The Rational Consumer Personal Statement Example | Topics and Well Written Essays - 250 words

The Rational Consumer - Personal Statement Example The alternative I have for buying gasoline is use of other types of fuels and public means of transport. However, in substituting these alternatives with buying gasoline, I must incur an opportunity cost. According to Hussain (2010), an opportunity cost is the cost incurred when one turns from using a product to using its best alternative. In this particular case, the opportunity cost for buying gasoline is the inconvenience of using public means of transport and engine malfunctions due to use of other fuels. Due to this opportunity cost, I will not be able to turn to zero consumption in the short run. However, I might later turn to zero consumption by acquiring an engine specifically made to use other fuels. In the short run, when the price of gasoline increases, the expenses on other goods will increase especially for substitute of gasoline. The reason for this is substitution effect. Substitution effect is the relative change in consumption of a product as consumers substitute it with cheaper substitutes (Hirschey, 2008). As the price of gasoline increases, I would substitute it with its cheaper alternatives and thus the income I spend on those other goods would

Tornadoes in the United States Essay Example for Free

Tornadoes in the United States Essay Introduction   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚   From the natural definition of tornado usually connotes a vortex of air that rapidly rotates and progress its contact with the ground. The rapidly circulating winds are very much capable of causing damage vast damage as a natural disaster. A tornado can move over a surface with few objects to be picked up and swirled about or you may not be able to see all the way to the surface beneath a funnel cloud because of intervening hills, trees, or buildings. Usually, the manifestations of these funnel clouds are already considered as indications of tornadoes, unless these manifestations are certain not to contact the ground[1]. The stretching that ultimately leads to tornado formation is due to the upward acceleration of the air at the base of the updraft[2]. Most manifestations of tornado illustrate extreme cyclonic force due to the effect called Corriolis, which connotes a counterclockwise movement of air in the northern hemisphere while the opposite direction of air’s movement in the south of equator. Anti-cyclonic tornadoes (clockwise-spinning in the northern hemisphere) have been observed[3]. Tornadoes most prominently manifest from the right side of air movement and the progress ahead from the storm center path as it touches the shores. In this discussion, the primary subject concerns with the occurrence and formation of tornadoes. The study tackles the principles comprising the formation of tornado in order to answer the main inquiry of the study. After which, the study analyzes the effects of tornado occurrence in the environment and the individuals in the perspective of its damaging effects. Lastly, the study covers the frequency of tornadoes in the United States and the most prominent parts in which tornadoes occur. Discussion Formation of Tornadoes   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚   Although the process by which tornadoes form is not completely understood, scientific research has revealed that tornadoes usually form under certain types of atmospheric conditions. The technology and studies in predicting the tornadoes’ occurrences are presently utilized by weather experts to eventually obtain even a crude prediction for tornadoes occurrences. Weather forecast can at least provide crude predictions for the occurrence of tornado, but this information can go inaccurate due to the wide scale of outside factors influencing the tornado’s characteristics[4]. However, even with continuous and vast studies being made to further understand the behavior of these tornadoes, predicting the occurrence of weather even with crude indications are still impossible[5]. Some predictions even fall into inaccuracy at times wherein those areas with less frequent tornadoes are being populated more than those areas with predictions of tornado occurrence but with little or no manifestation of the phenomenon.   Tornadoes, rather than being spread uniformly, as the case for solid body rotation, most of the vorticity and the ascent within the interior of the tornado vortex tend to become concentrated within a narrow ring, just inside the radius of strongest winds. Under certain conditions, this ring of extremely high vorticity can break down into multiple vortices, whose signatures are clearly evident in the situations of aerial debris[6]. In fact, nature’s most violent storms are usually quite small and localized. They are generated, shaped and dominated by powerful winds that whirl around a small area of extremely low pressure, creating a revolving storm with the characteristic swirling, funnel-shaped clouds[7].   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚   The easiest way to estimate the size of a tornado is by the size of the damage path. Usually, the common type of tornado’s path is from one to two miles wherein the width exceeds up to 50 yards. So far, the largest width the ever recorded accounts to one mile, while the smallest is considered 10 yards[8]. Tornado is formed and driven by a very low pressure winds present at its very core low pressure as its centre, which is often as much as 100mb lower than in the surrounding air. This scenario creates an overly steep pressure gradient that sucks in surrounding air and generates high wind speeds. The usual speed of the wind is in excess of 300 km/h are commonly present in Tornadoes. Geostrophic winds blow clockwise around tornadoes in the northern hemisphere and anticlockwise in the Southern hemisphere[9]. The widths of the tornadoes can vary during depending on the circulation of wind and other factors influencing their occurrences, because the size of the tornado can alter considerably during its lifetime. On other hand, the length of tornadoes’ path varies from the single point or the point of origin to more than 100 miles. The rotation in the tornadic supercell storm builds up gradually for a several hours, but the progression of the tornado itself usually occurs in much more speed than the usual expectation[10]. Typical tornado lifetimes are usually on the order of tens of minutes during which time move with the storm[11]. Most tornadoes have a diameter of less than a few hundred meters. A narrow rotating column of air that blows around a more or less vertical axis of low pressure and moves across the surface of the land is frequently described as a whirlwind[12]. The development of these Doppler radars provided a means for weather forecasters to at least obtain the status of characteristics, and event he chances of tornado for at least under circumstances. The National Weather Service has strategically located Doppler radars across the country which can detect air movement toward or away from the radar[13]. Detecting the progress of rotation within the tornadoes can enable the weather experts to determine and provide appropriate life-saving procedures. Most tornadoes eventually become surrounded by cooler, less buoyant downdraft air a the flanking line or rear flank gust front wraps around the mesocyclone, reminiscent of the way in which the cold air wraps around an occluding extratropical cyclone. As the mature tornado and its associated mesocyclne weaken and die, a new mesocyclone may form along the gust front, setting the stage for the formation of second tornado[14]. Somehow, studies have arrived to the most frequent time ranges when tornadoes usually occur; however, the accuracy of these time frames still vary according to other external factors, such as area, topographical location, climatic shifts, presence of storms, seasonal variations, etc. Tornadoes usually occur during late afternoon or early evening. They are most frequent during late spring or early summer[15]. A series of climatic cycles and transformations is thought to be the primary theory to support the ground basis for the formation of tornadoes. During its early phase, the initial event starts with the drying of cool air starts to meet up with the drying war air. In this sense, the air continuously overlaps with each other until humid air arises on the surface.   Progressing to the next phase, the warmer air begins to settle in the lower altitudes in order to increase the temperature inversion, which comprises of warm, dry stratum above moist or humid air surface layer. Due to the continuous advection or the horizontal airflow, the atmospheric changes under the temperature inversion continue to warm and moisturize. As the sun heats the air at the ground surface, it starts to ascend and cool, which then forms a large cumulonimbus clouds[16]. With tornado’s unpredictable character, tornadoes and the system for its formation are still being critically studied. So far, the studies have revealed the usual occurrence of tornado resides in isolated incidents or in great numbers along a storm front. In extreme cases, these tornadoes can even generate more than 300 miles (483 kilometers) per hour and may travel over 200 miles; the average tornado is much weaker and lasts for 5 to 10 minutes on the ground and traveling 2 to 5 miles[17]. A whirling mass of cloud and debris beneath a roiling sky is a truly awesome and frightening sight. The twisting winds inside a tornado average between 100 and 150 miles per hour, but some storms generate winds in excess of 200 miles per hour[18]. After which, a cold front settles in within the temperature inversion and force the surface air up through it into the cool air above. In this phase, the growth of the clouds progress rapidly although substantial in form but does not extend above the tropopause. In this scenario, a jet stream is being produced, which moves air away from the top of the cloud and convection occurs beneath it, making the storm more intense[19]. After this phase, the tornado is likely now to develop most especially if the position and curves of the jet stream is in very favorable condition. In addition, for a tornado to form, these should be enough air to flow into the bottom of the storm, which usually coincide with the tailing hail. This initiates the descending of the cold air produced in the initial phase, which somehow help to stimulate convection current and energy transfers. Finally, tailing hail and descending cold air initiate the production and initiation of convection of currents and energy transfers. Static electricity is now produced, which consequently aids on the development of the vortex present in the tornado’s body[20]. Effects of Tornadoes on Environment and People   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚   People and properties are usually threatened by the massive entrance of high wind speeds around the tornado, which tornadoes move across the ground. Many tornadoes move at speeds of between 150 and nearly 500 km causing massive damage in the area that it passes by. Fast-progressing tornadoes cannot be outrun, and people caught in their path are generally advised to shelter or drive away at right angles to the narrow tornado track[21]. The intensity and duration of tornadoes greatly affect the rate of damage done by this disaster to the path it passes by and the environment to which it occurred. They have vast destructive impacts on the land in which they touch whether it is city, town, country, ocean or forest. The effects of tornadoes on forests are similar to that of hurricanes wherein the strong downward circulating motions of the wind alter the composition of forest stands[22]. In emphasizing tornadoes effects in financial losses of the community, approximately $5 million a year (compared with $200 million for urban drought) is spent to provide and improve warning systems and to construct tornado shelters or storm cellars[23]. The government is ready to spend this amount of funds for the preventive preparations in order to further warn their citizens of the coming natural phenomena. This is one of the primary reasons why the number of tornado-related deaths in these tornado-prone areas tends to be lower than those with lesser risked areas. Warning time under the best conditions is not more than one hour ahead of the event. Tornadoes cause great damage they often cause total destruction where the touch the ground, because of the extremely strong winds and the powerful uplift is within them. They often follow quite well-defined paths along the ground, and this is evident in the trail of damage they leave behind including swathes cut through forest and narrow strips of buildings destroyed in residential areas[24]. On the other hand, although deaths from tornado have been reduced in recent years, the number is still relatively high, averaging about 120 a year. Economic damage from tornadoes averages about $125 million a year, as opposed to only $15 million for drought[25]. The tornadoes have been one of the most destructive events in decades, killing forty-seven people, destroying 2,000 homes and causing about US $500 million worth of damage[26]. On the other hand, from one of the most prominent site of Tornado, Kansas, several tornados were estimated to have caused $2.5-5 million in property damage. Four deaths were caused by 484 tornadoes over the 52 year period (from 1950-2002) only for this area. In terms of tornadoes’ damaging potential, a primary tornadic direct hit on one of the larger communities can cause much greater loss of life and property than in small country[27]. Areas of the U.S Being Hit the Most   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚   Tornadoes are the most violent and destructive disasters of the Earth’s atmosphere. About 200 tornadoes a year are recorded across the United States. They are even considered as the primary climatic hazards in central and eastern areas, and particularly in the valley of the Mississippi, which is most prominently known as the tornado alley[28]. In fact, during the years from 1920 to 1950, every country in Mississippi valley and those adjoining coastal plains of the Gulf of Mexico was struck by at least a dozen tornadoes that cause extreme property damages and the crude death rate of 2000 people[29]. Although tornadoes occur in many areas of the world, the United States has more tornadoes than any other country, with an estimated 30% to 50% of the world’s total. Canada ranks as the second place in the occurrence of tornado with approximately 100 to 200 tornadoes per year[30]. In additional, tornadoes occurring in these areas tend to be more aggressive and deadly than those in other countries. Such scenario is because of the clashing of air masses east of the Rockies. The most obvious tornado alley extends from the plains of northwest Texas eastward into north Texas and then northward across Oklahoma, Kansas, and eastern Nebraska. A second tornado alley, called Midwest Alley, is located over most of Illinois and Indiana. Finally, Dixie Alley[31] stretches eastward from Arkansas, Louisiana, and Texas through Mississippi, Alabama, and Georgia. Dixie Alley also extends southward into Florida[32]. A portable Doppler radar measured a wind speed of 318 miles per hour in a tornado that struck Oklahoma City[33] on May 3, I999.[34] In this incident of tornado, the immense manifestation of tornado was not predicted accurately by the weather forecast during that point or at least, the news of its intensive manifestation arrived late, which caused the immense damage[35]. During April 26, 1991, one of the most prominent tornado occurrences in Oklahoma occurred near Red Rock. The wind measuring for 286 miles per hour was incorporated within the storm that devastated parts of Red Rock Oklahoma. In an average year, more than a thousand tornadoes are likely to touch down across the United States[36]. However, it is fortunate for the community that weather analysts can provide advance warning for the coming or at least a crude prediction of tornado occurrence in their area. In this way, the public is able to prepare for the coming of tornadoes; hence, reducing the damage this phenomenon can cause. Knowing that these Tornadoes happen predominantly during the afternoon and early evening, the exact ranges of time frames based on previous historical occurrence of tornadoes state 2:00P.M. until 7:00 P.M local time. On the other hand, the time wherein tornadoes usually show immense activity is from 5:00 P.M. to 6:00 P.M. Such time frame is very much evident in smaller alley or regions such as the Dixie Alley[37]. A broad swath from central Texas to eastern Nebraska comprises the heart of ‘tornado alley,† which extends southward through the Gulf States and eastward to the Ohio Valley. No other place in the world experiences more tornadoes than the nation’s heartland, although twisters are not confined to the Midwest and southern states[38]. In addition, the national tornado season is clearly from April through July; however, tornado season in the United States never really begins or ends but is ongoing[39]. Most tornadoes tend to build up inside very large storms, and these are usually found in unstable environments in which wind speeds vary with height and where cool, dry air rests on top of warm, moist air, with a thin, stable layer separating the two air masses[40], a condition similar to temperature inversion in other settings[41].   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚   In the United States, those areas with high occurrences of tornadoes have relatively low rates of tornado-related deaths, partly because of variations in population density, but the provided proofs show a variation over time in the location of tornadoes, which is placing significant numbers of less well-prepared individuals and communities at risk. Death rates from tornado-related injuries in the United States are the highest among people living in mobile homes, the elderly (over 60 years of age) and people caught outside with no protection when the tornado passes by[42]. One of the most historical events that occurred in Pennsylvania was during 1998 wherein fifty-nine tornadoes, plus several waterspouts over the open waters of Lake Erie were counted for just one season. According to climatologist and weather analysts, the most damaging tornadoes that occurred within this area of Pennsylvania from 1865, 1896, 1944 and 1998 are only products of stronger western and southern storms that usually struck in late spring[43]. Conclusion   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚   As for the conclusion of the subject, tornadoes in the United States have indeed manifested in greatest terms wherein U.S has been considered as the top most destination for the occurrence of tornadoes. From the discussion of tornadoes, formation, it has been uncovered that the origin of these phenomenon are from the contacts of war and cold air that contradicts to form humid, moisture and temperature variance, which in the end, initiate static electricity that causes the formation of the vortex. From the discussion on the effects of tornadoes, it has been uncovered the main destruction caused by this event is on the property and physical aspect wherein significant economic cost decline are mainly affected especially for those occurring in larger communities. Lastly, the areas where tornadoes mostly occur are Nebraska, Oklahoma, Kansas, Texas, and those areas within the tornado alley or Mississippi. Bibliography Alexander, D. E. (2003). Natural Disasters. Springer. Barnes, P. L. (1999). The Oryx Guide to Natural History: The Earth and All Its Inhabitants. Greenwood Publishing Group. Burton et.al., I. (1993). The Environment as Hazard. Guilford Press. Essex, S. (2005). Rural Change and Sustainability: Agriculture, the Environment and Communities. CABI Publishing. Gelber, B. (2002). The Pennsylvania Weather Book. Rutgers University Press. Gunn, A. (2001). The Impact of Geology on the United States. Greenwood Publishing. Hagget, P. (2002). Encyclopedia of World Geography. Marshall Cavendish. Konvicka , T. (1999). Teachers Weather Sourcebook. Libraries Unlimited. Pack, C. C. (2001). The Environment: Principles and Applications. Routledge. Tawrell, P. (2006). Camping Wilderness Survival: The Ultimate Outdoors Book. Paul Tawrell. Wallace, J. M., Hobbs, P. B. (2006). Atmospheric Science: An Introductory Survey. Academic Press. [1] Tawrell, P. (2006). Camping Wilderness Survival: The Ultimate Outdoors Book. Paul Tawrell. p.674 [2] In a typical supercell storm the rate of ascent w increases from near zero at the ground to ~3 m   s-1. Hence, the e-folding time T for the amplification of the vorticity is 300s (Wallace, J. M., Hobbs, P. B. (2006). Atmospheric Science: An Introductory Survey. Academic Press. P.360). [3] Tawrell, p.674 [4] Tawrell, p.674 [5] Tornadoes usually form when warm, humid air is sucked into a low-pressure cell. There it arrives into contact with a cold front accelerating towards it from the counter directions. The steep temperature gradient permits the tornado to facilitate along the squall line either in front of or along the cold front. In the United States, tornadoes are most common in the Mildwest and along the east coast (Park, C. C. (2001). The Environment: Principles and Applications. Routledge. P.315) [6] Wallace, Hobbs, p.360 [7] Powerful updraughts within increasing column of air provide the tornado its strong vertical progression, and the circulating form is induced by strong winds that are drawn into the low pressure center (Park, p.315). [8] Tawrell, p.674 [9] Park, p.315 [10] Wallace, Hobbs, p.360 [11] On the other hand, non-supercell tornadoes form when a patch of boundary layer air with circulation about a vertical axis comes into vertical alignment with a vigorous convective-scale updraft. The source of the vorticity may be a gust front, a convergence line, or wind shear induced by flow around a topographical feature (Ibid, p.361) [12] Tornadoes form over dry land, but when the funnel-shaped vortex comes into contact with a lake or sea it sucks up particles of water and whirls them around in a spiral pattern as a waterspout (Park, p.315). [13] Tawrell, p.674 [14] Wallace, Hobbs, p.360 [15] Park, p.315 [16] Alexander, D. E. (2003). Natural Disasters. Springer. P.172 [17] The United States is the most tornado-prone country in the world, with the main characteristic of tornadoes that range from average to extreme. The usual area of occurrence relies in Great Plains or the Tornado Alleys (Barnes, P. L. (1999). The Oryx Guide to Natural History: The Earth and All Its Inhabitants. Greenwood Publishing Group. P.55) [18] Gelber, B. (2002). The Pennsylvania Weather Book. Rutgers University Press. P.135 [19] Alexander, p.172 [20] Ibid, p.172 [21] Park, p.316 [22] Tornadoes, by contrast, are intensive hazards that threaten about +0 million people living in the areas of higher tornado incidence in the Midwest, the Great Plains, and the Gulf States. Tornadoes are comparatively rare events with high energy outputs and arc highly localized, with a very rapid onset. Moreover, although between six and seven hundred tornadoes occur every year, the average path is quite small. There is little incentive, therefore, to invest in protective measures, since their likelihood of being needed in any one place is small and, given the force of a tornado, such measures are often not effective (Baumann and Sims, 1972; cited from Burton et.al., I. (1993). The Environment as Hazard. Guilford Press. p.42). [23] Burton et.al. p.42 [24] Park, p.317 [25] Burton et.al. p.42 [26] Park, p.316 [27] Essex, S. (2005). Rural Change and Sustainability: Agriculture, the Environment and Communities. CABI Publishing. P.175 [28] America’s known â€Å"Tornado Alley† or the Mississippi is the area with the most prominent occurrence of twister that entails great damage and destruction; however, few periods see as much activity as on one night in mid May 1999, when seventy-six twisters ripped through Oklahoma, Nebraska, Kansas and Texas (Park, p.316) [29] Hagget, P. (2002). Encyclopedia of World Geography. Marshall Cavendish. P.84 [30] Konvicka , T. (1999). Teachers Weather Sourcebook. Libraries Unlimited. P.200 [31] Tornado incidence increases in Dixie Alley in February. During the spring, tornadoes become more common farther west and north, extending into Texas and the Tennessee Valley. By May and June, tornado frequency increases in the plains of Texas, Oklahoma, Kansas, and Nebraska. In July, tornado frequency shifts 10 the Dakotas, the Upper Midwest, and the Great Lakes region while decreasing to a minimum in Dixie Alley. An interesting secondary peak is evident in November, particularly in Dixie Alley (Konvicka, p.200-201). [32] Konvicka, p.200 [33] Ibid, p.200 [34] On the evening of 3 May 1999 the worst tornado of the century, as far as costs are concerned, touched down on Oklahoma City. It was the nation’s first billion-dollar one. It was not alone. Other parts of Oklahoma. the state that gets more tornadoes per square kilometer than anywhere else on earth, were hit with 65 of these storms on that same evening, all of them in areas close to Oklahoma City. Within a period of five hours 8,000 buildings were in partial or total ruin as the rash of storms swept from southwest Oklahoma diagonally across the state toward Wichita, Kansas (Gunn, A. (2001). The Impact of Geology on the United States. Greenwood Publishing.p.205) [35] The difficulties involved in forecasting were evident on that fateful evening in May. The Storm Prediction Center (SPC), based at Norman. Oklahoma, issues bulletins every day, and on that morning’s statement announced it as unlikely that any tornado would appear during the day. By early afternoon SPC raised its estimate to moderate. Not until close to 4:00 in the afternoon did SPC change its prediction to high risk—and then only because a powerful computer had shown that storms were charging across the state (Ibid, 205-206). [36] Gelber, p.135 [37] Konvicka, p.200 [38] Gelber, p.135 [39] Konvicka, p.200 [40]  If a weather system reaches this unstable mass, the status quo is disrupted: The low-level air is forced upward, and a vertical vortex gradually takes shape as the warm air ascends, cools to the point of condensation, and then is triggered into faster ascent as the latest heat of condensation warms the surroundings (Gunn, p.206). [41] Ibid, p.206 [42] Pennsylvania experiences an average number of eleven tornadoes annually, based on the statistical period of 1954 through 1999. However, during a ten-year period from 1989 to 1998, the average number of Pennsylvania tornadoes doubled to twenty-two . (Gelber, p.135) [43] Ibid, p.135

Septic Shock Case Study: Causes and Effects

Septic Shock Case Study: Causes and Effects Introduction Septic Shock is a serious circulatory disorder often characterised by a whole- body inflammatory state and the systemic response to infection (Titheradge, 1998), with the most common cause being the contamination of blood with bacteria. Septic shock is defined as sepsis with hypotension which develops in almost half of all septic patients as a complication with a mortality rate of 40-60% (Titheradge, 1998). Septic shock often results in a progressive failure of the circulation to provide blood and oxygen to vital organs of the body resulting in impaired tissue perfusion and oxygen extraction (Thiemermann, 1997). The key symptoms include a severe fall in blood pressure (hypotension) with hypo-reactivity to vasoconstrictor agents (vasoplegia) which may lead to the dysfunction or failure of major organs including lungs, liver, kidneys and brain (multiple organ dysfunction, MODS) and ultimately death (Goligorski et al., 1997). Presently it is widely assumed that septic shock rarely shows similar symptoms in affected individuals and therefore it is difficult to detect and then consequently treat it (Groeneveld and Thijs, 1986). It is, however, also agreed that most of the therapeutic interventions invariably focus on the primary aim of fighting the refractory hypotension by the use of aggressive fluid infusions, glucocorticoids, large doses of vasoconstrictors (Baumgartner and Calandra, 1999) and occasionally renal replacement therapy (Wheeler Bernard, 1999). Yet these interventions do not offer consistent success (Parratt, 1997). In recent times, our understanding of the pathophysiology of septic shock has developed significantly through experimental and clinical trials, though the discovery of a suitable treatment with therapeutic efficacy is proving elusive (Baumgartner and Calandra, 1999). This is probably because of the heterogeneity of the clinical situations and the differences in host response to i dentical pathogens. Moreover evidence suggests that different pathogens which cause septic shock respond differently to the conventional treatments. Still, no effort has been made to treat patients according to the nature of the infecting organism (Gao, Anonymous, 1992). During the early 1990s nitric oxide (NO) emerged as a potentially substantial step towards the treatment of septic shock. This finding directed scientists to carry out numerous clinical trials and animal experiments with the objective of finding out more about the interrelation of NO and Sepsis (Cobb, 1999; Kilbourn, 1999). Later, the discovery of nitric oxide synthase (NOS) made this enzyme the primary target of therapeutic agents (Rosselet et al., 1998). However, recently a substantial amount of literature has been published with evidence contradicting the discoveries of earlier studies. Today more than a decade has elapsed without any resolution to the matter and even in this 21st century Septic Shock is invading the developing countries rapidly (Cobb, 1999; Kilbourn, 1999). This problem of a lack of significant advances in this field can be highlighted by the fact that 17 years have passed since the final publication of the Consensus Conference on sepsis and sepsis related syndromes (Rangel-Frausto, 2005). This paper conclusively defined sepsis and its symptoms with the hope of finding a suitable treatment in order to eradicate the disease (Rangel-Frausto, 2005). Today, however, the situation has not changed significantly with up to 750,000 new sepsis cases every year and 215,000 annual deaths in the United States (Trzeciak et al., 2008, Mitchell M. Levy, 2007). Additionally, in the population that survives such attacks, there is considerable morbidity with many scoring low in health related quality of life assessments (Kaarlola et al., 2003, Perl et al., 1995). Hence the 5 million lives campaign instigated by the US Institute of Healthcare Improvements, aims to minimize the prevalence of nosocomial sepsis (sepsis originating in a hospital) (Gao et al., 2008). This campaign aimed specifically at increasing safety and transforming the quality of hospital care (McCannon et al., 2007). Moreover, the Surviving Sepsis Campaign aims to improve the quality of life of septic patients using the best evidence available currently (Dellinger et al., 2004). Though the world mortality rates have declined in recent times, sepsis is gradually becoming more prevalent in the elderly in the developing countries (Gao et al., 2008).This is mainly due to the extended longevity of patients with chronic illnesses, the increased occurrence of immunosuppression, and the more frequent use of invasive procedures (Bone, 1991; Parrillo, 1993). Sepsis, severe sepsis, septic shock and multiple organ failure still dominate the mass cases of non coronary intensive care units (ICUs). This essay will attempt to explore the fundamental mechanisms leading to tissue and organ damage in septic shock through the investigation of a case study. Following this, the discovery and general biology of nitric oxide (NO) shall be discussed, and the experimental evidence implicating NO as an effector in sepsis, will be examined in detail. The results obtained from various pharmacologic interventions directed at NO in animal studies will also be considered. This report will also give an account of conventional and innovative treatments for the management of septic shock. Finally, data from the few available relevant clinical trials will be reviewed and possible future avenues of interest will be discussed. Systemic Inflammatory response syndrome and Septic Shock (Clinical Manifestation) Sepsis, severe sepsis and septic shock were inaccurately defined until a recently reviewed consensus conference in 1992 (Bone et al., 1992, Dellinger et al., 2004). In this meeting the term systemic inflammatory response syndrome (SIRS) was invented insinuating a clinical response arising from a nonspecific tissue damaging event (insult) (Rangel-Frausto, 2005). Sepsis as mentioned earlier is the result of substantial release of inflammatory mediators in response to an infection. However, often the same mediators are released in the absence of a documented infected in several medical conditions such as cardiopulmonary bypass (Wan S. et al., 1997), pancreatitis and trauma (Shanley TP. et al., 2006). Due to this, the early definitions of sepsis or septic shock were found to be misleading hence a North American consensus conference proposed a new terminology. In this conference sepsis was defined as a condition in which critically ill patients meet criteria for SIRS, in the context of infection. SIRS was defined as two or more of the following: 1) heart rate >90/min; 2) temperature >38Â °C or 12,000 or 20/min or a PCO2 3.5 L min-1 M-23; 2) hyperglycaemia (plasma glucose >120 mg/dL) in the absence of diabetes; 3) significant oedema or positive fluid balance (20 mL/kg over 20 h); 4) inflammatory variables: plasma C-reactive protein >2 SD above t he normal value or plasma procalcitonin >2 SD above the normal value and 5) mixed venous oxygen saturation (SVO2) >70% . (Dellinger RP et al., 2004). SIRS is generally not considered as a disease and its recognition does not provide any clinical conclusion. However, since it has proven to be a very useful for the identification of sepsis and its sequelae namely severe sepsis and septic shock it is regarded as a very important tool (Shanley TP. et al., 2006). Case Study: A 3-year-old boy was admitted to the intensive care unit because of fever, hypotension, and lethargy. A purpuric rash was noted on his arms and legs. Arterial blood gas analysis demonstrated hypoxemia and metabolic acidosis. The arterial lactate level was 10 mmol/L. He was intubated, resuscitated with crystalloid solution, started on broad-spectrum antibiotic therapy, and given dopamine to maintain a MAP above 55 mmHg. His chest radiograph revealed bilateral interstitial-alveolar infiltrates with a left sided predominance. Gram stain of the cerebrospinal fluid showed gram-negative cocci. The dopamine infusion was increased to 18Â µg kg-1min-1 for persistent hypotension and oliguria. Pulmonary and radial arterial catheter data yielded the following blood pressure, 85/30 mm Hg; MAP, 48 mm Hg; heart rate, 140 beats per minute; CVP, 10 mm Hg; pulmonary artery pressure, 22/14 mm Hg; PCWP, 12 mm Hg; cardiac index, 2.5L min-1m-2; and SVRI, 1226 dyne-sec-cm-5m-2. The boy was treated with ad ditional saline and an epinephrine infusion, which increased the MAP, cardiac index, and urine output. Arterial lactate levels decreased over the next 12 hours. Subsequent cultures of blood and cerebrospinal fluid grew Neisseria meningitidis. In this case the patient with acute organ failure and hypotension was diagnosed with septic shock. The young boy with meningococcal septic shock had a borderline-low cardiac index. Due to this a decrease in the cardiac index in this patient by the administration of an NOS inhibitor might not be desirable. This is suggestive of the fact that NO or its synthesising means cannot always be targeted in order to battle septic shock. I will attempt to go into further details with regards to this statement as we go along the essay. Nitric Oxide discovery: Joseph Priestly first identified gaseous NO in 1772. NO also named Nitrogen Monoxide is a very simple and tiny molecule consisting of one nitrogen and one oxygen molecule. Unknown of its fundamental physiological roles in the mammals, until the 1980s NO was widely considered as a mere toxic atmospheric pollutant (Konstantin J. Ovodov et al., 2000). In the 1980s researchers were examining how blood vessels expand (dilate) hence regulate the mean arterial blood pressure. Dilation of blood vessels, also termed vasodilation is a very important physiological response which partly regulates the blood pressure. By increasing the diameter of blood vessels, vasodilation causes the blood to travel more freely due to lower resistance (RF Furchgott, 1980). Since the blood vessel lumen widens during vasodilation, the blood imposes less outward pressure on the vessel wall hence reducing the blood pressure. In opposition, vasoconstriction reduces the diameter of the lumen increasing the BP. These physiological responses occur all the time in the human body regulating the BP and therefore are one of the most fundamental mechanisms of the human body. Dr Robert Furchgott and his group, later in 1980s investigated the role of acetylcholine in the smooth muscle relaxation and found that relaxation only occurred if a special class of cells called endothelial cells were present (RF Furchgott, 1980). These cells line the interior surface of blood vessels, forming an interface between circulating blood in the lumen and the rest of the vessel wall. Behind the endothelial cells are the smooth muscle cells which either relax or contract thus regulating the vascular tone (RF Furchgott, 1991). The same research group also discovered that smooth muscle were only able to vasodilate the blood vessels in the presence of endothelial cells. This indicated that there was some kind of factor that was being released by the endothelial cells which was involved in the dilation of the blood vessel. This factor was named Endothelium Derived Relaxing Factor (EDRF) and subsequently specified as NO (S Moncada et al., 1997). In 1977, Ferid Murad independantly investigated the mechanism of action of nitroglycerin and found that it worked by inducing the release of NO which in turn was able to cause relaxation of smooth muscle cells (F Murad et al., 1977). Louis Ignarro in 1986 finally resolved the whole perplex of EDRF and NO by declaring that EDRF was in fact NO. It was stated that both molecules showed identical properties when he compared gas Nitric Oxide and EDRF (Ignarro, L. J. Et al. 1987). In 1998, Nobel Prize in Physiology and Medicine was awarded to Drs. Robert Furchgott, Louis Ignarro, and Ferid Murad for their discoveries that vascular endothelial cells make nitric oxide (NO) and that such endothelium-derived NO stimulates cyclic guanosine monophosphate (cGMP) synthesis in the underlying vascular smooth muscle, causing relaxation (Kilbourn, 1999). Since the discovery of NO, vast number of its physiological roles in normal conditions have been reported including in the immune system, nervous system, reproductive system and other cellular functions. It has also been found to play important roles in variety of species ranging from mammals, to insects and plants. Role of Nitric Oxide in Biology Since it was first discovered to play a role in the dilation of blood vessels many new roles for Nitric Oxide (NO) have been discovered. In human body, NO is metabolised by its diffusion into red blood cells where it oxidizes the ferrous iron of oxyhemoglobin yielding methemoglobin and nitrate ions (NO3-) (J.M. Hevel et al., 1994 and Konstantin J. Ovodov and Ronald G. Pearl, 2000). This meachanism limits local NO build up and is particularly important in keeping NO concentration in naomolar range, at least in nonhydrophobic compartments (i.e. outside cell membranes) (Beckman Koppenol, 1996). Nitric oxide has been found to be produced by effectively every cell type in vivo and plays an important role in both controlling the normal function of cells as well as in regulating larger scale processes such as the reproductive, immune and nervous systems. A few of these biological functions for NO are described in more detail below. The Immune System Nitric oxide plays many important roles in the immune system although it is expressed in many cell types following endotoxin or pro-inflammatory cytokine treatment (C. Nathan et al., 1991 and R.G. Knowles et al., 1994). NO, in immune system, is produced in high amounts from specific cells called macrophages. Proceedingly to an infection, chemicals known as cytokines are release in vivo which activate the cells of the immune system such as macrophages, and help guide them to the site of infection (S. Moncada et al., 1991 and C. Nathan et al., 1991). NO produced by the macrophages is toxic to the bacteria and play an important role in their destruction (Fig 1). The production of nitric oxide in this way also helps protect against other types of infection including parasites and viruses (S. Moncada et al., 1991). However, too much nitric oxide production can not only lead to septic shock but has also been implicated in conditions where the immune system is too active autoimmune diseases like arthritis (Jang D and Murrell G A, 1998). The Nervous System Nitric oxide has been shown to be involved in both the peripheral and central nervous system. The three nitric oxide producing isotypes of enzyme (iNOS, eNOS, nNOS) (see section) in humans, one isotype (neuronal NOS (nNOS)) is found almost exclusively in the nervous system (Forstermann et al., 1995). nNOS is thought to be involved in promoting the transfer of interneuronal nerve signals. This is thought to take place by the stimulation of exocytosis (release) of endogenous chemicals called neurotransmitters of one neurone (Moncada et al., 1991; Forstermann and Kleinert, 1995). These NT then diffuse across the synaptic cleft (gap between neuronal terminals) and stimulate the neighbouring nerve cell terminal to transmit the signal (Otto Loewi, 1961). NO has shown to play a substantial role in diseases of the nervous system like Alzheimers and Parkinsons. In both diseases, the inhibition of NO has shown to slow down the progression of the disease in mice (Weill Cornell Team, 2005 and Jo hns Hopkins et al., 2004). Reproductive Biology Nitric oxide is one of the most important molecule in the course of reproduction and is involved in many aspects of it. As well as dilating the blood vessels and thereby helping to regulate maternal blood pressure, NO is also involved in implanting the early embryo in the uterus (Rogers, 1995). During pregnancy, nitric oxide is also suggested promote angiogenesis (a process in which new blood vessels are formed) (RayChaudhury et al., 1996). It is also known to play a role in the survival of trophoblasts (form placenta) (Enders et al., 1978). Furthermore deficiency of NO has been found in patients with preeclampsia (a medical condition in pregnancy) suggesting its partial role in growth of embryo (Yallampalli et al., 1994; Liao et al., 1996). In addition, drugs (Viagra) used to treat erectile dysfunction also affect nitric oxide signalling. Cellular function A notable number of cellular activities can be controlled by nitric oxide including cell division, cell movement and cell survival. The majority of cells in human body have the ability to undergo programmed cellular death. This is a self-destructive mechanism usually called apoptosis which often occurs when a cell is damaged and beyond repair, infected with a virus, or undergoing stressful conditions such as starvation (Kerr et al., 1972). Cells in these conditions go through apoptosis so that they dont hinder the proper functioning of the rest of the tissue. During apoptosis, the structures of the cell break down in an organised manner, forming a packaged cell that is smaller in size so that it can be easily removed by the cells of the immune system (Kerr et al., 1972). Nitric oxide was first shown to inhibit apoptosis hence promoting cell survival in human B lymphocytes (Mannick, J. B. Et al., 1994). Subsequently similar finding were reported in an ample number of other cells. However, high doses of nitric oxide also have deleterious effects. They can be toxic to many cell types and can lead to septic shock and multiple organ dysfunction syndrome (MODS) in which case NO causes cell death instead of promoting cell survival (Beal Cerra, 1994). Nitric Oxide and Inflammation (Pathophysiology of septic shock) This section will deal with mechanism by which wall fragments of Gram-negative or Gram-positive bacteria and other inflammatory agents induce nitric oxide synthase (iNOS) in cells and tissues. Exogenous toxins which enter the circulation stimulate the synthesis and release of a number of endogenous cytokines. During a gram-negative infection which can lead to septic shock, lipopolysaccharide (LPS) and endotoxins present on bacterial wall and many other inflammatory agents bind to a co-receptor (CD14) on the surface of specific immune cells like macrophages, resulting in their activation (J.C. Lee et al., 1996). LPS also bind to LPS-binding proteins which are produced by the liver. These proteins facilitate LPS binding to the CD14 co-receptor of the macrophages. The CD14 co-receptor is activated through the binding of LPS to a toll-like molecule (TLR4), (Re F, Strominger J. Et al., 2001) which is responsible for initiating the transmembrane signaling. TLR2 molecules act in the same way as TLR4, (Leppper PM et al., 2002) though; these are activated by gram-positive bacteria, mycobacteria and yeast. Gram-positive bacteria such as Staphylococcus aureus have further additional wall fragments such as peptidoglycan (PepG) and lipoteichoic acid (LTA). Both PepG and LTA have been shown to synergise to produce the characteristic features of septic shock, MODS and ultimately death in rodent models (S.J. De Kimpe et al., 1995 and G.M. Millar et al., 1997). These effects were not observed with either LTA or peptidoglycan alone, although high doses of LTA can cause circulatory failure but not MODS (S.J. De Kimpe et al., 1995). Gram-positive bacteria may also release other enterotoxins and exotoxins, for example toxic shock syndrome toxin 1, which are involved in the pathogenesis of sepsis (reviewed in (R.C. Bone et al., 1994)). The additional fragments released by Gram-positive bacteria bind to unknown receptors however, like LPS binding, cause the release of proinflammatory cytokines TNF-a, IL-1ß, and IFN-? (Thiemermann, 1997, Titheradge, 1999). These cytokines as well as IL-6 are often produced in response to immune stimulation of macrophages and monocytes hence also in septic shock patients. IL-1 and TNF each occur in two forms, a and ß. TNF- a and both forms of IL-1 are made by activated monocytes and macrophages, whereas TNF- ß is made by activated T lymphocytes (Review by J. Saklatvala et al., 1996). There are two receptors for both IL-1 and TNF and the two forms of each cytokine interact with the same receptors. IL-1 a and ß interact with the type 1 IL-1 receptor for signal transduction, whereas type II does not appear to transmit any signal and functions as an inhibitor of IL-1 action (J. Saklatvala et al., 1996). The two types of TNF receptor, p55 (type I) and p75 (type II) have different end effects; p75 mediates the proliferative actions of TNF- a while p55 receptor signals the inflammatory response and apoptosis (J. Saklatvala et al., 1996). Complex interactions between these different mediators produce intense pathophysiological modification, which eventually lead to diffuse tissue injury and ultimately sequential system failure (multiple organ dysfunc tion syndrome), which accounts for the majority of deaths among patients with sepsis, severe sepsis and septic shock (Beal Cerra, 1994). IL-1ß and TNF-a have a very short half life compared to IL-6 and therefore IL-6 is a very good indicator of cytokinemia. The initial studies of septic shock, showed a very strong positive correlation between IL-6 levels and fatal outcome (Casey L. Et al., 1993). NO is equally a very short lived molecule with an estimated in vivo half life of only 0.1 seconds hence again it is hard to measure its levels in order to detect the severity of cytokinemia hence the severity of sepsis or septic shock. There are several molecules that contribute to the pro and anti-inflammatory responses in septic shock (Table 4); however I shall only focus on a few due to the limited word allowance. In response to inflammatory agents in septic shock, the released cytokines (TNF-a, IL-1ß, and IFN- ?), bind to their specific receptors activating a protein kinase called tyrosine kinase leading to both the activation of the nuclear factor-kB (NF-?B) (a transcription factor) and the phosphorylation of intracellular protein (Gao et al., 2008). A precise mechanism by which these cytokines act was proposed by J. Saklatvala et al. in 1996 however this has yet to be confirmed. Nitric oxide producing cells contain I-?B which is an inhibitor of NF-?B. For the activation of NF-?B, proteolytic cleavage of I-?B from NF-?B is required which forms NF-?B. This biological change allows the activated NF-?B to translocate to the nucleus, where it binds to the promoter region of the iNOS gene inducing transcription. It has also been reported to induce other inflammatory agents, such as cytokines and leukocyte-endothelial adhesion molecules (Janssen-Heininger et al., 2000). Tyrosine kinase present inside the cell acts as a messenger molecule involved in the proteolytic cleavage of I-?B/NF-?B and hence in the activation of NF-?B and iNOS expression (Hecker M, et al., 1996). In septic shock, the translated products of iNOS mRNA subsequently assemble forming the iNOS protein which in turn causes local NO proliferation (Thiemermann, 1997). Fig 2 shows the signal transduction pathway of iNOS expression in response to inflammatory agents. The physiological role of iNOS is to enhance the formation of NO (due to iNOS activity), which in turn may contribute to either the pathophysiology of septic shock (clinbical symptoms) or the host defence (Reviewed in Gao et al., 2008). Fig 3 shows a simplified schematic of the Anti Inflammatory cascade in the context of septic shock. Excess NO produced by iNOS has been reported to both induce and inhibit NF-?B (Kalra et al., 2000; Umansky et al., 1998). In year 2000, it was proposed that low levels of NO may induce further NO production while high concentrations do the opposite exhibiting a feedback mechanisms that would oppose the over expression of genes regulated by NF-?B (Janssen-Heininger et al., 2000). In addition NO at high concentrations competes with O2 at the active site of NOS, thus providing a feedback mechanism of its own synthesis (Griscavage et al., 1995; Rengasamy Johns, 1993). Biological Synthesis of Nitric Oxide (Nitric Oxide Synthases) NOS structure and substrates for NO production: In mammals, NO is exclusively formed from the enzymatic oxidation of one terminal guanidino nitrogen of the amino acid L-arginine. When expressed in moles, this reaction utilizes 1 mol each of arginine and O2, and 1.5 mol of NADPH, yielding 1 mol of NO, 1 mol of L-citrulline and 1.5 mol of NADP (R.G. Knowles et al., 1994). The reaction sequence involves the generation of an Ng-hydroxy-L-arginine intermediate, followed by the oxidation of Ng-hydroxy-L-arginine in presence of molecular oxygen to form L-citrulline and NO (Dennis J. Stuehr et al., 1991 and R.G. Knowles et al., 1994). The enzymes that accelerate the reaction above are a family of relatively large heme proteins known as NO synthase (NOS) which resemble cytochrome P450 structurally (M. M. Chan et al., 2001 and Francois Feihl, 2001) (The general mechanism of NO production from NOS is illustrated in Fig 4). All members of this family share a similar homodimeric structure, where each monomer consists of a an oxygenase domain and a reductase domain, separated by a short amino acids (30aa) sequence for the attachment of the Ca2+-binding protein calmodulin. In addition to calmodulin attachment, enzymatic activity requires the presence of four cofactors: FAD, flavin mononucleotide (FMN), tetrahydrobiopterin (BH4), and heme (Francois Feihl, 2001). Fig 5 shows the general structure of the NOS enzymes. Nitric Oxide Synthase isoforms and their locus in the Human Body: There are three known isoforms of NOS, each the product of a different gene: neuronal NOS (nNOS or NOS-1), inducible NOS (iNOS or NOS-2), and endothelial NOS (eNOS or NOS-3). nNOS and eNOS were first described in rat cerebellum and bovine aortic endothelial cells, respectively, but their tissue distribution is far wider than suggested by their names. eNOS and nNOS are involved in regulating vascular tone (R.G. Knowles et al.,1992 and S. Moncada et al., 1991) and neurotransmission respectively, whereas iNOS is involved in the immune defence although it is expressed in many cell types following endotoxin or pro inflammatory cytokine treatment (R.G. Knowles et al., 1994). nNOS is typically expressed in skeletal muscle and myenteric plexuses. eNOS is ubiquitous in vascular endothelium, but may also be found in the kidney tubular epithelial cells, placenta (Forstermann et al., 1995), and neurons (Nathan Xie, 1994). In these tissues, the expression of nNOS and eNOS is constitutive, although it may be regulated (Michel Feron, 1997). For instance, the levels of transcript for eNOS in vascular endothelial cells is increased by shear stress (Topper et al., 1996; Uematsu et al., 1995) and exercise (Wang et al., 1997), reduced by inflammatory stimuli such as TNF-a (Nathan Xie, 1994) and variably affected by hypoxia (Le Cras et al., 1998; Toporsian et al., 2000). In the physiological state, the iNOS isoform is only present at a few locations, notably the respiratory epithelium, the gravid uterus (Nathan Xie, 1994), and perhaps the ileal mucosa (Hoffman et al., 1997). iNOS expression has been demonstrated in numerous cell types including macrophages, neutrop hils, vascular endothelial (Hoffmann et al., 1999), smooth muscle cells, endocardium, myocardium, fibroblast, mesangial cells, renal tubular epithelium (Kunz et al., 1994), neurons, hepatocytes, pancreatic islet cells and astrocytes (Nathan Xie, 1994). iNOS can be induced by a number factors including UV light; cyclic AMP-elevating agents; trauma; ozone and bacterial products described earlier (see section). On the other hand, many endogenous agents may oppose cytokine induction of iNOS. These include anti-inflammatory cytokines such as IL-10, chemokines such as monocyte chemoattractant protein-1 and growth factors such as tumor growth factor-ß (Forstermann et al., 1995). In all NOS isoforms, calmodulin binding is an absolutely vital for enzymatic activity. In the cases of eNOS and nNOS, this binding necessitates relatively high concentrations of Ca2+ (see Fig 7), in the range of 0.1-1 mM (Forstermann et al., 1995). In contrast, iNOS is able to bind calmodulin virtually independ ant of Ca2+ (Table 2). Therefore, once iNOS is expressed, NO synthesis may only be limited by the availability of substrates and cofactors (J. Stuehr, 1990). As NO produced from iNOS predominantly depends only on iNOS expression, it lasts much longer than NO formed from the other isoforms of NOS. In addition iNOS produces much higher concentrations of Ca2+ compared to the consecutive forms of NOS (Cobb et al., 1996). The production of NO by eNOS and nNOS, compared to iNOS, can be controlled relatively easily by decreasing or increasing intracellular Ca2+, whereas iNOS can only be controlled through transcription (Cobb et al., 1996). In most cell types iNOS protein levels are either very low or undetectable. However, stimulation of these cells by cytokines or growth factors, can lead to increased transcription of the iNOS gene, with subsequent production of NO. On the other hand, for the prevention of iNOS expression through endotoxins, TGF-ß (Szabo, 1995) and anti inflammatory gl ucocorticoids can be administered which lower the magnitude of vascular hyporeactivity. Glucocorticoids such as Dexamethasone inhibit iNOS activity by blocking arginine transport and inhibiting tetrahydrobiopterin biosynthesis (A.J.B. Brady et al., 1992 and Thiemermann C et al., 1993). Regulation of NO production In the normal as well as in extreme physiological states (e.g. during infection), nitric oxide is considered as one of the most important signalling molecules in vivo. It is however also highly reactive and highly diffusible due to it being a free radical (one unpaired electron) (see fig 8). It is therefore important that there is strict control and regulation of nitric oxide production. The synthesis of NO within cells can be regulated in several ways such as the cellular distribution of NOS, changes in NOS gene expression, enzymatic activation by phosphorylation and the presence of cellular inhibitors NOS activity. Intracellular distribution of NOS Nitric oxide is principally regulated through strict control over the location of NO production. The NOS isoforms can be targeted to different regions of the cell, where NO will be produced in close contact with its target proteins. The image below shows the distribution of iNOS (shown in green in image 1) and eNOS (shown in red) in a trophoblast cell. The nucleus is shown in blue. Co-localisation between iNOS and eNOS will show up as a yellow colour (Phil Dash, University of Reading). The image shows that eNOS and iNOS are fairly variably distributed inside the cell, with hardly any yellow colour suggesting very little overlap in their cellular distribution (Phil Dash, University of Reading).Although both iNOS and eNOS produce NO it is likely that their different cellular distribution will lead to NO interacting with different targets and therefore having different effects (Phil Dash, University of Reading). It is very likely that the distribution of NOS isoforms is an important mechanism for regulating when and where NO is produced. Therefore the current research on NOS mainly focuses on how endogenous signals trigger NOS transport and redistribution (Rahul S. Koti et al., 2005). Activation of NOS activity NOS enzyme synthesis is principally regulated by changes in intracellular calcium levels. The constitutive isoforms of NOS, (eNOS and nNOS) have shown to proliferate following increases in Ca2+, and therefore calmodulin levels, in the cell (Rameau et al., 2003). Additionally both nNOS and

William Faulkner’s Dry September and That Evening Sun :: Faulkner’s Dry September Essays

William Faulkner’s Dry September and That Evening Sun William Faulkner’s â€Å"Dry September†, and â€Å"That Evening Sun† have to very obvious things in common; they leave many unanswered questions. There is no real ending to either story, and the reader is left to imagine what happens in the end of each story. In â€Å"Dry September†, I was left wondering whether or not Will really did anything to Minnie Cooper. My intuition tells me no, that she was just an old lonely woman who wanted attention, or who construed this offense in her head. I was also left wondering whatever happened to the barber and Will. Did they return to town, only to be chased out again, or were they rebels no, forced to find a new home? The ending part about Mc Lendon when he is mad at his wife for waiting up for him, and she says â€Å"Don’t John. I couldn’t sleep....The heat; something. Please John. You’re hurting me† leaves me wondering still is he mad because he did not find Will once he had jumped out of the car, or is he all riled up because he has gotten Will, and doesn’t want his wife to know where he has been all night? â€Å"That Evening Sun† does not have a conclusive ending either. My first question while reading this was why is everyone so afraid of Jesus? On page 290, the Jason says â€Å"...father told us to not have anything to do with Jesus.† Why would father say this I wondered as I was reading the story. Nancy too seems frightened of Jesus. In section three of the story, Nancy is trying to get the children to ask their mother and father if she can spend the night because, though she doesn’t tell the children, she is afraid of Jason. In the end of the story, on page 307, Nancy says â€Å"I got it. It was on the table when I came in. It was a hog bone with blood meat still on it, laying by the lamp. He’s out there. When yawl walk out that door, I gone.† Faulkner never lets us know what exactly the hog bone represents, or if in deed it was really there, or this is just Nancy trying to lie to let Jason let her stay with him for the night. The story, however, ends before we learn what happens to Nancy, if anything.

Benefits of Social Networking

The Benefits of Social Networking Social media sites do more good than bad. They allow people to reconnect and create relationships, show creative expression in a new medium, and also bring people that share common interests together. Mark Zuckerberg said, â€Å"At Facebook, we build tools to help people connect with the people they want and share what they want, and by doing this we are extending people's capacity to build and maintain relationships. † Social media sites allow people to create new relationships and give them the opportunity to reconnect with friends and family.Increasing communication, even without being able to see a person, strengthens a relationship. Mike Chalmers wrote an article in USA Today that was about military families using Facebook and Skype to contact their families. Army Maj. Thomas Murphy would Skype with his wife and two daughters almost daily while his year in Iraq. â€Å"You could break away from the monotony of everyday stress and feel lik e you're back home for a bit,† said Murphy, (Chalmers). The connection made his deployment more bearable and eased his return home, said his wife.Bianca Murphy said, â€Å"He was part of their day-to-day life, so there was no adjustment that this was some stranger in a uniform,† (Chalmers). Some people have been able to keep friendships going after high school with social networking sites. Even though they can’t see that person as much as they once did they can see what’s still going on in their life. They’ve also been able to start new ones with the people they meet at college or work. Social media sites also allow for creative expression through blogging, messaging, photo storage, and much more.AC. Lowney and T. O’Brien presented a case of a 30-year-old patient with pontine glioblastoma multiform. On admission to the Specialist Palliative Care Inpatient Unit, he had a complete right hemiplegia. He would communicate with the staff by using t he notepad function of his iPad, and he would also use his iPad to update his blog. He’d updated the blog on an almost daily basis, describing his physical and psychological status, (Lowney). His blog also had messages of support from others with similar diagnoses.Blogging was this patient’s way to express the existential distress he was feeling since he was diagnosed with pontine glioblastoma multiform. He felt cheated on life, and being unable to hold his 1-year-old son was dreadful to him, (Lowney). Social media sites are a great way to express thoughts and feelings. Blogging is able to help people emotionally heal by connecting with people who also have the same problems and receive advice. Blogging is a creative way to inspire people, (Lowney). Finally, social media sites have the ability to bring people with common interests together. Highlight, works by rummaging through your Facebook account to see whom you know and what topics you like, (McCracken). It uses yo ur iPhone's GPS to inform you when a fellow conference attendee who's a former co-worker's buddy is in your immediate vicinity or when a good-looking patron who loves the same bands you do sits down at the other end of the bar,† (McCracken). Social media sites like Facebook, give people the ability to click on pages you’re interested to see other people with the same interest.Also, people who have a difficulty communicating in person could be more comfortable interacting over the sites, (McCracken). In conclusion, social media sites are able more good than bad. They allow people to reconnect and create relationships, show creative expression in a new medium, and also bring people together that share common interests. â€Å"The thing that we are trying to do at Facebook, is just help people connect and communicate more efficiently,† (Zuckerberg).

Medias Falsification of Anthrax essays

Media's Falsification of Anthrax essays -Our nation has been in a state of elevated anxiety following the September 11th attacks on New Yorks World Trade Center and the Pentagon. As Americans began to believe the war on terrorism was over, they realized it had only begun. The random mailing of anthrax-laden letters resulted in the first death on October 5th. Newsrooms across the country broadcasted this news-breaking story, ensuing panic in every community. During the anthrax attack, Wyatt, editor and publisher of the Medical Herald, put it best when he wrote, The role of the media will be critical if terrorists attack the civilian population...the medias response must be responsible reporting (63). Although the United States has been exposed to domestic and international terrorism over the last decade, such as the Oklahoma federal building bombing, the first car bomb attack on the World Trade Center, the embassies in Africa, and the Cole attack, is our nation truly prepared for the worst, for bio-terrorism? As the anthrax scare swept the nation, individuals questioned their safety, looking for answers in the wrong place: the news. As the United States scrambled for information on anthrax, families gathered around their televisions at home, desperate for calming news about protection from this new threat. The people of America had no such luck. From large networks like CNN and ABC to local news, the anthrax scare was blown way out of proportion. People were frightened to open their mail, or even drink from the citys water supplies. The news did not provide correct information on anthrax, frequently broadcasting conflicting stories that not even the government could support. For instance, ABC aired an exclusive report on the government finding of a substance in anthrax that was also found in Iraqs biological weapons program, implying that Saddam Hussein may be tied to the attacks. But, unfortunately for ABC, not...