Tuesday, August 6, 2019

Money Magazine Essay Example for Free

Money Magazine Essay It seems that Baton Rouge, Louisiana is surviving the current real estate crisis better than most cities. According to a Money Magazine article, â€Å"10 Fastest Growing Real Estate Markets† dated May 13, 2008, Baton Rouge was rated number nine. As of the date of the article, Baton Rouge showed a positive one year price change of 5. 7%; and a positive five year price change of 38%; even though the foreclosure rate had increased by 14% in the same time period. (Money, 2008). Some of the price stability in the real estate market there may be attributable to proactive legislation. If we count mortgage fraud as one of the key factors in the current economic crisis, then we can congratulate the state of Louisiana in the steps they took to prevent fraud. Louisiana’s state Office of Financial Institutions (OFI) took action in December of 2007 to join other states in passing legislation to prevent mortgage fraud. Legislators felt that even though there was not a reported high incidence of mortgage fraud, many of Louisiana’s homeowners were especially vulnerable because of the two recent devastating hurricanes, Katrina and Rita. OFI examiners sought legislative funding to assist with communication within its agency; analysis of statistics and tracking cases. Educating the public about mortgage fraud, including foreclosure help scams, became a top priority. The OFI also investigates allegations of fraud such as buyers pretending to purchase a house as an owner occupied dwelling when it is in fact an investment property. Appraisal fraud is also actively investigated. Appraisal fraud occurs when property appraisers inflate the value of a property to obtain a larger mortgage, often at the behest of a lender or mortgage broker. This scam may seem to boost instant equity in the property, but in truth is a huge detriment to homeowners. This type of activity is particularly insidious, because in the event of a market downturn, homeowners often suddenly owe more on their property than the property’s real value. (Thibodeaux, 2007). While researching this paper I became curious as to how foreclosures in Baton Rouge might compare to another city. I chose Hialeah, Florida to compare, because they are similar in size and not too far off in median age. Also, Florida is ranked in the top four states in foreclosure rates. California, Arizona and Michigan are the other three. As of July, 2007, Baton Rouge had a population of slightly over 227,000 residents; and Hialeah had a population of just over 212,000. Median age groups for both areas was between 30 and 37 years old, so neither is strictly a retirement area. The median household incomes for both areas were nearly identical at just over $32,000. per year. The similarities between these two areas ends there. (Citi Data, 2008). According to Zillow there are 66 foreclosures in Baton Rouge and a whopping 1326 foreclosures in Hialeah. I chose to use the information from Zillow rather than Realty Trac. Realty Trac displays as foreclosures properties in any degree of foreclosure; while Zillow displays houses as foreclosures after they have been sold at a foreclosure auction. Realty Trac when they display foreclosures includes as foreclosures any property anywhere on the foreclosure timeline. If a homeowner has been served with a Notice of Default or a Lis Pendens, it shows up on Realty Trac as a foreclosure. Some of these properties will not be sold at a foreclosure auction. There are many things that can happen between the time a homeowner is served with a foreclosure complaint and the auction at the county court house. A homeowner may remedy the foreclosure by paying all past due payments. The property may be sold as a short sale after a homeowner has received the foreclosure complaint. A short sale cures a foreclosure. Similarly, a homeowner may successfully negotiate a mortgage loan modification after having been served with a foreclosure complaint. A loan modification changes the terms of a mortgage loan to make it more affordable for the homeowner. Lenders have many tools at their disposal to make changes to the terms of the mortgage loan. It is within the lender’s power and discretion to lengthen the loan period for the mortgage, say from a 30 year mortgage to a forty year mortgage and adding the missed payments to the end of the loan period. This provides the homeowner with some immediate relief and the lender does not lose. Or a lender has the ability to change the terms of a mortgage from an adjustable rate mortgage to a fixed rate; or simply change the rate to a lower interest rate. Lenders also have within their power to reduce the principle of the mortgage loan, although lenders are understandably reluctant to do so. (Zillow, 2008). Besides the actual number of foreclosures in Baton Rouge and Hialeah there are also some other striking differences between their respective housing markets. Even though the median household incomes for both areas is nearly identical the median home prices are very different. In Baton Rouge the median home price in 2007 was $142,000. ; and the median home price in Hialeah for the same time period was $245,000. amounting to over a $100,000 difference. The rate of appreciation in the two housing markets also provides some insight as to why one area is so rife with foreclosures and the other is not. In Baton Rouge the median home price was $93,000 in 2000. The increase to $142,000. in 2007 represents about 5% appreciation per year over seven years. By contrast, Hialeah saw an increase from a median home price in 2000 of $102,000. to more than double over 100% in the same time period, which is around a 20% per year rate of appreciation. It is small wonder that so many homes in Hialeah have gone to foreclosure auction. (Citi Data, 2008). When I plugged the different principle amounts into a simple mortgage calculator and used an optimistic 6. 5% interest rate, and a 30 year fixed mortgage loan; the results were remarkable. The homeowner in Baton Rouge would pay $897. 54 per month for his $142,000. home; and the homeowner in Hialeah would pay $1,548. 57 for his $245,000. home. Both homeowners are working with nearly identical incomes. After researching the literature and the data collected for this paper, I wondered whether mortgage fraud played a large role in Hialeah, Florida’s foreclosure rate. According to the Federal Bureau of Investigation (FBI) Florida is one of the states where mortgage fraud is most common, and Louisiana is not mentioned in their report. The FBI defines mortgage fraud as the â€Å"intentional misstatement, misrepresentation, or misstatement by an applicant or other interested parties, relied on by a lender or underwriter to provide funding for, to purchase, or to insure a mortgage loan. † (FBI, 2007). â€Å"Analysis of available information indicated that mortgage fraud was most concentrated in the north central region of the United States. Data from law enforcement and industry sources were compared and mapped to determine which mortgage fraud states for 2007 were Florida, Georgia, Michigan, California, affected by mortgage fraud according to available sources included Arizona, Connecticut. † (FBI, 2007). Mortgage fraud is described as a low-risk, high yield white collar crime. Individuals in finance related occupations such as mortgage brokers, lenders, and accountants were most likely to engage in mortgage fraud. These perpetrators, since they are familiar with the mortgage loan process are best positioned to exploit the process’ vulnerabilities. Victims of mortgage fraud may not only include the borrower and the lender, but entire surrounding neighborhoods as well. If foreclosure rates due to high incidence of mortgage fraud, such as artificially high appraisals, the effect is that the surrounding neighborhoods values also begin to decline. (FBI, 2007). It seems clear that there are a couple of important factors that explain the differences in rates of foreclosures in the two cities examined, Hialeah, Florida and Baton Rouge, Louisiana. First, Louisiana government took steps to prevent mortgage fraud before it ever became rampant. Second, Louisiana enjoyed a relatively modest appreciation in home values during the boom years, home prices never exceeded an amount that a family living within their means could afford. The opposite is true in Florida. In fact, Florida rated number one in the incidence of mortgage fraud in 2006 and 2007. It is simple enough to imagine that appreciate rates in double digits could not last forever. If the galloping rate of appreciation during the real estate boom years was caused by mortgage fraud then the house of cards was destined to finally collapse. References Citi Data (2008). Baton Rouge and Hialeah. Retrieved December 11, 2008. http://www. city-data. com/city/Baton-Rouge-Louisiana. html http://www. city-data. com/city/Hialeah-Florida. html Daily Report (2008). Baton Rouge ranks near bottom for foreclosure activity Oct. 23, 2008 Retrieved December 10, 2008. http://www. businessreport. com/archives/daily-report/2008/oct/23/667/ Federal Bureau of Investigation (2007). â€Å"Mortgage Fraud Report† Retrieved December 10, 2008. http://www. fbi. gov/publications/fraud/mortgage_fraud07. htm Thibodeaux, Anna (2007). Buyers Beware. December 17, 2007. Retrieved December 11, 2008 http://www. businessreport. com/news/2007/dec/17/buyers-beware-fnc1/ Zillow (2008). Retrieved December 11, 2008. http://www. zillow. com/homes/map/Hialeah,-Florida_rb/ http://www. zillow. com/homes/map/Baton-Rouge,-Louisiana

Monday, August 5, 2019

CRM Prediction and CRM Validation Approaches

CRM Prediction and CRM Validation Approaches Since CRM is underlying the regulation of gene expression in tissue-specific manner, understanding the characteristics of CRMs is helpful to determine the potential CRM candidates for further applications such as tissue-specific gene therapy. As previously discussed the influential parameters to CRM activity include the types and arrangement of transcription factor binding sites (TFBSs) and epigenetic modification pattern[121, 124]. Therefore, these factors are taken into account for prediction of promising CRMs. Transcription factor binding sites are described as short DNA regions (6 to 10 bp in length) which are recognized and bound by various transcription factors[149]. One CRM can contain many TFBSs depended on its functionality[150]. Several experimental studies have been performed in order to map the TFBSs in DNA genome. Chromatin immunoprecipitation (ChIP) assay is a common method to identify the TFBSs in protein-bound DNA complexes in the solution[151, 152]. In addition, DNase footprinting, which relies on the digestion of exposed DNA region where it is not protected by target proteins, has also been used[153, 154]. The difference between these techniques is mainly involving resolution of transcription factor binding sites[155, 156]. To derive the TFBS motifs from raw data, these DNA sequences are used as the input to compute the similarity and the potential motifs are generated. To apply the information of transcription factor binding sites motifs on CRM prediction, it is relatively simple as this method requires solely genomic DNA sequences. The predicted motifs are mapped to the original genome and prospective CRMs containing clusters of TFBSs are identified[124, 157]. Due to the enormous spread of motifs in large genome, a lot of DNA regions showing the potency of being CRMs are indicated; however, only few DNA sequences are actually occupied by the target transcription factors[158]. In the erythroid cells of mouse genome showed approximately 8 million hits of GATA-binding factor1 (GATA1) binding site motifs, but only 15360 motifs were bound by GATA1 and all of bound motifs bore H3K4 monomethylation[159]. Indeed, relying on merely TFBS motifs is not sufficient to obtain the significant CRMs. The study on smaller-size genomes is one alternative to improve the quality of CRM prediction.[157] Another approach to determine the potential CRMs is the use of conservation of non-coding DNA among several species. The assumption is that the DNA sequences associate with gene expression are highly conserved in comparison to non-essential DNA after evolving through the purifying selection over time [157]. This method is not depended on the information on TFBS so that it offers another solution to prediction of CRMs in case tissue-specific enhancers have not been widely studied. At initial study about the DNA sequence alignment of more than 100 bp-long DNA between human and mouse, with the minimal conservation of 70%, was conducted and potential enhancers for certain genes such as interleukin-4, interleukin-13 and interleukin-5 were identified[160]. Later on this approach shows the promising results due to high validation rates in transgenic mouse embryo by using rigorous conservation constrain[160-163]. The conservation-based prediction is also applicable to discover novel TFBSs wh ere the information is not extensively elaborated. With the DNA sequence alignment between orthologous species, the short DNA sequences conserved in many species, namely phylogenetic footprints, could be the possible binding sites for transcription factors [164, 165], and mutations of the conserved boxes can lead to the reduction of gene expression as in the example of altered effect of variant E box on ÃŽ µ-globin reporter gene induction[166]. As the approach is mainly related to the evolutionary constrain among species it means that the use of this method may overlook the potential CRMs which are lately developed and the TFBS pattern cannot be aligned to the former population[157]. For example, in the ChIP-seq study the GHP68 enhancer, located at intragenic region of mouse abhydrolase domain containing2 (Abhd2) gene, does not contain the footprint of GATA-binding factor1 (GATA1) motif which is commonly found in Abhd2 genes of other non-primate species[167]. Indeed, the GHP68 enhan cer in primate genome possesses the unique protein binding pattern[157]. Another consideration on conservation-based prediction is that even though the conservation level of selected CRMs is extremely high among orthologous species, the actual activities of CRMs possibly vary from species to species in nature[168]. Due to the limitations of previous approaches regarding false positive prediction by highly redundant presence of TFBS motifs in large genome[158], as well as lineage-specific evolution of certain CRMs in different organisms[157], epigenetic regulation is considered the promising parameter of CRM prediction as a result of the strong correlation between hypersensitivity to DNA treatment/histone modification and enhancer activity[169-171]. Many CRMs have been found to localize at genome region where the response to DNase activity is very sensitive[153, 172]. In addition biochemical patterns of modification at enhancer are showed including histone acetylation[169], high H3K4me1 as well as low H3K4me3 modification[170], and occupancy of histone acetyltransferase p300[171, 173]. For active promoter, in contrast to usual enhancers, the major characteristic is the presence of nucleosome-free and high level of H3K3me3 modification[174, 175]. By using the reference genome database containing epigenetic as well as DNase hypersensitivity regions, where the information is obtained from ChIP seq [176], and DNase seq experiments, the substantial rate of validation of selected CRMs from 43 to 100% in many study models[169-171, 176, 177] indicates the robustness of the epigenetic-based approach. The idea is this method is optimized that the predicted conditions is not too stringent as evolutionary conservation method and the number of output is not too enormous as TFBS-based prediction[157]. Still, some potential CRMs can be overlooked using biochemical features[173, 178]. For instance, the study of heart enhancer identification showed that three different predictions yielded various amount of outputs. The possible CRMs were hardly obtained through comparative genomic DNA alignment while the use of p300 occupancy to identify the potential sequences gave rise to 130 output sequences with 75% validation rate[173]. In another TFBS-based study in heart by Narlikar and colleagues, the classifier, where its database relied on predicted and validated TFBS, was generated to select the putative CRMs from the non-functional DNA[178]. This prediction allowed them to distinguish 40,000 CRMs from genome and the validation rate was relatively considerable in comparison to the epigenetic approach[178]. This suggests the need of additional further study on biochemical pattern prediction to cover the missing CRMs. Using experimental and computational study, scientists are able to collect the extensive information about TFBSs, epigenetic modification and conservation of DNA among species. This data has been widely deposited in many open-access database websites, which become the significant information resources for further CRM identification[179]. The Ensembl Regulatory Build is recently developed to integrate the previous discovery of epigenetic marks and occupancy of transcription factors from different projects and build the better-defined regulatory regions in human genome[180]. Another commonly used database website is the University of California Santa Cruz (UCSC) Genome Browser Database, which provide all aspects of information for CRM prediction including experimental (DNase hypersensitivity clusters, epigenetic marks of histone proteins, and binding of transcription factors from ChIP seq) as well as computational (conservation level among vertebrates from DNA sequence alignment) study [181]. This aids the feasibility of enhancer prediction since the use combinatorial information would suggest more significant CRM outputs with higher validation rate[182-184]. For example, the sophisticated protocol designed by Nair and team to identify the liver-specific CRM was derived from the integration of experimental study from UCSC genome browser and the putative TFBS motifs from computational analysis[182]. To obtain predicted liver-specific TFBS motifs, the presumptive promoters, which are 1000-bp DNA sequences located upstream of transcription start sites, from highly-expressed genes were initially compared to ones from low-expressed genes in the liver, followed by computing the potential TFBS motifs which are likely to associate with liver-targeted gene induction based on distance difference matrix (DDM) and multidimensional scaling (MDS)[182, 185]. The DDM was primarily used to identify the difference between two protein structures by calculating the distance differenc e values from low distance matrices[186]. Ultimately the predicted TFBS motifs were mapped to the corresponding DNA sequences of liver-specific genes in UCSC genome browser where the experimental data of such genes was previously described[182]. The ideal CRMs were expected to show the coexistence of predicted motifs together with dense DNase clusters, high conservation level in vertebrates, and explicit histone modification patterns. In addition, the putative motifs should be consistent to the transcription factor lists from ChIP-seq experiment. The promising liver-specific transcriptional module from prediction was further validated and showed the remarkable activity to up-regulate hFIX expression up to 15 fold compared to control, reflecting the robustness of the prediction method[182]. The same approach has also been applied to design the CRMs targeting other target cells such as cardiomyocytes, and the 10-fold augmented expression of cardiac genes was noted upon validation in m ouse model[183]. Taken together, this suggests the increased power of using multiple parameters to determine transcriptional modules, and the combined data provided in UCSC genome browser is valid; the integrated data is nicely standardized so that the summary of information is reliable. However, the feasibility of combinatorial approach, relying on both computational data and previous experimental study, is the major concern due to the requirement of strong expertise on bioinformatics knowledge for computation of TFBS motifs. One possible alternative to circumvent this limitation would be the direct use of available information on UCSC Genome Browser for CRM selection by taking associated determinants (DNase hypersensitivity, transcription factor binding, histone modification, and conservation level among vertebrate) into consideration. There are several validation assays that have been performed to investigate the potency of CRMs to enhance gene expression. In general, the plasmids containing minimal core promoters and reporter genes such as lacZ, encoding ÃŽ ²-galactosidase, luciferase, and green fluorescence protein (GFP), are the backbone constructs, and the predicted CRM are cloned into certain position based on the validation methods[149]. Usually CRM sequences are inserted at the upstream of the promoters and the increased strength of overall construct expression is assessed after transfection or integration of plasmids[187-196]. In order to develop the downstream process to identify the target cells where CRMs are active, the use of heterologous barcode has been done so that the number of CRM high-throughput screening is up to hundreds or thousands [191-194, 196]. In some studies, the need of barcode is eliminated by targeting at enhancers directly, and the method is called self-transcribing active regulator y region sequencing (STARR-seq) [197]. Both transgenic animal embryos and specific cell lines [187-191, 193-196] are commonly used to study CRM activity. For example, transgenic mouse or fly (D.melanogaster) containing putative CRMs as well as reporter genes are initially generated, and the development of reporter gene signals later observed at the certain parts of embryos is identified depended on tissue specificity of CRMs[198]. To improve time and cost-effectiveness of the current approach, Gisselbrecht and colleagues developed the technique called enhancer-FACS-Seq (eFS), which makes use of the distribution of GFP signaling based on the tissue-specific CRM enhancement, to sort out the GFP-positive cells from the negative population using fluorescence activated cell sorting (FACS)[190]. Validation of the effect of CRMs on gene expression has also been reported in animal models and the delivery methods of CRMs are adjusted to be tissue-specific. AAV is the example of tissue-target ed delivery system since its tropism is relied on the serotype[182-184]. The use of AAV vectors to carry the predicted CRMs to the specific organs has been done in heart and liver enhancers by using AAV9, and the follow-up process was achieved through the reporter hFIX protein expression in the blood. In murine models, to reduce the cost of virus production, HD injection of plasmids containing CRMs in mice can be primarily done for initial screening[182]. This method is distinctive since the model simulates the actual situation of CRM activity in animal body for gene therapy application[182-184]. In addition, another advantage of using this approach is the longevity and the expression level can be observed continuously for long-term study as the mouse sacrifice is not required. Biology of hepatocellular carcinoma (HCC) Hepatocellular carcinoma (HCC) is one type of liver cancers which is highly prevalent in many regions such as East Asia, Africa, and United State[199]. Even though the incidence of HCC ranks the sixth in comparison to other cancers the rate of mortality is relatively high[200]. There are several etiological factors describing HCC development including Hepatitis B (HBV) and C (HBC) infection, aflatoxin-directed induction, alcohol consumption, accumulation of fat in the liver resulting in non-alcoholic steatohepatitis (NASH), sex-related influence, unbalance of microbes in gastrointestinal tract, and type II diabetes[201]. Each factor has specific mechanism to cause HCC, but in general most of factors ultimately lead to liver cirrhosis formation and subsequently HCC[202]. A number of staging system to classify HCC disease development stage have been designed for diagnosis; however, the gold-standard for staging remains challenging due to heterogeneity of HCC population[203]. To study the molecular mechanism underlying HCC development, copy number genomic[204-206], exomic[207, 208], whole-genome sequencing[209, 210], and transcriptomic[211, 212] studies have been conducted in liver cancer tissues. In copy number alteration analysis, both deletion (i.e. TNFAIP3, CDKN2C, WRN, PTEN, BRCA2) and duplication (MDM4, BCL9, ARNT, MET) of specific genes are found in HCC genomes[213]. Exome and whole-genome sequencing in HCC allow detailed investigation of genome structures at the levels of mutation in both coding and non-coding regions[213, 214]. For example, mutation of NFE2L2-KEAP1 and MLL genes were identified from 87 cases with HCC development using exomic approach[214]. Transcriptomic study gives another insight into HCC regarding the change of expression profiling compared to normal hepatocytes. Using in combination with whole-genome sequencing, transcriptome revealed the RNA editing mechanism implicating in up-regulation of gene expression in cancer developm ent[215, 216]. Taken together, the aberrant genes found in HCC are mapped to cellular pathways to explain the molecular mechanisms underlying disease development. The pathways which are postulated as the keys for hepatocarcinogenesis include cell cycle regulation (i.e RB[217], CDKN2A[218]), WNT pathway (i.e. APC[219], AXIN1[220, 221]), chromatin remodeling (i.e. ARID2[208, 210], MLL[222]), tyrosine kinase signaling (i.e. SOCS-1[223], IGF[224]), and NOTCH[225, 226] pathways. Apart from structural genes, miRNAs, small non-coding RNAs which control gene expression at post-transcriptional level through hybridization with the mRNA templates and subsequently leading to translation inhibition or RNA degradation[227], are implicated in HCC progression due to the evidences on differential miRNA expression between HCC and normal hepatocytes[228, 229]. In general, miR-92, miR-18 and miR-20 are significant in HCC stage progression[229]. Some altered miRNA expression is associated with etiological factors. For[MC1] instance, there is correlation between miR-126 down regulation and alcohol consumption[230]. The functions of miRNA in HCC pathogenesis are divided into two groups; oncogenic miRNAs and tumor-suppressor miRNAs. For oncogenenic miRNAs, three miRNAs including miR-221, miR-224 and miR-21 have been showed to enhance hepatocarcinogenesis. The miR-221 plays role in cancer invasion using two mechanisms; increasing cell proliferation targeting CDKN1B/p27 expressi on[231], and enhancing cell migration through AKT signaling[232]. The invasion of HCC is also supported by miR-224, but its mechanism of action is involved with homeobox D10 downregulation and induction of inflammatory pathway[233]. Another oncogenic miRNA miR-21 is reported to suppress expression of program cell death 4 (PCD4) [234, 235]protein which functions as tumor suppressor protein, and to increases cell proliferation through the regulation of mitogen-activated protein kinase-kinase 3 (MAP2K3) activity[236]. Apart from individual miRNAs, certain clusters of miRNA have been identified to contribute to HCC progression. For instance, the up-regulation of miR-17-92 cluster, which is composed of miR-17, miR-18a, miR-19a, miR-20a, miR-19b-1, and miR-92a-1[237], was found in HCC, and the attenuation of its expression diminished the ability of malignancy transformation[238]. The activity of miR-17-92 cluster affects the expressions of certain genes usually found in HCC such as PTEN, E2F1, and E-cadherin[239]. However, the individual miRNA members may function in the different ways. For example, up-regulation of miR-19 suppressed the formation of liver fibrogenesis through TFF-ÃŽ ² signaling[240]. A number of tumor suppressive miRNAs have also been discovered to diminish HCC development. The miR-122 function is to control the genes associated with tumor formation and metastasis including VEGF[241], RHOA[241], PKM[242] whereas miR-375 exerts its activity by suppression of ATG7 expression to block autophagy[243], the essential mechanism of cancerous cells to survive under hypoxic environment. The miR-125b prevents cancer proliferation by activation of p21(WAF1/Cip1) G1/S cell cycle arrest as well as repression of SIRT7 gene induction[244]. G1/S transition of cancer cells is also controlled by miR-26a activity[235]. The overall functions of HCC-associated miRNAs are implicated in STAT3, by modulating Bcl-2 and Mcl-1 functions, and NF-ÃŽ ºB inflammatory pathways, le ading to hepatocacinogenesis[245].

Sunday, August 4, 2019

William Shakespeare :: essays research papers fc

William Shakespeare William Shakespeare is an extraordinary poet and playwright. His works express all emotions and meanings. As you will read, you will explore the life and times of Shakespeare. You will learn about his successes and his struggles. William Shakespeare was a magnificent asset to the world. In Stratford, Avon in Warwickshire on April 23, 1564, a legend was born. His name was William Shakespeare. He was baptized in the Holy Trinity church three days later. Shakespeare also died in Stratford on April 23, 1616. Shakespeare’s father, John Shakespeare, was a leather merchant when he married Mary Arden, an inheritor of farmland. William Shakespeare was one of eight children. John Shakespeare later became a member of the city council and a respected bailiff. Due to his respectable position, John Shakespeare was given free tuition for his son, William to attend a Stratford grammar school. At the age of six, William Shakespeare began his education at school where he was involved in small parts of the school plays. In school, his strongest subjects were astrology, medicine, and law. Although Shakespeare did not attend a university, he had great knowledge of Latin and Classical Greek. As a boy, he also learned many things from places other than school. Shakespeare enjoyed the woods, fields, birds, insects, and small animals. Later, he was fond of outdoor sports such as, hunting, hawking, and fishing. At the age of eighteen, on November 28, 1582, William Shakespeare married twenty-six-year-old, Anne Hathaway. Their first child, Susanna, was born in 1583. Two years later in 1585, twins, Hamnet and Judith were born. Sadly, Hamnet died at the age of eleven on August 11, 1596. Shakespeare’s excitement for poaching caused him great trouble. In about 1584, he was caught hunting on Sir Thomas Lucy’s land. Because of this trouble, he was forced to leave his hometown and move to London. In 1592, at twenty-eight years old, Shakespeare was recognized as an actor and playwright, as well as being mentioned in another man’s book for the first time. In his book, Robert Greene, a playwright, accused Shakespeare of borrowing other people’s work. During the period of 1592 to 1594, when London theaters were closed, Shakespeare wrote his earliest sonnets and poems, â€Å"Venus and Adonis† and â€Å"The Rape of Lucrece†. Shakespeare’s childhood friend, Richard Field, printed both poems. Until 1598, William Shakespeare’s theater work was done in a district, northeast of London in the parish of Shoreditch.

Saturday, August 3, 2019

Ethics of Genocide and Eugenics Essay -- Biology Medical Biomedical Ge

Gene Therapy: Genocide and Eugenics or Striving for a More Perfect Population Controversy and Ethics Just as there are different types of people who look at one glass of water and describe it as half full or half empty, the public has many different views on the future of our society. Gene therapy is also a glass that can be viewed in different angles – different perspectives. Some say it has great potential to shape the ideals of our future, while others believe it signifies intolerance for disabilities, imperfections that supposedly deplete from a person’s interests, opportunities and welfare (quoted by Peter Singer, xviii). This global issue has brought people with different opinions in the open, arguing their views using history, morality and foresight. â€Å"It is human nature to strive to improve everything.† (as quoted from Ron Harris by Singer, xxii) As the world moves forward in science and technology, it seems that only humans themselves are lagging behind. Success and perfection are so important as to even play a role in determining human characteristics – once thought to be inalterable – right down to gene selection. In our increasingly capitalist society, parents want their children to be born with as much an opportunity to excel as others. It is the same well-meaning motivation that drives parents to make more money to buy a bigger house in a better community, so their children could live better and attend a higher-scoring school (Singer xvi). So with equal or greater conviction, they want their children to be born with a relatively high IQ, good looks and a healthy body. This mentality is adequately represented by a website: ronsangels.com, which sells eggs of women â€Å"with beauty and brains† to the highest bidder (... ...ne starts life with an equal chance of health and success. Yet, gene therapy can also be thought of as a straight route towards a dark outlook, where perfection is the first priority, genes are seen as the ultimate puppeteer, and personal freedom to thrive based on one’s self isn’t believed to exist. With the emergence of each new technological discovery comes the emergence of each new ethical debate, and one day, each viewpoint on this momentous issue may be able to find a bit of truth in the other. Eventually, our society may reach a compromise on gene therapy. Bibliography: Cambridge. The Ethics of Inheritable Genetic Modification. Cambridge: Cambridge Universtiy Press, 2006. Rpt. in The Ethics of Inheritable Genetic Modification. Collins, Francis S. "Foreward." Playing God? 2003. By Ted Peters. 2nd ed. Great Britain: Routledge, 2003. Rpt. in Playing God?

Friday, August 2, 2019

Pass the Potato Chips Essay -- Health Nutrition Food Papers

Pass the Potato Chips Has mankind discovered some fantastic substitute for fat to enable people to eat as many snacks as possible without gaining weight? Recently, Proctor & Gamble developed Olestra (sucrose polyester), a zero calorie fat-based substitute, at a cost of $200 million. This product has been approved by the Federal Drug Administration (FDA) with warning labels. What is olestra? The olestra molecule differs from a fat molecule in that it has six to eight fatty acids on a sucrose core, as opposed to three fatty acids on a glycerol core. The bulkier olestra molecule is not digested, absorbed , or metabolized, and thus provides no calories† (Stern & Hermann-Zaidins ,1992 ). It has the same taste and texture of fat, and even retains this texture in deep frying. One ounce of potato chips with olestra contains only 70 calories, as opposed to the usual 160 calories (http://plainfield.bypass.com/%7Etwilbur/olestra.html). What is the purpose of olestra? The purpose of olestra is two-fold. Consumers believe they can cut calories eating products containing olestra. Since this fat substitute decreases fat intake, the result is weight loss. More importantly, less fat in a person’s daily diet cuts down the risk of heart disease, cancer, and other illnesses. What products will contain olestra? Developed by Proctor & Gamble, olestra will be used in potato chips, in corn chips, in crackers, and in other snack foods under the name Olean. Consumers who are interested in purchasing olestra products should try Frito-Lay’s MAX line of snack foods (only sold in limited test markets in the United States). Frito-Lay MAX products will eventually be offered nationwide if test market consumers place these snacks in ... ...n. June 1996, Volume 63, No. 6, 891-895. Greenberg, E., Robert, M.D., et al. Mortality Associated with Low Plasma Concentration of Beta Carotene and the Effect of Oral Supplementation. Journal of American Medical Association. March 6, 1996, Volume 275, No. 9, 699-703. Seddon, Johanna M., M.D., et al. Dietary Carotenoids, Vitamins A, C, and E, and Advance Age-Related Macular Regeneration. Journal of American Medical Association. November 9, 1994, Volume 272, No. 18, 1413-1420. Stern, Judith S., Hermann-Zaidins, Mindy G. Fat Replacements: A New Strategy for Dietary Change. Journal of the American Dietetic Association. January 1992, Volume 92, No. 1, 91-94. Weststrate, Jan., Van hef Hof, Karin H. Sucrose Polyester and plasma carotenoid concentrations in healthy subjects. The American Journal of Clinical Nutrition. September 1995, Volume 62, No. 3, 591-597. Pass the Potato Chips Essay -- Health Nutrition Food Papers Pass the Potato Chips Has mankind discovered some fantastic substitute for fat to enable people to eat as many snacks as possible without gaining weight? Recently, Proctor & Gamble developed Olestra (sucrose polyester), a zero calorie fat-based substitute, at a cost of $200 million. This product has been approved by the Federal Drug Administration (FDA) with warning labels. What is olestra? The olestra molecule differs from a fat molecule in that it has six to eight fatty acids on a sucrose core, as opposed to three fatty acids on a glycerol core. The bulkier olestra molecule is not digested, absorbed , or metabolized, and thus provides no calories† (Stern & Hermann-Zaidins ,1992 ). It has the same taste and texture of fat, and even retains this texture in deep frying. One ounce of potato chips with olestra contains only 70 calories, as opposed to the usual 160 calories (http://plainfield.bypass.com/%7Etwilbur/olestra.html). What is the purpose of olestra? The purpose of olestra is two-fold. Consumers believe they can cut calories eating products containing olestra. Since this fat substitute decreases fat intake, the result is weight loss. More importantly, less fat in a person’s daily diet cuts down the risk of heart disease, cancer, and other illnesses. What products will contain olestra? Developed by Proctor & Gamble, olestra will be used in potato chips, in corn chips, in crackers, and in other snack foods under the name Olean. Consumers who are interested in purchasing olestra products should try Frito-Lay’s MAX line of snack foods (only sold in limited test markets in the United States). Frito-Lay MAX products will eventually be offered nationwide if test market consumers place these snacks in ... ...n. June 1996, Volume 63, No. 6, 891-895. Greenberg, E., Robert, M.D., et al. Mortality Associated with Low Plasma Concentration of Beta Carotene and the Effect of Oral Supplementation. Journal of American Medical Association. March 6, 1996, Volume 275, No. 9, 699-703. Seddon, Johanna M., M.D., et al. Dietary Carotenoids, Vitamins A, C, and E, and Advance Age-Related Macular Regeneration. Journal of American Medical Association. November 9, 1994, Volume 272, No. 18, 1413-1420. Stern, Judith S., Hermann-Zaidins, Mindy G. Fat Replacements: A New Strategy for Dietary Change. Journal of the American Dietetic Association. January 1992, Volume 92, No. 1, 91-94. Weststrate, Jan., Van hef Hof, Karin H. Sucrose Polyester and plasma carotenoid concentrations in healthy subjects. The American Journal of Clinical Nutrition. September 1995, Volume 62, No. 3, 591-597.

Automobile and Product Essay

1a. The company this case is about is a company named DoorGuard. DoorGuard is a company that is trying to create a new market that protects cars from getting dinged or dented. 1b. Strengths: DoorGuard strengths are that there is currently no one else who has a product that does the same thing, along with a big target market. 1c. Weaknesses: Doorguard’s weaknesses are that he couldn’t find a concrete way to distribute and promote their product. Another weakness is that DoorGuard is a pioneer product it could boom or bust, with a pioneer product you cannot predict as well how successful your product will be. 1d. Opportunity-There is a big opportunity for this product to take off if he sold to only 5% of his target market he would be making $6,100,000. 1e. Threat- DoorGuard’s threat is they are a product pioneer. This will be a high risk, high reward company. It could skyrocket or else it will fall right on its face. It could be ahead of its time or the economic times could take a large portion of his target market and sway them in a different direction. 2. The market described in this article is anyone who has a car that costs $15,000 or more. These people are normally people who have are from their mid-late 20’s to 60’s that have a well paying job. They market also teenage kids who come from a wealthy family. 3. There are no direct competitors in this case. There is some indirect competition though with AutoShades. This is a company that prevents the sun from coming into the car. Their strengths are that they are cheap, sometimes come with the car when bought new, and also have different designs. The companies weakness compared to DoorGuard is that it does not protect the car at all. 4. The people possibly consuming or buying this product ages range from the mid 20’s –60’s. Most of these people are middle-upper middle class. The majority of these people have kids. These people drive to places where this is tight parking (grocery shopping, schools (elementary, middle and high), malls). For these people this product could be valuable in the long run it’d cost less off AutoGuard doors compared to removing dings and dents. 5. The technological market is important to recognize because DoorGuard’s anti-theft mechanism still destroys the product the consumer bought. This could be a problem that an adaption to the anti-theft mechanism could prevent. Economic market should also be acknowledged because with bad economic times most of DoorGuard’s target market people who are in their mid-late 20’s-60’s who not extremely wealthy people are but ordinary everyday people will be less likely to buy a good that they want and don’t necessarily need. If the car door gets dinged or dented the car will still run it’s not a necessity. Problem Statement: Should Steve Harris take the next step with his product and look to distribute it? Steve Harris focuses on distributing to the top five automobile manufactures (Ford, Chrysler, GM, Toyota, and Honda). With Harris looking to distribute to the top five automobile companies in their retail stores. They would be stored on a car as the customer walk into the store or stored between the main entrance and the secretary’s desk. There is a By targeting these big 5 automobile companies Harris will maximize his productivity by reaching almost all of his target market, while also having time to work on other aspects of his company. Distribute to every automobile retailer out their. With Harris selling his product in every automobile retailer it will guarantee that he is able to access his entire target market. By targeting every automobile retailers it takes away a more of a majority of their time and money compared to targeting only the top 5 retailers or not selling to any automobile retailers. Advertise and open your business and sell as a wholesaler to the customer. The advantage of not looking to distributing to any retailers is that you save on shipping cost to retailers. Harris will also have a lot more time to figuring out how to advertise and promote his product. The weakness is that it will be very hard to advertise and promote his product without an automobile company supporting his idea. Have Harris distribute DoorGuard to two or three car companies. The strengths with this strategy is he’ll be able to target a decent amount of the market. The amount he targets varies depending on which companies he picks. Harris will be able not worry about distribution as much as if he was distributing to the top 5 automobiles companies or every automobile company. This will allow Harris to focus more of his time towards his product, and promotion of the product. By have only a few car companies distributing his product there is a great chance that these companies will remain loyal to you in years to come. There are some negative effects though to this distribution process. With so few of distributors your fate is in their hands. For example say you decided to distribute to GM and Ford. For some reason Ford goes bankrupt and out of business. That’s roughly half of your target market that disappears. If one of the companies Harris distributes to goes down, AutoGuard as well will be in serious trouble financially. Your target market will be so small that it will be hard to hit 5% of all people buying an automobile. You need a plan B (alternative option) incase you one of the few automobile companies drastically falter. Recommendation Mr. Harris should focus on only distributing to the top five automobile companies. This will allow him to target the majority of the market while still being able to spend a lot of his time worrying about all the other aspects of his company (promotion/ advertising, and improving the product). With targeting this large section of the market for such a small cost it will allow him to adapt other aspects of his business and should be able to 5% of his market.

Thursday, August 1, 2019

Culinary Cookware Essay

Sales Promotion is a key ingredient in marketing campaigns which consists of a collection of incentive tools, mostly short term that are designed to stimulate quicker or greater purchase of particular products or services by consumers or the trade. Sales contests/incentives: Aims at including the sales force or dealers to increase their sales results over a stated period, with prizes (money, trips, gifts or points) going to those who succeed Appropriateness: From the findings of the 2003 survey, 50% would buy new cookware even without price discount or a free gift => retailers who are already carrying all the four lines owing to its greater GM compared to competitors, would be induced to promote the brand by featuring, displays, etc. This stimulates sales clerks to push the products further more improving the brand awareness (15% for under $75000 and 25% for above $75000 – much lower than close competitors) as only 15% would consider upgrading to higher end products and improves off-season sales which were very low. Promotion allowances: volume rebate/ quantity discount Appropriateness: There is a possibility of forward buying problem, wherein retailers buy a greater quantity during the deal period and the manufacturer will have to bear costs of extra work shifts. Since the manufacturer is giving a 4% points additional benefit on GM to retailers over the competitors, giving a promotion allowance might not yield as many benefits as anticipated. However, an equal amount could be spent on advertising/display allowances as the channels chosen are upscale kitchen specialty chains, department stores and local specialty stores. Sweepstakes: Sweepstakes involve marketing promotions targeted toward generating enthusiasm to purchase among customers by enticing consumers to submit free entries into chance draws that are tied to product or service awareness wherein the featured prizes are given away by sponsoring companies. As there is no assurance of benefit in this case, the scheme may not be very attractive to entice first-time customers. Also the lottery system promotion may not reflect highly on the ‘Premium’ brand image of Culinarian Cookware. Thus sweepstakes are not a good promotion strategy for Culinarian Cookware Premiums: Premiums are promotional items that can be acquired through proof of purchase. Exhibit 3 states that 20 % of the people would be motivated to buy cookware because of a free gift. Also a free gift does not damage the premium image of the cookware brand and is widely used by other players in this segment. Since the premium can be shipped after receiving proof of purchase, it reduces opposition from trade channels who would not have to block shelf space for the premiums unlike in the case of free gifts Rebates: Rebate is an amount returned on what already has been paid. Rebates may require paperwork submission and this can put off customers. Culinarian cookware distributes through high-end retail channels and invests in well-trained staff to give the best experience to the customers. However, the rebate mechanism requires effort on the part of the customers and can affect the Culinarian premium brand image. Cooperative advertising allowance: Culinarian cookware can give some allowances to retailers who prominently display its products or give it the desire shelf space. Also it can be used to encourage retailers to push Culinarian products to the customers who are unsure about the brand. The lure of getting reimbursement and additional money for doing advertisement for culinarian products on the company’s behalf will motivate Slotting Allowance: In slotting allowance a fee charged to produce companies or manufacturers by supermarket distributors or retailers in order to have their product placed on their shelves. Most of the products sold by Culinarian Cookware is through retail outlets. Also most of the products are in the premium end. So Culinarian Cookware can go for slotting allowance. However it should negotiate with retailers to reduce the margin to industry standard of 48% as against 52% now. Trade shows: Generally in trade shows people look for discounted products. It would not be good for culinarian cookware to sell the products at a discounted rate in trade shows. Howvere it can take part in trade shows to increase awareness especially of its CX1 brand. Point of purchase displays (functional discounts) Culinarian Cookware should not go for functional discounts because they already give retailers higher profit margins of 52% as compared to 48% by its competitors. This is a big enough incentive for the retailers to encourage customers to buy Culinarian Cookware products. Thus, no extra functional discounts are required. Seasonal discount The buying pattern given in Exhibit 2 suggests that there are two peak seasons for the sale of cookware, one during the May- June months and the other during the months of November- December. Thus, seasonal discounts will be very effective in capturing the customers and increase sales because of this buying pattern If we study Exhibit 4, we can observe that the sale of product lines PROX1 and SX1 is higher in the spring season while that of DX1 is higher in the fall season. This cyclical buying pattern tells us that Culinarian Cookware can go for sales promotion twice in a year wherein it can give sales promotion for different product lines in different seasons of the year.