Tourism and Sustainability Whale

Characteristics for Development of Whale-Watching Industries On the social front, it is evident that although the community in the Vava’u area comprises of only 16,000 people, it has been on the forefront in whale conservation efforts and demonstrates a friendly nature to tourists. Additionally, the community has been effective in using promotional material involving the humpback whales to put Tonga on the world map.Advertising We will write a custom assessment sample on Tourism and Sustainability: Whale-Watching Industries specifically for you for only $16.05 $11/page Learn More On the economic front, it is clear that tourism is the economic mainstay of the Vava’u area due to the fragile nature of other economic activities mainly in the manufacturing, agricultural, forestry and service sectors, hence making the area a fertile breeding ground for the development of modern whale-watching industries. Concerning the natural environment, the Va va’u Island group in the Kingdom of Tonga is not only located in a tropical climate with warm, sheltered waters but also prides itself for hosting one of the whale species most popular for tourism. The high-quality marine environments in the area ensure the availability of humpback whales, which often visit the area for mating, birthing, and raising young calves. Non-Economic Impacts of Whales and Whale-Watching As demonstrated by the author of the article, tourism activities occasion both economic and non-economic impacts in the destination area or country. In the context of the Island of Tonga, whales and whale-watching activities are likely to occasion difficulties in hosting large numbers of tourists, environmental pollution and degradation, conflict between operators, resentment in the local community fuelled by increasingly large numbers of tourists, and internalization of vices such as prostitution and gambling among the local people. Other non-economic impacts of whal es and whale-watching activities likely to affect the Island of Tonga include inflationary pressure in the local economy, loss of local control on how local resources are managed and distributed, as well as environmental degradation due to the establishment of numerous whale-watching businesses in the area. However, a positive non-economic impact for the Island concerns the change of attitudes and value systems among the local community, especially in terms of valuing and conserving the humpback whales as a critical resource for social and economic development of the Kingdom. Factors influencing Potential Future Growth of Whale Watching Some of the factors that will guarantee the future growth of whale-watching industry in Vava’u Island group, as demonstrated by the author, include (1) developing adequate transportation, accommodation, and other elements of the tourism infrastructure, (2) attaining long-term political stability not only in the Island of Tonga but also in Sout h Pacific region, (3) establishing convenient and reliable airline connections to boost tourists’ arrivals, (4) dealing with unsustainable whale hunting practices, (4) establishing proper management practices for whale-watching activities, (5) dealing with negative social, economic and environmental impacts associated with tourism, (6) maintaining a stringent code of practice for whale-watching operators to minimise negative impacts associated with competition, and (7) establishing adequate conservation initiatives for the humpback whales to maintain their health and value.Advertising Looking for assessment on communications media? Let's see if we can help you! Get your first paper with 15% OFF Learn More It is important to note that several factors discussed in the article, including degradation of the natural environment, non-involvement of the local community and proliferation of unsustainable hunting practices may actually hamper the growth of the whale-wat ching industry in the future if immediate corrective measures are not taken. Overall, it can be suggested that the sustainability efforts undertaken to guarantee the expansion of the whale-watching industry in the Island of Tonga are bearing fruits. This assessment on Tourism and Sustainability: Whale-Watching Industries was written and submitted by user Nickolas U. to help you with your own studies. You are free to use it for research and reference purposes in order to write your own paper; however, you must cite it accordingly. You can donate your paper here.

Major General J.E.B. Stuart in the Civil War

Major General J.E.B. Stuart in the Civil War Major General J.E.B. Stuart was a famed Confederate cavalry commander during the Civil War who served with General Robert E. Lees Army of Northern Virginia. A Virginia native, he graduated from West Point and aided in quelling the Bleeding Kansas crisis. With the start of the Civil War, Stuart quickly distinguished himself and proved an able and daring commander. Leading the Army of Northern Virginias cavalry, he took part in all of its major campaigns. Stuart was mortally wounded in May 1864 at the Battle of Yellow Tavern and later died in Richmond, VA. Early Life Born February 6, 1833 at Laurel Hill Farm in Patrick County, VA, James Ewell Brown Stuart was the son of War of 1812 veteran Archibald Stuart and his wife Elizabeth. His great-grandfather, Major Alexander Stuart, commanded a regiment at the Battle of Guilford Court House during the American Revolution. When Stuart was four, his father was elected to Congress representing Virginias 7th District. Educated at home until age twelve, Stuart was then sent to Wytheville, VA to be tutored before entering Emory Henry College in 1848. That same year, he attempted to enlist in the US Army but was turned away due to his young age. In 1850, Stuart succeeded in obtaining an appointment to West Point from Representative Thomas Hamlet Averett. West Point A competent student, Stuart proved popular with his classmates and excelled at cavalry tactics and horsemanship. Among those in his class were Oliver O. Howard, Stephen D. Lee, William D. Pender, and Stephen H. Weed. While at West Point, Stuart first came in contact with Colonel Robert E. Lee who was appointed superintendent of the academy in 1852. During Stuarts time at the academy, he achieved the cadet rank of second captain of the corps and received the special recognition of cavalry officer for his skills on horseback. Early Career Graduating in 1854, Stuart placed 13th in a class of 46. Commissioned a brevet second lieutenant, he was assigned to the 1st US Mounted Rifles at Fort Davis, TX. Arriving in early 1855, he led patrols on the roads between San Antonio and El Paso. A short time later, Stuart received a transfer to the 1st US Cavalry Regiment at Fort Leavenworth. Acting as the regimental quartermaster, he served under Colonel Edwin V. Sumner. During his time at Fort Leavenworth, Stuart met Flora Cooke, daughter of Lieutenant Colonel Philip St. George Cooke of the 2nd US Dragoon. An accomplished rider, Flora accepted his marriage proposal less than two months after they first met. The couple were married on November 14, 1855. For the next several years, Stuart served on the frontier taking part in operations against the Native Americans and working to control the violence of the Bleeding Kansas crisis. John Brown. Photograph Courtesy of the Library of Congress On July 27, 1857, he was wounded near the Solomon River in a battle with the Cheyenne. Though struck in the chest, the bullet did little meaningful damage. An enterprising officer, Stuart invented a new type of saber hook in 1859 which was accepted for use by the US Army. Issued a patent for the device, he also earned $5,000 from licensing the design the military. While in Washington finalizing the contracts, Stuart volunteered to serve as Lees aide in capturing radical abolitionist John Brown who had attacked the armory at Harpers Ferry, VA. Fast Facts: Major General J.E.B. Stuart Rank: Major GeneralService: US Army, Confederate ArmyBorn: February 6, 1833 in Patrick County, VADied: May 12, 1864 in Richmond, VANickname: Knight of the Golden SpursParents: Archibald and Elizabeth StuartSpouse: Flora CookeConflicts: Civil WarKnown For: First Battle of Bull Run, Peninsula Campaign, Second Battle of Manassas, Battle of Antietam, Battle of Fredericksburg, Battle of Chancellorsville, Battle of Brandy Station, Battle of Gettysburg, Battle of the Wilderness, Spotsylvania Court House, Battle of Yellow Tavern Road to War Finding Brown holed up at Harpers Ferry, Stuart played a key role in the attack by delivering Lees surrender request and signaling the assault to begin. Returning to his post, Stuart was promoted to captain on April 22, 1861. This proved short-lived as following Virginias secession from the Union at the beginning of the Civil War he resigned his commission to join the Confederate Army. During this period, he was disappointed to learn that his father-in-law, a Virginian by birth, had elected to remain with the Union. Returning home, he was commissioned a lieutenant colonel of Virginia Infantry on May 10. When Flora gave birth to a son in June, Stuart refused to allow the child to be named for his father-in-law. The Civil War Assigned to Colonel Thomas J. Jacksons Army of the Shenandoah, Stuart was given command of the organizations cavalry companies. These were quickly consolidated into the 1st Virginia Cavalry with Stuart in command as colonel. On July 21, he took part in the First Battle of Bull Run where his men aided in the pursuit of the fleeing Federals. After service on the upper Potomac, he was given command of a cavalry brigade in what would become the Army of Northern Virginia. With this came a promotion to brigadier general on September 21. Lieutenant General Thomas Stonewall Jackson. Photograph Courtesy of the National Archives Records Administration Rise to Fame Taking part in the Peninsula Campaign in the spring of 1862, Stuarts cavalry saw little action due to the nature of the terrain, though he did see action at the Battle of Williamsburg on May 5. With the elevation of Lee to command at the end of the month, Stuarts role increased. Dispatched by Lee to scout the Union right, Stuarts brigade successfully rode around the entire Union army between June 12 and 15. Already known for his plumed hat and flamboyant style, the exploit made him famous across the Confederacy and greatly embarrassed Cooke who was commanding the Union cavalry. Promoted to major general on July 25, Stuarts command was enlarged to the Cavalry Division. Taking part in the Northern Virginia Campaign, he was nearly captured in August, but later succeeded in attacking Major General John Popes headquarters. For the remainder of the campaign, his men provided screening forces and flank protection, while seeing action at Second Manassas and Chantilly. As Lee invaded Maryland that September, Stuart was tasked with screening the army. He failed somewhat in this task in that his men failed to gather key intelligence regarding the advancing Union army. The campaign culminated on September 17, at the Battle of Antietam. His horse artillery bombarded Union troops during the opening phases of the fight, but he was unable to conduct a flank attack requested by Jackson that afternoon due to heavy resistance. In the wake of the battle, Stuart again rode around the Union army, but to little military effect. After providing routine cavalry operations in the fall, Stuarts cavalry guarded the Confederate right during the Battle of Fredericksburg on December 13. During the winter, Stuart raided as far north as Fairfax Court House. Chancellorsville Brandy Station With the resumption of campaigning in 1863, Stuart accompanied Jackson during the latters famed flanking march at the Battle of Chancellorsville. When Jackson and Major General A.P. Hill were severely wounded, Stuart was placed in command of their corps for the remainder of the battle. After performing well in this role, he was badly embarrassed when his cavalry was surprised by their Union counterparts at the Battle of Brandy Station on June 9. In a daylong fight, his troopers narrowly avoided defeat. Later that month, Lee began another march north with the goal of invading Pennsylvania. Gettysburg Campaign For the advance, Stuart was tasked with covering the mountain passes as well as screening Lieutenant General Richard Ewells Second Corps. Instead of taking a direct route along the Blue Ridge, Stuart, perhaps with the goal of erasing the stain of Brandy Station, took the bulk of his force between the Union army and Washington with an eye to capturing supplies and creating chaos. Advancing, he was driven further east by Union forces, delaying his march and forcing him away from Ewell. While he captured a large amount of supplies and fought several minor battles, his absence deprived Lee of his prime scouting force in the days prior to the Battle of Gettysburg. Arriving at Gettysburg on July 2, he was rebuked by Lee for his actions. The next day he was ordered to attack the Union rear in conjunction with Picketts Charge but was blocked by Union forces east of the town. Though he performed well in covering the armys retreat after the battle, he was later made one of the scapegoats for the Confederate defeat. That September, Lee reorganized his mounted forces into a Cavalry Corps with Stuart in command. Unlike his other corps commanders, Stuart was not promoted to lieutenant general. That fall saw him perform well during the Bristoe Campaign. Final Campaign With the beginning of the Union Overland Campaign in May 1864, Stuarts men saw heavy action during the Battle of the Wilderness. With the conclusion of fighting, they shifted south and fought a vital action at Laurel Hill, delaying Union forces from reaching Spotsylvania Court House. As fighting raged around Spotsylvania Court House, the commander of the Union cavalry, Major General Philip Sheridan, received permission to mount a large raid south. Driving across the North Anna River, he was soon pursued by Stuart. The two forces clashed at the Battle of Yellow Tavern on May 11. In the fighting, Stuart was mortally wounded when a bullet struck him in the left side. In great pain, he was taken to Richmond where he died the next day. Only 31-years old, Stuart was buried at Hollywood Cemetery in Richmond.

History Essay Example | Topics and Well Written Essays - 500 words - 5

History - Essay Example When industrialization came, machines replaced small weavers, farmers left their lands because of obtrusive laws, and many families had to work at factories and had to live in the cities. Life in the cities meant higher living expenses, working longer hours and extremely stretching of expenses. Wife and children had to work for eighteen hours and the only time family came together was to sleep. They had no choice but to live together in one housing unit with other families to save on costs. Thus life of family at the start of industrial revolution was unbearable because working families often lived in slum areas with unsanitary conditions. Children received little education, often sickly, and suffered stunted growth. Mortality rate was great with 50% of children dying before reaching age two. Another significant consequence was inequality in groups because women and children were paid less and were required to work more hours. Factory owners were happy to employ children because they could manipulate children easier than adults, often thru beatings. Children as young as eight years old were sent to textile manufacturing, coals and mines. Workers during this time were locked up in a system where they had no control. B. Discuss the relationship between the Industrial Revolution and the development of capitalism.

Critical analysis of ralph ellison's discrimination Research Paper

Critical analysis of ralph ellison's discrimination - Research Paper Example learns that the government and society promote and condone racism, and that racism stifles the ability of black people to reach their full potential as human beings. The government creates laws and institutions that promote institutional racism. Schools should be a place for equal learning, but Ellison reveals its true purpose: â€Å"[it was a] new public school †¦exclusively for whites† (Ellison page 66 par. 1). Blacks and whites are equally paying their taxes, but the public systems prefer to serve the whites. Clearly, the education is geared toward the education of the dominant race and aims to leave the poor minorities in a deep level of ignorance. Furthermore, Ellison’s daily experiences toward his school reflect the disparaging gap, not only between the rich and the poor, but between whites and blacks. He talks about the route of a â€Å"viaduct,† warehouses,† and â€Å"docks, even a â€Å"red-light district† on the way to school (Ellison 66.2). This kind of route is not appropriate for young students, but apparently, the blacks are located far enough from school and near their workplaces. The settin g indicates social segregation, where the whites have placed the blacks in their proper place. In addition, the government controls public entertainment spaces. Ellison wants to go to the zoo, but it is suddenly closed to black children. He wants to understand the reason why he cannot see the zoo, while white children can, but her mother says: â€Å"Quit asking questions, it’s the law†¦Ã¢â‚¬  (Ellison 66.4). The idea of no longer questioning the law indicates the political powerlessness of the blacks. When public spaces are white spaces, the government further entrenches the blacks in poverty and powerlessness. Society condones racism because of its inability to integrate the whites and the minorities as equals. The red-light district symbolizes the peripheral and subordinate treatment of blacks. The black prostitutes feed the white men’s desire, which reflects

Mona Lisa Assignment Example | Topics and Well Written Essays - 250 words

Mona Lisa - Assignment Example I find the facial expression of Mona Lisa somewhat vague and enigmatic as if there is some mystery behind her half smile. Her calm pose suggests the same. Her eyes and hair too have an innate power to attract the viewer. This is one of the special features of the painting because it is remarkable how Leonardo managed to capture such an emotional state within a portrait. It is not so much the attention to detail such as the folds on her sleeves for example, but capturing this mysterious expression and use of the sfumato (gentle toning down) (Queiros-Conde 2004) technique overall that demonstrates his true greatness as a painter. Others have described the painting in a similar way too but I do not believe it is hype. If the story about trying to amuse Mona before making her portrait (Vasari 2006) is true this shows in her expression but I still believe there is more hidden beneath the surface. Perhaps there is some truth concerning the recent nude Mona Lisa discovery (Lorenzi 2009). It s parallels with the original Mona Lisa could indicate that the painter and the painted had a special rapport and liking for each other. If so, this explains much of the natural yet mysterious expressions of the Mona Lisa. The Mona Lisa is a good example of the High Renaissance style because like the paintings of Raphael and Michelangelo, it is a portraiture and work of beauty showing an â€Å"artist’s individual skills and vision† (pbs.org). This was the typical style of painting at the time besides art for historical and religious purposes. â€Å"The idea that painters and sculptors might create from personal inspiration was new† (ibid) during the Renaissance period. But what makes the painting characteristically a work of Leonardo da Vinci are the painstaking effort that must have gone into it, the skilful use of the sfumato, the careful portrayal of perspective, and the strong sense of imagination coupled with

Gene-ablation and other genetic technique

Gene-ablation and other genetic technique How has the use of gene-ablation and other genetic techniques in mice altered our approach to scientific problems in pharmacology and physiology? 280 pts (8-12 pages, 11pt Arial font, double spaced) A gene is a region of DNA that controls a discrete hereditary characteristic, usually corresponding to a single protein or RNA1. Most scientists are interested in determining how genes, and the proteins they encode, function in the intact organism. One of the most direct ways to find out what a gene does is to see what happens to the organism when that gene is missing. Because mutations can interrupt cellular processes, mutants often hold the key to understanding gene function. A well accepted strategy for evaluating gene function is to create and characterize a gene knockout mouse. Virtually any gene in the germ line can be mutated through gene targeting in totipotent embryonic stem (ES) cells or to use gene ablation technology to knock-out either a specific gene or a specific cell type in an intact animal2. Both of these methods offer almost unlimited possibilities for addressing questions concerning the molecular and cellular biology of development, the relationship between geneti cs and biological function, unraveling the causes of disease, and enhance pharmaceutical research. ES cells are a versatile source of cells for repair of damaged and defective tissues in the adult body2. Totipotent embryonic stem cells have been used in vitro to generated precursors for oligodendrocytes and astrocytes. Transplantation of these ES cells into a model mouse of human myelin disease allowed the precursors to interact with host neurons and efficiently myelinate axons in brain and spinal cord. Further investigation of this mechanism could lead to pharmacological, physiological and therapeutic treatments. ES cells also make possible the most precisely controlled forms of genetic modification, allowing animals to be created with virtually any desired alteration introduced into their genome2. One way to produce a transgenic (knockout) animal is through gene targeting in totipotent ES cells. By incorporating a null allele into one allele of murine ES cells, and injecting these cells into early mouse embryos, one can create chimeric mice (heterozygous for the knockout allele) containing tissues derived from both host cells and ES cells2. Mating the chimeric mice allows one to confirm that the null allele is incorporated into the germ line and can breed these heterozygous chimeric mice to homogeneity producing progeny that are homozygous knockout mice2. A knockout mouse generated to carry a mutating apolipoprotein E (apoE) gene through inactivation by gene targeting in embryonic stem cells can be used as a model for atherosclerosis. apoE is a constituent of very low density lipoprotein (VLDL) synthesized by the liver and of a subclass of high density lipoproteins (HDLs) involved in cholesterol transport among cells. In humans a variant form of apoE, has been found to be defective in binding to the LDL receptor that is associated with familial type III hyperlipoproteinemia, a disease characterized by elevated plasma cholesterol and premature coronary heart disease. apoE deficient mice develop severe hypercholesterolemia due to a delayed clearance of large atherogenic particles from the circulation. A study was done to analyze the genesis of atherosclerotic lesions, including the nature of the cells involved, the sequence of cellular events and the anatomic location of specific lesion types over time on mice fed a normal or a high fat diet. They found that the lesions were distributed thought the arterial tree and contained many features of the specialized, chronic, inflammatory-fibroproliferative response characteristic of atherosclerosis with age. This mouse model is used to better understand the physiological role of apoE in lipid metabolism, atherogenesis, and nerve injury. The model can also be used as a way to test new pharmacological drugs in pre-clinical trials to determine drug interaction, new therapeutics or to develop variations of current drugs to better meet the needs of the vast array of genetic variability seen in the human population today. Gene ablation involves the homologous genetic recombination of a gene in such a way that the gene has been made â€Å"null†. Genetic ablation is a genetic engineering technique used to suppress selectively the growth of a specified cell line or cell type in an animal rather than suppress the activity of an individual gene2. Analyzing the in vivo function of cells can be accomplished through specific cell ablation. Using genetic ablation to produce a knockout mouse involves the injection of one or more transgenes (usually a DNA segment bearing its own promoter) into the pronucleus of a fertilized mouse oocyte, which, after reimplantation into a foster mother, gives birth to a transgenic mouse bearing one of several hundred copies of the transgene3. These mice again can be bred to produce a homozygous colony. An overexpression Sod2 transgenic mouse was generated through the use of pronuclear injection of the Sod2 gene into fertilized eggs. These mice overexpressed superoxide dismutase which catalyzes the conversion of superoxide anion to hydrogen peroxide and oxygen. Superoxide anions are reactive oxygen species (ROS) generated in the respiratory chain as a byproduct of mitochondrial respiration. ROS cause oxidative damage to key mitochondrial components, such as protein, lipids and DNA. They are thought to lead to an overall decline in cellular function and ultimately determine the life span of an organism. Sod2 trangsenic mice have been used to test the effects of overexpressing MnSOD on mitochondrial function, levels of oxidative stress or damage and live span in mice. They found that a two fold increase of MnSOD throughout the life of the organism resulted in a slight decrease in oxidative damage and enhanced resistance against oxidative stress. Oxidative damage is also associated wit h arthritis, heart disease, gastrointestinal disorders, multiple sclerosis, cancer and neurological diseases. This model can be used to physiologically improve ones understanding of oxidative stress and to develop pharmaceutical agents that can enhance ones ability to decrease or protect against oxidative damage. Customized gene targeted animal models include constitutive knockouts or knock-ins, or conditional knockouts or knock-ins of known genes, a gene family, mutant genes or artificially created reporters and gene constructs. A constitutive knockout is a model that provides a broad overview of gene function, by the inactivation of the gene of interest at the genetic level, by random mutation or targeted insertion4. The advantage of using this model is that you get a total inactivation of the gene in any cell4. The disadvantage of this model is that the phenotypes can be complex since all organs are affected4. A conditional knockout is a model that provides a research model of high potential, by targeting tissue-specific inactivation of the gene of interest, through the use of recombinase4. Recombinase is an enzyme that deletes the DNA fragment located between the two recombinase-specific sites4. This tissue-specific expression of the recombinase allows the inactivation of the gene of inte rest only in the tissue were the recombinase is expressed4. There are two advantages to using this model, the first is the inactivation is restricted to specific tissues and the second is that several tissue-specific models can be made in parallel4. The disadvantages of using this model include the efficiency of the excision and the inability to validate the recombinase system4. There are a number of other strategies that can be used in place of, or to complement, conventional gene knockout technology. Two such examples are regulatable gene ablation and temporary gene ablation (gene knock downs). Ablation of a gene can be spatially or temporally regulated, that is only the organ of interest is affected or the mutation occurs only in one particular developmental state5. Through the use of a regulator, the promoter can be regulated to control gene expression in the organ or particular tissue of interest. A gene knockdown refers to the technique by which the expression of one or more of an organisms genes is reduced, either through genetic modification or by treatment with a reagent such as a short DNA or RNA oligonucleotide with a sequence complementary to either an mRNA transcript or a gene6. These approaches offer a rapid and economical method to examine the specific actions of a gene product at a particular time point. Genes can be transiently down-regulate d by targeted blockade of gene expression, either systemically or within a specific tissue. Two such approaches are antisense technology and the use of short interfering RNA (siRNA). Antisense technology is the use of short modified DNA sequences complementary to the mRNA of the gene of interest2. These sequences bind to the 5UTR and the beginning of the coding sequence therefore preventing translation initiation and blocking ribosomal interaction with the AUG start codon2. Antisense oligonucleotide genetic-code blocking drugs might control disease by inhibiting deleterious or malfunctioning genes. siRNA on the other hand, utilizes small lengths of double stranded RNA designed against the gene of interest and is introduced into the cell where they interact with intracellular machinery to form RNA-induced silencing complexes (RISCs)2. These complexes unwind the siRNA strands and allow specific binding to the complementary mRNA sequence2. This binding causes cleavage and destruction o f the now double stranded mRNA, and subsequently prevents translation2. siRNA can be used to study gene function, manipulating gene expression, as well as drug development. siRNA compounds can be created and delivered into human cells were they are able to silence genes and viruses responsible for human diseases. Two other genetic techniques that are used to approach gene investigation include suppressor analysis and reverse genetics. Suppressor analysis is used to identify genes that are functionally related to another gene of interest7. A suppressor mutation is a mutation that counteracts the effects of another mutation thereby reducing its phenotypic effect7. Suppressor mutations may be intragenic (in the same gene as the original mutation) or intergenic (in another gene)7. Intergenic suppressor mutations can be either information suppressors or function suppressors7. Of the two, function suppressors are most valuable for the genetic analysis of cellular processes7. Reverse genetics is a process in which specific mutations are introduced into a cloned gene for the purpose of identifying functional domains8. One way to conduct reverse genetics is to do RNA interference (RNAi)8. RNA interference is an in vivo gene knock-down, which is used to insert a random shRNA construct into the mouse ge nome4. Here, double-stranded RNAs inhibit corresponding gene expression by inducing degradation of its mRNA4. RNAi can be used as part of the immune response to viruses and other genetic material; it can also be used to look at downregulation and upregulation of genes4. RNAi has been used to evaluate whether insulin-like growth factor binding protein-3 (IGFBP3) modulates gastrointestinal stromal tumor (GIST) cell response. Here, transfection of siRNA to knockdown IGFBP3 gene into GIST cells resulted in a significant loss of cell viability and therefore found that IGFP3 gene is required for GIST cell survival. IGFBP3 gene expression is lost in many cancer cells and reintroduction of the protein often results in cell death. On the other hand IGFBP3 has been linked to renal cell carcinoma, breast cancer, and metastatic melanoma, which suggests that IGFBP3 may contribute to tumorigenesis or disease progression. By studying IGFBP3 and the IGF pathway one can explore IGF for prognostic an d therapeutic value in GISTs and other cancers. In order to develop new treatment and preventative strategies for a human disease, we must first understand the biology and pathogenesis of the human disease itself10. A way to study human gene function is by mouse gene humanization. Humanization is the replacement of the murine gene by its human counter part4. Animal models of human disease have been crucial in elucidating normal organ biology, pathogenic mechanisms of the disease and developing new therapeutic strategies10. Animal models are being used instead of human studies, because human studies are limited by a number of factors such as: the variability seen in genetic background and environmental influences, the inability to readily obtain human tissues for molecular analysis and the small numbers of patients who may have a particular genetic abnormality10. Transgenic animals have already made valuable research contributions to studies involving regulation of gene expression, the function of the immune system, genetic diseases, viral diseases, cardiovascular disease, and the genes responsible for the development of cancer. Transgenic animal models are most effective if they have both construct validity and face validity. Construct validity is the degree to which the model corresponds to the clinical state in humans. Face validity is the animal model responds in an appropriate manner to the effects of different therapeutic agents. An animal model that can recapitulate at least part of the neuropathology and the cognitive and behavioral impairment is the most effective representative of the disease. Several rodent models of Alzheimers disease (AD) have been created. The first example of such a model has been created to mimic the cholinergic deficits of AD patients and to investigate the role of the central cholinergic system in the cognit ive and behavioral deficits observed in AD9. The second example of such a model has been created with acute or chronic injections of amyloid beta within the brain parenchyma of rodents, to overexpress AD-related mutated protein (amyloid deposits) in the central nervous system of rodents9. A third model of AD has been to create a transgenic mouse to express wild-type or mutant forms of the human APP and/or PS genes. All three of these models provide many insights into AD pathogenesis and approached to new therapies. By exploring and understanding of the neuropathological processes underlying the cognitive deterioration leading to dementia and investigating of the effects of potential new treatments on both AD neuropathology and cognitive deficits we will be able to test drugs that could potentially alleviate symptoms of the disease. Transgenic animals have also been used to develop animal strains that secrete important proteins in milk2. These animals are used to synthesize recoverable quantities of therapeutically useful proteins. These proteins can be harvested from the animal by simply milking the animal and then using separation techniques for protein purification2. For example cows have been used to purify collagen which can then be used to indicate burns and bone fracture2. Pigs have been used to purify human hemoglobin as a blood replacement for transfusion2. Goats have been used to make monoclonal antibodies for colon cancer2. In addition sheep have been used to make factor VIII and factor IX for hemophilia2. Despite the large amount of knowledge that can be gained by knockout studies, there are some important considerations to be taken when investigating the role of a particular protein or gene of interest. These considerations include but are not limited to: redundancy, lethality, delineating systemic vs. local effects, subtle effects, and specific pathogen free conditions3. Gene redundancy is the existence of multiple copies of the same gene in the genome of an organism. This problem can be overcome to some extent by the use of multiple knockouts or in some situations where multiple ligands bind to the same receptor, a dominant negative receptor approach can knockout the effects of all ligands at once5. Lethality phenotypes severely compromise the ability of the organism to function. Some knockouts are developmentally lethal, which means that the genetically altered embryos cannot grow in adult mice. Knocking out a gene may also fail to produce an observable (phenotypic) change in a mo use or may even produce different characteristics from those observed in humans in which the same gene is inactivated. In some instances, a particular organ of interest can be transplanted into a healthy wild type host in order to conduct the analysis on that organ. Local effect refers to an adverse health effect that takes place at the point or area of contact, for example the respiratory tract11. Systemic effect refers to an adverse health effect that takes place at a location distant from the bodys initial point of contact and assumes absorption has taken place, i.e. absorption into the blood stream11. Subtle effects are those that are so slight as to be difficult to detect or describe. For example, small changes in nutrient delivery to the fetus can program post-natal and adult metabolic status and lead to increased susceptibility to a range of adult onset disease, including stroke, hypertension and non-insulin dependent diabetes5. Specific pathogen free conditions refers to the fact that laboratory mice in research institution are generally housed in a specific pathogen free environment, and are therefore not challenged with the array of pathogens most mice and humans are exposed to. When comparing transgenic models to humans a key difference could be in the initiation of the development or process in the mouse that may not have a similar mechanism as the human development or process it is thought to represent. The presence of a specific mutation in the mouse from the time of its conception may enable a distinction between phenotypic changes due to the mutation itself and changes caused by adaptation and compensation for the mutation12. A gene can also be expressed in different tissues where it may have different functions; its alteration may induce unexpected consequences. Also, the function of two genes may overlap or a mutation in a single gene might not reveal an abnormal phenotype. There is also a possibility of random incorporation into genome, which may inadvertently disrupt other genes, or have a variable degree of gene silencing success. The gene may also induce gross morphologic or physiologic abnormalities that affect the gene directly. Note also, thes e animal models also only play a minor role in drug development, as relatively few human diseases are monogenetic12. In most cases, gene ablation and other genetic techniques must address the basic question as to whether a particular gene, wild type, or mutant is involved in the pathogenesis of a particular disease. If not a particular disease, it may also address whether a gene product which plays a role in a specific signaling process contributes to disease in conjunction with other predisposing conditions. Animal models are crucial in providing a unified understanding of how drugs work, developing new therapeutic agents, and obtaining critical data needed to advance compounds into clinical trails12. Animal models are an important tool for scientist to investigate human diseases, especially in order to conduct time-course studies or when studying early disease. Transgenic and knockout animals are also used to determine the molecular mode of action of a gene product and the downstream consequences of its misexpression on normal processes. Assessing the role of a specific gene can know be accomplis hed through the use of transgenic animals whose genomes have been manipulated to under- or overexpress a target gene, or express it in a modified or defective, nonfunctional form12. Animal models represent an attempt to imitate the pathologies associated with human disease states in a preclinical setting12. References: Molecular Biology of the Cell. Alberts, et. al. 4th edition 2002 Garland Science New York, NY. Crommelin, D.J.A. and Sindelar, R.D. (1997). Pharmaceutical Biotechnology: Fundamentals and Applications, Third Ed. Taylor and Francis. Philadelphia, PA. Seidman, J.G. (2009) Manipulating the Mouse Genome. Current Protocols in Molecular Biology. January 01. Reliable and Innovative Solutions for Transgenesis. Accessed on 11/4/2009. Ingman, WV. And Jones, RL. (2008). Cytokine knockouts in reporduciton: the use of gene ablation to dissect roles of cytokines in reproductive biology. Human Reproductive Update 14(2): 179-192. Gene knockdown. (2009, June 8). In Wikipedia, The Free Encyclopedia. Retrieved 13:53, November 8, 2009, from Fay, D. and Johnson, W. (2006). Genetic mapping and manipulation: Chapter 10-Suppressor mutations. Accessed on 11/5/2009. Bio-Medicine. Accessed on 11/4/2009. Dodart, J.C. and May P. (2005) Overview on Rodent models of Alzheimers Disease. Current Protocols in Neuroscience. November 01. Lind J. and Semsarian C. (2006) Overview of Model Systems for the Analysis of Human Disease. Current Protocols in Human Genetics. February 01. Local vs. Systemic Health Effects. Accessed on 11/3/2009. Moser, P. (2009) Animal Models of Disease. Current Protocols in Pharmacology. September 01. Katz, D.A. (2007) Overview of Pharmacogenetics. Current Protocols in Pharmacology. March 01. Barash, CI. (2001)Ethical Issues in Pharmacogenetics. Accessed on 11/4/2009. Frequently Asked Questions about Pharmacogenetics. Accessed on 11/4/2009. Bustle, O., Jones, K.N., Learish R. D., et.al.(1999) Embryonic Stem Cell-Derived Glial Precursors: A source of Myelinating Transplants. Science 5428(285): 754-756 Piedrahita, J.A., Zhang, S.H, Hagaman, J.R, Oliver, P.M, and Maeda N. (1992) Generation of mice carrying a mutant apolipoprotein E gene inactivated by gene targeting in embryonic stem cells. Proc. Natl. Acad. Sci. USA. 89:4471-4475. Nakashima, Y, Plump AS, Raines E.W, Reslow J.L, and Ross R. (1994) ApoE-deficient mice develop lesions of all phases of atherosclerosis throughout the arterial tree. Arteriosclerosis and Thrombosis 14:133-140. Jang Y.C et.al (2009). Overexpression of Mn Superoxide Dismutase Does Not Increase Life Span in Mice. Journal of Gerontology:Biological Sciences. 64(11): 1114-1125. Dupart JJ. Et.al (2009). Insulin-like growth factor binding protein-3 has dual effects on gastrointestinal stromal tumor cell viability and sensitivity to the anti-tumor effects of imatinib mesylate in vitro. Mol Cancer Nov 10;8(1):99 (Epub ahead of print) PMID: 19903356 Genes associate with drug responses can be grouped into three broad categories: those involved in pharmacokinetics (i.e. drug metabolism, transport), those encoding pharmacological targets (i.e. drug-target pathways) and those with physiological associations (i.e. homeostasis pathways)13. Pharmacokinetic pathways mediate drug absorption, distribution, metabolism and excretion13. Pharmacological pathways such as transcription factors and phosphorylation targets whose genes encode other proteins are also candidates for pharmacogenetic analysis13. Understanding the sensitivity of a particular drug and the genes that encode the drug metabolizing enzymes can help determine how the particular drug is transported and metabolized within the body. Understanding the gene variants and how they influence drug concentrations at the target site is a possible way to explain the differences in response to a particular drug dose among individuals. Pharmacogenetics is the study of how an individuals genetic differences influence drug action, usage and dosing2. The molecular compositions of enzymes are currently being identified through the use of the Human Genome Project. Scientists are able to study these enzymes and determine correlations between genotypic and phenotypic variability14. These current advances will allow scientists to use the molecular knowledge of enzymes to detect individuals who are likely to experience adverse reactions to medicines without having to use potentially dangerous methods of trial and error14. An offshoot of pharmacogenetics is pharmacogenomics, which attempts to understand not only the molecular composition of genetic variants associated with drug response but also the behavior of those variants14. Pharmacogenomic knowledge can be used to spot the disease before it occurs in a patient, increase drug efficacy upon pharmacotherapy, and reduce drug toxicity2. It could also facilitate the drug development process to improve clinical development outcomes, reducing overall cost of drug development and lead to development of new diagnostic tests that impact on therapeutic decisions2. Pharmacogenomics can be used by doctors to identify the optimal dose and medicine for each individual patient with greater efficacy and safety. As the dosage would be based on factors such as age, weight, diet, lifestyle, liver and kidney function. By using a pharmacogenetic test a doctor can determine the right dose for individual patients. There are phomacogenetic tests for cancer, HIV, depressio n, and cardiovascular disease15. These tests take in the factors which are most likely to affect the absorption and effectiveness of the drug. There are many benefits that can come from pharmacogenetics and pharmacogenomics. Pharmaceutical companies can use information obtained to create more powerful medicines based on proteins, enzymes, and RNA molecules associated with genes and diseases15. Again, doctors would be able to analyze a patients genetic profile and prescribe the best available drug therapy from the beginning instead of the standard trial and error method of matching patient with the right drugs. A more appropriate drug dosage could be determined by not only taking in a persons weight and age but also accounting for their individual body processes, such as the time it takes for their body to metabolize the drug. Pharmacogenetics could also provide advance screening for disease, better vaccines, improvements in the drug discovery and approval process and decrease the overall cost of health care15. Pharmacogenomics is still in the development stage in the research field. There are several factors that need to be overcome before many of the pharmacogenomic benefits can be realized. These include the complexity of finding gene variations that affect drug response, the limitation of current drug alternatives, disincentives for drug companies to make multiple pharmacogenomic products, and educating health care providers14. There are also ethical issues to consider, such as lack of data privacy, possibility that adverse reactions to drugs can occur during treatment, the cost of such designer drugs will be to expensive for everyone, and genetic testing can provide an array of diagnostic results (predisposal test) which may or may not be what the patient wants to know14.

The Possibilities of the Gap Year Essay -- The Gap Year Abroad

A gap year is a year off of academics, which provides time to explore interests and help determine career choices, containing both positive and negative aspects to consider. A gap year can be spent in a several ways from internships, working, volunteering, or traveling and exploring interests. It can provide students with life impacting traits that can provide a better future and greater outlook on life. If taken seriously, a gap year can have many positive effects on education and the motivation to continue school. Although gap years can be very expensive, it can overall be an opportunity of a lifetime, to create clear academic goals. Although a gap year is most often taken between high school and college, some students decide to take one after under-graduate school and before graduate school or entering the workforce. If a gap year is planned properly, it can help a students take school and life more seriously impacting their entire life. In the UK and similarly in Australia, 11% of university bound students take a gap year (MacDonald 1). Meaning, that almost one in ten students, in the UK and Australia, whom already were planning on attending a university, take part in a gap year. One reason gap years have become popular is that parents have noticed that students are going to college because it is expected of them or for the social aspect, not because they have clear education or career goals in mind (Bull 77). This causes some parents to rethink the idea of a gap year, because college tuition is increasing every year and they do not want to send their child to school if they are not going for the right reasons. Most ‘gappers’ choose to take a gap year because they want adventure, independence, or they want something more that... ...ons of College and Experiences of Stress Prior to and Through the College Career.† College Student Journal 47.4 (2013): 635-643. OmniFile. Web. 19 March 2014. MacDonald, G. Jeffery. â€Å"Gap Year ‘Before College Gives Grads Valuable Life Experiences.‘† USA Today 18 June 2008: 1-3. USAToday.com. Web. 14 March 2014. O’Shea, Joseph. â€Å"Delaying the Academy: A Gap Year Education.† Teaching in Higher Education 16.5 (2011). 565-577. Web. 16 March 2014. Sarouhan, Jane and Sarouhan, Jason. â€Å"Your Goals, Your Life, Your Gap Year.† CollegeXPress Magazine (2013): 22-25. OmniFile. Web. 14 March 2014. Sutherland, Paige. â€Å"College Offers to Pay Students to Take Time Off.† APFinancial News (2014): 1-2. Newswires. Web. 14 March 2014. Torpey, Elka Maria. â€Å"Gap year: Time Off with A Plan.† Occupational Outlook Quarterly 53.3 (2009): 26-31. Business Source Complete. Web. 14 March 2014.