnson S.H. (1994). Modelling of the heel strike transients during running. human Movement Science, 13, 221-244.Kopetka, B., and Stewart, S.L. (2005).The kinematic determinants of speed in the fencing lunge. (Part 1). Journal of Sports Sciences, 2, 105.Lafortune, M., and Hennig, E. (1991). Contribution of angular mot ion and gravity to tibial acceleration. Medicine and Science in Sports and Exercise, 23, 360-363.Lafortune, M. A., Hennig, E. M. (1992). Cushioning properties of footwear during walking accelerometer and force platform measurements. Clinical Biomechanics, 7, 181-184.Lake, M.J. (2000). Determining the protective function of sports footwear. Ergonomics, 43, 1610-1621.Lake, M.J., and Greenhalgh, A. (2005). Impact shock measurements during running correction for angular velocity of the shank is necessary. minutes of the 7th Symposium on Footwear Biomechanics. Cleveland, Ohio, USA.Nigg, B.M., Segesser, B. (1992). Biomechanical and orthopaedic concepts in sport shoe construction. Medicine and Science in Sports and Exercise, 24, 595-602.Nokes, L., Fairclough, J.A., Mintowt-Czyz, W.J., Mackie, I., and Williams, J., (1984). Vibrational analysis of human tibia The effect of soft tissue on the output from skin mounted accelerometers. Journal of Biomedical Engineering, 6, 223-226.Roi, G.S., and Bianchedi, D. (2008). The Science of Fencing Implications for Performance and Injury Prevention. Sports Medicine, 38, 465-481.Shorten, M.R., and Winslow, D.S. (1992). Spectral Analysis of Impact Shock During Running. International Journal of Sports Biomechanics, 8, 288-304.Stacoff, A., Denoth, J., Kaelin, X., and Stuessi, E. (1988). Running injuries and shoe construction some possible relationships. International Journal of Sport Biomechanics 4, 342-357.Whittle, M.W. (1999). The generation and attenuation of transient forces beneath the foot a review. Gait and Posture, 10, 264-275.Wild, AM., Jaeger, C., Poehl, C., Werner, A., Raab, P., and Krauspe, R. (2001). Morbidity profile of high performance fencers. Sportverletz Sportschaden, 15, 59-61.Zemper, E.D., Harmer, P.A. (1996). Fencing. In D.J. Calne, C.G. Caine, K.J. Lindner (ed.), Epidemiology of Sports Injuries (pp 186-195). Champaign, IL Human Kinetics.

Sunday, June 2, 2019

The Stand :: Essays Papers

The StandStephen Kings The Stand is a thrilling novel that portrays the forces of good against evil. In the family 1991, a plague strikes America, leaving only a few thousand people alive who are immune to the epidemic. Of the survivors, those who serve G-d instinctively join in Boulder, Colorado, while those who worship the Dark cosmos are drawn to Las Vegas, Nevada. The two groups separately re-build society, until one(a) must destroy the other. Franni Goldsmith comes very close to sidesplitting herself. She thinks she can not deal with her parents deaths, being unwed and pregnant, and having the only other survivor in her hometown of Ogunquit, Main be her recently deceased best friends weird brother Harold Lauder. Fran puts aside her personal feelings for Harold aside, and goes with him to the place in her dreams, to Boulder, Colorado. On their way, they meet up with six people from various states in the United States who joined them on their journey. Fran is disturbed by her dreams, as all of them are by their own. She dreams of an old lady named Abigail, in Colorado. This lady is kind and loving and promises to protect them from the evil. In the dreams thither is also a Dark Man. He is always there lurking, waiting to attack. Harold admits to himself that he is in love with Fran and goes crazy when he realizes how serious Fran has survive with Stuart Redman, one of the newcomers to their traveling group. Harold becomes insanely jealous and plots to separate them, even if it means murder. Harold doesnt admit it to any of them, but his dreams are different from theirs. In his dreams the Dark Man offers Harold power and respect, something Harold could never imagine in the past. Harold knows his destiny is to go to Las Vegas. The group arrives in Boulder, and soon after are joined by over one thousand others who dreamt of Abigail and this place. They inevitably form a society where they settled and has meetings to decide what they would do about the Dark Man. Abigail tells the people that three of them, including Stuart, must be sent to destroy the Dark Man. Meanwhile Harold secretly leaves with the Dark Mans bride-to-be, Nadine, to Las Vegas. Harold is ready to kill Stuart, but is killed instead by the will of G-d.

Saturday, June 1, 2019

Indecision, Hesitation and Delay in Shakespeares Hamlet - Needless Delay? :: The Tragedy of Hamlet Essays

settlements Delay The question of why Hamlet delays in ta pansy revenge on Claudius for so long has puzzled readers and audience members alike. straight off following Hamlets conversation with the Ghost, he seems determined to fulfill the Ghosts wishes and swears his companions to secrecy about what has occurred. The next appearance of Hamlet in the play reveals that he has not til now revenged his fathers murder. In Scene two, act two, Hamlet gives a possible reason for his hesitation. The spirit that I have seen / May be a devil, and the devil hath queen / T assume a pleasing shape (2.2.627-629). With this doubt clouding his mind, Hamlet seems completely unable to act. This indecision is somewhat resolved in the form of the play. Hamlet comes up with the idea of the play that is similar to the events recounted by the ghost about his murder to prove Claudius guilty or innocent. Due to the kings reaction to the play, Hamlet attains the view that the Ghost was telling the truth t he night of the apparition. In Hamlets mind, it is now his duty to avenge his fathers murder. This is where the real problem of inaction enters the play. Later that night, Hamlet has a sinless opportunity to kill Claudius, when he sees the King kneeling in prayer. He wonders if this is the time to kill him and get it over with, but decides not to. He claims that he does not want Claudius to go to heaven, so he would rather kill him when he is committing a sin. If this is the case, then why doesnt he simply wait bank Claudius has completed his prayer, accuse him of the murder and kill him in his sin of denial. Instead, Hamlet goes to the chamber of his mother and passes up his best opportunity at revenge. The argument gutter be made, however, that it is not a fear of killing that causes this inaction. He does not display an inability to end someones life when killing Polonius. He neither hesitates nor capitulates in sending Rosencrantz and Guildenstern to their executions. Why the n would the prince of Denmark hesitate to kill the one man he most justly could? Many literary believe that his inaction is the turn up of a vicarious Oedipus complex. Those who concur with this theory say that Hamlet, in his subconscious mind, has a desire to do exactly what his uncle has done that is, get rid of the king so that he can have Gertrude for himself.