Xenobiotics Metabolizing Enzymes Very Important Exogenous Endogenous Compounds Biology Essay

Xenobiotics Metabolizing Enzymes Very Important Exogenous Endogenous Compounds Biology Essay Xenobiotics metabolizing enzymes (XMES) are very important for metabolizing of exogenous and endogenous compounds [23]. They are involved in the biotransformation of exogenous compounds like procarcinogen, drugs, solvents. They are categorized into parts: phase I and phase II enzymes. Cytochrome 450 family comes under phase I enzyme. Cytochrome P450 family of enzymes is mainly involved in synthesis and metabolism processes of exogenous and endogenous compounds. CYP genes are located mainly in the liver and within the cell are present in the endoplasmic reticulum and also in the mitochondria. CYP family is divided into four main families: CYP 1, CYP 2, CYP 3 and CYP4. CYP has two main roles in the human body [24]. First, CYP is used by the body to metabolize and transform a range of hydrophobic xenobiotics (exogenous, foreign compounds such as pesticides, carcinogens, and pollutants) to more polar metabolites so that they can be readily excreted in the urine. By biotransforming potentially toxic compounds to less potent forms, CYP works as a natural detoxifying agent of the body. Large populations of CYP are found bound to the endoplasmic reticulum in mammalian liver cells, the primary site of metabolism. The gene families most commonly found in humans and involved in metabolism include cytochrome P-450 1, 2, and 3 (known as CYP 1, CYP 2, and CYP 3). Second, CYP enzymes are used in the synthesis of important signaling molecules, such as steroid hormones in the endocrine glands, fat-soluble vitamins and Metabolism of fats (cholesterol and fatty acids). CYP metabolisms have adverse effects as well as beneficial effects. CYP plays an important role in activating carcinogens, such as polyaromatic hydrocarbon (PAH), by an oxidation mechanism. They are also involved in the metabolism of certain medication that are ingested (endoplasmic reticulum) and also certain toxin/internal substances formed within the cells (mitochondria). These functions mainly depend upon iron present in it as a prosthetic group. Hence, they are called hemoproteins. Iron contains two 4s electrons and six 3d shell electrons in its valence shell. The function of this gene depends on the shifting oxidation state of iron between ferrous Fe2+ (loss of the 4s electrons) and ferric Fe3+ (loss of an additional 3d electron). As the ferric state results in a half-filled 3d shell, it is the more stable form of the two states. As a result, CYP can be readily reduced with the addition of an electron. It is a group of heme-thiolate monooxygenases and involved in an independent NADPH dependent electron transport pathway [24]. Fig1. Metal complex structure of CYP 450 5. MECHANISM 5.1. CARCINOGEN IDENTIFICATION The carcinogen from tobacco smoking is genotoxic carcinogens that are capable on inducing DNA lesion. This carcinogen is divided into two parts, first is direct carcinogens and second is procarcinogens. Direct carcinogens are highly reactive and having an electrophilic groups with surplus positive charge. They interact directly with DNA and form DNA adducts. The example of this carcinogens are N-nitrosoalkylurea, ethyl- and methylmethanesulfonate, N-methyl-N-nitronitrosoguanidine, sulfur mustard, diepoxybutane, beta-propiolactone, ethyleneimine, etc. Initially, procarcinogens are chemically in inactive form. When procarcinogens go inside the body, they interact with different types of enzyme that metabolise in the cell in two steps. In the first step, procarcinogen are activated and converted into electrophilic derivatives. In the second step, the metabolic products are neutralized by conjugation. The first step process is mainly done by CYTOCHROME 450 family and second step process is done by conjugating enzymes include acyltransferase, epoxidases, sulfotransferases, glutathione-S-transferases, UDP-glucuronyl transferases, and transaminases [6]. They are activated by oxidation process that is mainly done by CYP gene. The main procarcinogen in smoking that create negative effect on CYP1A1 genes are mainly polycyclic aromatic hydrocarbon group (Benzo(a)pyrene, Benz(a)anthracene, Benzo(b) fluoranthene, Benzo(c)phenanthrene) and N-nitrosamines (NNK) [8]. CYP1A1 does not form directly tumour, it only makes procarcinogen to carcinogen that forms tumour formation. Cytochrome p450 enzyme comes under the phase1 enzymes which convertes the mutagens to epoxides in the K-region as well as the Bay region of Benzo (a) pyrene [1]. CYP gene carry out oxidation and reduction of the hydrophobic ligands converting them into epoxides usually in the K-region which is then taken up by phase2 enzyme (GST) and metabolized into water soluble compounds (later excreted through urine). But if the epoxide is formed near the bay region then phase2 enzymes become idle without carrying out any metabolic process. The CYP gene metabolises the carcinogens to epoxides, which are highly reactive and binds to DNA and further activate d to diol epoxides. They covert the carcinogen B[a] P into B[a]P-7,8-diol-9,10-epoxides which has got high DNA binding capacity. These mutagens are termed as Bay epoxides as they have tumourogenic effects on DNA. The presence of motif reason of CYP 450 oxidizes the PAH. The motif reason of CYP450 is Phe-X(6-9)-Cys-X-Gly, where X is a specific amino acid. Cysteine binds to heme iron and takes part in the transfer of one atmospheric oxygen atom to the substrate that contained in the pocket of the substrate-binding site in the enzyme active center. In few cases, the life span of metabolites is very short (several milliseconds) due to their high reactivity and fast conversion into stable hydroxylated derivatives. In other cases, due to slow decomposition of metabolites they easily enter into the nucleus, mitochondria, and other cell organelles. The reaction catalyzed by cytochromes P450 is a monooxygenase reaction, e.g., insertion of one atom of oxygen into an organic substrate (RH) whi le the other oxygen atom is reduced to water: RH + O2 + 2H+ + 2e- → ROH + H2O Fig2. Substrate oxidation in the cytochrome P450 system Fig3. Bay and K region of Benzo(a)pyrene and epoxide formation of Bay region Fig4. Epoxide formation of B(a)P 5.2. INDUCTION OF CYP GENE The amount of CYP1A1 is responsible for tumour formation in organs. Basal expression of CYP1A1 is negligible. High amount of CYP1A1 increases the risk of tumour formation or cancer. It can create an imbalance condition between detoxification and activation that leads to adverse effects. It converts the procarcinogen to carcinogen by oxidation process. At high substrate concentrations detoxification becomes saturated and induction can increase the production of reactive metabolites compare to the capacity of cellular defenses, thereby producing toxicity or neoplasia [9]. Procarcinogen increases the amount of CYP1A1. CYP1A1 is induced by two pathways namely canonical and non-canonical signaling pathway of AhR. Canonical signaling pathway enhances the synthesis of CYP1A1 that causes tumour formation. There is no evidence to prove that Non-Canonical signaling pathway is the reason of tumour promoter. Our study show that the research is going on about non canonical signaling pathway. CYP1A1 is also called as AHH (Aryl Hydrocarbon hydroxylase). It is involved in the metabolic activation of aromatic hydrocarbon (polycyclic aromatic hydrocarbons). The studies on the mechanism revealed that ligand like B[a]P binds to the receptor AhR (aryl hydrocarbon receptor) (an intracellular protein that starts the induction process by biding inducer) in the cytosol. When B(a)P goes inside the body, it will pass through lipid membrane before reaching the cytosol. It is a hydrophobic as well as lipophilic compound that accumulates in the membrane of lipid bilayer, So that the membrane loses its reliability and an increase in permeability to protons and ions. Therefore, it creates imbalance the proton motive force and intracellular pH. In addition to the effects of lipophilic compounds on the lipid part of the membrane, proteins surrounded in the membrane are affected. The effects on the membrane-embedded proteins result to a large extent from changes in the lipid environment [7, 9]. So that PAH is able to go inside the cytosol and makes complex with Ahr receptor. Usually the AhR receptor is present as a part of the cytosolic protein complex which includes 2 hsp90, p23 and XAP2 or AIP (also known as co-chaperons). Once the ligand is bound to the receptor, the co-chaperons dissociate and the receptor is translolcated into the nucleus. This complex along with the ligand molecule heterodimerizes, with another molecule ARNT (AhR nuclear translocator). This heterodimer binds to the consensus regulatory sequences such as AhREs (Ah responsive elements), XRE s (Xenobiotics responsive elements) or DREs (dioxin responsive elements) to be found in the promoter region of AhR target genes such as CYP1A1, thereby initiating the transcription by RNA-polyII [1]. The transcription of CYP1A1 gene is inhibited by AhRR protein .The AhRR/ARNT heterodimer stops the transcription process initiated by XREs and also inhibits the heterodimer formation of AhR-ARNT [2,1]. Fig.5. Canonical signaling pathway of AhR 5.3. ALTERATION IN CYP1A1 Mainly four types of polymorphism happen in CYP1A1 that enhances the tumour formation in organs by increasing the oxidation process that makes procarcinogen to carcinogen. These four polymorphisms [19] are as follows: M1 (Msp1), T→C substitution at nucleotide 3801 in the 3-non-coding region. M2 (Msp2), A→G substitution at nucleotide 2455 leading to an amino acid change of isoleucine to valine at codon 462. M3, T→C substitution at nucleotide 3205 in the 3-non-coding region. M4, C→A substitution at nucleotide 2453 leading to an amino acid change of threonine to asparagine at codon 461. These mutations do not happen due to smoking; it can lead to enhance the more AHH (aryl hydrocarbon hydroxylase) activity. Each mutation has different function and plays an important role in the tumour formation. For example, CYP1A1 Msp1 (M1) increases the catalytic activity and CYP1A1 Msp2 (M2) is directly related to other functional polymorphism and creates more PAH-DNA adducts in white blood cells [30]. This mutations happen mainly in lung, larynx, pharynx, oral, breast, ovary, liver, colorectal and esophagus. The mechanism of CYP1A1 is same for all organisms and the formation of tumour in these organs depends upon geographical factor, demographic factor and number of cigarettes. Lung cancer In lung cancer generally Msp1 (T→C) mutations occur, but in Brazil Msp2 (A→G) mutation associates with lung cancer [17, 19]. B(a)P and NNK carcinogen mainly involve with liver cancer. Oral cancer, larynx and pharynx Msp2 and Msp1 mutation also associates with oral cancer, larynx and pharynx [15, 16, 18]. And PAH and NNN are associated with these cancer. Benzo[a]pyrene, NNN and NNK are carcinogens that enhance the oral cancer [29]. The studies of various articles show that CYP1A1 Msp1 (M1) mutation maximum associates with increasing the risk of oral squamous cell carcinoma. Breast Cancer CYPIAI (M1) and CYP1A1 (M2) increase the risk of breast cancer [20, 21].PAH forms PAH-DNA adduct in breast tissue that associates with increased breast cancer. Generally PAH is used for the study of tumor formation in breast cancer because of three reasons, first it is a good model for understanding the chemical mechanism of tumour formation by chemicals. Second the geometric resemblance of PAH and endogenous estrogen is same. Third estrogens and PAH have aromatic ring. PAH are activated by two pathways, first by electron oxidation and second by CYP1A1. DNA adducts are formed by metabolically activated PAH binding with the nucleophilic groups of the two purine bases, adenine (A) and guanine (G). Both adducts may be either stable or depurinating (It is the loss of purine (adenine or guanine) from DNA backbone). The stable adducts is formed by covalently bonding to DNA unless removed during repair, where the depurinating adducts are those that are released from DNA by deterioration of the glycosidic bond .Stable DNA adducts are created when PAH binds with the exocyclic amino group of A or G, where depurinating adducts are formed by covalently bonding of PAH at the N-3 or N-7 position of Adenine or the N-7 or, sometimes, the C-8 position of Guanine [26, 27].

The American Dream in Death Of A Salesman, by Arthur Miller Essay

Success: Accomplishing Your Dream Completing the "American Dream" is a controversial issue. The American Dream can be defined as having a nice car, maybe two or three of them, having a beautiful, healthy family, making an impact on the world, or even just having extra spending money when the bills are paid. In the play "Death Of A Salesman," by Arthur Miller, the "American Dream" deals with prosperity, status, and being immortalized. Willy Loman, a hard worker aged to his sixties never accomplished this goal. He always talked the talked, but never achieved to walk the walk. Willy Loman would always talk about who he's met and how he has always well known and liked, but truthfully he never was. "Willy: He's liked, but not-well liked†¦I got on the road and I went north to Providence. Met the Mayor. (ACT I, lines 232, 234)†¦Willy: And they know me, boys, they know me up and down New England. The finest people. And when I bring you fellas up, there'll be open sesame for all of us, 'cause one thing, boys: I have friends. I can park my car in any street in New England, and the cops protect it like their own†¦(ACT I, line 242)." Willy can talk of meeting wonderful and powerful men, but his limits stretch to the Mayor of Providence. Willy Loman's dreams seem to outlive Willy. Willy dreamed his life out, even to his death. He dreamed of dying the death of a salesman. All the powerful men he knew would attend his funeral. Cars would line up for miles and everybod... The American Dream in Death Of A Salesman, by Arthur Miller Essay Success: Accomplishing Your Dream Completing the "American Dream" is a controversial issue. The American Dream can be defined as having a nice car, maybe two or three of them, having a beautiful, healthy family, making an impact on the world, or even just having extra spending money when the bills are paid. In the play "Death Of A Salesman," by Arthur Miller, the "American Dream" deals with prosperity, status, and being immortalized. Willy Loman, a hard worker aged to his sixties never accomplished this goal. He always talked the talked, but never achieved to walk the walk. Willy Loman would always talk about who he's met and how he has always well known and liked, but truthfully he never was. "Willy: He's liked, but not-well liked†¦I got on the road and I went north to Providence. Met the Mayor. (ACT I, lines 232, 234)†¦Willy: And they know me, boys, they know me up and down New England. The finest people. And when I bring you fellas up, there'll be open sesame for all of us, 'cause one thing, boys: I have friends. I can park my car in any street in New England, and the cops protect it like their own†¦(ACT I, line 242)." Willy can talk of meeting wonderful and powerful men, but his limits stretch to the Mayor of Providence. Willy Loman's dreams seem to outlive Willy. Willy dreamed his life out, even to his death. He dreamed of dying the death of a salesman. All the powerful men he knew would attend his funeral. Cars would line up for miles and everybod...

The benefits of a well designed flat tax

In an effort to salvage our economic system, the earned income revenue enhancement rate for all U.S. taxpayers will be 18 % . A good designed level revenue enhancement would non merely cut down conformity and administrative costs but it would besides heighten productiveness and work inducements. In altering the revenue enhancement rate to an 18 % revenue enhancement payment program, it sets a standard payment rate for everyone alternatively of multiple revenue enhancement brackets and has the possible to cut down our state ‘s debt. The current U.S. revenue enhancement system consists chiefly of revenue enhancements on income, paysheet, gross revenues and belongings. Harmonizing to Clemson University ‘s Holley Ulbrich, in 2007, these revenue enhancements provided 92 per centum of federal income and 51 per centum of province and local authorities income ( Ulbrich 2 ) . Therefore, since income revenue enhancement is a important beginning of funding national, province and loc al exchequers, how it is collected is really of import. For intents of discoursing this amendment, the federal income revenue enhancement is the chief issue being discussed. State and local issues may be used as illustrations, but non in a manner that has impact on the level revenue enhancement being proposed. The proposed level revenue enhancement rate for all taxpayers will hold a positive impact on the economic system by increasing the figure of revenue enhancement returns filed, the lower costs of treating them, will promote investing and concern chances, and will increase the overall income to the authorities from higher Numberss of revenue enhancement returns being filed. Implementing a level revenue enhancement would cut down conformity and administrative costs for the authorities. Since the IRS employs over 100,000 people to treat revenue enhancement returns, simplifying the filing procedure would cut down the demand for the figure of workers to treat revenue enhancement payments and returns, which would salvage the authorities money ( Pascale ) . The current system today allows the IRS to roll up a higher per centum of net incomes as people ‘s income additions, while others pay small or no revenue enhancement at all. If everyone had to pay the same sum of revenue enhancements, the procedure of filing revenue enhancements would be easier, hence more people would register and there would be lower costs for the IRS to implement revenue enhancement filings. Harmonizing to Daniel Mitchell, holding a level revenue enhancement simplifies the procedure, makes things just and is good for growing ( 1 ) . Simplifying the revenue enhancement construction would ensue in more accurate and completed returns being filed, which would take down the costs of roll uping revenue enhancements from people who do n't register revenue enhancement returns, therefore salvaging the IRS money. Since there are so many tax write-offs available under the current revenue enhancement construction, there are many people who file revenue enhancement returns but pay minimum federal income revenue enhancement. In add-on to the hapless, this applies to middle category and affluent people, excessively ( Bartlett 2 ) . Peoples who earn more money are able to pass more money, so, under the current system, things like purchasing places, charity contributions and stock investings can cut down the sum of revenue enhancement people pay. By change overing to a Flat Tax system, the lowest income earners in the United States would non be capable to income revenue enhancement, but the in-between category and wealthy would non be able to subtract their revenue enhanceme nts for their places, which could go really expensive for them. Since the existent proposed level revenue enhancement collected ( 18 % ) would be well lower than their current revenue enhancement bracket ( 28 % -32 % , for illustration ) , even losing out on some tax write-offs may non hold much impact on overall revenue enhancements being paid by householders and the wealthy. Mitchell estimates that approximately 97 % of revenue enhancement returns paid would e the same or less compared to the current system. Simplifying the revenue enhancement construction should ensue in better conformity, more accurate returns being filed, and lower administrative costs, ensuing in an overall higher revenue enhancement gross base for the authorities. Adopting a level revenue enhancement for earned income would besides heighten productiveness and investing inducements for persons and concerns. By shuting loopholes and take downing rates, the efficiency of the revenue enhancement codification could increase and make more inducements for people to put With the current revenue enhancement system, some people do n't desire to put because they ‘d be paying excessively much in revenue enhancements investings if their investings earned excessively much money. By following the level revenue enhancement, investors would hold more inducements to get down and turn concerns, every bit good as brand other investings ( Mitchell 2 ) . With a level revenue enhancement system, people will cognize the sum of revenue enhancements they owe easy and can put and salvage money more efficaciously. The level revenue enhancement encourages people to put more freely without being penalized for gaining excessively much on their investings and therefore paying higher revenue enhancements. Converting to the level revenue enhancement system could ensue in America going a magnet for investings and new occupations. Another benefit of the level revenue enhancement would be the possible to cut down the U.S. National debt. Studies show that about 5-15 % of Americans do non pay their revenue enhancements because the revenue enhancement returns are excessively hard and excessively clip devouring to fix. With this new system, revenue enhancements become easier to finish and take less clip. Converting to a level revenue enhancement would merely necessitate two postcard-sized signifiers: one for labour income and the other for concern and capital income, which is dramatically simpler than the 893 revenue enhancement signifiers presently in usage. Since the complexness of the filing procedure would be reduced, fewer people would register extensions or avoid registering wholly. This should ensue in more people registering returns and with the simpler signifiers, the processing costs should be lower, excessively. The overall impact of more people registering revenue enhancements, coupled with decreased co sts in treating the returns, should be a dramatic addition of income for the authorities, which would let the U.S. to cut down its debt, as good. The acceptance of a level revenue enhancement is a alteration to the variable revenue enhancement construction. The beginning of income revenue enhancement on persons is by and large cited as the transition of the 16th Amendment. It was passed by Congress on July 2, 1909, and ratified February 3, 1913. Throughout history, revenue enhancements were enacted as a agency to hold the wealthiest people pay for the good of everyone else ( Pascale 1 ) . The level revenue enhancement would hold more people paying equal proportions of revenue enhancement, instead than holding the wealthiest people pay the most revenue enhancements. Other states have had success implementing a level revenue enhancement plan. The first state to follow a level revenue enhancement was Estonia in 1994, merely after the prostration of the Soviet Union. The other two states that enacted a level revenue enhancement were Latvia and Lithuania. For these states, the economic growing showed important betterment and the â €Å" Baltic Tigers † became function theoretical accounts for the part ( Mitchell 5 ) . Russia besides adopted a level revenue enhancement rate in 2001, which rapidly had positive consequences: the economic system prospered, and grosss poured into the authorities. Several other former Soviet states have followed suit and hold had good consequences. As Ahrens points out 24 states now employ a level revenue enhancement but, to be just, none of them has an economic system every bit complex as the United States. At the province degree, a new survey shows that most citizens of Utah are paying less under the province ‘s 5 per centum level revenue enhancement than they did under the old revenue enhancement system ( Bernick 1 ) . While this is non a federal income revenue enhancement illustration, it merely shows that the level revenue enhancement can profit people at the province degree. Still, the statement is that rich people are paying less revenue enhancement than they had been ( at the 7 % rate ) and that they are acquiring large revenue enhancement cuts under the new system at 5 per centum. The issue with the current revenue enhancement codification is that there are infinite loopholes and freedoms that normally end up profiting those who are in higher revenue enhancement brackets.A With this new system there are no loopholes and no one gets more benefit from it than anyone else.A The level revenue enhancement construction will besides assist people cut down the complication of fixing their revenue enhancement returns.A The end is to do revenue enhancement readyings so easy that people file their returns on a postcard.A The level revenue enhancement would profit the lower income households because families would have a generous freedom based on the household ‘s size.A A household off our would non pay any income revenue enhancement until its one-year household income exceeded $ 30,000 ( Mitchell 2 ) .A Since the lower income households would fundamentally pay no revenue enhancements, the load displacements to middle category and affluent people.A In world, this is no different than how revenue enhancements have been collected throughout history – the people who can pay supply for the people who can non.A Congressman Mike Pence said a level revenue enhancement could be a â€Å" major spot of revenue enhancement alleviation: for most Americans ( Terkel 2 ) .A The level revenue enhancement would non hold unvarying benefits, but due to its simpleness, it should hold minimum negative impact on current taxpayers.AThere are several expostulations to the proposed level tax.A As Bartlett states the benefits to single taxpayers would be comparatively little – the wealthy would profit is proportionally while many in the in-between category would profit merely modestly or would even pay more taxes.A Clemson University economic science professor Holley Ulbrich besides points out † aˆÂ ¦a level revenue enhancement would switch revenue enhancement duties from the rich to the hapless, and particularly the in-between category, and e xtinguish desirable revenue enhancement inducements for retirement nest eggs, place ownership and charitable parts † ( Ahrens 2 ) .A â€Å" Further, in her ain article, Ulbrich points out that the attractive force of simpleness fells a large alteration in the distribution of revenue enhancements among the hapless, the in-between category, and the rich † ( Ulbrich1 ) .A The ground that it has been hard to implement a level revenue enhancement is because it ‘s difficult to happen a revenue enhancement rate that to the full satisfies everyone – neither raising nor take downing the overall revenue enhancement load ( Bartlett 1 ) .A Harmonizing to Dean Baker, co-director of the Center for Economic Policy Research, there seems to be no grounds that a level revenue enhancement will ensue n growing or solves any current economic jobs ( Turkel 2 ) .A Those who oppose the level revenue enhancement feel that it will be a immense load to the in-between category and tha t it will non work out any of our current economic loads.AThe U.S. authorities has many concerns with respect to roll uping revenue.A Restructuring the income revenue enhancement aggregation method to a level revenue enhancement has many advantages.A It potentially reduces the load of revenue enhancement return readying for Americans and lowers the administrative costs of treating returns by the IRS.A By doing the earned revenue enhancement rate for everyone in America 18 % and distilling the revenue enhancement returns onto postcard-sized signifiers, the procedure of revenue enhancement readying, aggregation, processing and enforcement are dramatically streamlined.A The simplified construction should increase the sum of revenue enhancements collected, cut down administrative costs, and supply better inducements for concern and investings, ensuing in a important addition of gross for the United States authorities.

Discuss Various Theories of Management Essays

Discuss Various Theories of Management Essays Discuss Various Theories of Management Essay Discuss Various Theories of Management Essay pupils explore the risk of dying unexpectedly from various causes. They start from fears they know and, by comparing them with real-life data, they recognise that their perception of risk is often driven by presentations in the media. Pupils learn how to calculate the risks involved for various activities and how these are related to the base risk of death for typical people of different ages and genders. The emphasis is on order-ofmagnitude comparisons, reflecting the variations in risk level between individuals and over time. Pupils work with real data; they deduce information about small probabilities and use measures of average and spread in real life. They also work with orders of magnitude. They learn that mathematical thinking is essential for putting risks in perspective and that the media usually focus on stories rather than on information. In or out ? Pupils consider the evidence from a photograph about whether a batsman in cricket is ‘in’ or ‘out’. The original case arose from a controversial decision by an umpire in an Ashes test match (between England and Australia) in the 1960s. Pupils use mathematics to examine the photograph to assess whether the batman was ‘in’ or ‘out’. Initially, pupils construct a simple mathematical model of the situation by deciding what variables they need to measure and what assumptions they need to make. Using this evidence, they decide for themselves whether the batsman was ‘in’ or ‘out’. As the work develops, pupils explore these measurements and assumptions in detail, allowing them to refine their initial decisions and to understand that, sometimes, there is no single right answer! Pupils revisit their models, test their assumptions and apply their model to other situations. The mathematical skills and thinking that are required emerge gradually during ‘In or Out? ’ Keeping the pizza hot Keeping the pizza hot involves building a mathematical model in the context of homedelivery pizza. Pizza home-delivery is dependent on being able to deliver pizzas quickly, in an edible condition. In Keeping the pizza hot, pupils explore ways to keep a pizza warmer for longer and the implications of doing so. Pupils are asked to help answer the questions: how long does it take a pizza to cool, how far can it travel in that time and what difference does the packaging make? Keeping the pizza hot has a number of parts which include leading pupils to move from a practical problem of a cooling pizza to a mathematical representation of a cooling curve. This is a big step and is intended to induct pupils into the potential of mathematical applications. It demonstrates how mathematics can underpin scientific enquiry. The linking of the time to cool with possible distances of travel introduces further mathematics. Although not essential, this project would work well as a cross-curricular project with the science department. r4 Â © 2008 Bowland Charitable Trust of 9 My music My music uses the interest pupils have in music as an opportunity for mathematical investigations, using pupils own favourite music tracks as the raw data. Pupils work in small groups to listen to different tracks, take measurements and then interpret and present the results. They analyse the similarities and differences between types of track, looking first at tempo and then other variabl es such as track length, highest position or number of weeks in the charts, and album sales; they can also investigate trends in music over the years. My music can work as an introduction to statistical work, including: the collection of numerical data, performing basic statistical calculations, forming and testing hypotheses, making inferences about a population, and identifying potential sources of error in data collection and calculations. Although not essential, this project would work well as a crosscurricular project with the music department. Mystery tours Mystery Tours is a cartoon-based role play. Pupils take the part of the Tour Manager of a struggling tour operator; they are asked to plan a fictitious three day trip around the UK using tools and data in the software. They then lead a ‘simulation’ of the tour and write an evaluation report. There are three groups of tourists, categorised as ‘Nature Lovers’, ‘Thrill Seekers’ and ‘Culture Vultures’; data is available about the preferences of each group. Pupils work together in small groups, or individually, to create a successful trip. In the first stages of the exercise, the most important skills are working with data such as timetables and percentages. Other areas of mathematics are brought in when the trip begins. The tourists are quite demanding, and it is up to the pupils to keep them happy by solving any problems that may arise, presented algebraically or geometrically. Outbreak Outbreak is centred on an outbreak of a fatal virus. Pupils play the role of a scientist trying to contain the spread of the disease. Pupils have to develop a strategy which will help find the infected people, create an antidote and plan a vaccination programme to minimise the further spread of the virus. Pupils work with different experts to help with the challenges. Completing an activity in any one of the ‘bunker areas’, unlocks a code which can then be used in the Map Room to reflect the progress that individuals or groups have made. This provides the opportunity either for the whole class to work through different activities at the same time, or for independent progression. It also promotes group work discussion and real world interaction. PointZero PointZero is an adventure-driven puzzle game based around the central themes of survival, escape and the quest to uncover the truth. Pupils assume the role of three lead characters who have awoken trapped in strange and varying locations in an unfamiliar urban environment, following an undisclosed event. They are encouraged to use their mathematical skills to overcome problems so that each character can gain access to the ‘PointZero’ Building. Examples of activities include exploring complicated number sequences to scale a high rise building, using loci to find the way out of a complex underground network and reproducing geometrical patterns to deactivate a museum security system. PointZero encourages pupils to reflect on how numbers, algebra and geometry influence our daily lives, albeit in ways which may not be immediately apparent. r4 Â © 2008 Bowland Charitable Trust 7 of 9 Product wars Pupils are asked to create a new range of ‘smoothie’ drinks. They use proportional reasoning to analyse the nutritional value and geometry to design the packaging. In Product wars, pupils play the role of being part of a drinks company and work with other employees to research and design the ultimate range of ‘smoothie’ drinks. The Managing Director of the company, Brad King, asks pupils to carry out market research, develop mixes or some ‘smoothies’ and then design and create the packaging. Video is used at key points in the lessons to provide support and guidance. Activities include: using enquiry-based learning to collect and analyse information from peers in developing the product; using ratio and proportion, percentages and a spr eadsheet to mix the ingredients in different quantities to obtain the right nutritional value and taste for the target sector; and identifying suitable packaging designs. Pupils receive feedback via texts from members of the product team and video messages from Brad King himself. Reducing road accidents Pupils imagine that they live in a small town where, over the past year, there has been a large number of road accidents. The town council has set up an enquiry to see what could be done to improve the situation and has allocated ? 100,000 to spend on reducing the number of deaths and serious injuries. In Reducing road accidents, pupils choose from a wide range of possible initiatives, for example, to build new road crossings or roundabouts, to install traffic lights or to design publicity campaigns for specific groups of people. Pupils work in small teams to plan the most effective way to allocate the money. To support this work, the police have provided data on all the road accidents. Pupils use a specially constructed computer program to analyse this data and build a convincing case for their proposal. Save a baby kangaroo Save a baby kangaroo is an authentic context in which the pupils find a young orphaned kangaroo just twelve centimetres long and weighing sixty grams. Different species of kangaroo have different nutrient needs at different stages of their growth. Through video clips, photographs and data such as birth to adult weights, pupils become familiar with a range of data about the different species of kangaroo. They then use the data to identify which kangaroo they have found and develop a feeding programme to save the life of their own ‘Joey’ in a simulation. Finally they communicate what they have learned in order to help someone else save a Joey by making a poster for a Vet clinic. The mathematical content of Save a baby kangaroo includes creating alternative representations of data and communicating statistical information. Speed cameras Speed cameras are a continuing source of controversy, and even the experts are divided on their effectiveness. This is partly because the random nature of accidents makes it difficult to draw valid conclusions, which opens up possibilities for accidental or deliberate misrepresentation of data. Speed cameras uses video and newspaper resources to motivate discussion with and among pupils; this is combined with the use of spreadsheets to model the random occurrence of accidents over a year. Pupils realise that lower probabilities do not invariably lead to fewer accidents, and that the occurrence of more accidents in one year is not necessarily evidence of a higher probability. They learn that random variation can obscure r4 Â © 2008 Bowland Charitable Trust 8 of 9 underlying probabilities. These are difficult but fundamental concepts for pupils to understand, and the combination of ICT and continual referral to a real situation helps to bring them alive. The emphasis is on pupils interpreting and extrapolating from data and using data to support their arguments – and to examine the arguments of others. Sundials Sundials introduces pupils to the idea of using the sun to tell the time, applying a range of mathematical skills to understand some of the theory and to construct at least one sundial for themselves. A video about sundials provides the context, including footage explaining the history of sundials and how they work. An interview with Harriet James, a gnomonist (someone who makes sundials) shows how maths is essential to the construction of sundials. The classroom work is differentiated into three tiers. Depending on the route followed, Sundials uses symmetry and the drawing of angles, nets, origami, circle work and comparing data. Each route includes reading information from graphs and calculating time. Sundials invites pupils to reach out to the clockwork of the heavens! Water availability Pupils take the role of administrators for an international aid agency charged with providing water resources to countries in the Middle East and North Africa. Pupils examine ways to compare the availability of water fairly between the countries and then determine which country is most in need. In Water availability, pupils review documents that describe the importance of water in the region and assemble relevant data. Pupils come to recognise that a key aspect of data handling is to determine which data it is appropriate to use to answer a particular question. In Water availability, the analysis requires the creation of compound measures, such as per capita measures of water availability, which links to the maths of proportionality. Pupils realise that compound measures are important to enable fair comparisons to be made between countries of various sizes. You reckon? The media (and political speeches) are full of claims about how long things will take, how much things will cost and how tricky problems can be solved. People need to be able to judge if such claims are reasonable. You reckon? develops pupils ability to make estimates about unusual quantities based on only limited information, by posing interesting questions such as Is it possible to provide 20% of the diesel used for road transport in the UK by growing crops on ‘set aside’ land? . You reckon? develops mathematical thinking and requires pupils to communicate their solutions. Pupils see that the problems they are asked to solve are the same problems faced by aid agencies, governments, and salesmen! You reckon? helps pupils to recognise the power of even simple mathematics (together with smart thinking) when making decisions about important topics. r4 Â © 2008 Bowland Charitable Trust 9 of 9

Finances and Accounting

Finances and Accounting The Philosophy of Public Finance Mason Gaffney is one of the philosophers in the economic world who has created the philosophy of public finance. One of the principles of this philosophy is that a person does not pay taxes from the land, this is the land gives money for payment. Therefore, Gaffney draws a line between an owner and a land.Advertising We will write a custom coursework sample on Finances and Accounting specifically for you for only $16.05 $11/page Learn More Then, Gaffney refers to the ways when taxes should be either reduced or eliminated, these are the cases when money are gained for public purposes, when the owner uses the land to serve others and when he/she has to hire labor. The finances presupposed for taxes should be spend on other issues. Gaffney is also sure that people who possess land should pay more in comparison with those who do not possess it as it is obvious that those who have land have more income and can pat taxes in compari son with those who do not have land as additional indirect income. The â€Å"ability-to-pay† idea seems rather attractive to many philosophers of public finances. This point of view is interesting as it preserves incentives. The core idea of this philosophic idea is â€Å"a logical extension of the productivity theory of distribution where people are to be rewarded according to their contribution to the joint products of the economy† (Gaffney, 1998, p. 177). Considering the building on the new houses, the landowners in this case should be reduced from the taxation as new buildings promote the development of the city and land, in this case, is considered as public value. Additionally, the flourishing of a city increases the land taxation and the income for public needs. Governmental Accounting and Nongovernmental Accounting According to Governmental GAAP Guide 2009, governmental accounting deals with public corporations and the bodies which work with politics. Additiona lly, the entities may be considered as the government if they meet the following requirements, the elections to one or more states takes place, â€Å"the potential for unilateral dissolution by a government with net assets reverting to a government† (in Crawford Loyd, 2008, p.1-24) and an entity possess the power to enact a tax levy. Nongovernment accounting deals with the entities which do not possess any of these characteristics. Therefore, it may be said that the main difference between governmental accounting and nongovernmental accounting is the details of payment. If the financial operations are directed at elections and other supportive aspects, the accounting is governmental. If payment is directed at other particular purposes, the accounting is governmental. The Relationship between Budgeting and Financial Reporting in Government Reposting has become one of the most essential aspects of budgeting and governmental accounting. The information resented in reports is ai med at helping control budget expenses and follow the violation if it takes place. In most cases the information is delivered every 45 days after the end of a fiscal year, however, there are situations when reports are to be completed within a month or for special demand. The reports are created by the audits which work in and auditory companies.Advertising Looking for coursework on business economics? Let's see if we can help you! Get your first paper with 15% OFF Learn More Audits work in accordance with the particular rules and they bare responsibility for the reports they complete. Audits may give the company several days to eliminate the violations where they took place and present the report without those violations however with the mentioning that they were. Audit report is an important document which shows the current state of affairs in finances of the company. Crawford, M. A. Loyd, D. S. (2008). Governmental GAAP Guide 2009. New York: CCH. Gaffne y, M. (1998). The Philosophy of Public Finance. In F. Harrison (Ed.), The Losses of Nations: Deadweight Politics versus Public Rent Dividends (175-206). London: Othila Press.

Innovative E-Businesses Essay Example | Topics and Well Written Essays - 2250 words

Innovative E-Businesses - Essay Example The businesses services can be reached out of borders. The world has transformed into a global village and everyone has equal chances of accessibility to the services and products provided online. There are many e-businesses that have gained a sound reputation on the basis of their innovative strategies and internet related businesses processes. The businesses working online are many in number such as Google.com, Amazon.com, Wikipedia.org, Macromedia.com, Sourceforge.net, Postcast.com, Morgagebundles.com, Esure.com, Ebay.com and many more. This paper investigates four e-businesses in terms of their innovative strategies, business procedures and future strategies. The e-businesses included in this paper are Wikipedia.org, Sourceforge.net, Esure.com and Podcast.com. Wikipedia.org is an innovative e-business that is very successful online as we can see the website so often while searching any content online. Wikipedia is a free encyclopaedia that accommodates the internet users with all kind of information that is available online. The business has a wide range of content availability and is accessed by millions of people on monthly basis (Wikipedia 2009). The business allows the participation of the users in the improvement and betterment of the published content. The users are allowed to edit the content if they find anything wrong or erroneous. According to Wikipedia, Wikipedia is an offshoot of Nupedia, which allowed only the qualified writers to contribute their work online with the company but the content contribution was quite sluggish (Wikipedia 2009). However, with the foundation of Wikipedia, the content contribution improved to an extensive extent. Now, thousands of people contribute their knowledge with Wikipedia and the readers of Wikipedia on daily basis. The content that is published gains perfection and reliability with the passage of time as people discuss over it, edit it continuously and make it more reliable with their continuous efforts (Wikipedia 2009). User participation is a bold step taken by the organization and is one of the innovative strategies adopted by the organization. For writing articles voluntarily, the users are not restricted to have certain age limits or qualifications. Anyone can contribute in this writing encyclopaedia. Any information or content that is substandard or erroneous by any means is removed. The website is accessed all over the world due to which, it can be used by multicultural and multilingual people. By keeping this fact into mind, the organization has adopted an innovative strategy of provision of content in many languages due to which, it is liked to a great extent by people of different origins, cultures and speaking different languages. All the content available on Wikipedia can be seen in more than two sixty languages that is not a negligible total (Wikipedia 2009). Wikipedia is accessed daily for accessing and sharing knowledge. The content that is published on Wikipedia is interlinked or cross referenced (Wikipedia 2009). While reading the content displayed on Wikipedia, the users can find many links in between that take them to more descriptions regarding the content items. Wikipedia is a rich resource of information and content that accommodates its users to be writers, editors, readers and knowledge sharers. Wikipedia is

The Paradox of Wealth and Poverty Research Paper

The Paradox of Wealth and Poverty - Research Paper Example tion is said to have become wealthier according to the generally accepted measures, a significant portion of the population actually become poorer day by day. This gives rise to a paradoxical situation in which wealth and poverty simultaneously increase in an economy. An attempt in recent years to find a solution to this globally prevalent problem has been the made by nations by implementing the concept of â€Å"Microfinance†, which ensures provision of a wide range of financial services to the very poor. One of such most important financial services is the issue of â€Å"microcredit† to the poor, who are usually unable to get financial support from the conventional credit system due to a number of reasons. This revolutionary financial innovation originated with the establishment of the Grameen Bank by Muhammad Yunus, winner of the 2006 Nobel Peace Prize, who had started working on this issue back in the year 1976. This concept is today being applied in the developed co untries like the U.S. as well, where around 37 million people (12.6%) live below the poverty line (Wikipedia). However, it has been observed that replication of the original Grameen Banking model internationally is a very challenging task and large scale implementation of the concept may not be entirely possible. But given the promising results that this microcredit concept has shown, nations all over the world are trying to come up with policies in order to apply the concept to their respective economical and socio-cultural set up. In this essay, I’m going to describe the problem of economic and social inequality that microfinance seeks to address, and then explain in detail the concept of microfinance and microcredit, how did the concept