Alfred the Great Essay Example for Free

Alfred the Great Essay Alfred the Great ruled between the years of 871- 899. He was a son born to Aethelwulf, King of Wessex and his queen, Osburga, in 849 in Wantage, Berkshire London. He was born of the royal house of the Jutes of Wight. He was the fourth son born and had one younger sister. He became king only after each of his older brothers had ruled for some time. When he did rule he ruled at a time that they were battling the Vikings. In his period of ruling he defended the Vikings and became the dominate ruler of England. Alfred the Great was the first King of the West Saxons to style himself King of the Anglo-Saxons†. He was a king who encouraged education and improved his kingdoms legal system and military system. King Alfreds education as a child was important to his reign. He did not have a formal education and learned to read and write only after he became king in 871, but he did receive great instruction throughout his life. At the age of four, Alfred went to see Pope Leo IV in Rome for instruction. The Pope later adopted King Alfred as his spiritual son. Most of the Popes instruction to Alfred was concentrated on Christianity and not the liberal arts. This instruction was well giving for his future role as he would spend most of his reign defending the Christian Anglo-Saxons The word great was given to Alfred because of his great leadership of a king and of a leader of the military defeat. Although Alfreds greatest achievement during his reign was the defeat of the Danes, he also had other accomplishments. He pushed for better education and helped make learning important in the lives of the people of his land. This was necessary during his reign because education had declined due to the fact that the Danes were looting the monasteries and churches which were the center of education. Alfred believed that learning makes life more rewarding and enjoyable; the worst thing of all is ignorance. He also kept the Anglo-Saxon Chronicle and established a code of law based on the teachings of the Bible. This helped maintain social order. King Alfred the Great died on October 26, 899 and was buried in the Old Minster at Winchester. His death brought sadness to the people in his land that looked forward to Alfred the great being their leader. Alfred the Great was a great leader, Christian, and ruler of England for many years. His people established trust in him because of the battle he won for his people in his land. Alfred the Great is forever known in history. He is the only English monarch to be known as the Great. He is well-deserving of this title. He defeated the Danes and protected his people, but he also contributed his ideas for better education and social order.

The Structure Of Protein P53 Biology Essay

The Structure Of Protein P53 Biology Essay Protein p53, encoded by gene Tp53, is known as a tumor suppressor. Discovered in 1979 as a transformation-related protein (DeLeo et al., 1979) and protein which accumulates in the tumor cells binding with simian virus 40 (SV40) large T antigens (Lane et al., 1979), p53 was regarded as an important protein in the regulation of an apoptosis and cancerization. During the last 30 years, a large amount of studies was taken in p53 and its related mechanisms in cellular process. In 1980s, researchers cloned the Tp53 gene and determined the role of p53 as a tumor suppressor. However, the structure of p53 protein was uncertain until 2006, in which William and his colleagues determined the DNA binding core domain of protein p53 (William. C. Ho. et al., 2006). Plenty of researches focus on the regulatory mechanism of p53 and hundreds types of targets and regulators of p53 were found, e.g. MDM2, Cyclin H, ATR, ATM, etc. These molecules can interact with p53 and regulate the life process collecti vely. P53 plays a very crucial role in cell cycle regulation and apoptosis induction, the mutation of p53 would lead to the cancerization in cells and induce cancer. Bai and Zhu (2006) reported that the mutation or loss of p53 gene and protein can be found in over 50% of tumor cells in human all around the world. For these reasons, the application of cancer therapy through protein p53 and Tp53 gene is a very potential aspect in cancer treatment. This review will describe the structure and function of p53 protein, examine its role in natural and tumor cells and focus on the cancer therapy application through p53. The Structure of P53 Human protein p53 is a 53KDa phosphoprotein encoded by a 20Kb-gene; it has an intricate structure which is closely related to its function. Wild-type P53 protein contains five major domains. The N-terminus of p53 is a transcription-activation domain (TAD), with a major one at residues 1-42 and a minor one at residues 55-75 (Venot et al., 1998). The basic function of this domain is involvement in the regulation of the pro-apoptotic transcription. Following the TAD is a proline-rich region which plays an important role in apoptotic activities. The central core of p53 protein is a DNA binding domain which can bind and interact with special DNA sequence that contain 2 copies of 10bp motif 5-PuPuPuC(A/T)-(T/A)GPyPyPy-3 (Kern et al., 1991). This region is also responsible for binding with LMO3, which is an essential co-repressor of p53 (Larsen et al., 2010). A nuclear localization signaling domain (NLS) is located beside the C-terminus of central core. The C-terminus domain of p53 protein, called negative regulatory domain is involved in the down regulation of DNA binding in central core (Chen, et al., 2005), and is also an essential part for the induction of cell death. A homo-oligomerisation domain (OD) located between the negative regulatory domain and NLS. This part is involved in tetramerization, which is a main activity for p53 in vivo. The different domains of p53 protein have their functions respectively, nevertheless, they constitute an inseparable entirety to play the role as a tumor suppressor. The function of p53 As a cancer suppressor, the main function of p53 is the anticancer function. P53 plays a vital role in apoptosis, gene stability and DNA damage through a series of complex mechanisms. First, p53 can respond to DNA damage through activating the DNA repair protein. For example, upon DNA damage, p53 gets activated and initiates the transcription of repair protein XPC and DDB2. The complex of p53-XPC-DDB2 can repair the DNA damaged by UV (Adimoolam and Ford, 2003). In addition, p53 can arrest the cell cycle at S, G1, and G2 phase (Agarwal et al., 1995), which can provide sufficient time for proteins repair to fix the damaged DNA. Induction of apoptosis, the programmed cell death, is also the essential and most important anti-cancer function of p53. If DNA damage is irreparable, p53 can activate the expression of pro-apoptosis genes like p21, Gadd45 (growth arrest and DNA-damageinducible protein 45), Bcl-2 family, etc. Moreover, p53 can bind and interact with hundreds of protein to regulate the cellular process and apoptosis. P53 can also restrain the cell cycle by repressing the expression of genes include bcl-2, bcl-X, cyclin B1, MAP4 and survivin (Bai and Zhu, 2006). The physiological functions of p53 are to maintain the genetic stability and regulate the normal cell cycle through a complex regulatory network. The mutation of Tp53 gene would lead to the loss of function of p53 protein, resulting in a cellular canceration. Consequently, the essential function of p53 is preventing the cancerization of cells by repairing genes or inducing apoptosis, in order to achieve these function, p53 can interact with a n umber of downstream targets. The Regulation in P53 Level A large amount of cellular response and process is induced by p53 through a series of complex biochemical mechanisms. P53 achieves its function through activating, binding, interacting with myriad kinds of downstream target molecules including kinase, enzymes, etc. Generally, p53 interacts with its target by phosphorylation of transcription-activation domain in N-terminus. The most well-known target of p53 is a cyclin-dependent kinase (CDK) p21. P53 would initiate the transcription and transduction of p21 in response to cellular stress, p21 is necessary in G1 control, the increase of p21 arrest the cell growth and induce cell death (Yin, et al., 1999). P53 and p21 contribute to a cell-cycle check point in G1 phase. The damaged genes would not be allowed to express until they are repair. If most damaged genes cannot be repaired, the accumulation of p21 regulated by p53 would induce apoptosis. Another important target of p53 is MDM2 (also called HDM2 in human body). MDM2 is a p53 inducible gene and its product can bind and interact with p53. The product of MDM2 gene, called p90 or p95, can bind with p53 and combine with ubiquitinate which can induce the degradation of p53 (Buschmann, et al., 2000). MDM2 is the killer of p53 which can keep the amount of p53 proteins into an appropriate level. However, a series of cellular stress would cause the overexpress of MDM2 and result in the over degradation of p53, the cell would lose ground and transform to tumor cell. P53 has plenty of other regulation pathways that cannot be listed in detail. The hundreds of pathways regulated by p53 have two mutual purposes: repair genes and induction of apoptosis. Therefore, the core of the p53 regulation levels is to maintain the stability of genes and accelerate the death of damaged or diseased cells. The Role of p53 in Normal and Tumor cells In natural human cells, the wt-p53 protein can be regarded as a guardian of the cell and genome. It can monitor the vital process, repair the gene indirectly through interaction with repair protein and induce apoptosis when necessary (Hofseth, et al., 2004). P53 plays a crucial role in numerous cellular processes which are related to cell cycle and cell death. If Tp53 gene mutated, the tumor suppression function in the cell would partly reduce. As a result, people whose Tp53 gene was mutated are more susceptible to suffer from cancer. Tp53 gene is mutated in over half of tumor cells; the mutation would alter the structure of p53 protein, thus p53 would lose its function partly or completely. The p53-mutated cells can not die programmatically, and become tumor cells. The mutated p53 protein tends to accumulate in tumor cells because the mutated p53 lose its function to induce the express of MDM2, which can degrade p53 proteins in the cell. The accumulation of p53 protein is a significant feature for the tumor cells. In cancer treatments, tumor cells can be detected through the accumulation of p53. However, mutated p53 can also be an obstacle of the therapy because mutant p53 can inhibit the function of wide-type p53 (Blagosklonny, M. V., 2002). If the treatment strategy is transferring the wide-type p53 into tumor cells, how to eliminate the effect of mutant p53 is the problem which has to be solved first. Consequently, p53 plays crucial roles both in normal cells and tumor cells; it is a gatekeeper in normal cells and a marker for tumor cells; it is an effective target for cancer treatments, nevertheless it can also become a barrier in cancer therapy. Conclusion P53 is the best-known transcription factor and cancer suppressor plays multiple roles in the cell. In healthy cells and, it is a gatekeeper to monitor the cell cycle and prevent the mutation of gene. If some mutations happen in the genome, p53 serve as a doctor to activate the repair process of damaged genes. When cells suffer from an irreversible damage or oncogenic stress, p53 can become a killer of cancerous cells. P53 participates in a number of biochemical pathways which can respond to the stress, arrest cell-cycle, repair gene and induce apoptosis. In the 30 years after the discovery of p53, plenty investigation was devoted into this essential protein and received a number of great achievements. A large amount of downstream targets has been identified and the regulatory network of p53 levels became clearer. Although plenty of details about p53, such as the relationship between each pathway, are still unknown. There is still a potential application through p53 in cancer treatmen ts.

digital divide :: essays research papers fc

In this new era of booming technology and endless possibilities of what cyber space brings to our fingertips, leads us to question whether it depresses our economic and social stature. Over half the United States is now enjoying the online capabilities , while millions of people all over the world join the online community every year. With many businesses and schools relying on the Internet, it is important as basic phone service. Cell phones, computers, and plasma televisions are all taking us forward. But is this not a wellness for our society?   Ã‚  Ã‚  Ã‚  Ã‚  First, we must look at the importance the Internet means for the industrializing and developing society. Technology is definitely a boost to an economy in any nation. In a society that lacks the skills of technological advances, might leap the country economically. With the Internet, nations who weren’t well educated or behind in knowledge will greatly improve with the added IT. Whether it is medical, political, or social countries will profit from the technology. The Internet Age is growing; I believe you will see more unity between nations.   Ã‚  Ã‚  Ã‚  Ã‚  In many ways we are tying to break the digital divide in our own nation. In February 2000, President Clinton proposed a new plan to help bridge the digital divide. Offering two billion dollar tax break to private companies, new teacher IT training programs, and Community Technology Centers in low-income neighborhoods . I believe the digital divide will fade over time. Technology will adapt to society not the other way around. The Internet is going the same route that telephones and television went. The Westernized cultures are breaking the digital divide every day. Nevertheless in countries not well educated the bridge will be harder to break driven issues such as poverty. Technology is propelling us into a new age of information.

Goegraphy of Dominica :: Essays Papers

Goegraphy The geography of Dominica is quite unique. It is an island fortress unlike any other island in the Caribbean, and is the largest and most mountainous of the Windward Islands. The island was created by volcanic activity, and still today shows signs of active volcanic activity. Its steep mountains prevented colonists from completely taking over and have made the island a prime destination for Eco-tourists. The island contains over 3,000 peaks, the tallest of which are Morne Diablotin (4,747 ft) and Morne Trois Pitons (4,600ft). (www.delphis.com) The island itself is located between the French islands of Guadeloupe to the north and Martinique to the south. It is 29 miles long and 16 miles wide, and covers 290 square miles. Its exact location is approximately 15 degrees North and 61 degrees West (www.delphis.dm). The island of Dominica is home to the only surviving population of Carib Indians. This was only possible because of Dominica’s treacherous mountains. Early European colonist were not able to drive out or kill all the natives as they had done on other islands. The Caribs now live in the â€Å"Carib Territory†, a 3700-acre reservation on the northeast coast, which was given to them in 1903. The reservation has a chief and is home to between 300 – 3000 Caribs (the exact number of Caribs is hard to determine because without detail genealogy records it hard to prove or disprove that someone actually is a Carib). (www.delphis.dm) The recent boom in eco-tourism has made Dominica one of the premiere tourist destinations both in the Caribbean and in the world. In recent years Dominica has designated more national parks, forests and marine reserves per capita than nearly anywhere else in the world. Dominica’s largest national park is the Morne Trois Pitons National Park. It covers 17,000 acres (9% of the island), and is home to the world’s largest boiling lake. The lake is 70 yards across with an unknown depth and the lake is situated over a massive volcanic sulfur vent, which keeps the water temperature between 180 – 197 degrees Fahrenheit. The park is also home to several waterfalls over 100 feet tall. The average temperature range is between 75 and 85 degrees Fahrenheit. Average rainfall varies between 50 inches on coastal areas, and 300 inches with in the interior. The driest months are from January to June, and hurricane season which is usually between July and early October.

Emotional Hinderance :: essays research papers

Emotional Hinderance   Ã‚  Ã‚  Ã‚  Ã‚  Ã¢â‚¬Å"You must put your emotions into your work† is a phrase often heard in life. It proposes that emotions, which are often ignored, are a key to success. This holds true in many regards, however there are times when emotion should be restricted in swaying one’s thoughts. The pursuit of knowledge is to be completely objective. Thus, although emotional intelligence is necessary, it is more of a hindrance than a help, and should be controlled.   Ã‚  Ã‚  Ã‚  Ã‚  Since knowledge is justified true belief, it follows that the justification must be logical and true in itself. It must also be accurate, but broad. Emotional intelligence goes against this by treating subjective feelings as fact. Because the chain of logic is only as strong as its weakest link, knowledge built strongly with emotional intelligence can often turn out to be incorrect. Take, for example, an individual studying the disposition of dogs. If this individual had a traumatic childhood experience involving a dog (an attack, for example), this snippet of emotion will always taint the individual’s research, even if the circumstances are unrelated (the childhood dog may have been rabid).   Ã‚  Ã‚  Ã‚  Ã‚  Emotional intelligence is very important, however, in living life. That is why we evolved it. Revisiting the aforementioned dog and disregarding rabies, it is possible that there is something about this individual that entices hostility in canines. Although this says nothing about dogs, the childhood experience conditions the individual to avoid dogs in the future. This gives the person a greater chance of living longer, and procreating, the innate goal of man. Emotional intelligence is very important, however it is primarily for survival in everyday life. The pursuit of knowledge, however, is not an everyday event required for survival. It is part of a deep thinking about life, reserved for philosophers.   Ã‚  Ã‚  Ã‚  Ã‚  There is no question that emotional intelligence is required in the pursuit of knowledge. Without any emotional attachment, there would be no pursuit of knowledge, in the first place. Some may argue that emotional intelligence helps to guide us in the pursuit of knowledge. This notion is not logical in that it is subjective, itself. How are we to know whether or not we are being guided correctly? As illustrated earlier, just because something â€Å"feels† correct does not mean that it is.   Ã‚  Ã‚  Ã‚  Ã‚  Things that can be discovered through emotional intelligence can also be found objectively. Using emotional intelligence, one can infer that sugar is good for the human body because it gives the consumer pleasure.

Project Management Essay

1. Discuss why many information technology professionals may overlook project cost management and how this might affect completing projects within budget. Information technology professionals do not understand basic accounting and finance principles to be able to do a net present value analysis return on investment and payback analysis. It should also be considered that new technologies or software development expenses are very inaccurate as it is hard to put a figure on something has not been developed. The problems they face may be they estimate too quickly, do not have the estimating experience, may be biased towards underestimating and management may require more accuracy. The book states that IT professionals understand the value of a balanced portfolio aligned with business objectives but lack a well-defined and consistent process for managing the origination, evaluation and execution of IT investments. As far as contemplating projects with budgets it would not be an accurate estimate of cost unless all the stakeholders are involved to make these determinations. 4. Explain what happens during the process to determine the project budget. A project budget involves allocating cost estimates to individual work over the time of the project and is based on the WBS. The budget is determined using the cost estimates, basis of estimates, scope baseline, schedule, resource calendar, contracts and organizational process assets. The main goal is cost budgeting which creates a cost baseline for measuring performance and funding requirement and taking into consideration document updates. It is also important to understand how the company operates so the budget is created appropriately. 6. What is project portfolio management? Can project managers use it with earned value management? Project portfolio management allows organizations to collect and control an entire suite of projects or investments as on set of interrelated activities. Project managers can use it with earned value management as it is a performance measurement technique that let them know how well the project is meeting scope, time and cost goals by entering actual information and then comparing it to a baseline. 7. Describe several types of software that project managers can use to support project cost management. Spreadsheets are a common tool used for cost estimating, budgeting and control. Microsoft Project is a project management software that allows for the following to be created such as: cash flow, budgets, over budget tasks, over budget resources and earned value reports. Some project managers simply use the company’s accounting software and spreadsheets to receive more flexibility. They have also learnt to connect their accounting software to the project management software for more accurate information.

Project Estimating Techniques Essay

One of the most important factors to the success of a project is how well the project is estimated, as well as how overall costs are managed during the execution phase by the project manager. Project costs and estimates are vital to the success of any organization to remain competitive in the market. Cost estimating for organizations rely heavily on resources that can sometimes be difficult to obtain. Forecasting and utilizing historical return costs are just a couple of ways that organizations rely on estimating. Experienced planners are often a sought trade within the market; this paper will discuss some often used project cost estimating techniques. Types of Estimating The first type of estimating is analogous. This type of estimating utilizes estimates from a previous project that is similar, and uses them to build estimates for the new project. While this type of estimating is beneficial to the planning process, caution must be used to ensure that estimates carried over from the previous project are fair and reasonable. Parametric estimation takes historical data inputs, makes calculated assumptions based on market and statistical data, and then formulates the estimate. This type of estimating is useful as it does use historical data, coupled with statistical data; however, assumptions made by the planner can be skewed and lead to inaccurate estimates in my opinion. The next type of estimating is bottom-up. Bottom-up estimating utilizes information from individual estimates through the Work Break Down structure. This type of estimating is one of the most common types of estimating because it uses estimates from the floor tasks. These floor tasks are estimated by subject matter experts with years of experience, and can be very beneficial to ensuring that not only the estimate is accurate, but the scope of the task is correct. Another type of estimating is three-point estimating. Three-point estimating takes a look at the best, worst, and most realistic scenario to cost estimating the project. These three options obviously come with a  premium on cost, time, or quality. Dependent on what the project objective is will more than likely determine what route to take in this process. From my work experience with project planning, cost estimating can be a very difficult task. Most organizations have a method or process in how to cost estimate. Some utilize checklists, while others may standard operating procedures as part of an organizational policy. Regardless of what tools are available to a project team during the cost estimating process, knowing the overall goals and objectives of the project are keys to estimating a successful project. The burden of cost estimating is not normally the responsibility of one individual; it often lies within the project team. Multiple estimators from various skills are part of the process, and all types of estimating as discussed earlier are part of the process. Tools that my organization utilizes are bid specification review meetings that go over the material, labor, and rates that apply to the work being conducted during the project. In addition, an independent government estimate (IGE) is utilized to ensure that estimates are filled out thoroughly, and reviewed against the contractor’s estimates upon receipt. There are many other processes that can be used; however, these are the most commonly one’s used within government estimating. Conclusion Cost estimating is a very important part of the project planning process as it often dictates the duration of the project, and how much work can be accomplished during the project against the budget given for the project. Estimates of time and cost together allow the manager to develop a time-phased budget, which is imperative for project control (Larson & Gray, 2014, p. 131). While there are many different ways that estimates are created, there is no sure fire way in stating that one is better than the other. While some may think that historical data is a more accurate way, there is not telling that the estimate and return costs from a previous project were fair and reasonable. If the previous project cost was overestimated, then the current project would continue to be overestimated; therefore not proving to be a cost benefit to the organization. Cost estimating drives the project plan, and organizations need to ensure they utilize all the tools and resources they have available to them to make the  project a success. Reference Larson, E. W., & Gray, C. F. (2014). Project Management: The Managerial Process (6th ed.). McGraw-Hill.