ISP Essay Example | Topics and Well Written Essays - 1250 words - 1

ISP - Essay Example For individuals and small individual internet is provided by use of cables, broadband wireless, dial up, integrated services digital network (ISDN) and several other methods. For large organizations, Ethernet, gigabit Ethernet, asynchronous transfer mode (ATM) is used. The services that ISP provides are, provision of a world wide web, electronic mail service, internet relay chat for customers to chat with third party, servers that allow customers and interested parties to share on a forum or a certain topic online and a file transfer protocol that enables customers to store their data and other documents and for third parties to retrieve them Internet security has in recent times deteriorated because security measures have not been appropriately taken keen off especially by the individuals and small business owners who leave loopholes for fraudsters and boot-nets who then conduct malicious activity and send large amounts of spam. Some content that have been made available are threatening, malicious and even sexually violating. Internet service providers have been protected by the communication decency act sec 230 that free them of liability caused by irrelevant material posted by third party on the websites. The liability of an ISP may arise when a third party publishes malicious material on their communication infrastructure. With the increased accessibility of the internet to millions of people every day, the internet has become a big gateway of information to diverse people. The information that flows through it has content enough for any operation whether positive or negative. Therefore there is a need and a big one at that to provide protection for the people who use it at any given time. The communication decency act, section 230 provides immunity for internet service providers against material posted by third party. The section states that, â€Å"No provider or user of an interactive computer

The Effects of the English Language and Culture in Translating A Essay

The Effects of the English Language and Culture in Translating A Non-English Text into Film - Essay Example When a film is to be made in English that was previously in another language and in text format, there are a great number of considerations on how the language and the visual elements can be translated. Meaning in one language must be carefully translated so that not only the verbal language, but the visual language makes sense. Film is unique in that the cultural meanings that are implied through one language must be translated as well as the literature of the original language. Due in large part to colonialism and then to the Westernization of consumerism, the English language has become a part of most languages, English-isms emerging throughout the cultures as they become part of the globalized world. Homogenization creeps into cultures that had previously been very ‘other’ through interactions with the dominance of the English language in business, media, and in presence in the world as English speaking travelers have a dominant position in world travel. Creating Eng lish versions of pieces of work that are written in another language often means that the work itself becomes transformed by the differences between cultures. In dominance, sometimes, comes the arrogance of transformation rather than merely translation. Transforming a literary work takes the meaning from it that was specific to a culture and re-creating it to have meaning for another culture that may no longer hold the same key symbols or meanings that it did in its original form. In translating a piece of fiction into a second language visual experience there are a great many aspects of the work that must be taken into consideration. Coding the translated work so that it reflects both the audience and the language of origin is a difficult achievement. The nature of coding in a language supports cultural meanings of symbols, but in translations that are both visual and verbal that are trying to capture meaning from one cultural language into another the task can be daunting. In the example of the result of colonialism is the key to how to undertake a project that involves translation. Where in colonialism entire cultures were translated into new cultural patterns through the coercive influence of the colonizer, so to can a text be butchered by misunderstanding the meanings that are cultural relevant and stand apart from the Western mind and the English construction of a text to prepare it for film. In translating a text into a script and direction for a film, the numbers of factors that are relevant to the translation are deep and meaningful in relationship to culture and symbols. Translation includes more than just replacing words, but replacing the emotional and cultural context through which the work was expressing meaning. Language Coding In trying to determine the best approach to translating a text from its original language into a film, the cultural coding that exists within the language must be evaluated. The first thing that must be determined in tran slating a text in one language to that of another is if the film will be intended for a mixed language population. In other words, if the film is made for a location in which two languages are prevalent and the work is being translated from one language to the other, the coding will be different than if a text is from a geographically different culture than to the culture that the film will be intended as an audience. If a Chinese book is translated for an English audience it is very

The chemistry of drug metabolism

The chemistry of drug metabolism Introduction To describe and explain the chemistry of drug metabolism a basic foundation of knowledge is needed to understand the concepts. Metabolism is one of the methods for analysing the effect of drugs or xenobiotics on the body. It is basically a process of converting lipophilic drugs into more hydrophilic drugs to decrease pharmacological effect and increase subsequent hepatic or renal elimination. So it is essentially a process of inactivation and detoxification of a drug and subsequent elimination of the metabolite formed. The basic knowledge involves the all time classical reactions such as oxidation and reduction and those more advanced reactions including glucuronidation and sulfation. Despite energy being needed to drive such reactions to be in favour, metabolism cannot occur without the complex nature of enzymes catalysing the process. However, metabolism of drugs in human is not solely dependent on the enzymes alone it can be affected by natural micro flora in the small intestines. In an in vitro experiment conducted on ranitidine, it was found that N-oxide was cleaved and is therefore a source of drug metabolism. An alteration in the population of micro flora can affect the of drugs efficacy this is a source of interaction between antibiotics and Microgynon ®. Furthermore, some drugs are bioactivated by metabolism to form active metabolites with a desirable pharmacological function i.e. prodrugs. Unfortunately metabolism can transform an inactive drug or xenobiotic into a biologically active compound which can be carcinogenic to humans. Phenol is a readily formed metabolite of benzene metabolism before catechol and hydroquinone 3,6 which poses a major health concern for humans because it can cause acute myelogenous leukaemia 6 As the great founding father of medicine Paracelsus once said â€Å"all drugs are poison†. Therefore humans and animals have adapted many mechanisms for detoxifying xenobiotics, and these processes are divided into two phases phase I and phase II. It is important to bear in mind that some phase II reactions can occur without phase I metabolism, but phase I and phase II reactions are complimentary and not mutually exclusive. This report describes the chemical reactions of drug metabolism and explains how they occur in vivo. 3.0 Phase 1 Phase 1 metabolism involves the direct enzyme activity on drugs P450 isoform enzymes and esterases are responsible for reduction and hydrolysis of drugs respectively. Each P450 isoenzymes genetic expression varies and can either be inhibited or induced. Knowledge of these drivers of metabolism is essential not only to optimise the use of drugs, reduce harm, maximise benefits in poly pharmacy but also to serve as a template for novel drug development10. P450 and esterase enzymes are mainly found in the liver. Phase I metabolism consists of 3 main reactions: oxidation, reduction and hydrolysis. 3.1 Oxidation 3.1.1 P450 mono oxygenase system 3.1.2 Other oxidation reactions 3.2 Reduction reactions Reduction reactions are mainly interconversion reactions that occur in azo, nitro and epoxide groups and conversion of carbonyl to its corresponding alcohol. Reduction reactions are carried out in the body by P450 isoenzymes, NADH/NADPH reduction systems, carbonyl reductase or aldo-ketone reductase. Azo compounds are generally used in pharmaceutical and cosmetic products. Reduction of an azo group is a classical example of a reduction metabolic reaction. This reaction occurs in the presence of other enzymes and is inhibited in the presence of molecular oxygen. Mechanism of Azo reduction Azo reduction can also occur in the presence of NADH/NADPH system alone within the pH range 3.5-6.08. An azo group can either be reduced by 2 hydrogens to form hydrozo compounds or 4 hydrogens to form two aromatic amines which usually results in a colour loss10 Mechanism of Nitro reduction Nitro groups also undergo reduction reactions and these are catalysed by the same NADP systems. 6 e- are donated to the NO2 to form amine functional groups as in chloramphenicol. This then undergoes acetylation conjugation in phase II metabolism. Conversion of carbonyl to corresponding alcohols Many different enzymes have been identified that catalyse carbonyl reduction of xenobiotics, but most of them catalyse other endogenous substances including sugars and prostaglandins7 Oracin, an anticancer drug with a pro-chiral carbon is metabolised by 11 ÃŽ ²-hydroxysteroid dehydrogenase type I in the microsomes. These metabolites are stereo specific to form DHO7 as shown below in figure 3.2.4. Much of what is known about Oracin metabolism is from phase II clinical trials as its not licensed for use in chemotherapy yet. Mechanism of epoxide reduction This reaction is catalysed by microsomal epoxide hydrolase, a catalytic triad that consists of His 431, Asp226 and Glu 404. Their activity is limited because of a narrow hydrophobic tunnel in the active site and water. A water molecule ionises to form a OH and H+ OH attacks the oxirane ring and thus opens it resulting in formation of vicinal dihydrodiol. This reaction is slow in vitro without acid but in this case epoxide hydrolase catalyses the reaction. Vicinal diols formed are more water soluble thereby terminating genotoxic potential. Hydrolysis Most hydrolysis reactions occur at the ester and amide functional groups, with ester more prone to hydrolysis than amide. Amides are more stable than esters because nitrogen is similar to carbon in size, but less electronegative than oxygen so electrons are pulled into the carbonyl Ï€ electron systems which stabilise its structure. The ease of hydrolysis of esters is used in the development of prodrugs to avoid first pass metabolism, a major problem in orally administered drugs. In vivo hydrolytic metabolism of drugs occurs in the presence of enzymes present in various parts of the body. Hydrolysis of drugs and xenobiotics is generally carried out by esterases mainly in the plasma and intestine and not by P450 systems. The blood, GI tract and liver have the highest hydrolysing capacity. The most significant hydrolysing enzymes are carboxylesterases, cholinesterases, arylesterases and serine endopeptidases. Carboxylesterase is one of the major esterases involved in drug metabolism and xenobiotic biotransformation of drugs with esters, amide and thioester functional groups. In figure 3.0 hydrolysis of ester bond results in benzoylecgonine, a carboxylic acid metabolite. But this is not the only ester group present in the structure. The group present next to the benzene can also undergo metabolism to form benzoic acid. Cocaine in the presence of heroine can generate the toxic metabolite cocaethylene in the presence of alcohol, from concomitant cocaine abuse. Carboxylesterase exists in two different forms hCE1 and hCE2. hCE1 is a more effective metabolic enzyme which transports protein to the endoplasmic reticulum and processes fatty acids and cholesterol in the liver alongside other cholesterol enzymes. The general mechanism of drug hydrolysis in esters and amides is by nucleophilic acyl substitution reactions as shown in figure 3.2.6. Minor structural differences exist between heroine and its metabolites, but their activity differs. Heroin (diamorphine) is converted by hydrolysis to 6-acetylmorphine and morphine. hCE1 mainly cleaves the 3-acetyl linkage to form 6-acetylmorphine. The 6-acetyl linkage is cleaved which later forms morphine with a phenolic -OH and secondary allylic -OH. Diloxanide furorate is a drug of choice and an antiparasitic agent for treating asymptomatic patients with E. histolytica cysts in the faeces and cryptosporidiosis, an acute intestinal amoebiaosis in HIV patients. The drug is orally administered and extensively metabolised by gastro intestinal esterase to form diloxanide and furoic acid, thereby diminishing its effectiveness. This problem is modified by using cyclodextrin that prevents excessive hydrolysis of the drug. Carboxylesterases ability to form a stable complex enhances its presence in the blood and makes it ideal for treating cocaine overdose. It is also considered that as an active site for drugs, this would make it ideal for drug discovery e.g. sarin and VX gas. 4. Phase II Conjugation pathway The phase II conjugation pathway is often a detoxification mechanism. It terminates drug pharmacological activity by changing or masking functional groups in the parent drug or phase I metabolite into a more ionic polar product which aids excretion. The processes that commonly occur in phase II metabolism can be fundamentally divided into 3 groups which are glucuronidation, sulfation and acetylation. The nature and functional group of a drug molecule will determine which one of these processes be in favour e.g. acetaminophen undergoes both glucuronidation and sulfation, however at high doses glucuronidation predominates and at low doses sulfation predominate (Airpine Choonara, 2009). 4.1. Conjugation with sugars Conjugation with various sugars is possible in nature, and novel pathways for xenobiotic metabolism are discovered frequently (Ikenakaa, Ishizakab, Miyabaraa, 2007). However the most important reaction in humans is glucuronidation. 4.1.1 Glucuronidation Glucuronidation is essentially conjugation of a substrate with ÃŽ ±-D-glucuronic acid, shown in figure 4.1.1.1. As the name suggests, glucuronic acid is a derivative of glucose with the 6th carbon being oxidised to a carboxylic acid group. This in combination with the many hydroxyl groups gives glucuronic acid a solubility of 1g/10mL in cold water, which the British Pharmacopeia would class as â€Å"freely soluble† (British Pharmacopeia Commission, 2009) Glucuronic acid is present in vivo as the co-factor uridine 5-diphosphate-glucuronic acid (UDP-glucuronic acid). The reaction of UDP-glucuronic acid with a xenobiotic substrate is catalysed by the enzyme UDP-glucuronosyltransferase (UGT) (Kaeferstein, 2009), and an example of a glucuronidation reaction is shown in figure 4.1.1.2 Figure 4.1.1.2 demonstrates how glucuronidation can occur with a xenobiotic containing an acceptor nucleophilic group (for example COOH, SH or NH2, but in this case OH) (Kaeferstein, 2009) (Sakaguchi, Green, Stock, Reger, King, 2004). The lone pair of electrons on the hydroxyl group attacks at the 1st carbon of the pyranose ring, which is activated because of the adjacent electron-withdrawing oxygens, in an SN2 nucleophilic substitution reaction. The UDP glycosidic bond is cleaved off owing to the good leaving group properties of the phosphate group, and the xenobiotic has reacted with the glucuronic acid to form a ÃŽ ²-D-glucopyranosiduronic acid conjugate. Note that the reaction is known to be SN2 because the formation of an intermediate leads to an inversion of stereochemistry at the anomeric carbon. The resulting glucuronide conjugate has improved solubility due to the hydroxyl and carboxylate groups, and is usually excreted in the urine, although there is evidence to suggest that conjugates with a high molecular weight are eliminated in the bile. However the glucuronides undergo some important reactions within the body which affects their metabolism. A spontaneous intramolecular reaction can lead to esterification of the glucuronide, as shown in figure 4.1.1.4. The newly formed ester carbonyl is capable of reacting with the N-terminal of a protein residue to form a stable imine, i.e. this can lead to irreversible protein binding. Alternatively, depending on which species the glucuronic acid is bound to, nucleophilic substitution can again occur and the xenobiotic will react with the N-terminal of the protein and regenerate free glucuronic acid (Zamek-Gliszczynski, Hoffmaster, Nezasa, Brouwer, 2006). Pharmaceutical companies may therefore try to avoid designing drugs which are predicted to be metabolised by the glucuronidation pathway, not just to increase the half-life of the drug by avoiding conjugation and excretion but also to avoid the potential side-effects that can occur as a result of protein binding, such as cirrhosis of the liver. Interestingly, glucuronidation can also lead not just to metabolites that lose their therapeutic use and are toxic, but some glucuronides can continue to be pharmacologically active and may even be more potent than their parent drug. Morphine-6-glucuronide (M6G) is one such example. M6G and morphine are both potent analgesics M6G, despite having been conjugated with a large polar molecule, still binds strongly to ÃŽ ¼ opioid receptors to provide pain relief to the same extent as morphine. Morphine-3-glucuronide, another metabolite, binds preferentially to NMDA receptors instead, and causes allodynia, myoclonus and seizures (the side-effects associated with opiate usage). Morphine and codeine are so far the only known examples of glucuronides with high activity (Kaeferstein, 2009). 4.2. Glutathione conjugation Glutathione serves as a substrate for electrophilic drugs because of the nucleophilic thiol moiety on the cysteine residue (thus glutathione can be referred to in reaction pathways as simply GSH). GSH conjugation therefore involves a nucleophilic attack of the sulphur atom onto drugs with electrophilic carbon atoms, i.e. those bound to good leaving groups such as halogens, sulphate and nitro, as well as activated carbon atoms in ring strained systems such as epoxides and ß-lactones (Zamek-Gliszczynski, Hoffmaster, Nezasa, Brouwer, 2006). Conjugation leads to a thioether bond being formed between GSH and the drug molecule. Following this reaction, conjugates are typically metabolised further to yield more polar molecules which are better excreted in the urine and bile (Zamek-Gliszczynski, Hoffmaster, Nezasa, Brouwer, 2006). Figure 4.2.4 shows the possible biotransformation reactions of a glutathione conjugate. Transpeptidase and peptidase convert glutamate to NH2 and remove glycine, respectively. NH2 is then a target for N-acetylation (mentioned in section 4.4). Alternatively, two molecules of glutathione can react together to form a disulfide bridge, in the process donating hydrogen atoms to reduce another molecule. This is usually utilised in vivo when glutathione acts as an antioxidant (Forman, Zhang, Rinna, 2009), but also plays a part in drug metabolism as seen in the denitrification of the antianginal drug, glyceryl trinitrate (GTN) in figure 4.2.5 (Ji, Anderson, Bennett, 2009). To reiterate, GSH reacts with highly electrophilic species in the body. This prevents drugs with electrophilic groups from attacking important nucleophilic centres in biological molecules, such as DNA and proteins, which could lead to toxicity. This is explored further in section 5 where the consequences of insufficient glutathione conjugation of paracetamol metabolites are looked at. 4.3. Sulfation Sulfation is one of the classical processes of phase II metabolism. It allows the biotransformation of numerous xenobiotics and metabolites from phase 1 (shown in figure 4.3.1) to be sulphate conjugates. This gives protection against toxicity or the potential toxic effects from the numerous xenobiotics and metabolites not being conjugated. It also produces more polar, more water soluble metabolites, which means they are more easily and readily excreted in urine or bile. The sulphate conjugate possesses such advantageous properties by having a low pKa, allowing an increased aqueous solubility and excretion. It is an important reaction for drugs and hormones that contain the phenolic functional group to be metabolised by conjugation to a sulphate group examples include steroid hormones, catecholamines, neurotransmitters, thyroxine, bile acids and phenolic drugs. Examples of drugs and xenobiotics with a phenolic group attached: The chemistry behind the sulfation conjugation reaction emphasizes the important key features of the system. This includes the two enzymes sulfatase and sulfotransferase, alongside the co factor 3†²-phosphoadenosine 5†²-phosphosulfate (3†²-phosphoadenylylsulfate, PAPS) which plays an important role in sulfation conjugation. The availability of PAPS and its precursor inorganic sulphate determines the reaction rate as the total amount of sulphate is limited and can be readily used up. PAPS is formed enzymatically by ATP and inorganic sulphate. The enzyme sulfotransferase transfers the active sulphate from PAPS to the xenobiotic or a phase 1 metabolite forming the sulphate conjugate (VL Verdugo D, 2004). Sulphate conjugation is a reaction principally of phenols and to a lesser extent alcohols to form highly ionic polar sulphates. Sulphate conjugation is also important for steroids because steroid sulphates are not capable of binding to their receptor and so this reduces its biological activity. Sulfation of alcohol generates a good leaving group and can be an activation process for alcohols to produce a reactive electrophilic species. Mechanism of sulfation conjugation an electrophilic substitution reaction: The oxygen of the OH has a negative inductive effect on the benzene ring so it withdraws electrons towards it making it a more reactive nucleophile It attacks the electrophilic sulphur of the sulphate group of PAPS The hydrogen of the OH bond leaves in exchange for the sulphate group and UDP acts as a good leaving group This forms the sulphate conjugate which is soluble and readily excreted via the kidneys 4.4. Acetylation Conjugation Acetylation is also an important reaction in phase II metabolism as the majority of drugs contain a primary amine functional group. It is a major route for the biotransformation of hydrazine and aromatic amines. This means that acetylation of the arylamine or phase 1 metabolites can occur more easily to reduce their biological activity (Garcia-Galan Diaz-Cruz, 2008). The limitation of acetylation is that it produces conjugates that are less water soluble (Zamek-Gliszczynski, Hoffmaster, Nezasa, Brouwer, 2006) as well as it does not work for drugs containing secondary amine groups. The aim of acetylation is to convert the primary amine moiety into an amide because amides are more stable as peptide bonds are more resistant to hydrolysis. Like glucuronidation and sulfation this reaction is highly specific because of the nature of the enzyme involved. The main players of acetylation conjugation are N-acetyltransferase and the co factor acetyl Coenzyme which is a thioester . The reactio n undergoes electrophilic substitution similar to Friedal-Craft acylation. The NH2 attached to the aromatic ring makes it much more reactive and electron donating. NAT helps to transfer the acetyl group (CH3CO) obtained from Co enzyme A (CH3COSCoA) to conjugate with the drug at the amine site forming the amide bond. H-SCo-enzyme acts as a good leaving group. Mechanism of acetylation conjugation: The lone pairs of the nitrogen of the primary amine of sulphonamide attack the carbonyl carbon of the acetyl group of the acetyl coenzyme A. In this reaction nitrogen acts as a nucleophile, donating the pair of electrons to the electrophilic carbonyl carbon. The carbonyl carbon (ÃŽ ´+) is activated by the electron withdrawing oxygen (ÃŽ ´-) making it more susceptible to nucleophilic attack. This forms a temporary tetrahedral intermediate, which falls back to form an amide bond and SH-CoA acts as a leaving group. As a result the acetyl conjugation of sulphonamide is formed, and this is readily excreted via the kidneys. 4.5 Stereo selectivity Stereo selectivity is classed as a fundamental aspect of drug metabolism ever since the tragic case of the drug thalidomide. This has provided a broader knowledge on the understanding of drugs and xenobiotics and also the importance of their stereochemistry properties. As mentioned in section 4.1.1 (glucuronidation), drug metabolism may lead to stereochemistry inversion of substrates during the various reactions that occur. An example of how the understanding of stereochemistry in xenobiotic metabolism has practical applications can be seen with the non-steroidal anti-inflammatory drug ibuprofen. It has been found that in vitro, only the S-isomer is pharmacologically active in inhibiting cyclooxygenase enzymes. However in vivo the metabolism of ibuprofen is complex, involving glucuronidation at the acyl group and hydroxylation at the 2 and 3 positions, but most importantly the metabolism of the 2 enantiomers differs because there is a unidirectional enzymatic conversion of the R-isomer to the active S-isomer. (Chang, et al., 2008). The metabolism of ibuprofen is summarised in figure 4.5.2. For this reason drug manufacturers typically produce a racemic mixture of ibuprofen for administration to patients, since the R-isomer will be converted within the body, and producing an enantiomerically pure sample would be needlessly expensive. 5. Micellaneous Amino acid conjugation is important for metabolising, solubilising and eliminating carboxylic acids through the urine because it produces very soluble conjugates. Amino acid conjugation mechanism e.g. benzoic acid (Xu, et al., 2007): The carboxylic group of the benzoic acid is first activated by ATP to the AMP ester This is then converted to the corresponding coenzyme A thioester with CoASH. These first two steps are catalysed by acyl Coenzyme A synthase enzyme The appropriate amino acid N-acyltransferase then catalyses the condensation of amino acid and Coenzyme A thioester to form the amino acid conjugate. Methylation conjugation: Even though it is not a common reaction for most drugs and xenobiotics, it is worth mentioning methylation because it is the most common biochemical reaction for endogenous compounds such as catecholamines (Strous, et al., 2009). Methylation plays a key role in the inactivation of amines such as norepinephrine, serotonin, dopamine and histamine, and is also involved in the biosynthesis of epinephrine and melatonin. A source of methyl comes from the high energy nucleotide S- adenosylmethionine (SAM) which is transported by cathecol-O- methyltransferase. However, it has been reported that methylated conjugates do not have improved water solubility (a similar disadvantage to acetylation). Methylation mechanism the nucleophilic substitution of norepinephrine: The lone pair on the electronegative oxygen of norepinephrine (R-OH) attacks the CH3 of SAM The bond between the sulphur and carbon breaks (S-C) Drug Toxicity The toxicity associated with acute paracetamol overdose is due to its metabolism processes. In the human body, paracetamol is mostly metabolised 30% by the sulfation pathway, 60% via glucuronidation and the remaining 10% being either excreted unchanged in the urine or undergoing CYP450-dependent oxidation as shown in figure 5.3 to form N-acetyl-p-benzoquinoneimine (NAPQI) (Airpine Choonara, 2009). NAPQI contains an electronically activated ring system, capable of attacking nucleophilic molecules such as N atoms in cellular macromolecules and causing cell damage. However NAPQI will preferably attack the more nucleophilic sulphur atom of glutathione and therefore will also undergo phase II metabolism to form inactive conjugates a schematic summary of the metabolism of paracetamo In overdose situations, the glutathione supply is used up as it is conjugated with the excessive NAPQI in the system. This leaves the rest of the NAPQI free to bind irreversibly to proteins in hepatic liver cells (since P450 metabolism occurs predominantly in the liver) and this cause liver necrosis. Without the detoxification capacity of the liver, the human body will typically die within 2 weeks (Airpine Choonara, 2009). With the chemistry of paracetamol metabolism in mind, it is easier to understand why some patients are classed as â€Å"high-risk† and thus more susceptible to paracetamol overdose: Recent alcohol (ethanol) consumption causes induction of the P450 enzyme involved in the formation of the NAPQI molecule; this leads to an increased quantity of NAPQI being produced and therefore the bodys supply of glutathione for conjugation is more rapidly used up leading to toxicity. Other drugs which induce the same P450 enzymes will have the same effect. Eating disorders such as anorexia nervosa lead to a poor diet and therefore decreased synthesis of glutathione in vivo, so NAPQI detoxification conjugation can be overwhelmed at lower concentrations of paracetamol consumption.

Masses Need to Create Mass Transit Essay -- Transportation, Nationwide

We consume 85 million barrels of oil daily. Nearly 6,500,000 airline operations occurred in 2009. About twenty percent of those were delayed (â€Å"Title from H2† 1). As of January 2011, the average price of a gallon of gas was $3.08, and the annual average parking costs for a vehicle in a downtown business district was $1,930 (â€Å"Rising Gas Prices† 1). All these problems have one thing in common; they can be limited, if not solved, by a nationwide mass transit system such as a bus line. Americans have been using mass transit increasingly in the past few years. The only problem is that no system exists to ferry citizens from one metropolis to another one on the other side of the country. Building a ground-based mass-transit system that connects all the cities in the United States of America will lower the demand for oil, decrease journey times to nationwide destinations, and lower transportation costs. Again, we consume 85 million barrels of oil daily. According to this value, we consume a little over 31 billion barrels of oil in a year. Out of a 42 gallon barrel of oil, nearly 19 and a half are converted into gasoline, almost half of the barrel. The average person in America uses about three gallons of gasoline daily (â€Å"Barrels of Oil a Day† 1). Therefore the average American consumes about 945 gallons of gasoline yearly. If each American uses a public bus transit system, which has an average seating capacity of fifty people per bus, then 47,250 gallons of gasoline, or about 1,125 barrels of oil, would be eliminated per bus yearly. That value is before calculating how much gasoline each bus consumes. The American Public Transit Association, or APTA, stated that if Americans used public transit for ten percent of their daily travel, the... ...power private cars, lowering our dependency, and thereby lowering the demand. Most of the weather that would affect airplane travel would not affect bus travel, thereby lowering journey times for those who experience a flight delay. Finally, a one-time pass for a bus costs an extremely less amount than gasoline and parking costs. Other reasons involving why citizens would use this system, which makes the system worth the labor and funds it would take to create it, and how the funds would be collected and used, have also been explained. We as Americans need to convince legislation to create a mass-transit system that would connect all the cities in the country, pay the taxes that will allow it to be created, and, above all other actions, ride the transit system. If we do this, we can limit, if not solve, all three problems facing the United States of America.

Class Discussion Wills and trusts Essay

What consequences might there be if a will’s custodian fails to turn the will over to the probate court after the decedent’s death? If a will’s custodian fails to turn the will over to the probate court after the decedent’s death, the court may compel the custodian to produce the will this is if requested by the potential beneficiaries of the will, and if the custodian fails to produce the will, he or she may be subject to criminal charges (Herskowitz, 2014). When would a personal representative have to institute an ancillary jurisdiction proceeding? A personal representative would have to institute an ancillary jurisdiction proceeding if the decedent owned, at the time of death, real property in a jurisdiction from the jurisdiction they lived in. This is required because other jurisdictions are not allowed to make distribution decisions about real property outside of their jurisdiction. The purpose is to transfer the title of the real property to the jurisdiction the trustor lived in to keep the estate together. (Herskowitz, 2014). What steps might have to be undertaken to find the will of a decedent? To find the will the steps the family of the deceased should take are: 1. Search the decedents’ home and office first (ie: dresser drawers, file cabinets, desk drawers, closets, the refrigerator, the freezer, books, under mattresses, and the attic) 2. Search the safety deposit box if one exists. 3. The family can also check with all family members, an attorney or family friend that may have the will. (Herskowitz, 2014). What steps are required to prove a lost will? The person contending that the original will was lost must present a copy of the will, a proof of the wills execution and validity, by either, producing witnesses who will authenticate that the copy is a true and correct copy of the will or, a â€Å"self-proving† affidavit at the end of the will to the probate court. (Herskowitz, 2014). Sources Herkowitz, S. D. (2014). Wills, Trusts, and Estates Administration, 4th ed. Upper Saddle River, NJ: Prentice Hall.

Free Essays on Antisocial Behavior In Adolescents

Adolescent Antisocial Behavior To begin this essay, I will attempt to give a full description of the components of antisocial behavior in order to accurately depict my sister’s situation. The main purpose of this essay is to better educate myself on this particular behavior disorder and to better understand Brandi’s choices, actions, and behavior. According to the American Psychiatric Association manual, antisocial behavior, also known as conduct disorder or oppositional defiant disorder, is described as â€Å"a recurrent pattern of negativistic, defiant, disobedient, and hostile behavior toward authority figures that persists for at least six months†¦Ã¢â‚¬  (Nystul, 2003). The manual also states that a diagnosis of antisocial personality must meet several requirements: a failure to conform to social norms, consistent deceitfulness, impulsiveness, failure to plan ahead, irritability, aggressiveness, a consistent disregard for work and family obligations, a consistent disregard for the saf ety of oneself and others, and lastly, a lack of regret or remorse (Harvard, 2000). Oddly, clinical descriptions note that most adolescents displaying significant signs of antisocial behavior are of adequate intellect and do not display signs of thought disorder. These individuals simply fail to exercise good judgment in decision-making. Accordingly, these youths also have difficulties seeing the â€Å"consequences† and various outcomes of their choices and behavior (Pardini, 2003). Finally, other typical behaviors in adolescents affected by conduct disorder include: truancy, lying and stealing, engaging in physical fights, a tendency to run away, lighting fires, cruelty to animals, a tendency to use drugs, alcohol, and cigarettes at a early age, low self-esteem, learning difficulties, and aggression to others (Colman, 2003). Next, I will discuss proposed potential causes of these antisocial behaviors in children. The most prominent and rep... Free Essays on Antisocial Behavior In Adolescents Free Essays on Antisocial Behavior In Adolescents Adolescent Antisocial Behavior To begin this essay, I will attempt to give a full description of the components of antisocial behavior in order to accurately depict my sister’s situation. The main purpose of this essay is to better educate myself on this particular behavior disorder and to better understand Brandi’s choices, actions, and behavior. According to the American Psychiatric Association manual, antisocial behavior, also known as conduct disorder or oppositional defiant disorder, is described as â€Å"a recurrent pattern of negativistic, defiant, disobedient, and hostile behavior toward authority figures that persists for at least six months†¦Ã¢â‚¬  (Nystul, 2003). The manual also states that a diagnosis of antisocial personality must meet several requirements: a failure to conform to social norms, consistent deceitfulness, impulsiveness, failure to plan ahead, irritability, aggressiveness, a consistent disregard for work and family obligations, a consistent disregard for the saf ety of oneself and others, and lastly, a lack of regret or remorse (Harvard, 2000). Oddly, clinical descriptions note that most adolescents displaying significant signs of antisocial behavior are of adequate intellect and do not display signs of thought disorder. These individuals simply fail to exercise good judgment in decision-making. Accordingly, these youths also have difficulties seeing the â€Å"consequences† and various outcomes of their choices and behavior (Pardini, 2003). Finally, other typical behaviors in adolescents affected by conduct disorder include: truancy, lying and stealing, engaging in physical fights, a tendency to run away, lighting fires, cruelty to animals, a tendency to use drugs, alcohol, and cigarettes at a early age, low self-esteem, learning difficulties, and aggression to others (Colman, 2003). Next, I will discuss proposed potential causes of these antisocial behaviors in children. The most prominent and rep...

Balancing work and family Essays

Balancing work and family Essays Balancing work and family Essay Balancing work and family Essay From the really beginning, it is truly of import to understand that work life balance does nt intend to give equal period of clip to the work and household. Work life balance is a wide construct which includes proper prioritising between work and life. Work includes Career, aspirations, work burden, work duties and functions etc. Life includes household, Health, pleasance, religious development, kid attention, household functions and duties etc. Working life includes both, on occupation and off occupation lives of employees within their life-time. Employees off occupation functions and duties should non be ignored as it has immense impact on the work of the employees on occupation. It non merely has impact on work life, but besides has impact on the overall quality of life ( Sambasivan A ; Md-Sidin, 2010 ) . Therefore, any organisation should see employees off occupation issues and work- household struggles. However, no fixed definition has been defined of t he work-life balance. Different research show assorted definitions. Lazar, Osoian, and Ratiu ( 2010 ) specify Work Life balance as a satisfactory degree of engagement or fit between the multiple functions in individual s life. Work life instability may do to emerge assorted issues such as occupation dissatisfaction, less employee engagement, less engagement, less commitment towards organisation, low productiveness, hapless occupation public presentation, employee aggression towards organisation, household struggles and many more. Work life instability is a beginning of occupation dissatisfaction and backdown attitudes within employees ( Hughes A ; Bozionelos, 2005 ) .Thus, work life balance has become important subject of involvement for many organisations. The work life balance is a wide subject of country therefore this literature reappraisal will chiefly concentrate on inquiries like- what is the importance of work life balance? What are the Work life instability effects? What are the assorted current schemes practiced by organisation? What are the barriers while accomplishing work life balance? What are the deductions for Human Resources? The deductions for pull offing people have besides been discussed, based on the research. Importance of Work life balance Many surveies found assorted benefits and advantages of proper work life balance. Bilal, Rehman, and Raza ( 2010 ) suggest that, better work life balance reduces absenteeism, turnover rates and improved occupation satisfaction, working status, work environment, productiveness and public presentation. If there is a work life struggle, it has direct impact on single degree. There are assorted grounds which can do work life instability, such as long and inflexible hours, over work burden, work force per unit area, equal force per unit area, force per unit area from direction, working conditions, work struggles, household struggles etc. Therefore, work life balance has become really important issue for any organisation that should see many things whilst practising work life balance. Work household struggle is associated with employee s burnout, substance issues, mental wellness issues etc. Thus, work life balance is an of import issue for any industry in footings of organisational effect ivity and occupational wellness excessively. One survey besides found that work life balance lead to a more flexible, loyal and motivated work force, which are really of import facets of any organisation s fight ( May A ; Lau, 1998, p. 213 ) . The chief competitory advantage of any organisation are their employees. Work life balance increases employee s trueness towards the organisation. It increases the committedness towards organisation. Work life balance is associated with the mental and psychological wellness of an single employee. Obviously, proper work life balance makes employees happy and satisfied from their work which straight leads to actuate them. For the organisation success, motivated and committed work force is important and a competitory advantage. Proper work life balance makes the work force more motivated, happy, satisfied, and committed and loyal towards the organisation. Effective work life balance pattern leads to cut down absenteeism and lateness within employees. It improves the overall productiveness. By supplying proper work life balance to the employees, it will assist to enroll and pull more endowments from the endowment pool and it besides enhances the organisation image and becomes the employer of pick. Furthermore, work life balance increases keeping of staff employees and reduces turnover rates. Work life balance has assorted advantages to the employees every bit good as it reduces occupation emphasis and additions occupation satisfaction.The assorted benefits of work life balance are as follows ( May A ; Lau, 1998, p. 213 ) . Benefits to organisation Benefits to Employees Beginning: Lazar, Osoian, and Ratiu ( 2010 ) Work Life Imbalance Consequences Low productiveness One of the work life instability effects is a low productiveness. Body of research which includes, studies, surveies and literatures, clearly supports that there is a relationship between work-life balance and the productiveness. Quality of work life balance influences the productiveness of employees. It has been found that higher quality of work life balance encouragement productiveness. Long on the job hours are mark of lost in productiveness and efficiency ( Fenton, 2007 ) . Work life instabilities addition concern cost. A study conducted in Hong Kong, indicates that employees work an mean 51 hours/week which is 25 per centum higher than the maximal on the job hours set by the International Labour Organisation. The consequence of this survey shows that a 3rd of respondents said their productiveness has been affected due to long on the job hours and therefore these were doing them many wellness jobs. Therefore, flexible working agreements has become really common in many industries , which has been subsequently on discussed in this literature reappraisal. Similarly, one study has conducted in UK and 597 working parents were used as a sample for the survey. Lazar et Al. ( 2010 ) suggest that this survey investigated a correlativity between self-related productiveness, flexibleness and satisfaction with work life balance, and between satisfaction with work life balance and employee enjoyment. Beginning: Lazar, Osoian, and Ratiu ( 2010 ) The above figure demonstrates the relationship between work-life balance and the productiveness. It clearly indicates that if employees are really satisfied with their work-life balance so their productiveness degree is 42 % . The productiveness degree lessenings if they are less satisfied with their work-life balance Job dissatisfaction and backdown attitudes Employees, who have instability between work and household, are enduring from occupation satisfaction. One survey found that there is a strong positive relationship between work household struggle and occupation dissatisfaction ( Hughes A ; Bozionelos, 2005 ) . Employees, who have work household struggle, are more disgruntled from their work and more likely to discontinue the occupation. Harmonizing to this survey consequences, there is a clear relationship between work household instability and their backdown attitudes including high turnover and non echt ill absence. Organizational committedness Another effect of work life instability has found is organisational committedness. Work life Imbalance may take to diminish the employee s committedness towards the organisation. One survey was conducted to look into the relationship between work household struggle and the organisational committedness within the Malayan houses. This survey found that there is a positive relationship between work life struggle and the organisational committedness ( Daud, 2010 ) . Those employees, who have a higher degree of work household balance, have strong degree of organisational committedness. Those employees, who have more work household struggle shows lower degree of organisational committedness. Job public presentation Quality of work life balance has impact on employee s mental wellness and their occupation satisfaction. Therefore, it has indirect or direct impact on the employee s public presentation excessively. One survey investigates the relationship between quality of work life balance and occupation public presentation by utilizing questionnaires to study. 475 directors have been used as a sample in Malaysia. The consequences of this survey show that there is a positive relationship between work life balance and occupation public presentation. The consequences and grounds of this survey shows that work life balance is an of import factor like others that has direct or indirect impact in finding the public presentation of employees such as occupation satisfaction, committedness. It besides indicates that it has besides impact on the employees creativeness, invention and committedness in footings of their occupation ( Beh A ; Rose, 2007 ) . This diary shows how quality of work life influence s any single occupation public presentation. Furthermore, deductions for organisation have besides been discussed in this literature. QWL is found to significantly cut down absenteeism, minor accidents and discontinuing. Quality of life Md-Sidin, Sambasivan, and Ismail ( 2008 ) suggest that, work life struggle has a relationship with the quality of life. Quality of life includes quality of work life and quality of non-work life. This conducted to look into in Malayan houses, to associate the work household struggles with the quality of life as a whole. This survey found that the work-family struggle has a important negative relationship with the quality of work, quality of non-work and quality of life as a whole. This survey found that Quality of work life and quality of non work life has a strong positive relationship with the quality of life. Furthermore, the consequences of this survey indicate that the work household struggle has a strongest relationship with the quality of work life. Therefore, it is rather clear that the work household influence an person s personal life and working life and the quality of life as a whole. Work life balance schemes Lazar et Al. ( 2010 ) suggest that it is truly of import that the Work-life balance patterns should see as a strategic human resource direction determinations that can interpret into improved single and organisation public presentation. Due to demographic and workplace alterations, work-life balance patterns becomes more complex and strategic. For case, more adult females are coming in work force. Whist, implementing work-life balance schemes, an organisation should see many things such as work force alterations, workplace alterations, organisation size and civilization etc. An organisation should implement assorted schemes in order to implement the work life balance pattern to better its overall Quality of Work life. There is a broad scope of pattern that an organisation can implement such as flexi clip, compressed work hebdomads, telecommuting, portion clip work, occupation sharing, on side kid attention installation, parental leave etc. Furthermore, the organisation may supply ass orted installations and benefits to the employees such as wellness insurance for employee and dependent, assorted plans or services such as gym or yoga Centre, which improves employee s mental and physical wellness, assorted plans that supports their kids s instruction etc. Such patterns are discussed as bellowed. Flexi clip Flexi clip allows employees to find their start and finish clip. They are more flexible to their starting and finishing clip. Flexi clip pattern allows employees to concentrate on their household or personal life. This can let them to run into their societal committednesss and exigencies and let them to react to the predictable or unpredictable fortunes. This strategy can implement by assorted ways such as the employer may let employees to flexible timing. For instance.. Arrive for work between 7:00 am to 10:00am Lunch interruption between 12:00pm to 2:00pm ( flexible tiffin hr ) Leave between 5:00pm to 6:30pm The hours an employee work between these timings can recognition to that employee s peculiar history. Many strategies besides allow employees to recognition or debit borders. For blink of an eyes, if employees are supposed to work 50 hours per hebdomad and he/she really worked merely 40hours, so he/she will owe the employer 10 hours. ( hypertext transfer protocol: //www.borer.co.uk/pages/case_studies/flexitime.shtml ) . Telecommuting Lazar et Al. ( 2010 ) suggest that telecommuting allows employees to make some of the work from at place, instead than merely at office. Many organisations practising Telecommuting , as it is going really common these yearss. This gives an advantage to employees to equilibrate between their work and their personal life. This pattern can besides gives benefits to the employees such as cut down emphasis degree, let them to work in more comfy environment, cut down going costs and transposing clip and it is besides clip effectual as it reduces the traveling clip. This pattern is besides called as telework . By supplying these installations to the employees, they are more likely to work efficaciously and it will better their productiveness. However, there are besides such issues. The organisation may be concerned by the initial implement costs. Furthermore, it is besides hard to oversee the employees as they will be working at place. This pattern may impact the commitment degree of emp loyees towards the organisation. Compressed work hebdomads The strategy of Compressed work hebdomads , allows employees to work longer hours in a displacement and in exchange they can acquire a twenty-four hours off and cut down their figure of working yearss. For case, they work more hours in a hebdomad to acquire twenty-four hours off in a following hebdomad. This allows employees to acquire yearss off, so that they can pass more clip with their households. This allows employees to acquire long weekend or mini holiday. Again, it besides depends on the organisation civilization and size. For case, this pattern can work efficaciously where employees ca nt afford to cut down the working hours, but want to cut down the figure of working yearss in a hebdomad. This can be besides good for organisation in order to maximise production, better operational efficiency or constitutions of longer working hours that can supply good client service. Part clip work Part clip work improves skill development and allows employees to acquire some experience in their field. It will be good for employees with the wellness job or disable. Those employees who have had career interruptions can besides re enter in to the work force. For illustration, female parents who stayed at place to raise their kids. Lazar et Al. ( 2010 ) suggest that organisation benefits include it gives a flexible work force to an organisation, it besides helps to maximise the usage of Human resources. Job sharing It allows employee to portion their occupation. Two or more employees can work at the same clip on one undertaking. This pattern can be suited to a workplace where chances for portion clip occupations or other agreements are limited. There are assorted benefits of occupation sharing like it besides gives to employees more clip for other committednesss. It besides improves the development of partnership. The bonding between employees can go strong and employees can larn from each other. It besides improves staff keeping and it besides increases the productiveness as it combines broad scope of accomplishments, cognition and experiences in a individual occupation. Barriers while accomplishing Work life balance Managerial support Managerial support required for any organisation in order to implement a successful work life balance pattern. Directors play an of import function in order to better work household schemes, because their place has a really immense influence on employees to promote or deter. If director is more enthusiastic and supportive, so the employees are more willing to accept the work life balance pattern. The director must understand an single individual s issues to supply echt concerns. Some organisations are really much concern about managerial support in order to implement successful work-life balance schemes. For case, in organisation called Napp Pharmaceutical , all directors are expected to retrieve names of every worker at the production degree, their family name, their spouses name and their personal issues. This enables them to be more apprehensible and supportive to their employees ( McCartney, 2002, p. 36 ) . Career effect Lazar et Al. ( n.d. ) suggest that, successful execution of work life balance pattern can increase in organisation committedness, but merely those employees who felt free to utilize this pattern without any fright of calling harm. An American saloon association studies that although 95 % of the American houses have portion clip employment chance, merely 3 % of attorneies are utilizing it due fright of calling harm. Organizational clip outlook Another barrier in implementing the work life policies is the organisation outlook of the Numberss of hours employees are expected to work. For case, does the organisation let employees to take work at place? Many surveies found that long on the job hours refers as organisation committedness, success, productiveness and motive. Lazar et Al. ( n.d. ) suggest that, Fortune 100 company in the concluded that If one has to win, one has to be at work, one has to be at that place for long hours and one has to continuously perpetrate to work as a top precedence. Colleague s support One of the barriers of work life patterns is co worker s support. Many surveies suggest that workers who use of work life patterns are enduring negative perceptual experience from colleagues and supervisors. Workers who use work life balance patterns frequently fear from the negative perceptual experience from their colleagues or supervisors. Colleagues and supervisors may believe that the individual who is utilizing work life balance patterns, holding low degree of organisational committedness. Due to this perceptual experience from colleagues or supervisors, employees who use the work-life balance pattern frequently think that it will impact on their working calling such as, farther publicity chances or wagess like inducements or salary addition. Deductions for HRM Traditionally the HR attack to Work life balance is to back up employees in day-to-day work life issues and challenges, and supply advice to them. But HR approach these yearss is truly different and became more strategic. Human resources play an of import function in order to implement successful execution of work household balance schemes. There are assorted deductions for human resources. HR must develop appropriate policies for the on the job environment, which best tantrum with the pattern of work household balance. HR must develop such policies and implement those policies. HR must guarantee that those work life balance policies are invariably revised and reappraisals. They besides formalized, work household balance pattern are the portion of continues public presentation direction system or procedure ( Akdere, 2006 ) . In add-on of implementing policies, preparation and development besides supports to heighten the quality of household work balance pattern. It is truly of import that the HR should supply preparation and development to the employees in footings of work life balance. Furthermore, HR must develop a strong, appropriate and effectual enlisting and keeping system. They must enroll single whose values closely match with the civilization of the organisation. For illustration, If the Human resource direction at the enlisting degree, is non sing the work life balance patterns while enrolling employees, so the work life balance pattern will non be effectual to those employees whose values and belief is non fiting with the needed values of the work life balance pattern. Furthermore, communicating is besides of import in order to implement better work household schemes. HR must supply advice and preparation and development to their employees. It is truly of import that the current work force of the administration should cognize about the administration s policies and schemes. Employees should hold cognition of the current policies of work life balance. HR should guarantee that employees have a proper cognition and information of the work life balance policies. If the employees have a good cognition and information sing policies of work life balance, so they will be more supportive. Therefore, it is truly of import that the HR must pass on the policies to the employees ( McCartney, 2002, p. 37 ) . The HR attack towards work life balance is depends on many things like organizational construction, organisation s policies, organisation civilization etc. It may besides differ in different states as Work life balance is non the same in one state or one industry. Human resource direction should see such issues emerge from work life balance pattern, in footings of pull offing people. Changing Workforce Changing work force is one of the chief deductions that HR may hold to confront and should non be ignored. The work force is altering and going more diverse. The Numberss of adult females workers are increasing twenty-four hours by twenty-four hours. More adult females are come ining into the industry. These alterations in work force must be considered by the Human Resource direction. The issues of work life balance has gained new dimension, in that it involves such facets of gender, work and household dealingss, gendered clip, etc. For case, harmonizing to the white paper issued by the Australia Human Resource Institute, the current Australia work force is altering quickly. There are younger Asiatic Australia come ining in to the work force and going major portion at the workplace. Equally far as workplace is concern, the Asiatic civilization could be different. They are like more relationship oriented ( White Paper , 2010, p.42 ) . HR should see these work force alterations while implementing Work Life balance patterns. All these facets have impact on issues such as staff keeping, employee motive, portion clip works, long working hours, and leave from work for particular occasions. All the household responsibilities including kid attention are still more likely a adult females s duty. Furthermore, the household construction is besides altering. These alterations in household construction, manners of work and adult females s duty such as kid attention, have a meaning impact on the organisation.