The Cultivated and Vernacular Music in America free essay sample

Joanna Simon Cultivated music is type of music that Is Imported to another place or country, whereas Vernacular music is type of music that originally comes from the country. Then, evaluated music in America means that music from other countries that are brought to America. For example: Opera. Opera Is a music that originally from Italy. If It Is brought to America, It becomes cultivated music In America. In other hand, vernacular music in America Is music that Is originally from America which Is Jazz. According to Christopher Wilkinson, Jazz Is a creation of African American culture which emerged from American musical traditions around the beginning of twentieth century. Characteristics of Jazz music are Improvised, rhythmic complexity and related to dance. There are period Jazz as functionality which Is for dance and period Jazz as quasi art which is to be listened rather than to be enjoyed. Although Jazz music emerged around beginning of twentieth century, there was a long process from long time ago. We will write a custom essay sample on The Cultivated and Vernacular Music in America or any similar topic specifically for you Do Not WasteYour Time HIRE WRITER Only 13.90 / page The history of jazz started in 1619 when African were being forced to come to US (West Virginia) for slavery.Here, we are talking about the Diaspora African (African that went to US, but still taking their own African culture, styles, and songs) and specifically West Africa, Angola. The African brought various of traditions to America because African music was formed from numerous ethnic group that often being associated with daily activity and dance. Something that was interesting, European also came to US (also West Virginia) in 1607. European and African came to American almost at the same time and settled there for a long time. Both of them gave a big contribution to America. Christopher Wilkinson and WilliamHealer said that there were fusion between European and African traditions. It was proven by some similarities that were founded in both system which using of figure bass. Also, both had a same function dance. Then, the various styles of Diaspora Africa mixed with blues and ragtime later on being developed became Jazz. This blues style was used by African people to expressed their misery that were being slaved in America. The result of blending African cultures and some European elements formed into Jazz that was enjoyed by all American race, exported to other countries and interested by others. However, from 1619 till before the civil war, Jazz music was not allowed to publish. Finally around 1860, from the Impact of civil war, African American started to get freedom. The first Jazz was at New Orleans, Louisiana. In conclusion, there are cultivated music and vernacular music In America. Cultivated music Is any kind of music outside American originally music that Is brought to America. While Jazz Is the vernacular or Orlando music In America that rooted from the Diaspora African music, cultures, their expression of being slaved and European people that also came In the same time as African people.The Cultivated and Vernacular Music in America By Compassion Cultivated music is type of music that is imported to another place or country, Then, validated music in America means that music from other countries that are brought to America. For example Opera. Opera is a music that originally from Italy. If it is brought to America, it becomes cultivated music in America. In other hand, vernacular music in America is music that is originally from America which is Jazz. According to Christopher Wilkinson, Jazz is a creation of African American culture which emerged from American musical traditions around the beginning of twentieth century. Characteristics of Jazz music are improvised, rhythmic complexity and related to dance. There are period Jazz as functionality which is for dance and period from long time ago. The history of Jazz started in 1619 when African were being music was not allowed to publish. Finally around 1860, from the impact of civil war, Louisiana. In conclusion, there are cultivated music and vernacular music in America. Cultivated music is any kind of music outside American originally music that is brought to America. While Jazz is the vernacular or original music in America that and European people that also came in the same time as African people.

First Woman to Vote under the 19th Amendment

First Woman to Vote under the 19th Amendment An often-asked question: who was the first woman in the United States to vote the first woman to cast a ballot the first female voter? Because women in New Jersey had the right to vote from 1776-1807, and there were no records kept of what time each voted in the first election there, the name of the first woman in the United States to vote after its founding  is lost in the mists of history. Later, other jurisdictions granted women the vote, sometimes for a limited purpose (such as Kentucky allowing women to vote in school board elections beginning in 1838).   Some territories and states in the western United States gave women the vote: Wyoming Territory, for instance, in 1870. First Woman to Vote under the 19th Amendment We have several claimants to being the first woman to vote under the 19th Amendment to the U.S. Constitution. As with many forgotten firsts of womens history, its possible that documentation will later be found about others who voted early. South St. Paul, August 27 One claim to first woman to vote under the 19th Amendment comes from South St. Paul, Minnesota. Women had been able to cast votes in a 1905 special election in the city of South St. Paul; their votes were not counted, but they were recorded. In that election, 46 women and 758 men voted. When word came on August 26, 1920, that the 19th Amendment had been signed into law, South St. Paul quickly scheduled a special election the next morning on a water bond bill, and at 5:30 a.m., eighty women voted. (Source::Minnesota Senate S.R. No. 5, June 16, 2006) Miss Margaret Newburgh of South St. Paul voted at 6 a.m. in her precinct and is sometimes given the title of  first  woman to vote under the 19th Amendment. Hannibal, Missouri, August 31 On August 31, 1920, five days after the 19th amendment was signed into law, Hannibal, Missouri  held a special election to fill the seat of an alderman who had resigned. At 7 a.m., despite pouring rain, Mrs. Marie Ruoff Byrum, wife of Morris Byrum and daughter-in-law of Democratic committeeman Lacy Byrum, cast her ballot in the first ward. She thus became the first woman to vote in the state of Missouri and the first woman to vote in the United States under the 19th, or Suffrage, Amendment. At 7:01 a.m. in the second ward of Hannibal, Mrs. Walker Harrison cast the second known vote by a woman under the 19th amendment. (Source: Ron Brown, WGEM News, based on a news story in the Hannibal Courier-Post, 8/31/20, and a reference in the Missouri Historical Review Volume 29, 1934-35, page 299.) Celebrating the Right to Vote American women had organized, marched, and gone to prison to gain the vote for women.   They celebrated winning the vote in August 1920, most notably with Alice Paul unfurling a banner showing another star on a banner signifying ratification by Tennessee. Women also celebrated by beginning to organize for women to use their vote widely and wisely.  Crystal Eastman wrote an essay, Now We Can Begin, pointing out that womans battle was not over  but had just begun.   The argument of most of the woman suffrage movement had been that women needed the vote to participate fully as citizens, and many argued for the vote as a way to contribute as women to reforming society. So they organized, including transforming the wing of the suffrage movement led by Carrie Chapman Catt into the League of Women Voters, which Catt helped create.

Christology Essay Example | Topics and Well Written Essays - 750 words - 1

Christology - Essay Example Acts 2:32-32 says, â€Å"This Jesus hath God raised up, whereof we all are witnesses. Therefore being by the right hand of God exalted, and having received of the Father the promise of the Holy Ghost, He hath shed forth this, which ye now see and hear†. Some other instances where this resurrection is the central theme are Acts 3:13-18; 4:10-12; 5:29-32; 10:37-43, and so on. Similarly, one can find this resurrection as the main theme in the Epistles. To illustrate, in 1 Corinthians 15, Paul provides a number of reasons why this resurrection is the basis of Christian faith. When some people in Corinth fail to believe in the resurrection of the dead, Paul explains the various dire consequences in the absence of resurrection. First, the act of preaching Christ will be futile, and hence, even faith in Christ will be useless. If Jesus were not resurrected from the dead, no one would be redeemed from sin as promised. That means all the preachers would be liars and Christians would be come a pitiable lot on the earth. Thus, one can see that it is this resurrection which gave the disciples enough courage and faith in what they preached. Secondly, the late 60s AD witnessed persecution of Christians by the Nero-led Roman government. In 62 AD, both Peter and Paul were executed, and this persecution continued till the early 4th century. In order to make the early Christians face the cruelties boldly, and to sacrifice their own life for this great cause, Jesus’ success over death acted as a catalyst (Vinzent 143). With this spirit, Romans 12:1 says, â€Å"I appeal to you therefore, brothers, by the mercies of God, to present your bodies as a living sacrifice, holy and acceptable to God, which is your spiritual worship†. Moreover, the Old Testament is full of prophesy about the resurrection, and for those who believed in Scriptures, the saviour is the one who would win over death. To illustrate, Hosea 5:15 reads, â€Å"I will go and return to my place, till they

Economic analysis Essay Example | Topics and Well Written Essays - 1500 words - 1

Economic analysis - Essay Example Most of the economists believe that, this relationship between inflation and unemployment is in the short run, which leads to a trade off between the two undesirables. The trade off, which has been summarised in to the Phillip’s curve shows that since the invention of economics, there has been an inverse relationship between unemployment and inflation where, when inflation is low, the rate of unemployment is high and when the rate of inflation is high, the levels of unemployment are low. Government policies that are designed to lower the levels of unemployment, for instance, during recession will usually lead to increased rates of inflation in the short run while policies that are designed to lower the rates of inflation, especially during the boom cycle will most likely increase the levels of unemployment in the short run. When discussing inflation and the effects that it has in markets, another concept that cannot be ignored is the interest rates, this is because inflation l evels in a country are directly determined by the interest rates prevailing in that country. When interest rates in a country are lowered, it encourages businesses to get loans for expansion or to hire more employees; this increases money supply in the economy forcing prices to go up due to the increased demand for products and services hence inflation; however on the positive side is that more people will be employed in the economy. On the other side, if the government increases interest rates, businesses are likely to shy away from getting loans for expansion or to cover other expenses, this has the effect of reducing money supply in the market hence low demand, which in turn leads to low inflation rate. The negative side of this is that the less the amount of money that is available in the market, the higher the levels of unemployment since businesses do not have the money to hire new employees. Phillips curve The above Phillip’s curve shows the inverse relationship betwee n unemployment and inflation. Some economists have argued that this relationship is only applicable in the short run since the in the long run, influence of some other macroeconomic factors may cause inflation and unemployment to move in the same direction or fail to show any influence on each other. Keynes, one of greatest economist of the 20th century have argued that the most important term in economics is the short term since in the long run, we will all be dead. The idea of Phillip’s curve has been criticized especially in relation to the trade off between inflation and unemployment because as data from 1970 in most of the developed countries show, these two economic parameters moved in the same direction, a situation called stagflation. This phenomenon was experienced when in 1970; shocks resulting from fluctuating in oil prices ensure that there were high levels of inflation and at the same time high rates of unemployment. This deviation from the Phillip’s curve is as a result of the fact that workers and employers are likely to take into account the effects of inflation when signing new employment contracts, which would mean employees being paid at rates near the inflation. This would cause the levels of unemployment to rise at the same time meaning that in the long run, there is not trade off between unemploym

Systems Analysis and Design Assignment Example | Topics and Well Written Essays - 3000 words

Systems Analysis and Design - Assignment Example Unlike C++, which combines the syntax for structured, generic, and object-oriented programming, Java was built almost exclusively as an object-oriented language. All code is written inside a class, and everything is an object, with the exception of the intrinsic data types (ordinal and real numbers, boolean values, and characters), which are not classes for performance reasons. Java uses similar commenting methods to C++. There are three different styles of comment: a single line style marked with two slashes (//), a multiple line style opened with a slash asterisk ( ), and the Javadoc commenting style opened with a slash and two asterisks ( ). The Javadoc style of commenting allows the user to run the Javadoc executable to compile documentation for the program. Source files must be named after the public class they contain, appending the suffix .java, for example, HelloWorld.java. It must first be compiled into bytecode, using a Java compiler, producing a file named HelloWorld.class. Only then can it be executed, or launched. The java source file may only contain one public class but can contain multiple classes with less than public access and any number of public inner classes. A class that is not declared public may be stored in any .java file. The compiler will generate a class file for each class defined in the source file. The name of the class file is the name of the class, with .class appended. For class file generation, anonymous classes are treated as if their name were the concatenation of the name of their enclosing class, a $, and an integer. The keyword public denotes that a method can be called from code in other classes, or that a class may be used by classes outside the class hierarchy. The class hierarchy is related to the name of the directory in which the .java file is located. The keyword static in front of a method indicates a static method.

Tumour Supressor Genes and Retinoblastoma

Tumour Supressor Genes and Retinoblastoma Throughout our life time growth is constant. Barring a few cells, most cells continue to grow, divide and replace themselves. Such processes require a strict regulation and this is brought about by cell cycle processes. These processes are carried out by proteins which control the growth and development. Proteins are coded by the genes and when the genetic information is altered or is mutated, it leads to a protein which is dysfunctional and the cell might lose its restraint on growth processes. This in turn leads to an uncontrolled growth of the cells which then causes cancer. Cancer is a disease of the genes. At a molecular level, there are two major reasons which have been attributed for cancer induction. The first one is the gain of function in genes and the other one is loss of function of genes. The genes which gain function, that is, get activated after certain specific events are known as proto-oncogenes. They are typically activated in cancer 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 suppressor genes (Eeles et al 2004). Tumor suppressor genes are inactivated in cancer cells, resulting in loss of normal functions, such as accurate DNA replication, cell cycle control, adhesion within tissues. Tumor suppressor genes are named such because when they are expressed in a normal cell they maintain the cell in a differentiated state and do not allow unchecked proliferation of cells. Therefore, at least one functional copy is required to prevent tumor initiation. That there are tumor suppressor genes was proposed when it was experimentally found by Harris et al. (1969) in cell 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. Many 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 divided 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 growth by causing an increased mutation rate. Landscaper genes do not directly affect cancer cell growth but contribute 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 common malignancy of the eye, retinoblastoma. Retinoblastoma is the most common intraocular cancer in children. It generally manifests in children before the age of five years with a majority of the tumors occurring by the age of 2 years (Lee et al., Eeles et al, 2004). Clinical features of retinoblastoma: As the name implies, 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 was 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 secondary 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 two 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), keratitis, and vitreous hemorrhage (Vogelstein and Kinzler, 2002). A complete evaluation 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 also done to look for the presence of retinoma or a regressed tumor which may indicate a hereditary 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 as: Multifocal or unifocal disease, Site and dimensions of the tumor, Diffused or focal vitreous seeding, Age of the individual, 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 gland is also 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 explained by Knudson in his study. Genetics in retinoblastoma: Retinoblastoma occurs with a frequency of 1 in 13,500 (Mateu et al., 1997) to1 in 20,000 (Di Commo et al., 2000). It is seen in both hereditary and nonhereditary 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 credibility 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 region of chromosome 13. Retinoblastoma can be hereditary as well 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 reported 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 hypothesis: Alfred Knudson realized 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 explain 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 somatically acquired, whereas the second 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 occurrence of the first mutation (M1) in the germline and all developing retinal cells gives retinoblastoma tumor a head start 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 undergoing mutation at one of the alleles. Now, retinoblastoma is derived from the inner 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 will 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 bilateral 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 critical 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 still intact can survive to form retinoblastoma. Some mutations reduce expression of wild type pRB by targeting the promoter or splice sites. In-frame mutations result in a stable pRB with some aberrant functions. THE RB1 GENE: The RB gene family includes at least three members- RB1, RBL1, and p130. The RBL1 and p130 also show similar protein binding 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 sequence similarity resides in the pocket domain, which mediates interactions 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 humans on the long arm with locus 14.2 (Cavenee et al, 1971). The RB1 gene codes for a protein which is 928 amino 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 RB1 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 rich (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 C>T 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 protein: Initially, 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 Hybridization 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 the 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 terminal mitosis in peripheral nervous system, keratinocytes, and skeletal muscles (Di Commo et al, 2000). THE RETINOBLASTOMA SUSCEPTIBILITY PROTEIN: The 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, R motif, and A/B pocket (Di Commo et al, 2000). The N Terminal: The 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 Goodrich 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 domain: The 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 interactions of pRb including interaction with a variety of cellular proteins like E2F transcription factor (extensively characterized), tethering of pRb to nuclear structures (Skapek et al., 1997), phosphorylation during the G1 phase 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 terminal: The 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/K]XL that are important for Rb phosphorylation (Di Commo et al, 2000). RB AND CELL CYCLE: pRB 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 that 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 req uirements 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 sequentially 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 sequential action of cyclin D and cyclin E activated CDKs. As cells exit G0, cyclin 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 series 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 phosphorylation 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. Once DNA replication is complete, the cell enters another gap, G2 ÂÂ ­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: 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 cell 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 center of cellular proliferation and tumorigenesis through its interaction with various proteins. At least three distinct 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 pocket domain as pRb can simultaneously bind to c-Abl as well as E2F (Whitaker et al, 1998). The A/B domains are sufficient 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 ÃŽÂ ² 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 protein (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 means of a LXCXE motif (Kennedy et al., 2001; Gorges et al., 2008). p53 controls phosphorylation 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). Androgen 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 GENE: After 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). The 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 C>T. 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 scattered all along the genomic sequence. However, there are a few hotspots which show high recurrence. Most of the recurrences correspond to C>T changes in the sequence. Out of 351 nonsense mutations 271 (79%) are C>T 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 substitutions (60 %) are located in cyclin box B, underlined by exons 19 to 21.

Behaviorism Theory Essay -- Psychology, Watson, Skinne, Locke

A learning, or behavioral theory, in terms of human development, follows the view that the focus of psychology should be behavior, the way we act. A behaviorist places value on attributes that one can see and therefore study, as opposed to the invisible attributes, such as thinking, feeling, and other brain activity that occurs without one even knowing (Craig & Dunn, 2010, p. 14). There are three important modern behavior or learning theorists: Ivan Pavlov, John Watson, and B. F. Skinner. However, as stated by William Crain John Locke was the â€Å"Father of environmentalism and learning theory†, although Ivan Pavlov and B.F. Skinner were his â€Å"heirs† (Crain, 2011 p.3). To some, the behaviorist theories may seem limiting or incomprehensive, but one can see that all of the major theories play a role in our understanding of development. British philosopher John Locke developed theories in late seventeenth century that a child has no built-in beliefs or understanding of concepts until the child has experienced these things for themselves. He asserted in his writing that through observation of children’s behavior, children are like an empty, unfurnished room that one can select the furnishings for, especially in early years when children are most susceptible to suggestion and input (Crain, 2011). Locke believed that environment was a critical factor in development, but also saw that the way one gives a child input affects behavior as well. Crain, (2011) noted that Locke felt that a child’s good health was important to facilitate, and that beyond that, adults should help reinforce children’s behavior through reward and punishment. More than two hundred years later, B.F. Skinner saw the importance of reward and punishment as he studied oper... ...tson’s later innovations was to remove or de-condition fears, by very slowly introducing the feared object in a slow, incremental, and safe manner until the object no longer evokes a fearful response (Crain, 2011). All of these behavioral/learning theorists have made huge progress in understanding the psychology of human development through a rigid set of principles, through research, observation, and behavior modification experiments. One may be put off by the unyielding denial of cognitive processes in behavior and the relationship to development. To be sure, many theories and theorists have made progress in bridging the gap between behavior and environment only theories, and cognitive theories. One should not lose sight that all of these major theorists have made valuable contributions to our views of human development, including these unwavering behaviorists.

Assignment: Quiet American and the Vietnam War

Dilemmas of Democracy and the responsibilities of the West; he was determined†¦ O do good, not to any individual but to a country' (Greene, 18). He believed preventing the spread of communism would be beneficial for all. Based in the mysterious Asian country as a secret agent, his Job was to import weapons and set up attacks throughout the country. One incident describes: â€Å"that day all over Saigon innocent bicycle pumps had proved to contain bombs which had gone off at the stroke of eleven†¦. It was better from their point of view to let people assume that the bombs were communist† (Greene, 18-135). To stir up anti-communism the U. S. Litany put the blame for civilian casualties on the rebellious Viet Congo, giving a impelling reason to the American people for why they must be stopped. Bloods states how the United States went to Just about any extent â€Å"to prevent the Domino Theory†¦ The Communists taking South Vietnam and then the Philippines and march ing across to Hawaii and then on the shores of California† (Terry, 156). Consequently, government officials promoted fear with the Second Red Scare to incite their citizens to take a stand against the further spread of communism. American troops were placed in Vietnam up until spring 1975.Between that time American troops were let loose in this foreign country. Not only was there a huge culture shock, but also language played as a barrier. Little efforts to understand the Vietnamese culture became an issue in the war. One of the soldiers said, † this old man was running like back towards his crib†¦ I think people said halt† but we didn't know no Vietnamese words† and so they shot him (Terry, 7). Another case of miscommunication was when a soldier told a girl to did did AMA and her lack of effort to to why she remained on the road; she couldn't get through traffic or could not understand his Vietnamese.America showed no mercy and was brutal to anything ND anyone that stood in the way. With their endless supplies of artilleries â€Å"if something moved in front of you†¦. You fired at it† (Terry, 157). Lots of the poorly trained solders were blind in the Jungles of Vietnam, especially at night, aimlessly shooting to any noise. Americans treated the people of Vietnam poorly as well, women especially. Some of the captives were women and while being integrated they were abused. One of the African American hospital corpsman from the Navy was explaining how he saw a Vietnamese woman get a lit flare shoved in her during questioning (Terry).Pyle never hectically harassed a female, but saw Phonon (his Vietnamese lover) as an object. Disregarding her input, he was going to bring her to America as his wife (Greene). Poor interactions with the Vietnamese people, a negative ambiance was left behind by the Americans. Americans believed they were sincerely helping the Vietnamese. When in reality the people of Vietnam did not see the nee d for their intervention. A soldier explained, † I spent a great deal of time discussing the problem of Vietnam with the Vietnamese people, and what they thought about America's involvement.I learned right away the AR was not the right thing to from the people's point of view' (Terry, 67). The people of Vietnam could have cared less if they were getting military support from America. In fact they did not like the war that was happening on their homeland. â€Å"They want one day to be much the same as another. They don't want our white skins around telling them what they want† (Greene, 86). They want to go back to their daily simple lives before any war began. Their way of life is agriculture of rice patties not whether they have a communist or democratic government.Pyle was getting lectured about hat the Vietnamese people wanted, † do you think peasants sit and think of God and Democracy†¦ We've brought them up in our ideas† (Greene, 87). Before interve ne from America, people of Vietnam were not thinking of which government is suitable for them. Neutral Vietnamese said, â€Å"However win is the one we go with. The Americans are the ones that are crazy; cause they not gain anything. They lose their lives and their money here†(Terry, 67). America did not gain anything directly from this war. There were no significant natural resources and hundreds were dying everyday.As he war got dragged even Americans began to question their intentions of being in the war. While men were fighting for a better government, there was trouble back at the home front. Racism was a big factor still in the United States and that custom was brought overseas. Men of color were grouped together and were mainly put on the front end. An African American war veteran said, † more blacks were dying in combat than whites, proportionately, mainly because more blacks were in combat- oriented units, proportionately, than whites† (Terry, 167). White folks were still seen inferior to lacks.There were times were the whole squad would be of black men (Terry). This prevented white Americans from getting hurt during the war. Even though there was inequality, African-Americans were still treated better then in the States. While enlisted, they could hold some kind of power. â€Å"There weren't many opportunities for Where else could a black go and get that label Just like that? † (Terry, 221). African- Americans enlisted as an escape of racism and segregation because in the war zone they are all fighting together under one cause, democracy for the Vietnamese.One big issue in both books for the reason why they lost the war to the Viet Congo was the inability to establish who the enemy was. It was Vietnamese fighting Vietnamese- like the civil war. White folks could not identify whom to shoot, â€Å"It wasn't suppose to be nobody out at night but the marines. Any Vietnamese out at night was the enemy†¦ It was easy to get k illed by an American† (Terry, 7). The soldiers were trained to take down Vietnamese enemy. Everyone looked like the enemy to them. This became problematic of many innocent lives being killed. For this reason,Americans are seen as mechanical beasts across the globe and will strike at ease in order to win. Americans played different roles in the two books due to the time frame, but had the same goal of fighting for democracy. In The Quiet American being European or white was favorable. â€Å"An advantage of this war was that a European face proved in itself a passport on the field: a European could not be suspected of being an enemy agent† (Greene, 42). This is why Pyle was able to sneak around Vietnam with bombs. No one suspected Americans (whites) behind the attacks. Things were a lot more useful for Americans before they sent troops over.Once the military got involved, it was non-stop gunshots after gunshot. It got to the point where soldiers did not know why they were shooting, they were Just told to. Around this time, university students also began to question the government along with the upraising of segregation. Congress had a hard time dealing with upset citizens over the dead of Martin Luther King and the questioning of when the war will end. In the efforts to help Vietnam have a better life under Democracy, America suffered from the high death toll, expenses on weapons and supplies, and the extended years spent overseas.

Romeo And Juliet Essays (821 words) - English-language Films

Romeo And Juliet Essays (821 words) - English-language Films Romeo And Juliet Romeo and Juliet Romeo and Juliet, is a story of two young lovers, whose love was destined for destruction. They did not imagine that their love would lead to the tragedies that it did. These two young people did nothing wrong except fall in love. Three aspects of their destruction included the feud between the two families, the nurse and her betrayal of Juliet and the most important aspect of all is fate. The feud between the two families was one factor that contributed to the love of Romeo and Juliet being destined for destruction. From ancient grudge break to new mutiny. (Romeo & Juliet, Prologue, pg.2 l.3) The two families, Montagues and Capulets, had many problems. There was hate between the two families so much so that even the servants hated each other. This feud would have caused many problems for Romeo and Juliet: These two young lovers knew this and this is why they kept their marriage a secret. If their parents discovered their secret, they would have made their childrens lives miserable. Romeo and Juliet would not have been able to see each other. Both of these families were very stubborn and there was hardly any thing that would have made them become friends. In the prologue we learn that the only way the strife could be ended was by the deaths of Romeo and Juliet. Doth with their death bury their parents strife. (Romeo & Juliet, Prologue, l.8) Neither the Montagues or the Capulets would have accepted the marriage. Keeping the marriage a secret caused Romeo and Juliet to turn to other people for help. Sometimes these people gave them the wrong advice or just betrayed them. The Nurse was one of these characters who betrayed the young couple. The Nurse who was also Juliets friend turned against her at a very crucial time. The Nurse told Juliet that it would be best if she married Paris. I think it best you married with the county. (Romeo & Juliet, pg.101, III, v, l.219) This betrayal by the Nurse left Juliet alone. She was a wise young woman but it still would have been beneficial for her to have the help of the Nurse. Juliet was left on her own to make some very important decisions. I believe that if the Nurse had been around to help Juliet things may have turned out differently. Juliet had no one to turn to and ask for help. She could not have gone to her parents because they would not have understood. The Nurse was supposed to be one of Juliets best friends. Now when it was important for Juliet to have someone there, for her she was betrayed. When considering the destruction of Romeo and Juliet the most sifnificant fact you must think about is fate. Fate, above all, destroyed Romeo and Juliet. Many instances in the play reveals that the love of Romeo and Juliet would end in death. A pair of star-crossed lovers take their life. (Romeo & Juliet,pg.2, Prologue, l.6) From the very beginning it is evident that they were destined by the stars to bad fortune. Some people may think that there is no way to control fate or change what is in the stars. It could be that the love of Romeo and Juliet was destined for death so that their parents feud would be over. Also, in the prologue it states that the dreadful course of their love was destined for death. The fearful passage of their death marked love. (Romeo & Juliet, pg.2, Prologue, l.9) Both of these quotes show us that the love of these two was destined to end tragically. The masquerade party was above all the most important aspect of fate. The fact that Romeo was wearing a mask and his face was hidden allowed juliet to fall in love with him before she saw who it was. If Juliet had known who Romeo was she would probably have not fallen in love with him. Fate could not have been changed whatever was meant to be would happen and no one could change that. In conclusion, from the very beginning, the love of Romeo and Juliet was destined to be

Harry Bingham A Man Who Said No To the Worlds Biggest Publisher

Harry Bingham A Man Who Said No To the Worlds Biggest Publisher Saying "no" to the world’s biggest publisher - An interview with Harry Bingham For many first-time authors, indie publishing is rapidly becoming a natural decision when it comes to publishing their first book. But what happens when an experienced author who has published thirteen books with four traditional publishing houses decides to go it alone? Harry Bingham is one such author. Harry was first published by HarperCollins back in 2000 and over the last fifteen years has witnessed the all the excitement of the publishing evolution. In 2015, he decided to self-publish the US release of his latest book The Strange Death of Fiona Griffiths. Now, for the first time he has written about his experiences in Big Publishing and Me on his blog.Harry is also founder of The Writer’s Workshop - the world’s leading consultancy for first-time writers - and Agent Hunter - a comprehensive database of literary agents. He has also written books on Getting Published and How to Write among several others.With his unique experience, we had no choice: we simply had to talk to him. This morning Harry was kind enough to talk to him  about writing his latest book, his approach to marketing and the benefits of self-publishing. I’m very pleased to be interviewing Harry this morning and to ask him some questions about his latest book and his publishing process. So Harry, if you wouldn’t mind starting off by giving us a little teaser about your latest book.It’s called The Strange Death of Fiona Griffiths and it’s the third in the series I’ve been writing for a while. She’s a young Welsh detective who works in Cardiff, but that’s not really the USP. The USP is that she’s a really unusual person: the whole thing is written first person in her voice. She had a breakdown when she was a teenager and suffered from a real-life condition called Cotard’s Syndrome. In Cotard’s Syndrome, the sufferer believes themselves to be dead. So she’s a detective who spent two years thinking she was a dead person. And she’s got an interesting relationship with corpses and an interesting outlook on life, let’s put it that way†¦Sounds ama zing, wow! Written in the first person, how did that work?Yea, well the question I’m asked most actually is â€Å"You’re writing in the first person as a woman, don’t you think that’s quite hard?† I’m thinking, actually you know, I’m married to a woman, I know quite a lot of women and there are quite a lot of women in the world. Surely the question is: â€Å"You’re writing in the voice of somebody who used to think they were dead!† Isn’t that the bigger trick?In the end, writing fiction is make-believe and if you’re good at it, you should be able to make-believe. Of course, you should be able to write as a woman, or a man, or as people with weird conditions. Although this woman is very different from me, and she has a strong, emphatic voice of her own, I’ve never felt more comfortable writing everything, so what that says about me I don’t know!The most immediately striking thing about the book is the cover - it’s absolutely stunning. Can you tell me a little more about how you went about that?It’s slightly more complicated because I’m published all over the world. It’s published in Britain, France, Germany, Spain, Italy, America and other places too. Every publisher in their own market chooses their own cover and Orion in the UK has got a very strong look for the book and you can definitely tell there’s a series of books going on. In US I was published with Random House and I had a terrific editor there - the same editor who publishes Lee Child. Their cover for the book was fine, but not really stand out. Then for various reasons we will probably get into later, I started self-publishing in US - whereas I’m conventionally published everywhere else - and I commissioned that cover myself.I went to an outfit called 99 Designs, where you can put the design out to a large number of designers and people compete for a prize that you off er. I looked at literally dozens of high-quality designs, any of which could have graced the cover of any one of my books. The one I ended up picking is very striking: it works really well in thumbnail and it’s different - it doesn’t look like everything else there. Given that readers are looking at pages of Amazon thumbnails when they’re figuring out what next to buy, it had to work particularly well in that smaller size.Your publishing story is really fascinating. You’re clearly published with many traditional houses around the world and now this one’s partly self-published. How is it going, how are you finding the process?It’s early days. The minimal threshold for me is that I wanted to be able to publish the book properly, commission a good cover design, do some copy editing work and get the book properly formatted. I used proper professionals, I wasn’t using a â€Å"friend of my brother’s who knows something about photosh op†. By making the book available for sale before launch, I built up hundreds of pre-orders and the result was that on the day of publication I had paid off all my costs. So what I’m looking at now is how much money I make. It’s selling 20-30 copies a day, I’d like it to be selling 2-3 times that in due course.Readers don’t care when a book was published, so whereas in the print market you’re only on the shelves of the retailer in a prominent position for maybe 3-4 weeks, so that early window is everything for a regular publisher. Outside that window, you effectively get very little support from your traditional publisher. If you’re self-publishing, there is no window. The book is eternal and if I completely neglected the book for a year and then put some marketing energy behind it, no-one would particularly care. So it is early days and I’m not attaching too much significance to that early window, and at the moment things are g oing fine.You’ve written in your blog posts recently about how some books are very successful and that some can be published well and be great books but don’t work at all. Your attitude seems to be that â€Å"you can only do so much† since there are so many complex forces at play.Yes, to give it some background, I’ve been more-or-less a full time writer for 15 years or so. Not to boast, but in that time I have had significant relationships with significant publishers - I’m probably now on my fifth six-figure book deal with a conventional publisher, so I’ve played the big game with some big boys. As you know from my blogs, some of those things have worked out well, and some have been absolute car crashes. There is no certainty in this game. If you have a conventional deal with a publisher, you will get your advance, so in that sense there is certainty to traditional publishing. But the sales outcome is really a total unknown. I’ve had some absolute car crashes in traditional publishing, including instances where I’m certain I could have sold more copies of the book myself than via a traditional publisher. So there’s a roulette-wheel quality to the game, no matter if you self-publish or conventionally publish.One of the beauties of self-publishing is a) you retain control and b) if the first thing doesn’t work and the second thing doesn’t work, you can go onto the third and fourth thing - it never runs out like that. So at this stage I’m relaxed.Do you mean that in terms of retaining financial control, or creative control - which one is more important?Just everything! Certainly the book cover. Supposing I were to get negative feedback from readers on the cover, heck I could just change it! I wouldn’t have to be lobbying my publisher to do it, and my publisher would be intensely resistant because of the costs involved. Or if I needed to rewrite the ending I could do that. O r if I decided I was going to slash the price and put it out for free, or for 99c on Bookbub, I can do that and I can go on tweaking things whenever I want.Again one of the big tools in online promotion of any sort is email lists. Conventional publishers - I’ve really no idea why - but they make very little use of those things. With every book I’m selling, I’m asking people â€Å"If you enjoyed this, add your name to my email list.† I’m not going to fill their inboxes with corporate nonsense, but a couple of times a year they’ll get an email that a new book is coming out and if you’d like to buy that book, terrific.It’s those sorts of things that I can do. I can adjust my strategy and I don’t have to go through some sort of complicated corporate process to make those things happen. And the truth is, the author is largely outside that corporate process so that an author’s ability to impact on those things with a co nventional publisher is pretty restricted.Yes, a lot of what we’ve been trying to do at Reedsy is to make that process easier and to provide tools that will make the process of creating the book so much easier, so that authors can edit and have that flexibility.Exactly. At the moment there are three types of authors: conventionally published authors who are happy with the way things are - absolutely fine. There are indie-types who relish the process of designing covers and editing manuscripts - they like the entrepreneurial quality of all that. Then there’s definitely a group in the middle who think, logic says self-publish, but they don’t know how to put the whole package together and there will be services like yours who offer to integrate those in a pretty simple way, so that that blockage that is stopping some people making the leap, will become smaller.What is it that really lies behind your excitement for what you call the current â€Å"era† of publ ishing? Is the flexibility and freedom the biggest part, or is there more?I think often-enough big publishers have taken their authors for granted. Sure, they compete for them at that really early stage when a literary agent takes a book out for auction. But once that deal has been done, it’s pretty rare for authors to jump publisher unless something has gone badly wrong, which means the publishers can take their authors a little bit for granted.Some of the treatment I’ve had has been very very good indeed. Some of the treatment I’ve had from publishers has been not so good. And there’s never been a meaningful alternative to those Big-5 type publishers for the certain sort of books that I write. Just the existence now of self-pub, which really is only going to work for genre-type authors at the moment - there aren’t many signs it’s going to work for literary fiction yet - but for genre-type authors, we now for the first time have a meaningfu l alternative to just going with a regular publisher. Now there is another negotiating presence in the room: I don’t have to take your offer, there is an alternative. That has really not been present before, and I think that’s a fabulous thing for all authors, whether they take the self-publishing route or whether they don’t.From your position it’s interesting, because you’ve already established yourself for many years as an author working with traditional houses, your route to self-publishing means that you already have a name behind you. I think it will be interesting to see how authors who go straight into self-publishing establish a name for themselves: that is really interesting to me.Yes, and I think the emerging model of successful self-publishing is first of all, you probably need to be a genre author, secondly you need to be quite prolific, and third you need to apply the â€Å"write, publish, repeat† model. It’s possible, bu t not likely that your first book becomes a big viral hit, but let’s face it, loads and loads of good books never become viral hits: even though in principle they could, it just doesn’t happen. No one will ever be able to trace the reason why it doesn’t happen - in fact, the rule is that it doesn’t happen, it’s just that occasionally it does!So the â€Å"write, publish, repeat† model is incremental. It means your readership grows. Jumping from traditional publishing to self-publishing, yes sure I’ve got more interest in my books and more book reviews and so on than I would have otherwise. But in many ways it’s the same: I’m creating my email list from scratch and those things will just take time to build.The presence of an author’s back-catalogue online, that doesn’t disappear, means it’s much easier to bring back an older one, and a book that has been published previously could find an author that t hey’d not previously had.My first book The Moneymakers was published in the UK in 2000; I never sold the US rights. And I never sold the ebook rights, because no-one sold ebook rights back then. So, I retained the rights to that book, and I no longer had a manuscript because I’ve been through multiple computers since then. I sent the hard copy of the book off to a place in London that scans there things for  £10. They send me back a word document - that has some typos, so needs some careful copyediting. But for  £10 and a day of my time, I had a typescript of my original manuscript, popped it up online on Amazon and I make a couple of hundred quid a month. That’s not astonishing money, but hey, it’s a couple of hundred quid that I wasn’t getting otherwise.Exactly, your content goes so much further. How are you engaging with other online communities - what’s your approach?There’s an infinite amount of stuff that one could do. I thi nk there is relatively little evidence to suggest that Facebook and Twitter and that kind of thing is really a strong way of promoting books. There will be exceptions to every rule, but most books I don’t think achieve many sales like that. I have a couple of books-related websites: The Writer’s Workshop, which helps first time writers with their skills and Agent Hunter, which helps writers find literary agents. Between those two platforms, I’ve got websites that have traffic of 70-80 thousand visitors a month. I’ve got mailing lists of probably 15-20 thousand names. All of these people are writers, but therefore also presumably interested in reading books.I’ve used those things a bit, but not much: I don’t expect to get significant sales from them. It’s partly because I don’t want to contaminate those brands, but it’s also that I think people don’t like being marketed at and the online platforms that work well, w ork when there’s a really natural synchronicity between people’s interests in coming to the site, and the product you’re developing.So that means, if you like being active on Goodreads for example, that seems to me a really natural way to spend time. I don’t particularly enjoy it: that means I’m never going to be that committed to it, that probably means that’s not the right marketing route for me. But there are no general rules here: it really depends on each author and their own individual preferences, their own particular book, and what kind of existing digital presence they already have.It’s about authors remaining true to themselves.Yes! You can’t fake it can you? There are people who enjoy engaging in Twitter: they’ll make friends, engage in conversations, and when they do have something to market, they have a community of people who don’t feel they are being exploited for their wallets. They are Twitter fri ends and have been over the months and years. I’m just not like that. I hate Twitter. I use it as little as I can. I do pump stuff out now-and-again because I kind of think I have to, but it’s never going to be a strong channel for me. But there are online communities of every sort.And new ones which will develop in the future. The beauty of publishing is that so many different types of authors will find so many different types of routes: not just through various distribution channels, but routes that can create a much closer fit with online communities.Yes, in the end it’s always going to be a word-of-mouth thing. There will come a point where you might be able to initiate a fire, but in the end it’s going to come from readers, talking to friends about books they’ve recently enjoyed.You might be able to take sales from 2-3 a day to 20-30 a day, by really pushing the marketing routes that you have, but to achieve sales beyond that point, youâ€℠¢ve actually got to get a community of people going â€Å"Hey this book is great!† and they are talking about it with their friends and book groups. That’s how any viral process - whether traditionally or self-published - is created.Thanks so much. I think this is going to be of great help to so many of our readers on Reedsy.Just to end on a note that would be positive to both you and your community, which is, there is still a perception of self-publishing as â€Å"I wasn’t good enough for traditional publishing, so I’m self-publishing† and that perception has certainly changed, but there’s no question it’s still there. I am a conventionally published author and I’ve had some terrific book reviews, and I’m self-publishing because I want to, and for me it really isn’t because â€Å"I couldn’t cut it with the big boys†, but actually that I wasn’t prepared to take what the big boys were offering me. I didn’t want it.I preferred the risks and the rewards and the opportunities of self-publishing to working with what is the world’s biggest publisher. I’ve definitely hedged my bets, because I’m still conventionally published here in the UK, but I love this model of being a hybrid author and I think people will go both ways: successful self-pub authors will become hybrids in the other direction. I do think it’s a new world we’re now living in.That’s a very inspiring message to pass on to our readers. Thank you very much and best of luck with it all!Follow Harry and Reedsy on TwitterDo you think it’s better to be self-published today, or to go with a traditional publisher?

Criminal Justice Policy Issue (Immigration in Arizona) Essay

Criminal Justice Policy Issue (Immigration in Arizona) - Essay Example Therefore, in order to prevent illegal immigration in the American States, it is relevant not only to take strict measures, but also take into account human rights, the rights of immigrants and develop immigration policies in accordance with socially favorable norms and conditions. Immigration policy in Arizona The main goal of the immigration law in Arizona is to make stricter regulations on immigration measures. For example, a failure of having immigration documents is positioned as a crime and the police have power to detain anyone who is in the country illegally. Such measures are considered to be acts of discrimination focused on Hispanics. The rights of the Mexican residents are in danger in terms of this immigration law. Moreover, this policy is even named â€Å"Nazism†. There are numerous court challenges, which occurred in the result of this policy implementation. There is an evident intimidation for the community distrust, increased level of crimes, expensive litigat ion, national repercussions (Engstrom, 2010). Arizona immigrants are obliged to carry the identity documents, which underline their legitimate presence on the American land. Nevertheless, the developers of this law project are more focused on a facilitation of law carrying out. Law enforcement measures are introduced at a governmental level and there is a need to act in compliance with the laws. There was a striking event concerning the background of law enforcement. A rancher in southern Arizona was killed and it triggered Ms. Brewer and other governmental leaders to intensify the protection on the National border by the National Guard troops. Therefore, there are hostile moods among Hispanics and they are against intensification of their immigration. On behalf of the police, it is currently relevant to detain those people who are suspected to be on the American lands without authorization and identification. Only medical treatment of a suspected individual or his/her involvement i n an investigation would hinder this process. Moreover, local government is under pressure and scrutinized attention from the community because it can be sued in case it violates federal or state immigration law enforcement. There is an essential social turmoil in the State because of the immigration law enforcement introduction. Hispanic voters are much concerned about this law and they can be influenced in the process of elections in case of law enforcement prevention. Thus, it is relevant to create a favorable atmosphere of immigration law enforcement. In case it is prevented in different states and cities, it is relevant to talk about removal of â€Å"sanctuary rules† at the federal level. State Sen. Russell Pearce (R-Mesa) invented the Immigration Law of Arizona State and he underlines that the positive changes of the law enforcement are the following ones: Immigrants would be unable to avoid obtaining adequate alien registration document. Officers would be enabled to ar rest immigrants in case the latter cannot show their legal identification of presence on the American lands. Soft immigration enforcement and sanctuary rules would be disabled and would not be regulated by local governments. Street traffic will not be on halt because of overcrowding due to immigrants looking for employement. Evidently, these are rather strict measures taken against immigrants in the State of Arizona. Brewer experienced protesters’ demands of reforms prevention, but promised to treat everyone fairly

The Lizard Lick Fine Paper Mill Essay Example | Topics and Well Written Essays - 3250 words

The Lizard Lick Fine Paper Mill - Essay Example Its prominence can be gauged from the fact that this was the single place where executives wanted to be posted for furthering their career in the group. Â  Similar is the case of George Golden, Plant Manager, who was posted here three years ago, to be groomed for an eminent position in the group headquarters as the career-ending spell. He is known for his hard-driving force and capability of setting high standards in every division and for his ability to lobby in the highest echelons for the benefit of the company. Â  LLF commenced business on D-Day; the day of the Allied invasion of Europe and ever since has been a model of productive competence. It is the sole provider of jobs for seventy-five miles around and the area has seen a transformation since its inception. Until a few years ago it had a daily routine production of high-quality paper of 700 tonnes. The Return on Assets (ROA) was an astounding 32%. It produces fine paper, as distinguished from Kraft paper by its white color, smoothness and fiber content that is used for stationery, photocopying, and printing. It is packed in large rolls of 1000 pounds each and shipped in Box-cars from the adjacent rail-yard. Unfortunately, the production has fallen to 550 tonnes per day and there are complains from 50% of customers on quality. Â  The mill itself consists of various machinery used in the four processes required for producing paper. Starting from Pulping, proceeding to Liquoring and then to the continuous-process machine, the size of ten football fields, to produce huge sheets of paper that are rolled into 1000 pounders at the last stage.