Thursday, November 28, 2019

Russian Economy Essays - National Accounts, International Finance

Russian Economy The global economy has been brought about through innovation, technology and de-regulation. To the extent the government prints more Rubles than the equivalent of the hard currencies earned on exports, it will lower the real exchange rate value of the Ruble. In effect the government makes itself a forced partner of anyone with Rubles, whenever it prints Rubles for which there was no corresponding production of goods. By laws and policies it transfer this money from the poor to the rich. Printing Rubles is the same thing as collecting a tax. But it is a tax on possession of money not production of money and is therefore parasitical. If a country runs a current account deficit it needs to finance it with a capital account ?surplus? (i.e. inflow). If it has a current account surplus, it must have a corresponding capital account ?deficit? (i.e. outflow). Comparing 1979-81 with 1985-88 West Germany's capital balance moved from an inflow of $8 billion to an outflow of $40 billion. Japan's from an inflow of $5 billion to an outflow of $75 billion, and America's from an outflow of $2 billion to an inflow of $129 billion. But this yardstick is hardly of any use: it is inaccurate and misleading. A balance of payments yardstick for capital flows gives a misleading impression because they show net rather then gross flows of capital. In 1980 total world bank cross border and foreign currency lending was $324 billion. By 1991 it was $7.5 trillion. The combined GDP (Gross Domestic Product) of the 24 industrial countries in 1980 was $7.6 trillion; in 1991 it was $17.1 trillion. 1996 GDP of Russia as half a trillion. So during the past ten years bank lending has risen from 4% of GDP (Gross Domestic Product) of these 24 nations to 44%. From 1970 to 1988 the ownership of American bonds by foreigners increased from 7% to 17% and for Germany from 5% to 34%. Turnover in foreign exchange is now $900 billion each day. There are now 35,000 trans-national companies with 147,000 foreign affiliates. Finance has become totally global. History shows that the countries whose governments do not involve themselves in business and have the fewest regulations about business, get the most investment. Russian budget ?investments? are not investments at all but subsidies. They is no substitute for real capital. Neither are Western government budget allocations investment. Elimination of regulations about business (Freedom) is what develops economies. Currency risk is the greatest deterrent to investment. In an international economic system of global integration, differences between interest rates precisely match the expected changes in the relevant exchange rates. If a one year dollar assets yields 5% and a one year Ruble asset yields 600%, investors must expect the dollar to appreciate 595% against the Ruble over the next 12 months. It is more difficult to steer economies with Monetary policy and fiscal policy when capital flows freely in a global economy. Financial interdependence has neutered government economic policy makers. Monetarists believe that all you have to do to control inflation is control the supply of money. The ?quantity equation? of monetarists says that the supply of money in circulation multiplied by the number of times it turns over in the economy each year must equal the price level, multiplied by the amount of output produced. Under these conditions slowing the growth of money will slow the growth of demand. The events of the 1980's have obliged us to disregard this theory. It has however been accepted that output is driven by supply-side factors and not by demand. For monetarism to succeed it must be possible for the government to control the supply of money and there must be a stable relationship between the amount of money and the amount of demand in the economy. Due to financial innova tion and the expansion of global finance neither of these conditions was met in the big industrial economies in the 1980's. Raising interest rates no longer controls the money supply. Domestic interest rate policy is undermined in a global economy. Higher interest rates increase exchange rates. If governments chose to limit exchange rate fluctuation they cannot increase interest rates. The truth is that there is no longer any

Monday, November 25, 2019

Creative Writing Prompts for High School Students

Creative Writing Prompts for High School Students Whether youre a student or a teacher, these writing prompts for  high school students are going to come in handy if youre looking to inspire better writing. Often, kids get stuck – confused, exasperated, irritated – putting their thoughts on paper, because theyre bored with the same old book reports, essays and summaries. But one of the only ways to become a better writer is to keep at it whether the assignment is motivational or not. Youre never going to become a better 3-point shooter if you dont stand behind the line and make the shots. Writing is the same way. You have to get in there and give it a go. Here are some writing prompts for high school students that may just inspire you or your students to give those ideas rattling around in your brain some room to breathe. 4-Item 1-Paragraph Story Come up with four things: A specific source of light (a flashing neon light reading: 21 and Over, a flickering fluorescent bulb, moonlight filtering through drawn shades)A specific object (a pink hairbrush with blonde hair matted in the bristles, a discarded replica of a Dali painting, a baby robin poking its wobbly head from a rickety nest)A sound using onomatopoeia (the pinging of a glass bottle ricocheting across a cobblestone street, the ching of a handful of coins in a mans pocket, the wet splat of phlegm hitting the sidewalk from the old lady smoking near the laundromat)A specific place (the dingy alley between Brooks St. and 6th Ave., the empty science classroom filled with glass beakers, hot plates and frogs floating in formaldehyde, the darkened, smoky interior of Flannigans Pub) Once you create the list, write a one-paragraph story using each of the four items and a single protagonist of your choosing. The story has to briefly introduce the protagonist, put him or her through a struggle (large or mild) and resolve the struggle in one way or another. Its much more fun to write if you keep the list items as random as possible and to put them all together at the end. Dont plan your story prior to creating the list! Teacher Alternative Students must write one of each list item (light, object, sound and place) on a slip of paper, and then place each in separately marked boxes on your desk. To write the story, students must draw an item from each of the boxes and write their story after, ensuring they cant plan the story prior to selecting the items. Crazy Lyrical Dialogue Go to a lyrics website and select a song randomly, preferably one youve never heard or one to which you dont know the lyrics. For instance, Fergies A Little Party Never Killed Nobody (All We Got).Then, scroll through the song and select the craziest lyric you can find that would be appropriate for school. In Fergies song, it might be What do you think, GoonRock? because its the nuttiest phrase on there.Repeat this process twice more, selecting two more songs and two more crazy lyrics.Then, start a conversation with the first lyric you selected between two people very unlikely to use the phrase. For instance, you might write something like, What do you think, GoonRock? Aunt Ida asked Bernie, sitting two wheelchairs away in Serenity Meadows Assisted Living Center.Once you get the conversation going, insert the other two lyrics elsewhere, shifting the dialogue to make sure the conversation between the two characters makes sense. Continue until you can end the conversation definitively, with a resolution that meets the needs of one of the characters. Teacher Alternative Have the students complete the first part of the assignment themselves, then exchange lyrics with people next to them so they end up with a set of three theyve never seen. Assign a dialogue length or number of exchanges and grade the punctuation. 3 Voices Choose three popular characters. They can be cartoon characters (Ren from Ren and Stimpy, Michelangelo from TMNT), protagonists from plays or novels, (Bella from the Twilight series, Benvolio from Romeo and Juliet) or characters from movies or TV shows (William Wallace from Braveheart, Jess from New Girl). Choose a popular fairy tale. (Snow White and the Seven Dwarves, Goldilocks and the Three Bears, Hansel and Gretel, etc.) Write three, one-paragraph summaries of your selected fairy tale using each of your chosen characters voices. How would William Wallaces version of Tom Thumb differ from Bella Swans? Think about the details each character would notice, the words he or she would use, and the tone in which he or she would relate the story. Bella might wonder about the safety of Tom Thumb, whereas William Wallace might commend him on his bravery, for example. Teacher Alternative After going through a novel or play with your students, assign one character from the unit to each of your students. Then, group your students in threes to write a summary of an act in the play or a chapter in the novel from each of the three  characters  perspectives.

Thursday, November 21, 2019

Conduct Disorder in Young Children Research Paper

Conduct Disorder in Young Children - Research Paper Example It can, however, be extremely difficult to diagnose a mental disorder in young children because the criteria used to recognise the symptoms of disorder in children are same as those used in adults. Diagnosis becomes even more complicated because children often do not have the skill to verbally communicate their thoughts, feelings and reactions towards certain situation. The difficulty in diagnosis also arises from the normal growth and development of young children. There are several symptoms like anger ‘outbursts, irritability, sadness, shyness’ which can be considered as characteristics of emotional disorders among children but such symptoms can also be features of normal adolescent behaviour under specific circumstances (Walker & Melvin, 2010, pp.1-2). This paper focuses on conduct disorder which is a specific kind of behavioral disorder common among children and adolescents. Conduct Disorder Characteristics Conduct disorder is a common type of mental or emotional problem that happens to children and adolescents. Children who suffer from conduct disorder generally show persistency in patterns of disregard for rules and antisocial behavior for a long time. There are some typical symptoms like aggressive behavior, running away from home at night and causing destruction to property. These symptoms increase with age as children pass on to their adolescent stage (Searight et al., 2001). Conduct disorder among young children can also result in deterioration of academic performance because children suffering from the disorder can exhibit learning inabilities that apparently do not have any â€Å"intellectual, sensual or health† reasons. It becomes difficult for them to maintain normal interpersonal relationships with friends and teachers. Even in normal situation they tend to behave in abnormal manner. Moods of depression can be seen in them all the time and they show signs of disobedie nce towards parents and teachers. These children also develop a fear in relation to personal and school related problems (Behavior Disorder/Emotional Disturbances, n. d.). Young children with conduct disorder can display certain patterns in their behavior at home and schools. Negative traits are seen in them like bullying, threatening or intimidating other people. Such children can often get involved in physical fights and can use dangerous items as weapons to physically harm people and animals, something like knife, gun or a broken bottle. It is also common among these children to get engaged in stealing. Other people can be forced into sexual activity by them. Properties of others can be destroyed by these children by setting fire on them. Another trait that can be seen in them is that they can stealthily enter into other people’s houses or get into their cars. These children often show tendency to lie to obtain things they want and can also get engaged in shoplifting. The rules of schools and home are violated by them as they play truant at school or run away from home at night. (Facts for Families: Conduct Disorder, 2004, p. 1). Prevalence There are different ways to evaluate the prevalence of conduct disorder and, hence, it becomes difficult to compare results from different studies. While some studies show prevalence during a definite period of time, there are other studies which show â€Å"cumulative prevalence†. Different studies are conducted during different age ranges of children and methods also vary with each study. As a result of this, different studies produce different estimates for the prevalence of conduct disorder. The prevalence of conduct disorder generally gets enhanced among girls as they leave childhood and move into adolescent periods. This feature is not common among

Wednesday, November 20, 2019

How Symbolism, Setting and Characterization Contribute to the Power of Essay

How Symbolism, Setting and Characterization Contribute to the Power of 'Coalinga, Half Way' - Essay Example It soon becomes apparent that is imagery is extended to his wife, 'her big eyes' seeming to relate to the cattle's eyes. The moaning of a single cow links with her gasp, the 'horrible thud of shock in her chest, the slaughtering of the animals, the killing of her hope. Further symbolic images imply guilt, dread and destruction as the man sees pieces of garbage: This man may perceive himself to be the criminal here, for what he is thinking and intends to do. The symbolic links with the animals and their fate are continued when he believes himself to be crying, just as 'the steers set up a long series of desperate bawling', then, like him drop off into silence again, as does the piercing shriek of the circling hawk. The hawk itself suggests a symbol of something circling for the kill, bringing destruction somewhere, as the man destroys his family. The words 'will you meet me halfway' signify much more than a drive or geographical point on a map, as does the statement, 'he knows he's gone way past halfway'. The imagery of himself as something 'deep inside a muscle' calls to mind the hypodermic needle of an addict, and sure enough, he is soon no longer himself, but 'some scared boy.' Words and voices, with particular reference to the telephone also play a large part in the action.

Monday, November 18, 2019

Is there a conflict between the new public management and ethics Essay

Is there a conflict between the new public management and ethics - Essay Example A minimum ethical standard is expected from the behaviour of public servants and this has become a major issue for every government. NPM involves maintaining proper allocation of responsibilities for public servants, managing budgetary constraints and implementing innovations in public services. In this era of globalization, where almost every country is participating in the international trade of goods and services, it has become even more vital that public services be conducted in ethical manner to enhance international economic relations. For conduct management of public servants, it is necessary that an efficient management system be in place. The principles that are to be used by any government should comply with the socioeconomic structure of its country. These principles can be used by political leaders to assess how efficiently ethic management regulations are followed and how well ethics is maintained at every operational level of the government. The Basics of New Public Man agement The overall success of NPM and its businesslike approach depends on further development of management principles to ensure that NPM is effective in sustaining ethical efficiency in public sector. The purpose is to manage integrity in public services within the framework of NPM. ... The three aspects are virtues that need to be developed, rules that need to be duly followed, and focus should be on getting positive results. In order to work within the framework of the triangle, certain drawbacks of public services need to be avoided like overstating the advantages of any proposal, hiding errors, not making maximum usage of established systems, practicing favoritism, not accepting responsibilities for a mistake, etc. In order to do maximum good to the maximum number of people in a community, emphasis should be on doing the right thing according to the set rules (Bowman, et al., 2010, pp.78-79). The principle of NPM includes various elements like consistent increase in efficiency, use of recently developed technologies, public servants with the goal to maintain discipline in their activities, proper implementation of professional management role, and managers being given liberty in performing their tasks (Kolthoff et al., 2007, p.400). However, in spite of the abov e mentioned elements, the businesslike approach of public administration can have a serious negative impact on democracy because such technique is faced by a consistent accountability problem. Even the strong advocators of public entrepreneurship policies in democratic governance cannot ignore the questions of accountability. The elements attached to public entrepreneurs like promoting own virtues, tendency towards non-compliance with rules and regulations, striving for power, taking risks, all these conflict with the democratic theory (Terry, 1998, pp.197-198). Ethics is often defined as acting in accordance with one’s â€Å"good personal conscience† (Somerville, 2004, p.284). This is not always right as doing ethics is a long and complicated process. One aspect of public

Friday, November 15, 2019

Human African Trypanosomiasis Treatment

Human African Trypanosomiasis Treatment THE synthesis of novel hydrazone compounds to determine the potential anti-parasitic properties and efficacy in the treatment of Human African Trypanosomiasis. ABSTRACT Human African Trypanosomiasis is caused by two sub-species of trypanosome, Trypanosoma brucei gambiense and Trypanosoma brucei rhodeisense. The protozoan parasite has complex mechanisms to evade immune destruction and hence survives in the host, leading to eventual death without treatment. Treatment such as Suramin and Melarsoprol are limited and have high toxicity, often leading to further complications. Alternative therapies are drastically needed to combat trypanosomal infection, with novel hydrazone compounds currently in development promoting trypanocidal activity. The aims and objectives of this research project include the synthesis of novel hydrazone compounds, with aims of high efficacy and low toxicity, namely against Trypanosoma brucei rhodesiense. This was achieved through a series of reactions, with proton NMR spectra used to confirm the structures of novel hydrazone compounds, and biological screening analysis used to assess the trypanocidal activity in vitro. IC50 valu es were obtained for all hydrazones synthesized, the best results coming from HD1, 9.29 ÂÂ µM, and HD6, 16.18 ÂÂ µM. Overall, the presence of chlorine in the compound typically lowered trypanocidal activity when compared to HD1, which lacked chlorine atoms. Despite other compounds in literature having much lower IC50 values, the results remain promising, demonstrating trypanocidal activity against T. brucei brucei, the infective form of trypanosome that affects animals. Trypanocidal activity against Trypanosoma brucei brucei suggests potential activity against Trypanosoma brucei rhodesiense, signifying the IC50 values obtained from novel hydrazones. Furthermore, the biological properties of hydrazone structures demonstrate the potential to develop additional analogues and derivatives, which could contribute to combatting Trypanosoma brucei rhodesiense infection. Likewise, alternative therapies that can cross the blood-brain-barrier are another interest regarding research i n the field. Trypanosoma brucei rhodesiense proceeds rapidly once an individual has been exposed to the parasite, with severe side effects and high mortality rates. This reinforces the need for better and more effective treatment and management of the disease. Key words: Trypanosomiasis, Trypanosoma brucei rhodesiense, hydrazone, Suramin, Melarsoprol, proton NMR, IC50 values 1.1. Background of Human African Trypanosomiasis Human African Trypanosomiasis (HAT), or African sleeping sickness, is a disease affecting a large proportion of Africa, with a suspected 60 million people at risk (Kennedy, 2013).It is caused by two subspecies of trypanosome, a unicellular and flagellated protozoan parasite, with Trypanosoma brucei rhodesiense (T.b.r) causing East- African sleeping sickness, and Trypanosoma brucei gambiense (T.b.g) causing West-African sleeping sickness. West African sleeping sickness is much more prevalent in terms of the whole continent, with 6228 cases reported in 2013. Incidence has decreased massively since 2000, with 25,865 reported cases, although this figure is suspected to be higher due to unreported disease incidence. It is the causative sub-species in 98% of cases. The other 2% of cases are classified as East-African sleeping sickness, with 86 cases reported in 2013, approximately 88% lower than in 2000 (709 cases reported) (Franco et al., 2014). Despite the low incidence of T.b.r infectio n, symptoms are severe and death occurs in almost all patients without treatment. Treatment for suchinfections are limited and have high toxicity, signifying the need for development. Transmission of the protozoan parasite is via the vector, the tsetse fly. Infections with T.b.r proceed rapidly, with entry of infectious metacyclic trypomastigotes into the human bloodstream, lymphatic system and cerebrospinal fluid (CSF) following the initial bite, where proliferation occurs. The tsetse fly ingests a blood meal from an infected animal, with cattle and ungulates acting as reservoirs (Palmer Wells, 2012), and hence ingests trypomastigotes. Various cell divisions and binary fission occur in the mid-gut of the fly to form procyclic trypomastigotes, and conformational changes occur to allow the trypomastigotes to bind to the salivary epithelia. Once attached, the parasite can once again replicate via asymmetric division (Pepin, 2014) to form metacyclic trypanosomes. It is in this way that a person becomes infected with T.b.r (Langousis Hill, 2014). 1.2. Immunology The causative parasite manifests in hosts due to the evasion of the immune system through antigenic variation, delaying the immune response and therefore allowing the parasite to complete its complex lifecycle (Stijlemans et al., 2016). The parasite expresses variant surface glycoproteins (VSGs) on its cell membrane via a glycophosphatidylinositol anchor to serve as a protective barrier. While the immune response induces antibody development against the VSG being expressed, the parasite can switch VSG due to the large amount of VSG genes the genome possesses. This causes new antibodies to form against the newly expressed VSG, and the parasite continues to change VSGs to avoid destruction. Furthermore, the parasites alter their energy metabolism and internal structure, presenting further issues for the immune system (Stijlemans et al., 2016). T.b.r. is resistant to human trypanosome lytic factors (TLFs) containing apolipoprotein L1 (ApoL1), and this is due to the existence of the seru m resistance protein (SRP) coded for by the SRA gene. This binds to TLF-1 and therefore prevents ApoL1-mediated lysis of the infected parasitic cells (Kennedy, 2013; Bart et al., 2015). Kato et al. noted the upregulation of certain cytokines following T.b.r infection, namely IFN-ÃŽÂ ³, IL-10, IL-6 and TGF-ÃŽÂ ² (Kato et al. 2015). Furthermore, these cytokines may play a key role in the inflammatory immune response. IL-6 and IL-10 were upregulated upon CSF examination of late stage patients, and those with CSF trypanosomes had higher levels of WBCs, positively correlating with IL-6 CSF levels. Despite this, no significant changes in levels of cytokines at different stages in HAT were noted. Both subspecies of trypanosome cause non-specific inflammatory responses, resulting in non-specific symptoms. This demonstrates the difficulty in diagnosis and staging of T.b.r infection, and therefore poses a hindrance in regards to timely treatment (Lamour et al. 2015). 1.3. Symptoms Symptoms, typically manifesting 1-3 weeks after bite, include myalgia, hyperplasia of the lymph nodes and spleen, and weight loss in the haemolymphatic stage, and there is clear central nervous system (CNS) involvement in later stages (Pepin, 2014; Kennedy, 2013). It is in this meningoencephalitic stage where patients often exhibit behavioural and motor disturbances including tremors, speech complications, anxiety, confusion, personality changes and others. Further complications may manifest, including ocular difficulties, acute renal failure, multi-organ failure and chronic lymphocytic meningoencephalitis. Death is highly likely to occur in those who do not receive treatment. Trypanosoma brucei produces an aromatic compound called tryptophol, and this induces sleep in humans. Other complications with sleep include irregular patterns of sleep or interrupted sleep, insomnia during the night and sleepiness during the daytime. 1.4. Current problem Current pharmaceutical treatment including intravenous Suramin or Melarsoprol is ineffective and potentially toxic, with patients suffering with neurological dysfunction and post- treatment reactive encephalopathy. Co-administration with eflornithine and nifurtimox has been used to treat T.b.r infection also, but remains somewhat ineffective. Suramin is provided intravenously as the first line treatment for the haemolymphatic stage of T.b.r infection, however this treatment can lead to side effects such as renal failure, peripheral neuropathy and anaphylactic shock, amongst others. It acts by binding to enzymes in the glycosome and disrupts glycolysis within the trypanosome (Babokhov et al., 2013). Should the parasite cross the blood-brain barrier in the later stages of the disease, the treatment options are toxic and limited to the arsenic compound, Melarsoprol, which acts by disrupting trypanosomal redox mechanisms. Treatment with this can lead to further complications such as post-treatment reactive encephalopathy seen in 10% of patients (Palmer Wells, 2012), subsequently causing comas, seizures and cerebral oedema for example. Co-administration of eflornithine with nifurtimox, a hydrazone of 5-nitro-2-furaldehyde, has been shown to demonstrate trypanocidal activity, and is routinely used to treat T.b.g. It has shown trypanocidal activity against T.b.b in mice, however has been relatively ineffective against T.b.r. Furthermore, although eflourthrine abides Lipinskis rule of five in theory, in practice it is a highly hydrophobic compound, and is therefore unlikely to cross inner membranes once administered (Gilbert, 2014). It is therefore administered intravenously. Due to there being no self-cure for T.b.r, treatment is required for a recovery to be made. Furthermore, many of the drugs developed are only applicable to bloodstream trypomastigotes, rather than those that have crossed the blood-brain barrier (Palmer Wells, 2012). Factors such as this demonstrate the problematic nature of the disease, as well as the need for alternative therapies to combat the infection. 1.5. Current research Currently, novel treatments are in development with the hope that toxicity is reduced and efficacy is increased against trypanosomal parasites, namely T.b.r and T.b.b. To determine whether a proposed therapeutic compound is likely to be membrane permeable and therefore orally bioavailable, the Lipinskis rule of 5 is applied. To be within the limits of the rule means that the compound is orally bioavailable and easily absorbed by the body (Leeson, P. 2012). The rules state that the molecular weight of the compound must be less than 500 Daltons, the lipophilicity value is less than 5, represented as a LogP value, the number of hydrogen bond acceptors must be less than 10, and the number of hydrogen donators must be less than 5. Hydrogen bond acceptors include highly electronegative atoms not bound to a hydrogen atom and with free electrons on its outer shell, including oxygen and nitrogen. In newer literature, fluorine may be considered and counted as a hydrogen acceptor. This contrasts with a hydrogen bond donor, any atom that donates a hydrogen atom that it is bound to break or form a bond. All novel compounds are assessed under these rules to dete rmine properties involved in pharmacokinetics (absorption, distribution, metabolism and excretion). Oral administration is non-invasive, more bioavailable and simpler for patient use, all of which is desirable for a new treatment for T.b.r infection. Furthermore, a compound designed may still be orally bioavailable if a single rule is not adhered to. Benzoxaborole compounds have recently been suggested as a new, novel treatment for Trypanosoma brucei (T.b.r and T.b.g) in vitro, namely SCYX-7158 oxaborole(Jacobs et al., 2011). The orally-active treatment is suggested to have high efficacy for both acute and chronic stages of the disease due to the treatment being permeable to the CNS, and properties such as distribution, metabolism, elimination, absorption and toxicology are apparent in vitro. A viability assay combined different whole cell T. brucei spp.and the novel compound to gain positive results of anti-parasitic activity. This treatment demonstrated concentration-dependency, and most trypanocidal activity came from the first 8 hours of a 24-hour exposure. Furthermore, the irreversibility of trypanocidal activity was noted during a short exposure. In vivo, SCYX-7158 was examined against an infection with T.b.b to monitor passage across the blood-brain barrier, with mice models providing an 80% cure rate over a 7 day-treatmen t. Benzoxaboroles, like hydrazones, have demonstrated anti-cancer, anti-fungal, anti- bacterial, anti-viral, anti-inflammatory and anti-parasitic properties with a low intrinsic toxicity similar to table salt when decomposed (Liu et al., 2014). This is due to the metabolites of benzoxaboroles being found to be boric acid and oxidative deboronation products, both with very low toxicity. Per Lipinskis law, it is an orally bioavailable drug with very low IC50 values ranging from 0.19 to 1.008 ÂÂ µM, demonstrating high trypanocidal activity in vitro. An IC50 value is value is the inhibitory concentration value at which 50% inhibition of target cells has occurred. It is important when comparing the difference in the potency of compounds. A higher value represents less efficacy, with smaller values representing good trypanocidal activity in this case. It is a pharmacokinetic parameter, measuring the relationship between drug target and drug. Other research at the forefront include the development of hydrazone compounds of 5-nitro-2-furaldehyde and adamantine alkanohydrazine (Foscolos et al., 2016). Adamantine and derivatives have been previously shown to have trypanocidal activity, increasing for the more hydrophobic, phenyl and cyclohexyl substituents. These compounds and derivatives demonstrated good trypanocidal activity, approximately 20 times greater than nifurtimox. The lowest IC50 value obtained was 0.386 ÂÂ µM. Following the same study, it was found that in the absence of the nitro group, no trypanocidal activity was demonstrated, highlighting the trypanosomal nitro reductase mechanism these novel compounds work by. In terms of the structure-activity relationship, it was seen that the selectivity of compounds against T. brucei species increased when the distance between the carbonyl group and the adamantine skeleton was increased, with derivatives containing 3-cyclopentyl and 3-phenyl being more biologically active than other compounds. In conjunction, the lipophilicity and conformational structure contributed to the efficacy of these novel compounds, with increased lipophilicity and conformational flexibility promoting trypanocidal activity. 1.6. Aims of research Better pharmaceutical treatments with high efficacy and less lethal side-effects are drastically needed for T.b.r infection. Current research demonstrates the potential use of hydrazone compounds and derivatives in combatting parasitic infections, amongst others. Guidance from project supervisor Dr A Bhambra was given throughout the project regarding the structures of compounds. Hydrazones are defined as having the structure R1R2C = NNH2, the N=H bond is conjugated with a lone pair of electrons on the functional nitrogen atom (Verma et al. 2014). Research suggests hydrazone compounds also demonstrate anticancer, anti-inflammatory and anti-HIV properties, signifying biological variety and the potential to treat other diseases (Verma et al., 2014). It is because of these properties that new hydrazone compounds are in development, with the aim of synthesising novel compounds which demonstrate similar properties when applied against Trypanosoma brucei infection, and hence a potential the rapeutic for T.b.r. 2.1. Chemistry/ experimental synthesis The synthesis of four novel hydrazone compounds of reactants A-D and Pentafluorophenyl hydrazine (PFH) (Figure 3) was performed. All solvents and reactants were commercially available. Reflux condensation reactions with relevant reactant (3 mmol) and PFH (3 mmol) were performed, with continuous heating (oil bath) and stirring of compounds at 100-150 ÂÂ °C approximately. Compounds were separated with ethyl acetate (60 ml) and distilled water (50 ml). Excess magnesium sulphate was added to remove any excess water and products were vacuum filtered. Recrystallization reactions with boiling ethanol (10 ml approximately) not in excess were performed, and compounds were vacuumed down to give final compounds. Thin Layer Chromatography (TLC) analysis was performed for all compounds throughout the stages of experiment to monitor the constituents of the final product. Prior to NMR analysis, compounds were dissolved in chloroform (800 ÂÂ µL) with exception of HD6 (with reactant D), dis solved in DMSO (400 ÂÂ µL). 2.2. Biological Screening Analysis Further viability tests were carried out to assess the trypanocidal activity of each compound. Compounds were sent to the London School of Tropical Medicine for biological screening analysis against T.b.b. Stock drug solutions were prepared in DMSO at 20 mg/ml and further diluted appropriately. All assays were performed with use of 96-well microtiter plates, each well containing 100 ÂÂ µL of parasite culture, and serial dilutions of the compound in triplicate. Wells were incubated at 37ÂÂ °C for 72 hrs in 5% CO2. Control wells contained no compound, and blanks consisted of medium only. Following this, the MIC was determined and assurance of growth in control wells. 20 ÂÂ µL of Alamar Blue was added to wells, and plates were incubated for 2-4 hrs more. Plates were read on Gemini Plate Reader with an excitation wavelength of 530 nm and emission wavelength of 580 nm. Following this, IC50 values were obtained. Four novel hydrazone compounds were synthesised, shown in table 1. The electrophilic carbonyl group of appropriate reactants A-D reacted with the nucleophilic nitrogen (hydrazine portion) of PFH by nucleophilic addition. IC50 values gained demonstrated potential, especially HD1 and HD6. Proton NMR analytical results from spectra obtained are demonstrated below, showing the amount of hydrogens (or protons) in each compound as well as their corresponding intensities. Throughout synthesis, TLC was performed for each compound to visualize the two reactants, the formed product and any other substance that may be present. Rf values and appropriate TLC analysis results are illustrated in alongside compounds in table 1. 3.1. HD1 Beige crystals (50% yield); ÃŽÂ ´H (CDCl3) 7.28 (1H, s), 7.32-7.42 (3H, m), 7.64 (2H, dd), 7.82 (1H, s). 3.2. HD4 Pink crystals (50% yield) ÃŽÂ ´H (CDCl3) 7.30 (2H, s), 7.35 (1H, s), 7.45-7.50 (1H, m), 7.62 (1H, s), 7.73 (1H, s). 3.3. HD5 Beige crystals (H (CDCl3) 7.32-7.38 (3H, s), 7.54-7.60 (2H, d), 7.78 (1H, m). 3.4. HD6 Red crystals (H (CDCl3) 7.37 (1H, s), 7.45 (2H, s), 7.70 (2H, s). 3.5. Biological screening analysis Results obtained from the London School of Tropical Medicine included IC50 values for all hydrazones synthesised. These are listed alongside appropriate compounds in table 1. HD1 had an IC50 value of 9.29 ÂÂ µM; HD4 34.37 ÂÂ µM; HD5 34.09 ÂÂ µM and HD6 16.18 ÂÂ µM. Formation of all compounds HD1, HD4, HD5 and HD6 (table 1) followed the general mechanism illustrated in appendix 1. R1 should be substituted with relevant reactant (A-D) benzene rings. Electrophilic reactants accept free pairs of electrons from the nucleophilic nitrogen atom of PFH by nucleophilic addition. The formation of a biologically active centre was documented (Verma, 2014). All compounds synthesised contain phenyl groups, which has been suggested in literature to promote trypanocidal activity (Foscolos et al., 2016). Hydrazones synthesised are also non-polar and hydrophobic compounds, meaning that they carry no net charge and are not soluble in water. Furthermore, an increase in hydrophobicity also promotes trypanocidal activity, however has been suggested to make the compound less bioavailable (Gilbert et al., 2014). Proton NMR spectra demonstrate relative intensities in parts per million (ppm) of protons or hydrogens in the compound. Despite only hydrogens being of interest, it is important to consider the other electronegative groups that exist within the compound such as phenyl groups or -OH groups, which produce different peaks. The solvent peak demonstrates as a sharp, well distinguished peak to exclude it from the compound results. Singlet, doublet and Name Reactant Structure IC50 value (ÂÂ µM) TLC (illustrated- not to scale) Rf value (cm) HD1 Benzaldehyde (reactant A) 9.29 0.73 HD4 3-chlorobenzaldehyde (reactant B) 34.37 0.48 HD5 4-chlorobenzaldehyde (reactant C) 34.09 0.43 HD6 3,4-dichlorobenzaldehyde (reactant D) 16.42 0.57 multiplet peaks were all demonstrated on the spectra. NMR analysis reflects the structures synthesised, confirming the number and positioning of hydrogens. The spectra observed demonstrated some sharp peaks and others more broad. Furthermore, some peaks were somewhat distorted due to the presence of chlorine on the aromatic benzene ring. Limitations of the experimental synthesis included low yields obtained from synthesised hydrazones. This could have been possibly due to the recrystallization step or some of the reactants not converting into product. Factors such as this could have been improved to gain better results. In addition, yields were estimated due to not weighing compounds beforehand, therefore weighing the compounds when they were initially synthesised would improve the data. 4.1. HD1 From the NMR spectra, HD1 contained 7 hydrogen atoms, one at 7.28 ppm as a singlet peak, three at 7.32 7.42 ppm as a mutliplet peak, two at 7.64 ppm as a doublet peak and one hydrogen at 7.82 ppm as a singlet peak. All novel compounds synthesised differ in terms of the aromatic benzene ring on the relevant reactants, therefore the positioning and amount of chlorine attached to this aromatic ring demonstrates the difference in IC50 values. This coincides with the biological activity against T.b.b. HD1 is formed of benzaldehyde and PFH, and therefore does not possess any chlorine atoms. The IC50 values were the lowest for HD1 at 9.29ÂÂ µM, which suggests that the presence of chlorine in the compound may decrease trypanocidal activity. 4.2. HD4 HD4 contained six hydrogen atoms, two at 7.30 ppm as a singlet peak, one hydrogen at 7.35 ppm as a singlet peak, one hydrogen at 7.45-7.50 ppm as a multiplet peak and a one hydrogen as a singlet peak at 7.73 ppm. HD4 contained a chlorine group on the 3rd carbon of the reactant benzene ring, with displacement of chlorine by (bio)nucleophiles, facilitated by the electrophilic carbon centre determining biological properties observed. However, it has been suggested that the presence of a chlorine atom at a non-reactive aromatic double bond diminishes reactivity (Naumann, 2003). The IC50 value for HD4 was 34.37 ÂÂ µM, the highest value from all the compounds synthesised. This supports the notion that chlorine atoms present in the compound reduces trypanocidal activity rather than improving it. 4.3. HD5 HD5 also contained six hydrogens, with three hydrogens at 7.32 7.38 ppm in a singlet peak, 2 hydrogens at 7.54 7.60 ppm in a doublet peak, and one hydrogen at 7.78 ppm in a multiplet peak. HD5 also contained a chlorine atom but on the forth carbon of the benzene ring, as opposed to the third. Altering the position of the chlorine atom did allow for an improved IC50 value to be obtained, which was 34.09 ÂÂ µM. This however remains much less effective than HD1. 4.4. HD6 HD6 contained five hydrogen atoms, one at 7.37 ppm as a singlet peak, one at 7.35 ppm as a singlet peak, two at 7.45 ppm in a singlet peak, and 2 hydrogens at 7.70 ppm in a singlet peak. Despite the presence of chlorine in both HD4 and HD5 causing less effective activity against T.b.b, HD6 contained two chlorine atoms attached to the benzene ring, and the IC50 value obtained was nearly half that of HD4 and HD5 at 16.18 ÂÂ µM. This suggests that the presence of one chlorine atom existing at any carbon on the benzene ring does not promote trypanocidal activity, however the presence of 2 attached chlorine atoms did aid activity. 4.5. Oral bioavailability Per Lipinskis rule of 5, all novel compounds fall within the laws except from HD1, which contains 6 hydrogen bond donors. HD1 therefore would be more bioavailable if administered intravenously, however may still be orally bioavailable as only one rule has been violated, with the rest all being adhered to. Despite this, the other novel compounds alone demonstrate progression in seeking an orally bioavailable treatment for HAT, linked with reducing toxicity amongst being easier and more accessible for those who require it. Furthermore, the use of PFH incorporates many fluorine atoms, which increases lipophilicity (Citation), increasing activity in vivo, as well as increasing fat solubility and therefore allowing the compounds to easily pass through membranes in the body. Retaining fluorine is a desirable property due to the improvement of metabolic stability as a result of the high strength C-F bond. It is a relatively small molecule, with a high electronegativity value. All properties such as this contribute to biological responses within the body. 4.6. Comparison to literature IC50 values HD1 and HD6 demonstrated the most promising results of 9.29 and 16.18 ÂÂ µM. For comparison intentions, alternative novel therapies at the forefront of science such as adamantine alkanohydrazine hydrazones and benzoxaborole SCYX-7158 have IC50 values of 0.386ÂÂ µM and 0.19 to 1.008ÂÂ µM respectively (Foscolos et al., 2016; Jacobs et al., 2011). Although the results from the synthesised compounds are promising and suggest trypanocidal activity against Trypanosoma brucei, both SCYX-7158 and the adamantine alkanohydrazine hydrazones have much lower IC50 values, suggesting that the structures of novel compounds could be improved and altered to gain better trypanocidal activity. Furthermore, current treatment Melarsoprol and Suramin have IC50 values of 0.046 and 0.004-0.009 ÂÂ µM, much lower than the compounds synthesised (Torreele et al., 2010). However, as stated above, these treatments offer high toxicity and high mortality rates following administration, and the fa ct that the novel compounds synthesised (HD1 especially) have low IC50 values remains promising. Furthermore, both Suramin and Melarsoprol are administered intravenously, posing more problems in terms of accessibility as developing countries where the disease is endemic possibly do not possess the facilities to administer treatment. This is unlike the synthesised hydrazone compounds, which all theoretically can be administered orally, therefore moving towards better treatment and management of T.b.r infection. HD4 and HD5 demonstrate lower trypanocidal activity than HD1 and HD6, therefore further progression on HD1 especially would allow for potentially more effective trypanocidal compounds, represented by lower IC50 values upon testing. Furthermore, new compounds in other literature with the highest trypanocidal activity, namely 5-nitro-2-furaldehyde and adamantine alkanohydrazine hydrazones and benzoxaboroles, provide a platform for future work and development of structural analogues of hydrazones to promote trypanocidal activity. To confirm that the novel compounds synthesised are in fact effective against T.b.r, further testing is required in a controlled level 3 laboratory where the p

Wednesday, November 13, 2019

life :: essays research papers

I felt the warmth of my mother’s hands on my soft skin while she held my face. Her soft voice whispered in my ear â€Å"good night†. It was a cold winter night after Christmas as my mother tucked me in to bed, like she always had. After telling me good night her lips hit my cheek to give me the last kiss she ever would. As she walked out, I told her â€Å"I love you with all my heart and always will.†   Ã‚  Ã‚  Ã‚  Ã‚  In the, morning the warmth of the sun hit my face and woke me up like any other morning, but something was different, something just wasn’t right. I lay in my warm bed, trying to ascertain why I wasn’t feeling right. I jumped out of bed and woke my little brother up to go eat breakfast. As we walked down the hall, I heard my dad pouring a cup of hot coffee. â€Å"Daddy is mom still sleeping,† I asked. Mom will be gone for a while but baby, don’t worry he told my brother and me in a sad voice. We will be just fine. I didn’t understand why my mom would be gone though. I asked myself â€Å" will she ever come back?†   Ã‚  Ã‚  Ã‚  Ã‚  Seven years have gone by and still my mom is gone, and my life has changed more than I thought it would. â€Å" Jess, get Drew’s clothes ready for school tomorrow,† my dad would admonish me every night before going to bed. Making sure my brother would be ready for school every morning, making sure he ate breakfast before he left for school, and making sure his homework was done everyday was what my mother used to do every morning and day; but now she is gone. Now that she is gone I have to take that place.   Ã‚  Ã‚  Ã‚  Ã‚  Now that I am the only lady in the house, I have to be the mother. No more going out on Friday nights with my friends, no more doing whatever I want. Every Friday, my friends would go out to the movies, and have fun without me. I had to stay home and make sure everything was right for my family. Now I have responsibilities like my brother who is now like my son. He thinks of me as not only a sister but a mother too. When you hear an eight year old boy call you mom and you are as young as me, it’s the scariest feeling you can have.

Monday, November 11, 2019

Why the Hawaii Light Rail Should Be Built.

Harold Ano Ho Argument Paragraph Second Draft 9/26/12 ENG22 T/Tr 1:30 Why the Light Rail Should Be Built. The light rail project will benefit Oahu in many ways, and should be constructed without delay. The first reason that the rail should be constructed is because it will help the economy. One example of how the rail will benefit the economy is that it will create many lasting jobs for workers due to the fact that the rail is a massive project that will last years.Additionally, once the rail is completed it will increase tax revenue, and eventually the taxes used to complete the project will be gained back through the project itself. The second reason why the Light rail should be built is that it will benefit the community. For example, traffic is getting worse by the year, and it will continue to do so unless we do something about it. The rail will provide an alternate means of transportation that is safe, quick, and more efficient than our current transportation.Those who wish to ride the rail will be saving money on gas, and those who wish to drive their cars will be able to do so in less traffic due to the decrease in cars on the road, so everyone wins. The third and final reason why the rail should be built is that it will help protect the environment. The pollution from cars is immense, and there is no way to remove the damage already done, only reduce the amount that we are damaging it by. The rail is electric powered, which is eco friendly.The more people who ride the rail, the less cars there will be on the road; the less cars there are on the road, the less pollution there will be. Those who are against the Light rail claim that during the construction it will cause more traffic, instead of decreasing it. While this is true, it is very short sighted and they are only looking at the small picture. The reality of the matter is that there are more cars on the road every passing year, and if we don’t do something now, it will eventually become so bad that the time spent in traffic will become infinitely worse.Spending a few years with slightly worse traffic is worth it if it will improve traffic matters for many decades to come. Another thing opponents say is that the rail will be disruptive to neighborhoods. They would be correct in this if the rail was at ground level, but since the rail will be elevated above the ground, the sound will be no worse than a freeway. For these reasons and more, the construction of the Light rail should be allowed to be continued, and completed.

Friday, November 8, 2019

10 Ways To Reduce Stress At Work

10 Ways To Reduce Stress At Work Workplace stress can be so prevalent that it begins to feel like just another part of your job. But this can lead to many long-term ill-effects on both your career and your health. Short of quitting your job for a less stressful one, however, there are a few strategies you can employ to tone down the work stress in your current job. Here are a few great methods  for reducing your stress at work.1. Act, don’t react.If you’re constantly reacting, you’re not doing your best work- and you’re not carefully considering situations as they come at you. Stay in control by stopping before acting and taking a moment to assess and properly strategize. The more you practice this, the less the stress hormone reaction will kick in each time something new gets dropped in your lap.2. Don’t forget to breathe.When you’re stressed, chances are you forget to breathe more often than not. Take a minute or two out of every hour- or after stressful meetings- to mak e sure you get a few deep breaths. Inhale, hold, exhale, hold. Repeat. Three minutes of this can make you feel as calm as if you’d just taken an hour long yoga class.3. Sit up straight.Your posture can actually impact how well you do on the job. De-clutter your workspace and make sure you have enough space to sit up rather than slump over your laptop or your phone. You’d be amazed how much more powerful and capable you’ll feel.4. Get organized.Once you de-clutter your space, do the same for your project lists and your email inbox. Keep things neat and you’ll feel much more nimble when it comes to decision making. Group your papers and projects into action types- â€Å"call back,† â€Å"file,† â€Å"send out,† or â€Å" complete.†5. Make realizable goals.If you set goals for yourself that are too unreasonable, you’ll find you never quite meet them- and you’ll start to feel rather discouraged when you keep failing t o get things done.6. Eliminate interruptions.The worst thing for your productivity is a constant barrage of interruptions. Interruptions are inevitable, and you can’t let them get to you. But you can try and minimize them. If you have a really important project to work on, try turning the ringer off on your phone, and notifications off on your email- even if just for a few hour-long stretches at a time.7. Set a daily schedule.At the beginning of your day, or the end of the day before, come up with a rough schedule for how you will go about tackling your tasks. Don’t forget to block out chunks of time for intense concentration to get your productivity score up, as well as breaks for refreshing yourself, and time to sort through minor administrative tasks as they come up.8. Take care of yourself.Don’t underestimate the power of plentiful sleep and healthy eating, both on your wellbeing and your productivity. Eating crap and not getting enough sleep will only make you more tired, sluggish, and stressed at the lack of your own output.9. Don’t self-impose stress.Fair enough, plenty of your stress is external. But there may be stresses that you’re imposing on yourself- and needlessly. Make sure you’re not too caught up in others’ perceptions of you. Shift your focus off of others and do your own work, as calmly and measuredly as you can.10. Prioritize wisely.Not everything can be a red-hot urgent priority. Have a think about which of your â€Å"top priorities† are actually top priorities, then tackle those. Learning to realize that not all projects and crises have equal weight is a great step towards maturity and minimizing stress.

Wednesday, November 6, 2019

The eNotes Blog Explaining the Kindle toDickens

Explaining the Kindle toDickens Recently, Rachel Walsh, an illustration student at the Cardiff School of Art and Design, was given the following project: Explain something modern/internet based to someone who lived and died before 1900. Cardiff chose the Kindle and to explain it to Charles Dickens. She took forty books Dickens either wrote, were among his noted favorites, and a few books of her own selection she thought he would enjoy. Then she painstakingly created miniatures of each work, rendering their covers in minute detail, carved small portals into a regular sized book and placed each tiny tome in the spaces. That way, she could show Dickens how an eReader stores dozens (in reality, hundreds) of books in a single slim volume. What else might we explain about our modern/connected world to someone who died before the turn of the twentieth century? Here are some suggestions from loyal Official Blog readers: Explaining Farmville to John Chapman (Johnny Appleseed) How do you explain the thrills of virtual farming to the man who single-handedly, and largely on foot, populated the American Midwest with apple trees? Explaining Wikipedia to Noah Webster I wonder how Webster, called the Father of American Scholarship and Education, would feel about this equal-access encyclopedia. Maybe hed be fine with it, but I have my doubts Explaining Match.com to Jane Austen Somehow I do not think Ms. Austen would be amused. Explaining Google Earth to Christopher Columbus Native Americans probably wish this had been around. Explaining Modern Crime Scene Forensics to Sherlock Holmes (Okay, we know Holmes is a fictional character, but you get the idea.) How about you?   Wed love to hear what sorts of modern marvels you might try to explain to a person living before 1900. What would your pairing be?

Monday, November 4, 2019

Tourism in Moab Utah Research Paper Example | Topics and Well Written Essays - 750 words

Tourism in Moab Utah - Research Paper Example The town’s population increases to over 100,000 mountain bikers annually. The surroundings are characterized by stark red rock, and a hot and arid environment. â€Å"The La Sal Mountains nearby provide a cooler escape† (Buckley 423), and Moab also functions as a minor destination for amenity migrants. The town has been transformed as a result of tourism. Moab is located in a valley fifteen miles long and three miles wide within the heart of the Colorado Plateau, in the American West. â€Å"The biblical name Moab was adopted in 1880 when a mail route was established between Salina, Utah, and Ouray, Colorado† (Moabhistory, 2011). Moab was among the last parts of colonized America to be â€Å"civilized†, with the first permanent white settlers appearing well after the Civil War, in the 1870s. Prior to their arrival, Native Americans had inhabited the valley. â€Å"Butch Cassidy and the Sundance Kid, the Hole in the Wall Gang, and the Wild Bunch rode to hide-outs around here† (Ricks 50) after robbing banks in Colorado mining towns. Farms, ranches, a community school, railroad and ferry services across the Colorado river were established by 1885, and a three-span steel bridge by 1912. In 1890 Moab became the county seat of Grand County, was designated as a town in 1903, and as a third-class city in 1936. The area’s economy based on farming, ranching and Utah’s finest fruit growing industry declined with the uranium boom of the early 1950s which brought in an influx of prospectors, miners, speculators and workers. New facilities such as markets, schools and businesses developed. In 1911 the first commercial oil well was drilled, and the oil boom that enriched the Moab economy lasted into the 1960s. With the demand for uranium declining by the early 1960s, potash became the next boom industry. A modern potash plant and a railroad spur line to connect vital points were constructed in 1963 (Moabhistory, 2011). For over the last quarter of a

Saturday, November 2, 2019

General Public Lacks the Knowledge and Time to Contribute To Debates Essay

General Public Lacks the Knowledge and Time to Contribute To Debates about New Technologies - Essay Example This paper discusses the issues involved with public communication of risks related to new technology. Researchers have come up with models to explain the lack of knowledge regarding various risks. This paper aims to focus on exploring these models and evaluating them in the reference to the public’s views. Modern day examples of new technology risks such as Three Mile Island, Chernobyl and the recent Fukushima accidents have been discussed in detail to ascertain the level of knowledge that the public has on certain risks. New technologies have undoubtedly changed the life of man, mostly for the better. However, these same technologies also come with inherent risks that can cause untold damage to the environment, property and to human life. It is concluded that, the general public lacks the knowledge and time to contribute to debates about new technologies. This is mainly due the assumptions made by policy makers and experts on the level of information that people should acces s regarding new technology risks. Proper information dissemination during a disaster helps emergency officials to properly carry out rescue missions and damage control. Understanding the perception of the public regarding risks and disasters can go a long way in effectively communicating issues and facts to do with the risks. The public should be involved in debates and discussions about the risks that come with new technologies. This is one way of ensuring that all is taken into account when formulating policies to do with disaster management.