Vaccinations Research Paper Example | Topics and Well Written Essays - 250 words

Vaccinations - Research Paper Example Also, disease-causing bacteria and viruses usually occur in different forms referred to as different strains (Miller, 2008). In most cases, vaccines are designed to handle certain strains. For instance most flu shots available presently are designed to work against the common strains of flu virus which has been in existence for quite a while. Thus, such vaccine cannot prevent against new strains of flu. This explains why vaccines do not give a lifetime protection against diseases. As explained above, vaccines are usually designed to work against certain strains. Yet, every now and then, new strains emerge which are often stronger than the previous ones. This therefore renders the incumbent vaccination ineffective. Usually, vaccines do not guarantee full protection from a disease. Their strength fizzles out with time. Thus, one has to have another shot of vaccine so as to continue strengthening their immune system. Health care workers should be subjected to regular and extensive training so as to acquaint them with the new occurrences with regards to diseases. This enables them to keep abreast with the new strains that emerge. Such information is important as it enables the m to update their vaccines so as to stay effective. Equipped with knowledge about the new merging diseases, health workers get to know what to use and when to use so as to guarantee effectiveness in the fight against outbreaks. As stated, new strains of disease-causing bacteria and viruses develop from time to time. Regular training and updating of information regarding such strains is essential l as it enables the health workers to discard old vaccines that have been rendered obsolete, and develop new effective ones. This enhances effectiveness of vaccines and accelerates the fight against various

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.

Free Yellow Wallpaper Essays: National Identity :: Yellow Wallpaper essays

National Identity and The Yellow Wallpaper Gilman is an author whose writing is based on individuals making up America's collective identity. "The Yellow Wallpaper" is from the vantage points of being a woman, at a time when women were not supposed to have individual thoughts and personalities. At this time in history, the social roles of women were very well-defined: mothers and caretakers of the family, prim and proper creatures that were pleasant to look at, seen but not heard, and irrational and emotional. The identity of women were presupposed on them by men. At the time this story was written, social criticisms were on the rise and writers had more of an outlet to express themselves. Women's suffrage provided by many female writers, such as Gilman, the means to air the wrongs against women. The main character (a sort of parallel to Gilman herself) experiences post-partem depression, and at this point in time, there was no knowledge of this condition. It was generally thought that the nervous condition suffered by women after birth was caused by a weak moral/mental state. The narrator's husband, John takes her to an old, gothic house, away from all the care and stress of the world. This is supposed to be for her own good. To get some rest and to heal her "weak" mind, she lies in bed, almost locked in her room, left to stare at this ugly, yellow wallpaper. The ugliness of the wallpaper begins to consume her mind as the room turns more into a prison than a place of healing. The main character's though processes become apparent as the story progresses. When she first talks of the pattern, she only describes the pattern and the color briefly: "I never saw a worse paper in my life. One of those sprawling, flamboyant pattern committing every artistic sin... The color is repell ent, almost revolting..." But the pattern becomes more detailed-- in a sense, she has given the pattern life: "Looked at in one way, each breadth stands alone; the bloated curves and flourishes- a kind of 'debased Romanesque' with delirium tremens- go waddling up and down in isolated columns of fatuity." As she begins to pay more attention to detail, her mind starts becoming more and more unstable. However, with this deterioration comes her realization of the situation she is in. At the end of the story, it is evident that the woman trapped in the wallpaper represents the main character-- she has started to talk in first person: "'I've got out at last,' said I, 'in spite of you and Jane.

Fires on the Plain: a Reflection

Fires on The Plain: A Reflection Fires on the Plain is truly the most depressing, haunting, and sad story I have ever endured reading. The complete abandonment of the Japanese soldiers on the island of Leyte by the Japanese Army is revolting, as well as the complete disregard for each others well being among them. It becomes a battle between one another for survival. The lack of comradery among the Japanese soldiers is dumbfounding, and leads me to believe that it may very well have been there demise.The weaknesses we see in Tamura and the other soldiers not only have a great impact on their unfortunate outcome, but are also a result of a weakness within the Japanese Army itself. The awful fate of these soldiers, at the hands of their own command, is infuriating. Shohei's story holds powerful, and several dangerous implications of what war is like and what it's effects can be on those who fight in them. I would like to start by talking about comradery. Comradery can be defined as the spirit of friendship and community in a group, like a group of soldiers.Tamura's story shows zero evidence of any sort of comradeship, he even describes the way in which it he saw it disappear on Leyte, â€Å"Before long any comradeship that we once felt for each other had virtually disappeared. †(pg. 9). I could also see this in the way they treated each other. Initially, Yasuda and Nagamatsus' relationship could be mistaken for comradeship, but I realized that they were only using each other and did not care at all about the others well being. Which becomes quite clear at the end of the book.I have no doubt that this complete lack of comradery was mostly a result of their horrific situation, but I also believe that it could have existed before it. The way in which Tamura laughed while watching his fellow soldiers run around like â€Å"insects†(pg. 59), and the fact that Nagamatsu would hunt, kill, and eat his fellow soldiers are disturbing examples of the complete d isregard they had for one another. These instances serve as proof to me that there couldn't possibly have been much of a comradeship between these men at any point. One dangerous implication that this story holds expressed directly byShohei, â€Å"For people like us, living day and night on the brink of danger, the normal instinct of survival seems to strike inward, like a disease, distorting the personality and removing all motives other than those of sheer self-interest. †(pg. 9). While this certainly seems true for the Japanese soldiers in this story, I refuse to believe it to be true for all men. My personal experiences from being a Marine and doing two tours in Afghanistan have showed me what true comradery is. My fellow Marines and I would have gladly died for one another, and some did.In class, we discussed how the way in which these Japanese soldiers turned on one another when torn down to their most animalistic nature, could be true of all men or soldiers when under the same circumstances. The fact that somebody could believe that to be true is not only offensive, but scary. It is scary to me that examples from a book written by someone who is clearly insane, could be generalized to all men or all soldiers of every kind. What really irks me about this is that Shohei, portrayed through Tamura, shows absolutely no characteristics of a soldier.I think his most accurate depiction was when he said they resembled domestic animals â€Å"helplessly uprooted and perplexed†(pg. 35). I believe that he portrays someone with certain mental weakness. He wonders about the island countryside, it seams, waiting for his death to come. He has no plan but death. I understand that his circumstances are beyond my understanding, but they way in which he so easily abandons any hope of surviving, and doesn't put up any real fight for his survival, doesn't sit with me.It makes me realize that this weakness is most likely due to reasons beyond his control, such as the way in which, and the culture in which, he was brought up. As well as the poor military training and/or lack there of, did not properly prepare him for the nightmare of a situation he was put in. Which forces me to re-evaluate my initial reaction to write him off as a pathetic, weak individual who should have shot himself right then and there after he murdered the Filipino women.I am sympathetic for poor Tamura, who was drafted into the army and clearly given incredibly insufficient training. Tamura did not belong there and, I feel, none of them belonged there. The infuriating part of this story is the way in which these men were sent to what any person with intellect could tell was a certain, horrific death. Not only were they ordered to go that island, to that shit hole of a situation, it seams as if the people who ordered them there just left them for dead. Even his commanding officer told him that the best thing he could for his country was kill himself.They were given abso lutely no support against an enemy whose support was rivaled by none. Which resulted in them fighting each other for survival. Fires on the Plain is a very disturbing story from a war that resulted in many awful things. It has many implications of what war can be like, but I want to emphasize that not all wars are the same, and the men and women who fight in these wars certainly are not either. I would hope that those who read this understand that they shouldn't generalize the behavior of these poor Japanese soldiers to all soldiers or fighting men.I believe that the circumstances surrounding this horrific example of what war can be like are incredible and the ingredients that went into making this shit sandwich are hard to come by all at the same time. My final thoughts of this story are wrapped around Shohei's idea that life is nothing more than â€Å"a mere succession of chances†(p. 233). I have been debating over this idea with myself ever since I came back from my last t our in Afghanistan, and I can't say that Shohei's story has helped me in making a decision.

Prescriptive Grammar Essay

This lesson highlights the important fact that linguists describe the grammatical system of a language on the basis of what people actually say, not what they should say. To a linguist, grammar consists of those constructions judged acceptable by a native speaker’s intuitions. This is what it means to say that linguistics is descriptive and not prescriptive. Linguistics is descriptive, not prescriptive. Many people associate knowing a language with speaking and writing it according to the grammatical rules established for that language in grammar books and dictionaries. The study of linguistic competence does not include the study of prescriptive standards that claim that one sentence rather than another is correct. Instead, linguists are interested in what speakers of a language actually say and what they accept as possible in the language, regardless of whether the construction matches the grammar rules posited by the grammar â€Å"police.† This approach to grammar is descriptive rather than prescriptive. Descriptive grammar is what speakers say, and when, why and how they say it (and not whether they should or shouldn’t say it.) Linguists concern themselves with discovering what speakers know about a language and describing that knowledge objectively. They devise rules of descriptive grammar. For instance, a linguist describing English might formulate rules such as these: 1.Some English speakers end a sentence with a preposition (Who do you want to speak to?) 2.Some English speakers use double negatives for negation (I don’t have nothing.) 3.Adjectives precede the nouns they modify (red book, nice guy) 4.To form the plural of a noun, add -s (1 room, 2 rooms; 1 book, 2 books) 5.The vowel sound in the word suit is produced with rounded lips. Linguists don’t make judgment calls as to whether the speakers should or shouldn’t speak a certain way. Descriptive grammar, then, is created by linguists as a model of speakers’ linguistic competence. Prescriptive grammar is what speakers should or shouldn’t say. When most people think of â€Å"grammatical rules,† they think of what linguists call rules of prescriptive grammar. Prescriptive rules tell you how to speak or write, according to someone’s idea of what is â€Å"good† or â€Å"bad.† Of course, there is nothing inherently good or bad about any use of language; prescriptive rules serve only to mold your spoken and written language t o some norm. Here are a few examples of prescriptive rules; you  can probably think of others. 1.The subject of a sentence must agree with the verb (The instructions are clear NOT The instructions is clear.) 2.Use much for count nouns. Use many for non-count nouns (We don’t have much coffee AND We don’t have many cups of coffee.) 3.Capitalize the first letter of a sentence (The television is broken. It needs to be fixed.) 4.Use subject pronouns after the verb be (It was I who called you NOT It was me who called you.) 5.Use the definite article the before names of rivers and geographical areas but not before the names of lakes or continents (the Nile, the Middle East AND Lake Tahoe, Asia) Notice that the prescriptive rules make a value judgment about the correctness of an utterance. Descriptive rules, on the other hand, accept the patterns a speaker actually uses and try to account for them. Descriptive rules allow for different varieties of a language; they don’t ignore a construction simply because some prescriptive grammarian doesn’t like it. If linguistics is descriptive and not prescriptive, then why do we have prescriptive rules anyway? So, if prescriptive rules are not based on actual use, how did they arise? Many of these rules were actually invented by someone. During the 17th and 18th centuries, scholars became preoccupied with the art, ideas, and language of ancient Greece and Rome. The classical period was regarded as a golden age and Latin as the perfect language. The notion that Latin was somehow better or purer than contemporary languages was strengthened by the fact that Latin was by then strictly a written language and had long ceased to undergo the changes natural to spoken language. For many writers of the 17th and 18th centuries, the rules of Latin became, whenever remotely feasible, the rules of English. It is somewhat surprising that rules that do not reflect actual language use should survive. There are several reasons, however, for the continued existence of prescriptive rules. 1.Rules provide a standard form of a language that is accepted by most speakers of that language. Adherence to prescriptive rules allows a speaker to be understood by the greatest possible number of individuals. This is especially important for a language such as German, which has dialects so different from one another that their speakers cannot always understand each other. 2.A set of standard rules is necessary for students learning English (or any other language) as a second language. Imagine the chaos if there were no guidelines for learning English  (or Spanish, or Japanese, or Arabic, etc.) Thus, rules serve a very useful purpose for language teachers and learners as well. 3.Most importantly, there are social reasons for prescriptive rules. Nonstandard dialects are still frowned upon by many groups and can inhibit one’s progress in society. The existence of prescriptive rules allows a speaker of a nonstandard dialect to learn the rules of the standard dialect and employ them in appropriate social circumstances. Therefore, prescriptive rules are used as an aid in social mobility. This does not mean, however, that these judgments about dialects are linguistically valid. The idea that one dialect of a language is intrinsically better than another is simply false. From a strictly linguistic point of view all dialects are equally good and equally valid. To look down on nonstandard dialects is to exercise a form of social and linguistic prejudice. We’ll learn more about language and identity in our next module. According to the Merriam-Webster Online Dictionary, the term dates from 1706 and is defined as â€Å"a person who adheres strictly and often excessively to a tradition†, especially â€Å"one preoccupied with the purity of a language and its protection from the use of foreign or altered forms.† A purist is one who desires that an item remain true to its essence and free from adulterating or diluting influences.

Free Essays on Sumerian

By: jason E-mail: jason211@hotmail.com Sumerian vs Egyptian Deities The Sumerian and Egyptian cultures developed a rich and detailed mythology over the thousands of years of their existence. Each culture developed its own complex, polytheistic system of deities and worship. There are many aspects of both of these two culture's gods that are similar, but for one to truly understand the relationship between these two cultures one must delve deeper and look at the differences. The Sumerians had four leading deities known as creating gods. These gods were An, the god of heaven; Ki (Kiki), the goddess of earth; Enlil, the god of air; and Enki (who later became Ea), the god of water. Like these "creator gods", most Sumerian gods are the personification of local elements and natural forces. (Kramer) The Sumerian gods were grouped into three levels indicating their importance and power. The highest level was that of the primary deities or creator gods who were created for creating all life on earth life. The next level of gods we re known as "The Seven Who Decreed Fate". This group not only consisted of the four primary deities but also included Nanna, his son Utu, the sun god and a god of justice, and Nanna's daughter, Inanna, goddess of love and war. Most of the gods were in the next level that was known as the fifty "great gods" or the Anunna. The bottom level consisted of lower gods, demigods, and in some cases heros. Sumerians believed humans were created as labor saving devises for the gods. Each family and town had a patron god that might interven in troubled times to help the people. Most towns also had a ziggurat in which they worshiped that city's god. The ziggurat also served as the home of the high priest. The high priest was considered divine and it was his job to tell the people the other gods' will. This was usually done by reading sheep or goat entrails.(Siren) One myth known as the "creation myth" sums up a lot about how t... Free Essays on Sumerian Free Essays on Sumerian By: jason E-mail: jason211@hotmail.com Sumerian vs Egyptian Deities The Sumerian and Egyptian cultures developed a rich and detailed mythology over the thousands of years of their existence. Each culture developed its own complex, polytheistic system of deities and worship. There are many aspects of both of these two culture's gods that are similar, but for one to truly understand the relationship between these two cultures one must delve deeper and look at the differences. The Sumerians had four leading deities known as creating gods. These gods were An, the god of heaven; Ki (Kiki), the goddess of earth; Enlil, the god of air; and Enki (who later became Ea), the god of water. Like these "creator gods", most Sumerian gods are the personification of local elements and natural forces. (Kramer) The Sumerian gods were grouped into three levels indicating their importance and power. The highest level was that of the primary deities or creator gods who were created for creating all life on earth life. The next level of gods we re known as "The Seven Who Decreed Fate". This group not only consisted of the four primary deities but also included Nanna, his son Utu, the sun god and a god of justice, and Nanna's daughter, Inanna, goddess of love and war. Most of the gods were in the next level that was known as the fifty "great gods" or the Anunna. The bottom level consisted of lower gods, demigods, and in some cases heros. Sumerians believed humans were created as labor saving devises for the gods. Each family and town had a patron god that might interven in troubled times to help the people. Most towns also had a ziggurat in which they worshiped that city's god. The ziggurat also served as the home of the high priest. The high priest was considered divine and it was his job to tell the people the other gods' will. This was usually done by reading sheep or goat entrails.(Siren) One myth known as the "creation myth" sums up a lot about how t...

School Term Paper Topics

School Term Paper Topics A school term paper belongs to the family of long research papers which students write over an academic term or a semester. A school term paper is an important part of a student’s academic life as it accounts a large part of a grade and covers up much of the course. Term papers are usually written about some events, detailed description of concepts or arguments on a specific point. There are some important points which must be taken into consideration while starting to write a school term paper. It is very important to choose the right topic for a student as a large amount of knowledge and information is needed to write a term paper. One of the most important things is to make your term paper interesting to read. As there are many students writing the term paper at the same time it is very important to prove your term paper to be unique and interesting for the reader to read. Much attention should be paid to the format of the term paper. In school term papers the format doesn’t mean only structure and technique but it also refers to the approach and style of paper. A term paper can be argumentative or persuasive. Many students get confused while choosing their topics. There are a lot of interesting school term paper topics to choose but as told before a student must know how to choose a right topic, considering the amount of knowledge and information they have on the specific topic and how much interesting facts they can incorporate into the term paper topic. Usually school term paper topics are very wide, so, students should make their topic specific in order to provide better impression and coverage. For example, violence is a broad topic so, in order to give your term paper a complete and fascinating coverage students can choose violence on television, gang wars, school violence or racism depending on their interests. Similarly you can choose drug addiction, universe, human development, science, history, political issues and many more. If you have a lack of topics for your school term paper or you don’t have enough information about topics, you can contact our professional term paper writing service. We offer you the best school term papers written because we have over 735 professional writers always ready to help you out with your problems.

The Chemical Composition of Wood Smoke

The Chemical Composition of Wood Smoke Smoke is something that we will deal with all throughout our lives, in everyday situations as well as in emergencies. But not all smoke is the same in fact, the smoke will vary depending upon what is being burned. So then what, exactly, is smoke made of? Smoke consists of gasses and airborne particles produced as a result of combustion or burning. The specific chemicals depend on the fuel used to produce the fire. Here is a look as some of the principal chemicals produced from wood smoke. Keep in mind, there are thousands of chemicals in smoke so the chemical composition of smoke is extremely complex. Chemicals in Smoke In addition to the chemicals listed in the table, wood smoke also contains a large amount of unreacted air, carbon dioxide, and water. It contains a variable amount of mold spores. VOCs are volatile organic compounds. Aldehydes found in wood smoke include formaldehyde, acrolein, propionaldehyde, butyraldehyde, acetaldehyde, and furfural. Alkyl benzenes found in wood smoke include toluene. Oxygenated monoaromatics include guaiacol, phenol, syringol and catechol. Numerous PAHs or polycyclic aromatic hydrocarbons are found in smoke. Many trace elements are released. Reference: 1993 EPA Report, A Summary of the Emissions Characterization and Noncancer Respiratory Effects of Wood Smoke, EPA-453/R-93-036 Chemical Composition of Wood Smoke Chemical g/kg Wood carbon monoxide 80-370 methane 14-25 VOCs* (C2-C7) 7-27 aldehydes 0.6-5.4 substituted furans 0.15-1.7 benzene 0.6-4.0 alkyl benzenes 1-6 acetic acid 1.8-2.4 formic acid 0.06-0.08 nitrogen oxides 0.2-0.9 sulfur dioxide 0.16-0.24 methyl chloride 0.01-0.04 napthalene 0.24-1.6 substituted napthalenes 0.3-2.1 oxygenated monoaromatics 1-7 total particle mass 7-30 particulate organic carbon 2-20 oxygenated PAHs 0.15-1 Individual PAHs 10-5-10-2 chlorinated dioxins 1x10-5-4x10-5 normal alkanes (C24-C30) 1x10-3-6x10-3 sodium 3x10-3-2.8x10-2 magnesium 2x10-4-3x10-3 aluminum 1x10-4-2.4x10-2 silicon 3x10-4-3.1x10-2 sulfur 1x10-3-2.9x10-2 chlorine 7x10-4-2.1x10-2 potassium 3x10-3-8.6x10-2 calcium 9x10-4-1.8x10-2 titanium 4x10-5-3x10-3 vanadium 2x10-5-4x10-3 chromium 2x10-5-3x10-3 manganese 7x10-5-4x10-3 iron 3x10-4-5x10-3 nickel 1x10-6-1x10-3 copper 2x10-4-9x10-4 zinc 7x10-4-8x10-3 bromine 7x10-5-9x10-4 lead 1x10-4-3x10-3

Shifts in Values from Renaissance to Modern Age Research Paper

Shifts in Values from Renaissance to Modern Age - Research Paper Example This text explores such differences and similarities between these two ages. In terms of philosophy, it is evident that certain cultural values have changed from the Renaissance to today. Perhaps, it is of uttermost importance to start the text by defining the most crucial terminologies involved. Most historians would describe the Renaissance as a cultural rebirth that commenced in Florence, Italy, before dispersal to the other parts of Europe from approximately 1300 to 1600. During this time, â€Å"Europeans underwent a transformed interest in Roman and classical Greek civilization, and consequently, in learning mathematics, science, philosophy, science, and the arts† (Adams, 2005, p. 87). Christianity took a center stage during the renaissance and its influence can be felt in the dawn of modern science. Men during the renaissance were expected to be outstandingly well-rounded and learned in various subjects. The Renaissance brought about the end of the middle Ages and embrac ed for the first time the ideals of the modern world. For this reason, it is seen as a changeover era between the middle ages and modern times. As Adams (2005) asserts, â€Å"no single ideology or philosophy dictated the intellectual life of the Renaissance period† (p. 143). Humanists during the early days had stressed a supple approach to the issues of society and the fast life in service of all human beings. Renaissance philosophers, during the second part of the 15th century including Marsilio FICINO in Florence, embraced metaphysical speculation. Nonetheless, Plato never replaced Aristotle as the leading philosopher in many universities. However, there was an effort aimed towards philosophical syncretism, to combine conflicting theories and philosophies, and establish common ground for accord with regards to the truth just like Giovanni Pico Della Mirandola. Renaissance science comprised largely of the study of physics, medicine, and mathematics, depending on old masters, such as Aristotle, Euclid, and Galen. Experimental science in alchemy and anatomy led to the invention within and outside university surroundings. It is this invention of the university environment that ushered in the modern times. Many of the philosophical though today happens in the confines of universities and institutions of higher learning. Philosophy has taken the form of a discipline. However, the Renaissance had a darker side. Despite interest in philosophical ideas, violent and pestilent death was frequent, and warfare was widespread. There was lots of interest in things that embraced the occult, astrology, and magic. It is during this time that the formally authorized persecution for witchcraft commenced. A number of intellectuals felt a deep cynicism about the corruptions and evils of society as evident in the frequently savage humanist opposers of Desiderius Erasmus and Giovanni Francesco Poggio Bracciolini. Nicolo Machiavelli, one of the supreme Renaissance thinkers ca me up with a realistic science about human nature with regards to reforming the Italian society and the making of a civil life that is immensely secure. Cassirer & Domandi (2010) state that, â€Å"Machiavelli’s republican ideals influenced by a realistic viewpoint of politics and the inevitability of vibrant change were the most innovative contribution of the Renaissance towards the modern world† ( p. 75). Undoubtedly, the Renaissance Era was influential in that it lived on in instituted standards of literature and taste and an

IRB Critique Essay Example | Topics and Well Written Essays - 1000 words

IRB Critique - Essay Example My proposed dissertation research study is made up of mixed method design, with one dominant and one secondary components of data collection. The proposed quantitative research will facilitate me with my investigation on how the academic performance of a student coincides with the job fulfillment of a teacher. In this concurrent study design, the proposed qualitative method will allow me to test specific hypothesis that will affirm my research inquiries in a moderate sample size of educators. In line with this, the following are formulated: (a) Proposed qualitative survey to be shelled out to a random sample composed of 25 K - 12 teachers, and (2) proposed structured formal personality test to be conducted to the 25 chosen participants. The research will conducted at one of the six schools in the county. Surveys and the Myers Briggs will be administered before the conclusion of the seminar. The survey will be a maximum time of 10 minutes and the MBTI will be a maximum time of 45 minutes ***May you give me some pointers with this? Totally confused *** The proposed research study will be conducted to one of the six schools in the county. Prior to the conclusion of the seminar, surveys and the Myers - Briggs Type Indicator (MBTI) will be administered separately. A maximum time of 10 minutes will be spent for the survey, and a maximum time of 45 minutes for MBTI. The data gathered thru the survey and MBTI will be recorded, incorporated, and analyzed by the researcher. The result of this investigation will determine the teachers’ personality and job satisfaction. Inclusion: My population will be K-12 educators (both men and women) of various ages and years of experience. 2 teachers from each grade level with one opening for a vocational or fine arts teacher. (I don’t get this). Inclusion: This study will focus on the K - 12 teachers of both sexes, and of various age

BP Essay Example | Topics and Well Written Essays - 500 words

BP - Essay Example In order to achieve the above strategic aims of the organization, the bank developed a balanced score card for each of the 4 perspectives .This score card was developed by BP in 2003 .We will see what this score card was- (Anderson, 2003) BP made the mistake of separating quality from normal day to day business activities. Quality managers were seen by most team as outsiders who came to overlook their work. Due to this quality concept was not internalized but workarounds were developed which were used whenever the quality team visited. As is this case for any standardized software which is launched across a mammoth organization, launch of Echoke met with resistance from employees. Echoke was supposed to find out the choking points of the operation team – the areas where problem occurs again and again and thus create a standardized benchmark – however it failed to factor the human factor in this software. (Bamberg, 2000) New safety manual were launched by BP in 2004 .These manual were uniform with slight variations from place to place. However the problem was that regular training on these manuals was stopped when BP faced financial crunch. This lead to the employees reverting back to their old ways quickly. GOLD stands for Global Operational, Leaders, and Display. Gold was the ERP project launched by BP.GOLD was supposed to accumulate information available from different countries BP operates in and present it to the top management in a comprehensive manner. Initially GOLD failed to capture the prevailing conditions in different countries as they were vastly from each other which made the data skewed. There were also compatibility issues with echoke which took a lot of time to be resolved. Safety audit teams faced the same fate as quality managers. Deep thought was not given over the composition of these

Critical Thinking and Informatics Assignment Example | Topics and Well Written Essays - 500 words

Critical Thinking and Informatics - Assignment Example In contemporary times, nurses’ assessment relies upon technology, which yields much reliable results. It has not negatively affected the assessment skills of nurses and in fact it has transformed the assessment methods that have improved the clinical assessments (Webb & Shakespeare, 2008). Though technological tools may have errors, but the results are more accurate than human assessment. According to the study of Powell-Cope & Patterson (2008), the use of patient care technology has become complex with the passage of time, and this is because of the reason that the before the use of technology, nurses relied more on their sense of sight, touch, smell and hearing to detect the change in the patient (Powell-Cope, Nelson, & Patterson, 2008). Now, the excessive use of technology tools has suppressed the sense of nurses to detect changes in the patient (Powell-Cope, Nelson, & Patterson, 2008). As cited by Powell Cope in ‘Patient Care Technology and Safety’ nurses relied on change in the skin color and mental status of he patient to determine the changing in oxygen saturation. This reflects that before the invention of pulse oxygmetry nurses were able to identify the oxygen saturation in the patient determining their physical and mental condition. Similar has been cited by Zalumas in ‘Caring in Crisis’ as he states that the overdependence of nurs es on the technology has declined clinical assessment skills (Zalumas, 1995). The legal implication and computerized data has increased the burden on the technical environment. Inducement of Patient Care Technology has provided new dimensions for the clinical practice as nurses are relying more on these technologies that has discarded old methods. On the other hand, scholars believe that the technology has resolved major issues related to nurses assessment (Dickerson, Brewer, & Kovner, 2007). According to Rudy and Bertman,

Introducing Paulaner Beer in Indonesia (Demographics sections) Research Paper - 1

Introducing Paulaner Beer in Indonesia (Demographics sections) - Research Paper Example Muslim population, the issue of alcohol consumption in Indonesia has raised debates in the country for a long time with the current debate revolving on the possibility of banning alcoholic drinks in the country. Although the rate of alcohol consumption in the country remains relatively high, strong Islamic beliefs held by most Indonesians has made it difficult for investors to invest in alcoholic beverages. Consequently, most alcoholic beverages consumers in Indonesia are tourists. However, some Indonesian youths engage in alcohol drinking although this is mostly restricted to urban areas (Grant 98). The country’s ban on alcohol advertising on media would also mean that Paulaner has limited platform on which to market its products. As a way of regulating alcohol consumption, the government of Indonesia in 1990 banned alcohol advertising on media which has since made it difficult for new entries in the market to thrive. Other forms of alcohol advertising in the country are also governed by strict rules further making it difficult to reach new markets. Laws on certification on alcoholic products in Indonesia are also strict and can involve a long process before one gets a license. The country further classifies alcoholic beverages in the closed business field meaning that commercialization of any business related to alcoholic beverages is illegal (Grant 98). Consequently, businesses in this industry are restricted from expansion through investment. When the above factors combine, they present a significant challenge to any investor planning to invest the alcoholic beverages industry in Indonesia. Among the factors that might negatively impact on a business is poor quality products coupled with poor customer services. Equally detrimental is the effect of negative actions by an employee within a business more so when it comes to dealing with clients. Additionally, irresponsible financial management that includes ill-advised investment can also impact on a

Experiential learning-case study. MSc in HRM Essay

Experiential learning-case study. MSc in HRM - Essay Example Experiential learning therefore directly addresses the needs and desires of the learner, rather than being dictated by the instructor. In the context of organizations, individuals acquire different skills, ideas and concepts by observing what others are doing within the organization itself. Practical solutions to problems and obstacles that confront the learner motivates him to work out solutions to problems by either observing how others do it or innovating a way of doing it that others may later imitate (Rogers & Freiburg, 1994, p 16). Starting a business for instance is usually a response to a certain need that the business is envisaged to meet. Once the business takes off however, it may not survive by sticking strictly to the original plan since other unforeseen needs arise that are met experientially. Many business organizations therefore survive through constant learning brought about by varied experiences (Rogers & Freiburg, 1994, p 17). This case study focuses on the Wegman’s Food Markets. It analyzes how the company has established a reputation, and won awards in the process, as one of the organizations with the best human resource management practices. This has been achieved almost entirely through the practice of experiential learning (Bingham, & Galagan, 2005). Though from the foregoing, experiential learning is a self-motivated process, the concept can be used to initiate and effect interventions in employee training and development by organizations (Rogers & Freiburg, 1994, p 18). One such example is Wegmans Food Markets. It is a huge chain of supermarkets ranking as one of the biggest private companies in the US. In 2005 Fortunes magazine rated it the best in among the top 100 employee friendly companies in the US (Bingham, & Galagan, 2005). The Company has some 35,000 employees in its 69 stores located in New

Introducing Paulaner Beer in Indonesia (Demographics sections) Research Paper - 1

Introducing Paulaner Beer in Indonesia (Demographics sections) - Research Paper Example Muslim population, the issue of alcohol consumption in Indonesia has raised debates in the country for a long time with the current debate revolving on the possibility of banning alcoholic drinks in the country. Although the rate of alcohol consumption in the country remains relatively high, strong Islamic beliefs held by most Indonesians has made it difficult for investors to invest in alcoholic beverages. Consequently, most alcoholic beverages consumers in Indonesia are tourists. However, some Indonesian youths engage in alcohol drinking although this is mostly restricted to urban areas (Grant 98). The country’s ban on alcohol advertising on media would also mean that Paulaner has limited platform on which to market its products. As a way of regulating alcohol consumption, the government of Indonesia in 1990 banned alcohol advertising on media which has since made it difficult for new entries in the market to thrive. Other forms of alcohol advertising in the country are also governed by strict rules further making it difficult to reach new markets. Laws on certification on alcoholic products in Indonesia are also strict and can involve a long process before one gets a license. The country further classifies alcoholic beverages in the closed business field meaning that commercialization of any business related to alcoholic beverages is illegal (Grant 98). Consequently, businesses in this industry are restricted from expansion through investment. When the above factors combine, they present a significant challenge to any investor planning to invest the alcoholic beverages industry in Indonesia. Among the factors that might negatively impact on a business is poor quality products coupled with poor customer services. Equally detrimental is the effect of negative actions by an employee within a business more so when it comes to dealing with clients. Additionally, irresponsible financial management that includes ill-advised investment can also impact on a

Managing finanical in health and social care organization Essay

Managing finanical in health and social care organization - Essay Example However. a number of hazards have been associated with the use of mercury-in-glass thermometers. Due to its invasiveness and potential risks, alternatives to mercury-in-glass thermometers are considered. Alternative devices include electronic digital thermometer, tympanic infrared thermometer, chemical dot thermometer and handheld infrared thermometer. The preferred option is chosen through benefit weighting, option appraisal weightings and cost-effective analysis. Consequences on levels of neonates or staff activity for agreeing or not agreeing the option and recommendations are discussed. The process of this business case is discussed in the following paragraphs. There are several mission objectives in my hospital: 1 providing quality hospital care to patient delivered by a team of competent professional staff using advanced facilities and technologies, 2 educating and training health professional who are for patients, their families and the community, and who strive for professional and team development, 3 establishing partnership with like-minded community organizations to achieve a healthy, progressive and productive community, 4 promoting a healthy lifestyle and advocating a compassionate community and a caring family culture for the Hong Kong community (Hospital Report 2005). Among them, I would like to introduce advanced facilities and technologies for delivering patient care in my dept. The hospital has only one neonatal unit, which allows admission of newly born infants. The total number of beds is 40. manpower of the neonatal unit includes 20 nursing staff, 8 health care assistants and 6 amah. There are 5 nursing staff, 2 health care assistants and 1 amah in every morning or afternoon shift. We have to work the delegated job when we are on duty. Nurses are responsible for accurate measurement of body temp. (Browne et al., 2000; Potter, 2001). Thermoregulation is a vital body function, which

Emotional Response To Music And Happiness Psychology Essay

Emotional Response To Music And Happiness Psychology Essay The objective of this research is to examine the correlation between emotional response to music and happiness among the undergraduates of UTAR: Perak Campus. Besides that, the gender differences in emotional response to music and gender differences in happiness will be examined as well. The findings show that there are more than half of the participants scored more than 4 out of the maximum score of 7. It means that they mostly have an average level of happiness. There are only few participants fall in low happiness level which scored less than 3 and about more than quarter of participants fall in high happiness level which scored 5 or above. Emotional Response to Music and Happiness This research found that there is a significant correlation in emotional response to music and happiness among the universitys undergraduates. The level of emotional response to music among both male and female undergraduates is correlated to their respective happiness level. This is supported by Lamont (2011) where the study results show that young adults are likely to have strong positive experience from music listening, especially if it had had a prominent strong impact in their lives. This result show the correlation between emotional response to music and the pursuit for happiness as music may provide a possible connection to various aspects to find happiness or to reach a peaceful state of mind free from any side effects. (Lamont, 2011) Another research that can support the result of this finding states that music listening was claimed to be mostly relaxation, mood improvements, and as well as decreasing negative emotional well-being such as being under stress and anxiety. (Kal linen Ravaja, 2008) Other than that Saaikallio, Nieminen Brattico (2011) support the results of the researchs as it was found that it is not necessarily only happy music that can evoke feelings of happiness in the listener. It was also found that sad music can induce positive feelings such as happiness as well, which may be due the individuals need to preserve happiness despite the sad (musical) stimulus, or also because the need to not be overly emotionally affected or touched by the particular piece of music. (Saaikallio, Nieminen Brattico, 2011) With this notion, it can further support the correlation between emotional response to music and happiness, as the type of music does not become a barrier in the obtained positive feelings of happiness through listening to music. In a similar study Van Goethem Sloboda (2011) found that music plays an important role in the creation of happiness as well as relaxation. Other findings include: (1) music is effective in helping strategies of regulating emotions such as distraction. (2) music is quite a successful device for affective regulation alongside with other types of mechanisms of coping. (Van Goethem Sloboda, 2011) The research also indicates that happiness is the highest percentage affect being regulated with music which supports this researchs result on emotional response to music and happiness relationship. Listening to music can regulate ones emotions and with happiness being the easiest emotion to regulate through music listening, the stronger ones emotional response to music the happier they are. Despite the disagreement that happiness is induced from the music Konecni, Brown Wanic (2008) found that the overall measure of the participants after listening to music was leaning more towards the positive emotion of feeling happiness which is felt through the recollection of their life-events that seems to be rather attached to the emotions felt through music. The findings also suggested the big difference between originally experienced real life events emotions and the induction of happy-sad emotion by music proceeding to state that emotions induced in music solely triggers the listeners imagination (recollection) of that emotion once felt. (Konecni, Brown Wanic, 2008) Hence, the emotional response to music can be applied by listening to happy music to induce positive emotions such as happiness. Happiness and Gender This research showed that there are is a significant difference in happiness level in male and female. According to a research conducted by Yang (2008) showed that there are gender differences in happiness level where women tend to be happier than men before old age but their happiness level seems to declines when in old age; while men are tend to be happier in old age. This is supported by Easterlin (2010) that is showing the same result displaying evidences between genders and generations, men and women are equally happy and unhappy when look on the whole; but when looked closer at different life stages, women turns out to be happier than men in early life but less happy and the end. (Easterlin, 2010) Inglehart (2002) found that women who are below 45 of age tend to be happier than man. While the longitudinal research done by Stevenson Wolfers (2009) shown that there is a declination of happiness level in female across the years. According to Zaidi (2010), women have bigger orbital frontal cortices compared to men because there is highly significant difference in the ratio of orbital grey to amygdala volume. The ratio between the orbitofrontal cortex (part that in charge in regulating emotions), and the size of the amygdala, are mixed up in order to produce emotional reactions. The ratio appears larger in women than men. On average, women might be more proficient of handling their emotional responses. (Zaidi, 2010) Biological differences and gender roles are the most probably to lead distinction between male and female and presenting the differences of happiness among genders. In another research conducted by Crossley Langdridge (2005) showed gender differences among the perceived happiness: Men scored better in sexual activity, being liked, sports and owning a good social life; whereas women scored better in having a close family, loved by loved one, assisting others, good social life and being liked than men in assisting them to achieve happiness. (Crossley Langdridge, 2005) Hence the difference of happiness level between genders. Emotional Response to Music and Gender This research showed that there are is a significant difference in emotional response to music level between male and female. According Chentsova-Dutton Tsai (2007) women were more emotionally reactive than men as they exhibited larger changes in overall reactivity, where they report the more extreme emotions while reliving rage and feelings of affection for recollection of past events. The study suggests that at some level, gender differences on emotional response may persist even across ethnic groups. (Chentsova-Dutton Tsai, 2007) Hence the gender differences in emotional response to music. According to Nater, Abbruzzese, Krebs Ehlert (2006) research on participants reactions to different musical stimuli (relaxing classical music, and unpleasant metallica), women have the tendency to exhibit hypersensitivity to repulsive musical stimuli hence displaying the gender differences in emotional response to music. In a similar research, Istà ³k, Brattico, Jacobsen, Krohn, Mà ¼ller Tervaniemi (2009) found gender differences for some emotional when describing music terms such as touching, feelings evoked, ugly, and drab, additionally male participants have higher tendency to express with negative adjective compared to female participants. Multiple researches suggests otherwise, Rickard (2004) found that gender difference may not contribute to difference of emotional response to music in terms of physical arousal as the music with emotional power treatment induced significantly greater increase in skin conductance and number chills equally in both gender. Lundqvist, Carlsson, Hilmersson Justin (2009) show similar results with no gender differences in emotional response to music in terms of both physical and mental response, as both male and female have equal response level to music stimuli. Limitations and suggestion This research had faced difficulties in finding journals of gender differences on level of happiness, gender differences in emotional response to music no matter of Malaysia context or others because there are limited sources and research on this topic. The researcher had faced difficulties especially in locating journals or articles to compare on happiness level and emotional response to music. Therefore, this research is to make contribution to the studies gender differences on happiness level, and emotional response to music and happiness. In this research, it only involved a hundred participants (fifty male students of UTAR: Perak Campus, and fifty female students of UTAR: Perak Campus) which is not enough to generalize on the population. Further research need to increase the sample size and different backgrounds of participants so that the result obtained could be generalized to the whole population. Furthermore, the participants of this study are mostly Chinese. Due to the same ethnics and belief systems they have, may contribute to this result which is no gender differences in happiness level. Thus, further study has to be done by involving more ethnicities and culture values in order to find out a more thorough study. Moreover this research only focuses on the effects of gender differences on emotional response to music, and level of happiness which is not enough to study on the outcome of the research. Other demographic aspects should be included in future study on this research, such as age, ethnicity, race, field of study and so forth. A suggestion for more accurate reliability of this research is to conduct a cross-cultural study to determine the effects of cultural differences on the outcome of the research. Conclusion This study is proposed to find out the correlation between emotional response to music and level of happiness, the gender differences in emotional response to music, and gender differences in happiness. The results show that there is significant correlation in emotional response to music and happiness which means the level of emotional response to music and level of happiness interrelates with each other. There is also a significant gender difference in emotional response to music, where this study found that female have higher level of emotional response to music compared to male. Lastly, gender differences in happiness have a significant outcome as well, where female was found to have a higher level of happiness than compared to male. This research has made contribution to emotional response to music and happiness researches in Malaysia context. In order to improve the outcome of this study, more research as a bigger sample range should be conducted to increase the validity and generalization.

Concepts of the Body, Medicine and Madness in Mary Shelley’s Frankenste

I intend to examine to what effect concepts of the body, medicine and madness are presented in Mary Shelley’s Frankenstein (1818). I shall perform close analysis to parts of the text referring to explorations in new technologies, advances in medical science, and there psychological impacts. I shall discuss social implications of the growth of man’s technological evolution during the eighteenth and nineteenth century. Mary Shelley’s Gothic science-fiction novel Frankenstein (1818) was written and published between two major historical events. It followed The French Revolution (1789-1799) a period of radical social and political upheaval, and was written during The Industrial Revolution between the eighteenth and nineteenth century, a time of great socioeconomic and cultural effects. The French Revolution acted as ‘the single most crucial influence on British intellectual, philosophical, and political life in the nineteenth century.’ (David Cody, French Revolution: 2010). The Industrial Revolution marked ‘the transition from a world of artisan manufacture to a factory system.’ (Shirley Burchill et al. The Industrial Revolution: 2010). The advancements in machine based manufacturing brought social implications of anxiety. Frankenstein can be viewed as a reflection of the turmoil and change seen within society during the eighteenth and nineteenth century, thro ugh the explorations and growth in man’s technological evolution. Frankenstein is an epistolary novel, comprised of letters, journals and diary entries, allowing the reader a sense of verisimilitude – a sense that it might have actually occurred, enabling the author to change points of view when required to further the plot. The story follows a young grief stricken ... ....com. Unabridged. Random House, Inc. 2011. Available from www.dictionary.reference.com/browse/Prometheus, [accessed 12th January 2011]. Russell A. Potter, A Chronology of Frankenstein. Available from www.ric.edu/faculty/rpotter/Frank-chron.html, [accessed 12th January 2011]. Robert W. Anderson, Body Parts That Matter: Frankenstein, or The Modern Cyborg, 1999. Available from www.womenwriters.net/editorials/anderson1.htm, [accessed 12th January 2011]. Shirley Burchill, Nigel Hughes, Peter Price & Keith Woodall, The Open Door Website, The Industrial Revolution, 2010. Available from www.saburchill.com/history/.../001.html, [accessed 12th January 2011]. U.S. National Library of Medicine, National Institutes of Health, Frankenstein Penetrating the Secrets of Nature, 2010. Available from www.nlm.nih.gov/exhibition/frankenstein.html, [accessed 12th January 2011].

Universality of Death of a Salesman :: Arthur Miller

Death of a Salesman's universality comes from its fundamental themes and ideas which will adhere to place and time period it is. They have the ability to connect with such a universal audience because they take into account human nature. We, as readers or viewers, of the play can connect with the concepts presented because they are part of our everyday lives. Let's start off with one of the major themes in the play, which is the pursuit of a dream. For Willy Loman, it is the American dream. His false notion of this dream, which he believes with firm conviction, if you are "well liked" and "personally attractive" you will do well in business and life. The American dream is something that can be pursued, but not the way Willy perceived it. For example, Chris Gardner, the successful owner of stock brokerage, went from being a homeless man sometimes sleeping in public bathrooms to opening becoming a multimillionaire. His rags to riches story, like many others, show hard work and dedicati on can help you achieve your goals. Thousands of people come into the U.S. each year, many of them with the hope of building a better life in the "land of opportunity." Dreams can vary. We all have dreams because we want to achieve more so we can have a better life, whether it is in terms of wealth, health, family, or happiness. However, even with dreams and achievements, we may not always be able to get what we desire. Willy Loman was unable to see this. Even with defeat staring at him, his denial as well as his inability to face it, blinded him from accepting the truth. Another thing that makes this play timeless is the idea that, regardless of who we are, each one of us is a salesman and we will continue to be salesman. For example, teachers sell their beliefs and ideas to their students. People aspiring for a job sell themselves to the employers. The same thing goes when applying for colleges or when finding a mate. So, in that sense, we have a little bit of Willy Loman in us making this connection we can relate to him and hope not to make his mistakes. Death of a Salesman is just as significant in this time period as it was in 1949 is because a common man is trying to make it in his world.

Agree or Disagree: Your Job Has Greater Happiness Than Your Social Life Essay

Society changes at an unprecedented speed. So does people’s views toward their jobs. This has aroused a heated discussion whether people’s jobs own more happiness than their social life dose. From my point of view, compared with working, my social life means more. To begin with, admittedly, there exist some people who relish their job and consider it whole part of their life. For instance, an honorable professor in my university spends all his lifetime with his students and colleagues. He poses all his heart to the studying field of Chinese film. Only by referring to this concerned field, can he have the eyes lustrous. Without any other social activities, he lives a very satisfying life. However, it literally differs person to person. As for me, job is merely one aspect of my life. True, it provides the opportunity to enlarge my vision on profuse communicating methods and help me be seemingly mature. But the vision is limited to certain fields, knowledges without any connections with job still stay in an uncultivated state, such as skills of veraciously making friends, spirits of exploring new areas, kindness to others and so on. Lacking these crucial elements, I wonder whether it can be a happy life. Perhaps even more significantly, social life can help maintain a good health status. People could select a multitude of activities which make benefits for their physical health. For people like me, I play tennis every weekend, resulting in that I have not caught a cold for almost three years. And this offers the requisite basic of a happy life. In addition, social life also could be make advantages of by diverting concentration then assuage spiritual pressure. We could travel and spot various scenery with diverse people, make fun of different circles of friends, experience other’s lifestyles, explore deeper information of beloved fields. In sum, social life could better life quality and life contentment due to many reasons discussed above. Therefore, not only working, but also combining social life, life could be more variegated.

Injustice in the Adversarial System Essay

Donald Black discussed in his book The Behavior of Law, when a society begins to grow and become more complex so does its legal system. The United States uses a system that may no longer be fit for handling all the complex problems it is faced with. Society has come to learn through the justice system that truth is very hard to find. The nature of the adversarial process may prevent it from reaching the true goal of every legal system: justice. This writing argues that the system in place now is not the correct one for the stage society is in now. The adversarial process in place does not search for the core values of â€Å"Justice† and â€Å"Truth†; its inadequacies create errors in the legal system. The legal system should abolish its value of â€Å"winning at all cost† and the methods it uses to achieve this outcome. This paper will not only shed light on the flaws in the legal system, but present other structures that may be better suited for the present stage of society. Blueprint A few brief critiques of the adversarial process include that during a trial procedure both sides are given the opportunity to present facts to the jury or judge, this allows attorneys to withhold evidence and benefit the side they represent. This confuses the courts instead of elucidating the truth. Cases such as this should not be able to come to a guilty or not guilty verdict, because guilt cannot be proven with a degree of accuracy (Meadow, 1996). Stratification in law does lead to inequality and perpetuates injustice in society. The procedure that is used in our criminal justice system has the ability to lead to a false confession and create mistrust in the system. Bias in our legal system does lead to injustice. All of these factors do create injustice in our legal system by sending innocent people to prison and/or by letting convicted felons free. There are many theories in how to solve the problems with the adversarial process and the legal system in general, but society must change the way it reasons before anything can truly change. History of Common Law and the Adversarial Process To better understand the adversarial process it must first explain through its history and origins. Common law practice developed the adversarial process; England adopted common law and made its practice known throughout the world. Legislators began codifying the law, this later became common law. It was written so that it could be interpreted by the court system. When the courts make a decision in how that law is to be applied it is preserved, and able to be used as a guideline for other cases of the same nature. This proved to be a problem, decisions made by judges were based on the customs of the time period, which became rigid and did not easily allow for change (Cantor, 1997). The English form of common law prohibited representation in court however, during the eighteenth century some courts where beginning to allow legal representation in English common law. Eventually as time progressed, the role legal representation, lawyers, would grow and be more influential in society. The part the Lawyers played in the court system would eventually be the aspect that separated the adversarial process implemented today in the United States from the processes in England. Law became more and more complex so the use of lawyers or professionals of the law was essential in American law making. New research by Randolph N. Jonakait, New York Law School professor, suggests that the United States adopted an adversarial process that somewhat resembled the English model at the time. Besides the already mention use of lawyers, the U.S differed greatly from England, during the 18th century; America had prosecution with a public defender present in the court room compared to no legal representation for the accused in the English model. Also in New Jersey around the same time period, attorneys usually appeared for the prosecution and the defense which in England was rarely practiced. These findings demonstrate that the United States was a forerunner in the creation of the adversarial process that is present today (Jonakait, 2009). Search for Truth: Lawyers and Their Tactics One of the main concepts of the adversarial system is the oppositional presentation of facts. The belief behind this is it will discover all truths to the matter. This leads to the conclusion of the first flaw: that realistically everyone involved in the case is not in search of the truth. â€Å"Lawyers are more apt to hide the evidence that is not favorable to their side regardless of whether it would prove the innocence or guilt of the person on trial† (Schroeder, 2012). Clients hire lawyers to win; the economic state of the client is directly related to the skill level of the lawyer they can afford. Lawyers who are more expensive will use any tactics necessary to ensure a win. The search for truth is not a key value; it’s keeping your client pleased, being the defendant or the state. Attorneys are known to use questionable tactics so that they have the best possibility of winning their case. These tactics include: creating doubt in the jury of guilt or innocence, or even by hiding evidence from the jurors. The search for truth and the execution of justice cannot be fully performed if lawyers proceed to use unethical tactics. Solutions to the Hiding of Evidence A purposed solution to hiding evidence can be demonstrated with a value demonstrated from the inquisitorial system, everyone in the court room works together in search for the truth and justice. The judges, or investigative magistrate, are trained in their profession, taking specific schooling about law making them a vital resource to the legal system. While court is proceeding the judge is allowed to ask questions to keep a case in order. Using a system that does not glorify winning would help the hindering of evidence and other tactics being eradicated form the court room. Although, one flaw with this system is the judge is granted too much power and control over the proceeding, more justice is still found here searching for truth. Stratification in Law It is proven that â€Å"once arrested, black and minority defendants are fare worse in the criminal justice system than their white counter parts† (Westervely & Humphrey, 115, 2008). This is due to racial stratification in law and a bias based on race in convictions. Instrumentalist would say law is used to dominate groups, and is structured so that it can benefit certain groups by disadvantaging other groups, by allowing this to happen it perpetuates inequality (Bucher, 2012). Many minorities are unable to pay for legal representation; in this situation the courts provide representation for them. This disadvantages minority individuals in low social class because they lack resources to secure a good lawyer, while high social status clients are able to easily obtain skilled lawyers. This perpetuates stratification because upper class individuals can evade the penalties of the legal system, unlike lower class individuals who cannot afford strong legal representation (Vago, 2012). Marxist theorists would confirm that laws serve the interest of the upper class, and because they use them like a tool, keep the upper class in power. This reinforces inequality in society through the criminal justice system, because the upper class will always be able to have access to more resources they will also always use those resources against the lower class (Bucher, 2012). Process in Criminal Justice Is Justice Served? The pressure felt in a case created by media and the public eye have the ability to cause investigations to be sped up. The endangers the adversarial process to make mistakes and possibly out of convenience and pressure convict the first person they think committed the crime. Once police officers make an arrest they tend to not pursue any other possible leads until the person they have in custody is proven to be innocent. This hurts the search for truth because officers become close minded and search only for evidence to convict that individual. Another factor that can deter the search for truth is false confessions. False confessions, among other factors, are commonly created due to unethical interrogation tactics or confused eye witnesses testimony. â€Å"A confession is one of the most powerful pieces of evidence that can be presented in court† (Westervely & Humphrey, 36, 2008). Even if the confession is false, juries have been known to take into consideration testimony even when told not to. False confessions are usually given by suspects who are coerced, confused, have doubt in-self, or shame. All this can be attributed to the psychological games used by interrogators, intentional or unintentional (Gudjonsson, 1992). Can true justice be served when police use unethical tactics to get their confession? This is a question scholars who study ethics have pondered with for decades. Bias in Law There are many principles to consider when a jury is deciding a verdict. Racial beliefs, media and number of factors can influence a jury’s verdict (David F. Hall, 1984). Since each individual interprets the process of the trial differently it greatly influences the decision of case. The way society is socialized leads to certain bias to people of different races, genders, sexuality, and backgrounds. These factors greatly influence a cases outcome, even though lawyers are allowed to select their jury it is impossible to know each person individually (Albonetti and Hagan, 1982). In common law, legislature creates the laws that are written down and left for interpretation by the judges of the court, this is called statutory interpretation (Bucher, 2012). The strength of this system of law is the ability that law has to change; downfall is that it leaves room for bias in the interpretation of law. Some scholars suggest that law and the legal system is patriarchal. The feminist legal theory suggests that the legal system is male dominated and perpetuates gender discrimination (Bucher, 2012). Language can be biased in law; the United States suffers from this weakness. In the Declaration of Independence biased language is evident. â€Å"All Men Are Created Equal† a line from the Declaration of independence has brought forth discussion and conflict because of biases behind the words. Women have fought for their rights to be considered equal because society takes the patriarchal documents literal, progress is slowly made. Everything, including law, can be interpreted differently, making the judge’s job detrimental to the court process. The discretion of the authority in the court system, although important, also creates inconsistency in the legal system. African Americans account for 49.4 percent of the 1.3 million Americans in prison (Westervely & Humphrey, 2008). Two different theories can explain the bias in society that explains the high population of African Americans. These theories are the Individual Explanation Theory and the Structural Explanation Theory. Individual Explanation Theory This theory focuses on the behavior and traits of those involved in a trial. Racism is a factor in explaining why an innocent person is tried. This happens because the adversarial system does not focus on searching for the truth and allows the jury to makes a decision on beliefs and prejudices of a certain race. Stereotyping is also included when a jury convicts someone on account of preconceived notions of a group (Westervely & Humphrey, 2008). Structural Explanation Theory This theory provides two explanations for the bias. The first is the Blalocks Power-Threat Hypothesis. The hypothesis states that the increase in minority conviction is due to whites trying to keep power and control over minority races by disadvantaging them. The second explanation states that the treatment of minorities in the criminal justice system is a reflection of societal beliefs. â€Å"Equality in the criminal justice system is not possible until everything else is equal† (Westervely & Humphrey, 128, 2008). Plea-Bargains and its deficiencies Due to the amount of offenders that go through the U.S. court systems prosecutors are more likely to use plea-bargains to settle cases quickly. â€Å"It is estimated that roughly 90-95 percent of all criminal convictions are arrived through plea–bargains† (Vago, 118). This tactic can be linked to stratification and inequality, when a person on trial does not have the finances for a good lawyer the assumption is that they will lose. This makes a plea-bargain more appealing, as it is the best option to avoid a longer sentence (Kipnis, 1976). â€Å"The Standing Committee on Legal Aid and Indigent Defendants summarized the state of representation as follows: â€Å"Overall, there is abundant evidence in this report that defense services for the poor are inadequately funded. As a result, millions of persons who have a constitutional right to counsel are denied effective legal representation†Ã¢â‚¬  (Mosteller, 2011). This is another factor to cause change in the legal system so that truth can properly be found. The ability to plea-guilty hinders the search for truth and justice. In the inquisitorial system guilty pleas and plea-bargaining are not allowed so that the system can properly search for the truth. It does not give the accused rights, unlike the United States. While in the United States the adversarial process gives the accused the ability to plead guilty for a lesser sentence which some would consider â€Å"soft† on crime. In the adversarial process after a confession is given, the investigation is typically over even if the individual is innocent. In the inquisitorial system a confession is not warranted since it is the duty of the court to come up with evidence and prove guilt (Berger, 1972). Injustice With all this bias in our legal system this gives room for errors in justice. â€Å"An error in justice is any departure from an optimal outcome of justice for a criminal case† (Frost, 2004). There are two types of errors that can be described: systematic and random. Systematic is when there is an error within the law that consistently creates injustice. When a law is in enacted and it oppresses a certain group consistently this is systematic injustice. Random errors are created while criminal justice officials are enforcing the law and the error is sporadic (Frost, 2004). Both of these can create errors of due process, which is when the rights of the accused are violated. The first error is miscarriage of justice; an example of this is when an innocent man is convicted of a crime. The second type of error of due process is error of impunity, when an error in the procedure of due process is committed and as a result guilty convict is set free. Both of these do create great mistrust in the legal system and deter people from getting involved within its legal processes (Sherman, 2002). This can lead to what Black was suggesting when he stated that law will shift back to a more primitive family based form of sanctions, because of mistrust in the authority that was supposed to protect them. Change With new understandings of societal factors (race, gender, sexuality) the adversarial system needs to be revised so that it aids the search for truth or it will be blinded by these factors. Society has grown complex and so has its problems with in the legal system. The courts must come up with different resolutions for crimes and convictions, not just a â€Å"one size fits all solution†. In essence the adjudication system is not wrong, but the misuse of evidence and human error leads to mistakes. One might ask should we change the adversarial system entirely or fix the many flaws within the system. The current process being used relies on the state (prosecutor) to determine if the court should or shouldn’t present the evidence accumulated from the crime, or if that would benefit the accused in some way. All evidence should be given to a neutral party, such as the court, and have the court system decide what should be done. This would remove the ability of the prosecutor to hide facts that could be essential to the investigation (Westervely & Humphrey, 2008). In an ideal system the court should base their decision after learning all the facts, without any evidence withheld from either side. There can be a mixture of different processes, which can better achieve justice in a complex society. For example, a different process would be needed to determine if a dangerous criminal is guilty than that of finding parental rights. Forms such as the inquisitorial investigation, mediation, private problem-solving, group negotiating processes could be used to search for truth. Conclusion The adversarial systems values do not match what the goals of the system should be. In the ideal system restorative and rehabilitation justice would be utilized to the fullest in order to help the people going through the criminal justice process learn and become productive members of society. Society’s beliefs are that of retribution and vengeance. Society as a whole wants to see criminals punished for crimes that they feel where committed upon them. To completely change the beliefs of the criminal justice system, society needs to change its values from retribution and vengeance, to a form of justice that will help society instead of looking for revenge. Values in the criminal justice system represent what that society believes in. The belief in winning shouldn’t be enforced, like the adversarial process has done, because it does not accomplish what the main goal of the criminal justice system is: to provide justice to the citizens of the country the system serves, along with the search for truth. The values of rehabilitation and restoration should be the foundation on which we build our new system. If this is done than our society will begin to help its self in creating a strong nation that is just and true. References Albonetti, Celesta and Hagan, John. Race, Class, and the Perception of Criminal Injustice in America. American Journal of Sociology, Vol. 88, No. 2 (Sep., 1982), pp. 329-355 Berger, Moise. The Case Against Plea-Bargaining. American Bar Association Journal. Vol 62.pg621.(1972) Black, Donald. The Behavior of Law. The University of Michigan, Academic Press. 1976 Bucher, Jacob. Law and Society. Lectures. Baker University. 2012 Cantor, Norman F. Imagining the law: Common law and the foundations of the American legal system. HarperCollins Publishers (New York). 1997. David F. Hall et al., Post event Information and Changes in Recollection for a Natural Event, in Eyewitness Testimony: Psychological Perspectives124 (Gary L. Wells & Elizabeth F. Loftus eds., 1984) Frost, Brian. Errors of Justice: Nature, Sources, and Remedies. Press Syndicate of the University of Cambridge.2004. Gudjonsson, Gisli H. The psychology of interrogations, confessions and testimony. Wiley series in psychology of crime, policing and law. Oxford, England: John Wiley & Sons. (1992). xii 362 pp. Humphrey, John A. & Westervely, Saundra D. Wrongly Convicted: Perspectives on Failed Justice. Rutgers State University Press. 2008 Jonakait, Randolph N. The Rise of the American Adversary System: American Before England. New York Law School. Widner Law Review. V14.2009. Kipnis, Kenneth. Criminal Justice and the Negotiated Plea. The University of Chicago Press. Ethics , Vol. 86, No. 2 (Jan., 1976), pp. 93-106 Meadow, Carrie M. The Trouble with the Adversarial System in a Postmodern, Multicultural World. William and Mary Law Review. V.38. 1996. Merrill B. Hintikka & Jaakko Hintikka, How Can Language Be Sexist?, in Discovering Reality, supra note 31, at 139. Mosteller, Robert P. Failures of the American Adversarial System to Protect the Innocent and Conceptual Advantages in the Inquisitorial Design for Investigative Fairness.2011. University of North Carolina School of Law. Sherman, Lawrence W. Trust and Confidence in Criminal Justice. NIJ Journal, March (2002): 23-31. Vago, Steven. Law and Society. Pearson Education, Practice Hall.2012.