Animal Cruelty Intresting Introduction to Speech

Cages upon cages are stacked in a plain room. Each contains a monkey that will live there the rest of its life which could be years or days away. From isolation and insanity they pace round and round in circles. When they are taken out different tests are performed on them. Among these brutal experiments, is being shoved in tubes to be bled, having tubes shoved down their throats, and being painfully injected several times. These animals will never be free. Human clinical and epidemiological studies, cadavers, and computer simulators are faster, more reliable, less expensive, and more humane than animal tests.Ingenious scientists have developed a model â€Å"microbrain† from human brain cells to study tumors, as well as artificial skin and bone marrow. We can now test for skin irritancy on cells in a test tube, produce vaccines from human cell cultures, and perform pregnancy tests using blood samples instead of killing rabbits. Says Gordon Baxter, cofounder of Pharmagene Labor atories, a drug research company that uses only human tissues and computers to develop and test drugs, â€Å"If you have information on human genes, what’s the point of going back to animals? â€Å"Every year around 1 million animals are subjected to potentially dangerous drugs that may cause severe pain both physically and psychologically to the animal. Can you not see the irony in this? Every year around 1 million animals are subjected to potentially dangerous drugs that may cause severe pain both physically and psychologically to the animal. Visualize the pumping of chemicals into a rats' stomach, hacking muscle tissue from dogs', and putting baby monkeys in isolation chambers far from their mothers. Is there a purpose for this? When picking out your mascara or eyeliner, do you even stop to see what kind of makeup you are using?You could be supporting animal cruelty and not even know it. Today many makeup products, such as mascara, are being tested on animals. Helpless a nd defenseless animals are being performed on for different types of experiments all around the world. Animal testing is animal cruelty. It's something that goes unnoticed every day because of the benefits for people that are a result of it. You are most likely connected with it every day; it's the new cosmetic line that you just bought, your shampoo you use daily, or maybe even a vaccine. It's something that's overshadowed by advancements in the medical field.

Food and Culture Essay

That is, both mother and child are being watched, judged, and constructed by society since making a good obento may please her child and also affirm that she is a good mother, and child consuming their entire meal in a appropriate manner is considered well-taught. This social phenomenon represents that culture is constructed with power which exerts a force which operates in ways that are subtle, disguised, and accepted as everyday social practice. Another essay Carole Counihan’s â€Å"Mexicanas’ Food Voice and Differential Consciousness in the San Luis Valley of Colorado† uses the case of Ryubal to suggest how women can display differential consciousness through their practices and beliefs surrounding food. In society where traditional division of labor in cooking is still prevalent, a Mexican women Helen Ryubal challenged the traditional views of women and cooking by rejecting cooking, making husbands respect women who cooked, and involving husband in cooking. Her strategy not only minimized the subordinating dimensions of reproductive labor but also valued and benefited from the help of her mother, sister, and husband. Her attempt has been based on her ideologies which was developed from differential consciousness which is â€Å"a key strategy used by dominated peoples to survive demeaning and disempowering structures and ideologies† (175). Both essays are focusing on the relationship between food and gender through each case. Allison considered obentos as a container of cultural meanings, and social expectations from women and their performance and effort in obentos. Counihan’s ethnographic research of Ryubal also provided evolved relationship between women and food which could be possible due to her differential consciousness. Two authors both used a certain level of methodology to associate with their claim such as Ideological State Apparatus and differential consciousness. This utilization strongly supports their claim and strengthens the relationship between gender and food in culture. Moreover, both authors imply the relationship food is not a mere subject but rather deeply involved with society and its ideology. As the readings focus on the relationship between gender and food, it is evident that this relationship is deeply rooted in cultural representation. To be more specific, culture constructs what is considered as normal, custom, reasonable, acceptable under ideology. The hegemonic view from this culture forms women’s custodial relationship with food. As an asian woman, I also have countless experience relating to food. Similar to most of asian culture, the society’s expectation from woman is still traditional- cooking is women’s role and they are suppose to serve their men and rest of the family. Like Ryubal’s challenge, the counter-hegemonic view toward woman’s relationship to food and reasonable, modern alternatives are necessary.

Asylum : Refugees Denied Of A Home

In the early 1900s, Britain became a new home for thousands of Black, Asian, and other refugees and immigrants seeking asylum from their own countries. The issue of discrimination and prejudice became prevalent and the outcry of blacks all over Britain was no longer ignored. It showed that there was not peace in a place that highly values their reputation. Britain’s leaders valued their reputation consisting of positive things related to aesthetic and class. Yet, there were people marching in their†¦ world of refugees. According to the 1951 United Nations Convention Relating to the Status of Refugees: a refugee is a person who, owing to a well-founded fear of being persecuted for reasons of race, religion, nationality, membership of a particular social group, or political opinion, is outside the country of their nationality, and is unable to or, owing to such fear, is unwilling to avail him/herself of the protection of that country (Refugee, 2008). The current crisis of refugees around†¦ treatment of refugees who land on Australian shores. â€Å"At the end of 2015, the number of refugees reached 65.3 million, revealing that 1 in every 113 people are displaced from their home.† This constant rise in refugee number highlights the importance for Australia’s government to move towards better solutions for the management of asylum seekers. This essay will consider the political context that surround refugees, giving the perspectives on the debate of whether to accept or deny refugees. This will†¦ The Unfair Treatment of Haitian Refugees compared to their Cuban Counterparts. According to the United Nations High Commissioner for Refugees (UNHCR), there are more refugees today than ever before—and more than half of them are believed to be children. Most of these people have left their homes in search of better living conditions and economic opportunities. This is especially true for Cuban and Haitian refugees. Living in a forever-changing world, we have to start rethinking our old immigration†¦ Asylees and Refugees Refugees and Asylees are defined as, â€Å"Under international law as being outside their home country and having a well-founded fear of persecution based on race, religion, nationality, political opinion, or membership in a particular social group, according to Bridging Refugee Youth & Children Services article, â€Å"Refugee 101.† In the United States, refugee and asylees resettlement was reestablished in the 1980’s. So far, 1.8 million people came to live in the US and†¦ Category: The Blog SEO Key Term: Refugees Is this from the topics needing covered tab: Yes 10 Facts About Ecuador Refugees The 7.8-magnitude earthquake in April 2016 killed over 650 people in north-western Ecuador, across the provinces of Esmeraldas and Manabà ­. Rubbing salt into the wound, two strong aftershocks in May of M6.7 and M6.8 injured 90 people and devastated the two provinces. The United Nations Refugee Agency has called on donors to immediately provide monetary support of US$73 million†¦ Question: â€Å"How has Australia protected human rights of asylum seekers in Immigration detention centers?† My Research Project was motivated by a movie screening I had attended during Refugee Week. The film viewed was â€Å"Mary meets Mohammad† (2013), which documented the commencement of Tasmania’s first Immigration detention Centre in 2011. From this involvement I was inquisitive as to how alacritous Australia’s society is in supporting asylum seekers and refugees. Having limited prior knowledge on this divisive†¦ his/her country of origin due to political reasons. When the person requests for protection from a foreign country he/she is accepted as an asylum. The country offers protection to the person as a political refugee. Those who seek asylum are normally persecuted for political reasons (Oxford journal, 2011). Those who confess to the Muslim religion view political asylum and migration with great importance. This is due to the political situation of the Muslim states. The region experiences the challenge†¦ The securitization of Asylum Seekers by Australia Orin Troyer Introduction By the conclusion of 2014, in accordance to reports of the United Nations High Commissioner for Refugees (UNHCR) there are approximately 59.5 million displaced people globally as a result of conflict, violence, environmental degradation and human rights violations. Of these, approximately 19.5 million are classified as an asylum seeker or refugee collectively. A refugee is a person who is unable or unwilling to return†¦ Norwegian freighter MV Tampa rescued 438 refugees off a sinking fishing boat named the Palapa (Doherty, 2011). It was an event that ushered Australia into what is now more than a decade of constant failures to meet humanitarian conventions and international laws outlined by the United Nations and ratified by the Australian government. Federal politicians will often exhort to the use of exclusionary, and often divisive language whenever asylum seekers or refugees are discussed, particularly in the public†¦

History Essay Example | Topics and Well Written Essays - 250 words - 25

History - Essay Example In order to coordinate government efforts the Bureau of Refugees, Freedmen, and Abandoned Lands ("Freedmens Bureau") was created on 4 March, 1865. The purpose of the new body was to help millions of just emancipated slaves with recourses and education means. The Bureau was responsible for distribution for food, fuel and clothing to impoverished freedmen and for supervision of â€Å"all the subjects relating to their condition† (Howard, 10) in former Confederation states. Nevertheless in spite of all its accomplishments, the Bureau is also notorious for its corruption and lack of efficiency. The agents often abused their authority to wring money out of those whom they were supposed to help. The Bureau of Refugees, Freedmen, and Abandoned Lands existed officially for a year. Lacking both manpower and funding, affected by corruption it failed to complete what was a really tremendous task the Bureau nevertheless did really much to provide just emancipated former slaves with access to education, fair practices in labor and equal

Conjunctiva in Contact Lens Wear Research Proposal

Conjunctiva in Contact Lens Wear - Research Proposal Example In a study conducted by Aragona P, Ferreri G, Micali A, Puzzolo D. in 1998 to detect the morphological changes of the conjunctival epithelium in contact lens wearers evaluated by impression cytology, it was found that cellularity, nucleus to cytoplasm ratio and goblet cell distribution were altered. In another study by Knop E, Brewitt H. in 1992 , where they discovered using the impression cytology technique on contact lens wearers that enlargement of the conjunctival cells took place as well as flattening of their cells. They also noted a decrease in the number of goblet cells. The late finding was contrary to what Connor C.G., Campbell J.B., Steel S.A., Burke J.H. have found in 1994 of an increase of goblet cells in daily contact lens wearers. As the conjunctiva has an important functional demand on the eye helping in keeping the eye moist and its cleansing effect through tears, it is thus an important first defence against debris and pathogens. Direct in vivo observation of the co njunctiva at a cellular level using the confocal microscope is likely to provide important new insights into the impact of contact lens wear on the ocular surface. This study is aimThis study is aimed to conclude results from in vivo research of those contact lens wearers. The significance of this research is to give more focused results on the effect of contact lenses contributing to add more knowledge to this specific aspect and whether or not any compromisation of the conjunctiva takes place. Please add a new paragraph as follows:- Program of research and investigation: - Under this heading, I would like you to write about To Clearly State the research problem, research key questions, sub question or hypotheses or key issues that will be tested or addressed This research will perform its investigation to describe the possible effects of lens wearing on 20 candidates to discuss the conjunctival hazardous effects (if present) and either confirm or deny the hypothesis in question. Inspection will be done at a cellular level to further investigate any changes that may occur in the conjunctiva cells including epithelial cells, goblet cells and cellular density. According to Adar S, Kanpolat A, Surucu S, Ucakhan OO 1997 "Epithelial changes were noted to be more frequent and more severe in symptomatic patients than in those without any complaints." Moon JW, Shin KC, Lee HJ, Wee WR, Lee JH, Kim MK. 2006 also found that "The ocular surface changes in keratoconus may be directly related to contact lens wear" The hypothesis is that contact lenses do not produce any significant effect on the conjunctiva, mainly superficial conjunctival epithelial cell density (it is unclear whether this would be an increase or decrease) and results in a decrease in

Personal Professional Ethical Code Essay Example | Topics and Well Written Essays - 1250 words

Personal Professional Ethical Code - Essay Example Therefore, organizational ethics refers to the principles and standards that guide the operations and interactions in an organization. This expresses the values that an organization holds to its employees and its other entities regardless of government laws. In making my ethical decisions, the process would have six core components – problem recognition, identification of alternatives, evaluation of alternatives, decision making, decision implementation and decision evaluation. The first is problem recognition where I evaluate moral standards and analyze to identify where discrepancies exist. This indicates areas with problems. It would be followed by identifying possible alternatives. These would be options adopted to ensure observance of moral obligations. Thirdly, these alternatives would be evaluated where the strengths and weaknesses of each option would be considered. The fourth core component in this process would be decision making where the decision that needs to be made would be given a thought. The critical component of implementing the decision would then follow where the decision would be made into action. Finally, the evaluation of the decision would cap the process, determining whether the implemented decision was effective and whether there would be need to start the process all over again. My professional code of ethics regards the code of ethics observed in a plastic manufacturing firm, particularly under product management. Plastics are known to be an environmental menace if not handled properly. As such, respect for environment forms one of the basic code of ethics for my profession. This would promote efforts towards designing and manufacturing products that have minimal impact to the environment. Going by the argument by Pojman and Fieser (2008), environment is an example of intrinsic good as it is just good by nature. Through the Environment, Health and Safety policy, this

CoOrdinate implementation of customer service stratergies (certificate Essay

CoOrdinate implementation of customer service stratergies (certificate III in sales) - Essay Example 6 Private Contractor 7Architect and Private Contractors 8 Company approves Interior Design and Store Lay-out Milestone 3 9 Interior Designer starts work 10 Interior Designers ends work 11 Merchandisers fix store lay-out Milestone 4 12 Booths/kiosks for sports and apparel finished 13 The interior designer makes final touches to the store lay-out 14 Company opens store to the public Milestone 5 GANNT CHART OF MAJOR TASKS TO BE DONE BY PERSONNEL IN ACQUIRING THE PRODUCTS (SPORTING GOODS, EQUIPMENT, APPAREL AND ACCESSORIES) Task Task 1 Planning Sports Equipment Task 2 Generating and Selecting list of suppliers Task 3 Checking Quality of Merchandise and Final Choice Task 4 Planning Store Lay-out for Sports and Apparel Task 5Installation Task 6 Sporting Goods are placed in Display Booths Task 7 Store is open to the Public Reports & milestones Duration of Project - months 1 Store Merchandising Manager and team Milestone 1 2 Merchandising Team 3Merchandising Team 4 Quality control Manager and team of assistants Milestone 2 5 Marketing Director and Merchandising Team 6 Architect, Marketing Director and Merchandising Team 7 Architect and Private Contractor Milestone 3 8 Architect and Private Contractor 9 Architect and Private Contractor 10 Architect and Private Contractor 11 Marketing Director and Merchandising Team Milestone 4 12 Merchandising Team 13 Merchandising Team 14Marketing Director, Merchandising Team and Architect Milestone 5 Identification of Project Stakeholders The project has several stakeholders. The first group of stakeholders is the...Through special coordination with the company's high-quality suppliers, product testing demonstrations will take place on-site for our customers to appreciate. This system will allow the customer to appreciate the features of the sports equipment and accessories, and they will be able to receive detailed equipment performance information right from the manufacturers' representatives. The Shop employs sports specialists and athletes who are familiar with the various sporting goods and equipment. The shop caters to university students and sports enthusiasts who live in the community. The shop has a strategic location as it is close to Deakin University Waterfront campus, college and high school libraries, department stores and supermarkets, cafes, restaurants, entertainment sites, city hospitals, designated sporting grounds and the beach. The project has several stakeholders. The first group of stakeholders is the end consumers consisting of the family households comprising of the parents, the teen-agers who are university students, the children and other family members who will purchase the sport equipment, apparel and accessories. The company must provide high-quality goods at affordable prices.

Roles of an operations manager Essay Example | Topics and Well Written Essays - 1000 words

Roles of an operations manager - Essay Example The paper tells that in operations management, the focus of the management team is to utilize the few resources available to achieve the organizational goals, hence bringing up immense satisfaction from the target customers. Essentially, there is an aspect of conversion of inputs to outputs, in all the resources that are critical in a firm such as energy, labor, and raw materials. Primarily, the term organizational outputs may refer to the products or services that the firm does target to distribute to their target clients. Stevenson in his research found out that operations management is a field in which the managerial team does focus on ensuring smooth flow and success of technical and physical functions of a firm. Additionally, the functions of manufacturing development and production also fall under the same department. First, it is necessary to have a picture of the functions of an operations manager, which are classified into four categories. These categories include developmen t of operational strategies, business operations improvement, management of the daily operations of the business, and personal knowledge development. In addition to that, the operation manager does cut the control costs in any business organization as Stevenson and Sum expound. Most significantly, a well-managed organization can have a clear reflection of the effect of its good management through an upsurge and consistency of profitability. To ensure that the profit is maximum, an operations manager wills hence make a clear evaluation of the costs involved in the production process, and critically reduces the increase or eliminates any unnecessary costs. Through such, an operations manager becomes the heartbeat of an organization. He will aid the organization to serve its client better. The manager will oversee the daily delivery of the products and services of the firm. Achievement and success of the function are facilitated through liaising with other department’s multi-sec toral approach.

Declaration of Independence Essay Example | Topics and Well Written Essays - 1500 words

Declaration of Independence - Essay Example Citizens have natural rights that the government cannot bestow or take away. The country was founded by people who believed this concept and wrote the Constitution to forever protect personal freedoms, a concept not reflective of attitudes toward freedom. To what extent personal freedom should be permitted is not the issue. Personal freedoms are an American birthright that is slowly but surely eroding over time. Whether or not the American people have the courage to protect and restore these freedoms is the real issue. The Founding Fathers displayed courage when they broke away from a tyrannical, oppressive King of England who ruled over the most powerful military at that time to establish a country where personal autonomy was considered the most precious commodity in a society. The seeds of the Founders’ concept of law and freedom emanated from Britain. The Constitution was inspired by the Magna Charta and British philosopher John Locke helped to lay the foundation for the Fo unders’ deep belief in personal freedoms. Locke defined each individual as having the right to â€Å"life, liberty and estate† (Locke, 1960 p. 448). These words have an almost identical mirror in the beginning paragraphs of the Declaration of Independence written nearly 70 years later: â€Å"We hold these truths to be self-evident, that all men are created equal, that they are endowed by their Creator with certain unalienable rights that among these are Life, Liberty and the pursuit of Happiness† (â€Å"Declaration of Independence† 1776).

The Issues Concerning Identity Theft Essay Example for Free

The Issues Concerning Identity Theft Essay Abstract â€Å"Identity theft has been around since the Internet became more than just the stuff of science fiction. The benefits of being in the Network has been undisputed but it has its drawbacks especially recently†. The increasing sophistication of hacking technology and the ever-widening use of web-based communication have made the danger of identity theft loom even larger in the horizon. Recent statistics illustrate just how serious the situation is with cyber criminals increasingly focusing on small companies and individuals, who are considered soft targets. Countermeasures are fighting a losing battle and experts state that individual vigilance is the only really effective way of stemming the flood. Introduction There was a movie in 1992 starring Robert Redford and Ben Kingsley, called â€Å"Sneakers.† They played the parts of college computer geeks who managed to hack into a government computer system as a sort of teenage prank and got caught. Later in the movie, the character of Ben Kingsley becomes a high-powered high-tech executive determined to rule the world with the use of information technology that could hack into any system in the world. At the time of the movie, such scenarios were the stuff of science fiction, but that is precisely the situation today. The dependence on cyber infrastructure has become so ingrained into everyday life that vulnerability to attacks takes on new dimensions. The consequences of this vulnerability are far-reaching, as indeed information has become the new currency in this fast-paced, Web-based world. But ensuring the security of digital information is fraught with difficulty, as hackers and programmers are coming up with smarter and more destructive ways to wreak havoc with both public and private networks. One type of malware that illustrates the increasing sophistication of malicious code uses a JavaScript tool called NeoSploit. It can attack a system using seven distinct exploits that could be customized depending on the specific weakness of the system it is currently attacking. It is double obfuscated so that it easily evades most automated detection. It is a â€Å"smart† bug and adaptable as well. [33] The concept of identity theft is not new. Anybody with a computer and access to the Internet have been warned never to reveal personal information to unverified sources and to keep avoid financial transactions online unless the site is vouched for a by a reliable verification site. But identity theft is so much more, and recently, there has been a disturbing rise in incidents of identity theft beginning in 2004. The threat to networks has become more complex, as illustrated by the distributed denial-of-service attacks in 2000 and the 2001 CodeRed worm. [30] The cost to consumers and businesses of identity theft is significant. According to the Federal Trade Commission, it has been maintained at more than $50 billion in the US alone. [18] Such occurrences are not only occurring in the US, however. In South Africa, Standard Bank local and foreign clients were choused out of thousands of rands by a Trojan installed in public internet cafà ©s which captured bank information. In France, a 2005 report described how terrorists routinely used stolen identities forged onto false identity documents. [26] The effect of such security breakdowns on e-commerce is particularly horrendous. Such enterprises rely on the trust and confidence of their clients that their confidence will be secure during online transactions. It only takes one instance of invasion for clients to shy away from doing further business. This paper investigates the issues pertaining to the technology behind identity theft, the countermeasures being enacted to prevent it and the current unresolved problems. Requirement Analysis To more fully appreciate the problem, a definition of identity theft may be in order. Identity theft was first coined as part of the Identity Theft and Assumption Deterrence Act of 1998, better known as ID Theft Act. It is defined as a criminal act to: â€Å" †¦knowingly transfer or use, without lawful authority, a means of identification of another person with the intent to commit, or to aid or abet, any unlawful activity that constitutes a violation of Federal law, or that constitutes a felony under any applicable State or local law.†[1] Because of the increasing sophistication of ID theft techniques, the US Federal Trade Commission felt it incumbent to provide more specific definitions of what constitutes an â€Å"identity† or â€Å"identifying information†, to wit: â€Å"(a) The term ‘identity theft’ means a fraud committed or attempted using the identifying information of another person without lawful authority. (b) The term ‘identifying information’ means any name or number that may be used, alone or in conjunction with any other information, to identify a specific individual, including any (1) Name, Social Security number, date of birth, official state- or government-issued driver’s license or identification number, alien registration number, government passport number, employer or taxpayer identification number. (2) Unique biometric data, such as fingerprint, voice print, retina or iris image, or other unique physical representation. (3) Unique electronic identification number, address, or routing code. (4) Telecommunication identifying information or access device.†[1] Looking at what comprises identity, it seems highly possible that at one point any one using the Internet or a private network will disclose one or more of the data above on a daily basis because it is almost impossible to go through a typical day without at least once using a network application such as an ATM machine or logging on to an e-mail service. Going to a hospital or school and it is highly likely an RFID is required in some form, whether as a school ID or a medical card. Schools are especially vulnerable to attack because security is not particularly high on the list of priorities for school districts working with a budget. The benefits that accrue from digital technology in the school setting is massive, but there has been no corresponding enthusiasm for establishing even the most basic of security measures. The fact is, cases such as the schools in California and Florida in which students themselves hack into the unsecured database for a prank or for profit, or the Ohio student who accidentally deleted student records which had not been backed up, are not unusual. Some of the most iconic movies are about tech savvy students who pull a fast one on uptight school administrators or against terrorists. However, in real life, security breaches for academic and medical records of students are carry consequences just as serious as those for government and corporate information. [43] It is not surprising that with the rapid digitization of information databases in all sectors, there are more and more incidents reported of some type of invasion. In 200 Techniques used in Identity Theft Physical methods computer and backup theft direct access to information dumpster diving, or searching trash theft of a purse or wallet mail theft and interception shoulder surfing skimming dishonest or mistreated employees telemarketing and fake telephone calls Internet-based methods hacking and unauthorized access phishing, or the use of spam and mirror sites pharming, or interception between an IP address and the target server. redirectors advance-fee fraud or 419 fraud fake IRS form keylogging and password stealing There has been such emphasis on Internet-related security breaches that the fact escapes most people that identity theft can happen physically as well as over the Ethernet. According to the Identity Theft Resource Center, there were more than 300 breaches in security in companies involving the loss of data storage tapes that contained the information of more than 20 million people in 2006. However, cyber-crimes is much harder to prevent because it can be done off-site and insiduously. It is also harder to detect because often the theft is done in small batches. Source: http://www.eset.eu/press_release_threats_march McAfee Avert Labs recently released a report called â€Å"Identity Theft† that identified keylogging, malware that keeps track of keystrokes to capture passwords and other sensitive information, as the tool being increasingly used to perpetrate identity theft. The report also tracked the occurrence of phishing attacks which increased 250% from January 2004 to May 2006. [26] In March 2007, ESET reported that the top malware threat was the Trojan keylogging malware called   Win32/PSW.Agent.NCC, followed by Win32/Netsky.Q or simply Netsky P, which has the power to replicate and to spread itself as an attachment through e-mail. In third place is Trojan Win32/TrojanDowloader.Agent.AWF which is used to download malware that creates botnets that in turn creates spam and disruption-of-service attacks. [4] The use of Internet Relay Chat (IRC) bots, a string of codes or independent program that attaches to the IRC channel of a system and appears to be just another user, by hackers has been developed to be transmitted through IM, mass mailing and peer-to-peer communication. While useful for managing channels, maintaining access lists, and providing access to databases, it has become dangerous in the hands of malicious users, who activate the bots to infect and reside in systems with a view of passing on confidential and sensitive information. It is difficult to detect and to clean because the bot is configured to disable anti-virus software and firewalls. Moreover, bots can edit registry entries to hide its presence. [44] Avenues used for Identity Theft Credit Card Fraud Individuals find themselves victims of credit card fraud when they transact with smaller merchants online merchants that utilize generic shopping cart software and failing to keep up with the latest software security patches. Web-based vulnerabilities, which provide cyber-criminals the soft patches in which to invade and infiltrate, is found in many different Web-based applications because of the failure to be vigilant. One example is that of Cellhut.com which uses third party Website security provider Hackersafe which is supposed to have passedthe FBI/SANS Internet Security Test. But experts are circumspect regarding the effectiveness of these tests as evidenced by the number of reports of fraud, which is actually only a part of the actual number of cases that actually occur. Small online companies are not required to report all incidents, making statistical data difficult to gather. [17] E-mail as a gateway In 2003, the number of spam or jank mail outstripped the number of legitimate e-mail in corporate America, indicating an unrelenting onslaught on computer defenses. Malicious code such as SoBig, Mimail, and Yaha, which wreaked havoc on personal computers and servers alike,   was disseminated through e-mail. As a reaction, companies allocated 8.2% of corporate budgets were earmarked for cyber-security but the economic lure for hackers have made them more inventive and devious as well. Phishing, the art of deceiving unwary users with cleverly disguised e-mail, has become the fastest-growing non-violent crimes against banks. One sneaky example was that of Swen, an e-mail virus that masquerades as a Microsoft security fix, complete to the last detail so that it looks authentic. The unwary unleashes the virus in the system when the message is opened or previewed. It then breaks down firewalls and antivirus, leaving the system open to infiltration. Instant Messaging, Instant Invasion Instant Messaging or IM has also become popular of late because it is, well, instant. Many companies believe they have increased productivity significantly with the use of Yahoo Messenger, Skype, MSN Messenger and AOL Messenger. However, these may bring more than messages into the picture. IM allows users not only to exchange messages but to transfer files as well, which may have malware or a virus riding on it. It also provides backdoor access to hackers because IM bypasses firewalls and gateway perimeter scans. The peer-to-peer network is especially open to exploitation because of this bypass, and the worms spread rapidly, testing at 10 to 20 seconds in some tests. Some antivirus software that work on the desktop level have some success in catching these worms, but only in restricted cases. Another way for hackers to open a portal is to hijack the connection using a man-in-the-middle attack and impersonate the hijacked user. The hacker is then in a position of trust and may solicit information from the unsuspecting person on the other end. The use of a network sniffer could also steal information from an open portal during an instant messaging session, and a trojan is not even needed. This is especially dangerous in a corporate network. [37] Voice-over-Internet Protocol (VoIP) The use of VoIP has the potential security risk as that of most data streams. While it may seem to be much like a telephone service, the architecture for VoIP is not the same as the conventional telephone line, where security is more established and any interception will require a physical presence on the specific telephone wire or PBX. VoIP transmits the voice as a data stream, similar to that of any other web-based application, and is vulnerable to the same kind of invasion or interception. The defense against such invasion is through the same combination of firewalls, antivirus and   encryption. [23] Because VoIP is comparatively new, it is still in its early stages of development, and has not excited the same attention for identity thieves as other forms of data exchange, although there are some spyware the specifically targets VoIP. Cookies Cookies are normally written by a website into the computer’s harddisk to store personal data about the user relevant to the application which stores the text-only code. Flaws in the generation of the cookie identity has been identified by Security researcher Michal Zalewski as potentially vulnerable to hacker attack because the overwrite protection feature can easily be bypassed and allow malware to remotely plant user information on another persons computer that can be accessed remotely when the user visits specific websites. [35] Malware is more than just malicious in that it is motivated by economic gain rather than any kind of grudge or misdirected sense of humor. A more appropriate term for these economic-driven malicous software is spyware. Spyware is much more focused and quite destructive because it can reside in a system for weeks or even months before it is discovered. Aside from the fact that transmits confidential information to its creator, it also slows down computers if enough of them reside in the system, even disbling some applications from working at all. There is loss of productivity as well as information. Sometimes it is simply annoying, popping up as adware or altering the home page to redirect the browser to specific websites. It sometimes masquerades as an end-user license agreement and most users just click on it as a matter of course, inadvertently allowing the spyware to be embedded in   the system. Whichever form it takes, it cuts down on productivity, uses up RAM and CPU resources. [27] Many IT professionals consider spyware the top security threat as revealed by a WatchGuard Technologies survey in 2005. Consequently, anti-spyware software is also on the rise, making it the top security technology for 2005. Since people make money from it, it is most likely that hackers would bring it up to the level of a serious enterprise. Particularly vulnerable are banks and financial institutions, such as PayPal, which was targeted by a variation of the Mimail worm. The pathogen redirected the user to a false PayPal verification window which then asked for sensitive financial information. PayPal had hitherto enjoyed a reputation for reliability, so the potential to victimize a large number of people makes the strategy particularly effective. The tendency to use a few core applications is another reason hackers are so effective: they only need to focus on circumventing the security of a few systems to ensure a good haul. [25]One of these core applications is Microsoft’s Windows. The vulnerabilities of these products are more numerous than ever, mostly because its widespread use has made it the target of concentration for   many hackers. And though improvements in the security features in the products have managed to deflect more than 100,000 variants of the malware circulating, it requires more vigilance on the part of the caretaker to maintain the system to the leading edge of the available updates and security patches.   [36] There has even been evidence that cyber-criminals have become loosely organized, expert hackers working together with spammers and fraudsters to extend the sophistication and reach of the attacks on peer-to-peer networks. The focus is now on compromising integrity rather than the random destruction of files and networks. The treasure in this hunt is for information, and since there is no immediate, discernible damage, it is only when the credit card bills come in or the security system springs an alarm that the invasion becomes apparent. In the instances that a pathogen succeeds in infiltrating a good system, more damage is done than its predecessor, and true to the nature of its name, the virus appears never to completely die, but rather to go into stasis, just waiting for the next improved bug to re-activate it in an evolved state, such as the Phatbot in 2004 which exploit known and newly-discovered vulnerabilities in multi-frontal attacks. [36] Profile of a Cyber Criminal [26] Organized crime groups The involvement of organized crime groups has served to coalesce otherwise individual hackers. The motive for the involvement is not only profit but to establish a supply of readily available identities to be used in the course of their criminal activities. Terrorists It has been established that terrorists use various identities to avoid detection by government agencies that are on the alert for their appearance in under their true identities. They acquire employment and obtain financing for their activities. One instance was reported in Spain where a terrorist cell made purchases with the use of stolen credit cards and used fake passports and travel documents to open legitimate bank accounts to finance their operations. Petty criminals These are the freelancers, out to make easy money and with no other motive but money. [26] Literature Survey of Solutions Research grants In 2002, $877 million in government grants were earmarked to fund the Cyber Security Research and Development Act and H.R. 3400, the Networking and Information Technology Advancement Act that would beef up the network security of vital infrastructure. The ATT Foundation has also made contribution by providing grants in 2004 to the University of Texas at Dallas and Syracuse University to support cybersecurity research. Similarly, National Institute of Standards and Technology gave a grant to George Mason University School of Laws National Center for Technology Law and James Madison University in Harrisonburg, Va. to collaborate on what is know as the Critical Infrastructure Protection Project. â€Å"The project is aimed at providing outreach and education, serve as a pool of knowledge, and development of special programs for small businesses and information sharing†.   [41] However, the grants are part of a reaction to 9/11, which seeks to promote research in counterterrorirsm and national security. The problem of identity theft is much closer to home, or at least need not be on the scale of national security. Generally, identity theft can occur to as small as the scale of a home computer. A report by Internet security solutions provider Preventon has shown that in the UK, approximately 67% of   the surveyed consumers manage their own security software, mostly anti-virus, firewalls or anti-spyware software. However, only 22% considered â€Å"phishing† a serious threat to their security. New Products For financial call centers, a product has been developed by EMC’s Security Division called the RSA[R] Adaptive Authentication for Phone, which seeks to provide a reliable authentication protocol for telephone banking as required by the Federal Financial Institutions Examination Councils Authentication in the Internet Banking Environment guidance. It is an offshoot of the RSA Adaptive Authentication for Web in use by 35 of the largest financial institutions and banks in the world. The system makes use of the voice biometric solution based on Vocent technology and Nuance’s voiceprint engine. It is designed to conduct a risk-based assessment by analyzing voiceprint and user behavior based on predetermined parameters during retail and commercial banking transactions. Aside from the technology, users of the product will also have access to the database of the RSA eFraudNetwork community which has fraudster profiles. [10] There has been some opinion that an overlap approach may be more effective, where a combination of firewalls, intruder protection and detection and vulnerability testing be used in concert instead of isolation. [25] A software that goes one step further is PCImmunity, which is designed to combine the security features of Norton, McAfee, SpyBot, SpySweeper, Ad-Aware, ZoneAlarm, Avast, and AVG while supplementing them with a restart feature in cases where one or more of the active applications is deactivated by a hacker or virus. One of its maintenance features is the automatic update of these software and the daily scans of anti-spyware software. [14] Two projects that are geared towards anticipating industrial-grade security measures for VoIP has been initiated by the VoIP Security Alliance, or VOIPSA, which aims to establish a â€Å"threat taxonomy† and and a list of VoIP security requirements These protocols will be of particular use for session border controllers, or SBCs, which serves as an intermediary between the unique architecture of VoIP and web-based protocol that would otherwise be incompatible with VoIP. VoIP with SBC    Source: http://www.cisco.com/warp/public/cc/general/bulletin/software/general/3001_pp/3001_p24.jpg Other functions of the SBC is to enable network address translation, VoIP peering and compliance with   the Communications Assistance for Law Enforcement Act.   Security-wise, SBCs as the â€Å"man-in-the-middle,† is theoretically in a good position as the front-liner for any unauthorized access or interception. SBCs also serve to mask the presence of VoIP systems and softswitches and other devices. However, the integrity of its security features has yet to be rigorously tested. [40] The JavaScript malware that confounds most automated detection needs special treatment, using decoding tools such as NJS, SpiderMonkey or Rhino which separates the malware from the browser tool at the command-line level after cleaning up the HTML. It decodes in layers until the malware is completely stripped of its code. The tools are based on JavaScript and designed to be a re-entrant. It is not guaranteed, however, because such tools have limitations and it is only a matter of time before hackers find a way around it as well. [33] Another breakthrough that is a double-edged sword is a framework being developed by security expert Roelof Temmingh called Evolution. Though still in its infancy, the framework can be used as both a hacker’s tool as well as a security application. What it does is to use any identity information and extract other hidden data. For example, it can transform a domain into e-mail addresses and telephone numbers with the use of the Whois domain name lookup service, so hackers need only one type of information to get a whole slew of information. It can also identify targets for client-side attacks and war-dialing ranges. In the interest of security, however, Evolution can be invaluable in various ways. It can be used as a footprinting to identify phishing sites and identify alliances with weak security postures. In the long run, however, Evolution can be used to illustrate the future capabilities of hackers and research to pro-actively counteract such developments would be of immense benefit. [33] The important development from a security standpoint is that many companies are finally coming to terms with the magnitude of the battle before them. In a conference in Phoenix, the focus was on new products that were designed to renew the onslaught on incidents of phishing, adware and spyware spurred on by Web 2.0. Products such as NewsGator Hosted Solution allows companies to put an RSS aggregator in their websites, eliminating the need to get feed directly from the original content originator. For security compliance, LogLogic produced the appliance-based solution LogLogic 3 r2 that allows tracking of Microsoft Exchange log activity to identify security risks. [16] One product with added features was announced recently by Barracuda Networks which helps identify spam messages even if it is being sent by an apparently innocuous e-mail address. The Spam Firewall e-mail security appliance is now able to analyze sender behavior, facilitating reputation analysis. When a previously normal nehaving e-mail address suddenly stars unloading massive amounts of email, it is presumed that it has been infected by a botnet and turned into a spam server. [20] DIY Security Protocols With the rise of DIY security came the development of self-help websites that provide security tips and information as well as recommended freeware for downloads. One such website is the Gibson Research Corp. website (www.grc.com) headed by Steve Gibson. He provides three suggestions: Stealth or hide seldom-used ports, of which a typical system has 65,000 for an internet scanner to exploit. Disconnect services not in use, which Windows provides and connects by default but which only represents a vulnerability. Bind only the modem to the TCP/IP. Windows binds all network resources to the Internet by default as well, such as a shared printer, which is unnecessary and potentially dangerous. Among Gibson’s offerings that have provided some security is Shields Up! and LeakTest scans, and Gibsons DCOMbobulator, Shoot the Messenger, Socket-Lock, UnPlug n Pray and Xpdite make security a little tighter.   Another website that may bear investigation is The Human Firewall (www.humanfirewall.org) which focuses more on companies. [36] In IM, the best way to prevent identity and other information theft is to use an IM service that allow encryption. Unnecessary file tranfers via IM should also be restricted. Another suggestion is the use of Really Simple Syndication (RSS) as an alternative to joining an e-mailing list. The RSS feed is secure because here is no need for an e-mail address, it merely gets the desired material from the feed’s server. It makes the inbox and spam mail easier to manage as well as reducing the risk of spyware infiltration. [31] To confound IRC bots, McAfee experts suggests the use of IRC servers in constructing and IRC honeypot and a network sniffer. The sniffer identifies the IRC channel used by the malicious bot and the IRC honeypot routes all IRC channels to pass through it and an outbound query is allowed. A rogue bot will try to home into the attacker’s IRC server and the honeypot then issues commands to unistall the bot. [44] Enterpise Security Governance On the executive level, the Carnegie Mellon Software Engineering Institute (SEI) reports in â€Å"Governing for Enterprise Security† that the need to address information security as an enterprise-level governance concern is paramount. It identified several characteristics that define a company that employes governance in enterprice security: Security is given the same importance as other aspects of business; Security is part of the organization’s strategic planning cycle; Security is considered an integral part of all enterprise functions; Key executives and network staff alike have an appreciation of the responsibilities and issues involved in network security. Because of the prevalence of confidentiality breaches in the corporate world and the high costs involved in such breaches, an enterprise with a strong, healthy respect and care for the security of the information in their care but still with the ability to communicate efficiently and effectively with their clients will come across as a company that can be relied on and trusted. [29] ATT’s Research Labs president Hossein Eslambolchi agrees that security cannot be an afterthought, and states that the state of network security is so pathetic that hackers can bring down a whole network with very little effort. [13] Government Initiatives The US government has come to realize the real threat of security and information breach, especially when it involves government agencies. Several intitiatives deal with ensuring vigilance in both public and private enterprises that deal with network security. E-Government Act 2002, a privacy assessment mandate that is designed to protect the personal information of citizens who volunteer their data on government sites, is touted as one of the most significant privacy guidelines. The aim of the mandate is to ease the government into e-government, overcome resistance to change and to emphasize the need for cyber-security and privacy as well as coordination concerns. [21] Another government mandate is the Health Insurance Portability and Accountability Act of 1996 (HIPAA) which came into effect in April 2005 which regulates the use of e-mail and other Internet-based communications by health professionals in efforts to secure sensitive medical information. The guidelines are particularly focused on some key points that may arise in a clinician-patient communication. The rule of thumb is that the e-mail is mos probably not secure, and ealth professionals should not solicit confidential patient information via email, nor should patients supply such information. If it is absolutely imperative, the guidelines require tat such e-mail be encoded and encrypted. In cases of sharing benchmarking information and statistical data, it would be advisable to take out pertinent patient information as much as possible. There are 18 HIPAA Patient Identifiers that should be taken out, a list available on the HIPAA website (www.hipaa.org). [3] With regard to schools, some efforts at the district levels are being made to establish some security guidelines to protect the integrity of school records. The Consortium for School Networking, together with the Mass Networks Education Partnership in Allston, Mass., has produced the Cyber Security for a Digital District program (www. securedistrict.cosn.org) which provides administrators with an outline of what constitutes a secure database. [43] However, cost is still a major consideration for many school districts, one that has no immediate solution unless administrators and school boards alike are convinced of the importance of cyber-security in the schools. There have been some suggestions that law enforcement agencies take a more offensive take on cyber criminals and ISPs that host such activities, but this move is fraught with legal and ethical issues. Cyber crime is difficult to pin down because it is nealy amorphous in character. Unless it is proven without doubt that such a person or ISP is knowingly involved in the commission of cyber crimes such as identity theft, any law enforcement actions against what may prove to be an innocent party who may in turn be victims themselves would be ineffective. A recent development has been an unprecedented move by the US District Court in Alexandria, Va. On behalf of Project Honey Pot of anti-spam company Unspam Technologies, a $1 billion lawsuit was filed against spammers as well as those who harvest e-mail addresses for spammers. The lawsuit is the first and largest of its kind made possible by the efforts of members of Project Honey Pot who have been able to gather enough data to prosecute the alleged perpetrators with the use of the honey pot software, which identifies spam mail and IP addresses of the e-mail harvesters. The gathered data will enable prosecutors to subpoena ISP records for the involved IP addresses and its owners. The results of this litigation could well provide cyber criminals at least a pause in their activities. [28] Outstanding Issues One of main problems with countering unauthorized invasions is the lack of government spending on network security. Moreover, universities are churning out an inadequate supply of graduates with enough knowledge in network security to come up with practical and effective counters to what hackers can come up with. According to National Academy of Engineering (NAE) president William Wulf, there are perhaps about 200 serious computer security researchers in the US. Academic research is also notoriously slow in coming out with publications, much too slow to be of practical use in the rapid development of cyber-crime. Much of the brain drain is due to the demand of private enterprises, which pays a lot better than academic research, for talent to staff short-term projects that has nothing to do with security research. Purdue University Professor Eugene Spafford characterizes the attitude to security issues as most people view insurance. Software Engineering Institute’s Timothy J. Shimeall agrees as senior technical staff member of its Networked Systems Survivability Program. Not enough attention and resources is being devoted to security issues until it becomes a problem. For those who are involved in academic research in security, most are theoretical, with little or no practical basis, according to Columbia University computer science professor Salvatore J. Stolfo. [30] Another issue that has yet to be addressed is the management of the distributed-computing environment, in which the traditional, centralized concept of a security perimeter, known as the Orange Book architecture of the US Department of Defense’s Trusted Computer System Evaluation Criteria, is of little use. What is needed is long-term, systemic, non-theoretical view of the problem, rather than disaster management and short-term product cycle thinking. A survey, called the Risk of Sharing, of 300 companies in the US, UK and Australia revealed gaps in the business communications process due mainly to lack of process auditability, inadvertent exposure of confidential data, review cycle inaccuracies and resource loss through dealing with spam, amendments and approvals. [5] It has also been observed that many companies fail to make full use of the security softwar they already possess, and the reason for this appears to be data overload. When security software provides audit information for instances of attempts at invasion, it spews out a lot of information, much of it extraneous. Systems analysts must figure out which are the significant entries out of thousands of entries, and some companies resourt to outsourcing the work. [25] Conclusion The story of infected networks and compromised information has become all too familiar, a state of affairs that has begun to make itself felt with a vengeance. Of particular concern is the increasing number of incidents of identity theft. It is of concern to the individuals and corporations that are directly affected by it, but it is also a matter of national security, especially since the onslaught of terrorist attacks on the US. One side of the hackers economics is selling of legitimate identities to identified individuals who are persona non grata in the US. Identity theft is should thus be a priority for individuals, business entities and government agencies alike. Efforts by researchers to come up with defensive foils to stem the malware tide have met with mixed success as each step to successfully battling existing threats is countered by newer, more sophisticated and more dangerous threats. The economics behind the hacking industry has become huge as the world becomes more and more enmeshed in the cyber world, and the opportunities for profit is increasing as more and more industries are hooking up. However, the benefits of being connected still outweighs the drawbacks and the key to maintaining equilibrium is vigilance. On the far end of the security spectrum is government agencies that exact compliance for security regulations to deter cyber crime. Businesses follow suit as required because it is also to their benefit to do so, although many small companies have resistance because they have yet to feel the squeeze of an all-out hack attack. Big enterprises are more in the picture because they are bigger targets, although hackers are migrating more and more to softer targets whose resistance to regulations make them more vulnerable to attack. On the other end of the spectrum is the individual user, whether in the office or home setting. It is the responsibility of each user to be aware of the dangers, whether they are hooked up to local area network with the potential to infect from two to 50 other terminals because of a security suite that lacks maintenance, or the home user with an address book full of friends and family which has the potential of spreading malware with the ease of a click of a mouse. The tools to combat malicious cyber crime is available but users need to be educated about their responsibilities. Users need to be vigilant about their computer use, with their e-mails, with their IM sessions, even with their browsing behavior. As Uncle Ben said to Peter Parker, â€Å"with great power comes great responsibility.† Being interconnected has unleashed great power, and the responsibility to harness this power for the common good is very much in the hands of each user. Acknowledgment References â€Å"Bill authorizes $877 million for cyber security research.† Communications Today. December 7, 2001. Retrieved April 27, 2007 from http://findarticles.com/p/articles/mi_m0BMD/is_228_7/ai_80639935 â€Å"CinTel develops a network security solution that enables content filtering proxy.† EDP Weekly IT Monitor. August 8, 2005. Retrieved April 27, 2007 from http://findarticles.com/p/articles/mi_m0GZQ/is_30_46/ai_n14939952 â€Å"Do your e-mails comply with new security regs? HIPAA regs cover security and confidentiality.† HealthCare Benchmarks and Quality Improvement. May 2005. Retrieved April 26, 2007 from http://findarticles.com/p/articles/mi_m0NUZ/is_5_12/ai_n13759944 â€Å"Global threat trends in March 2007.† com. April 3, 2007. Retrieved April 27, 2007 from http://www.eset.eu/press_release_threats_march â€Å"New research uncovers security and audit risks.† International Journal of Micrographics Optical Technology. Retrieved April 27, 2007 from http://findarticles.com/p/articles/mi_qa4077/is_200501/ai_n1363351 â€Å"Organisations fear network security threats from Instant Messaging.† Internet Business News. October 3, 2005. Retrieved April 27, 2007 from   http://findarticles.com/p/articles/mi_m0BNG/is_2005_Oct_3/ai_n15658965 â€Å"Research by prevention reveals UK home PC user are turning to DIY security.† Internet Business News. July 6, 2005. Retrieved April 26, 2007 from http://findarticles.com/p/articles/mi_m0BNG/is_2005_July_6/ai_n14724817 â€Å"RSA survey reveals online security concerns.† Internet Business News. August 22, 2005. Retrieved April 27, 2007 from http://findarticles.com/p/articles/mi_m0BNG/is_2005_August_22/ai_n14924483 â€Å"Security appliance protects consumer data with encryption.† ThomasNet, Incorporated. February 27, 2007. Retrieved April 27, 2007 from http://findarticles.com/p/articles/mi_m0PIL/is_2007_March_19/ai_n18727208 â€Å"Security system strengthens phone authentication processes.† Product News Network. November 13, 2006. Retrieved April 27, 2007 from http://findarticles.com/p/articles/mi_m0PIL/is_2006_Nov_13/ai_n16836088 â€Å"Security.† Telecom Asia. August 2003. Retrieved April 26, 2007 from http://findarticles.com/p/articles/mi_m0FGI/is_8_14/ai_108312261 â€Å"Security.† Telecom Asia. December 2004. Retrieved April 27, 2007 from http://findarticles.com/p/articles/mi_m0FGI/is_12_15/ai_n9481318 â€Å"Security.† Telecom Asia. June 2005. Retrieved April 27, 2007 from http://findarticles.com/p/articles/mi_m0FGI/is_6_16/ai_n16879846 â€Å"Software automates and maintains PC security programs.† Product News Network. September 28, 2005. Retrieved April 27, 2007 from http://findarticles.com/p/articles/mi_m0PIL/is_2005_Sept_28/ai_n15636236 A paper that is focused on a current security research issue of your own choosing. â€Å"RSS network optimization, fraud prevention tools take demo stage.† eWEEK.com. February 6, 2006. Retrieved April 27, 2007 from http://www.eweek.com/article2/0,1759,1920117,00.asp?kc=EWNKT0209KTX1K0100440 â€Å"ID thieves turn sights on smaller e-businesses: for online shoppers, security seals no guarantee that hackerts aren’t watching.† Washingtonpost.com. September 28, 2006. Retrieved April 27, 2007 from http://findarticles.com/p/articles/mi_m0NTQ/is_2006_Sept_28/ai_n16753298 â€Å"Can ID theft be solved with more regulation?† eWEEK.com. February 8, 2007. Retrieved April 26, 2007 from http://www.eweek.com/article2/0,1895,2092459,00.asp Prince. â€Å"Report shows spike in online identity theft.† eWEEK.com. January 16, 2007. Retrieved April 27, 2007 from http://www.eweek.com/article2/0,1895,2084453,00.asp [20]  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚   C. Garretson. â€Å"Barracuda Networks enhances reputation analysis technology with behavior data.† Network World. April 17, 2007. Retrieved April 27, 2007 from http://www.networkworld.com/news/2007/041707-barracuda-e-mail-security-appliance-profiling.html Webb. â€Å"Government IT Review.† Washingtonpost.com. October 2, 2003. Retrieved April 27, 2007 from http://findarticles.com/p/articles/mi_m0NTQ/is_2003_Oct_2/ai_108454056 Chandler. â€Å"Storage services for data security: big business byte for enlightened operators.† Telecommunications Americas. August 2005. Retrieved April 26, 2007 from http://findarticles.com/p/articles/mi_m0NUH/is_9_39/ai_n15631277 Khun, T. Walsh and S. Fries. â€Å"Security considerations for Voice over IP systems.† January 2005. National Institute of Standards and Technology, Gaithersburg, MD 20899-8930. Sweeney. â€Å"Focus turns to network security: while many consider the telecoms infrastructure a vulnerable target for terrorists, the more immediate threats are attacks by individual hackers and authors of malicious code, which are presenting new security challenges for service providers.† Telecom Asia. January 2005. Retrieved April 27, 2007 from http://findarticles.com/p/articles/mi_m0FGI/is_1_16/ai_n9772934 Shein. â€Å"Spy vs. spy: companies are spending billions on network security, but staying ahead of hackers may be a pipe dream.† CFO: Magazine for Senior Financial Executives. February 2004. Retrieved April 27, 2007 from http://findarticles.com/p/articles/mi_m3870/is_2_20/ai_113051525 Paget. â€Å"Identity theft.† McAfee Avert Labs. December 15, 2006. Retrieved April 27, 2007 from www.mcafee.com McPartlin. â€Å"Somebodys watching you: spyware has come in from the cold to become corporate Americas top security threat.† CFO: Magazine for Senior Financial Executives. Summer 2005. Retrieved April 27, 2007 from http://findarticles.com/p/articles/mi_m3870/is_9_21/ai_n15787661 Vijayan. â€Å"E-mail harvesters hit with $1 billion antispam lawsuit.† Computerworld. April 26, 2007. Retrieved April 27, 2007 from http://www.networkworld.com/news/2007/042607-e-mail-harvesters-hit-with-1b.html Whitley. â€Å"Report stresses security governance.† Internal Auditor. October 2005. Retrieved April 27, 2007 from http://findarticles.com/p/articles/mi_m4153/is_5_62/ai_n15763501 [30]  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚   L. Paulson. â€Å"Wanted: More Network-Security Graduates and Research.† Computer Science at the University of Virginia. February 1, 2002. Retrieved April 27, 2007 from http://www.cs.virginia.edu/csnews/show.php?artID=79 Seltzer. â€Å"Security watch: Windows wireless threat†¦not.† PC Magazine. January 2006. Retrieved April 26, 2007 from http://findarticles.com/p/articles/mi_zdpcm/is_200601/ai_n16015170 Seltzer. â€Å"Security Watch: Windows, Firefox, Winamp, all report flaws.† PC Magazine. February 2006. Retrieved April 26, 2007 from http://findarticles.com/p/articles/mi_zdpcm/is_200602/ai_n16043071 Vaas. â€Å"Tools will help personalize ID theft by 2010.† eWEEK.com. April 19, 2007. Retrieved April 27, 2007 from http://www.eweek.com/article2/0,1895,2115879,00.asp Vaas. †JavaScript attacks get slicker.† eWEEK.com. April 18, 2007. Retrieved April 27, 2007 from http://www.eweek.com/article2/0,1895,2115638,00.asp Hines. â€Å"Cookie holes expose browsers.† eWEEK.com. January 31, 2006. Retrieved April 27, 2007 from http://www.eweek.com/article2/0,1895,1917283,00.asp Hogan. â€Å"Not-so-good fellas: keep the bad guys at bay with these steps to improve your companys computer security.† Entrepreneur. June 2004. Retrieved April 27, 2007 from http://findarticles.com/p/articles/mi_m0DTI/is_6_32/ai_n6055133 Hindocha. â€Å"Instant insecurity: security issues of instant messaging.† Security Focus. January 13, 2003. Retrieved April 27, 2007 from http://www.securityfocus.com/infocus/1657 Roberts. â€Å"FBI computer crime survey finds widespread attacks.† eWEEK.com. January 20, 2006. Retrieved April 27, 2007 from http://www.eweek.com/article2/0,1895,1913633,00.asp Roberts. â€Å"IBM predicts 2006 security threat trends.† eWEEK.com. January 23, 2006. Retrieved April 27, 2007 from http://www.eweek.com/article2/0,1895,1913864,00.asp Poe. â€Å"VoIP industry moves to bolster network security: new group to define requirements.† America’s Network. May 2005. Retrieved April 26, 2007 from http://findarticles.com/p/articles/mi_m0DUJ/is_5_109/ai_n15622587 Roach. â€Å"Cybersecurity research at two schools gets boost from ATT Foundation.† Black Issues in Higher Education. July 1, 2004. Retrieved April 27, 2007 from http://findarticles.com/p/articles/mi_m0DXK/is_10_21/ai_n6145384 Roach. â€Å"Virginia universities team up on nations cyber security; focus on public policy and law gives research effort unique focus.† Black Issues in Higher Education. June 20, 2002. Retrieved April 26, 2007 from http://findarticles.com/p/articles/mi_m0DXK/is_9_19/ai_89077199 Lafee. â€Å"Cyber security at the distriCt level: are you ready to prevent unlawful, unauthorized or simply misguided use of your technology?† School Administrator. April 2005. Retrieved April 27, 2007 from http://findarticles.com/p/articles/mi_m0JSD/is_4_62/ai_n13667747 Thomas and N. Jyoti. â€Å"Defeating IRC bots on the internal network.† McAfee Avert Labs. February 6, 2007. Retrieved April 27, 2007 from www.virusbtn.com

Cellular Molecular Mechanisms Of Hutchinson Gilford Progeria Syndrome Biology Essay

Cellular Molecular Mechanisms Of Hutchinson Gilford Progeria Syndrome Biology Essay Hutchinson-Gilford Progeria Syndrome (HGPS or progeria) is a very rare autosomal dominant disorder which results in premature aging and eventually death. Patients are often very underweight at birth and will display conclusive symptoms of premature aging within 18-24 months, such as reduced body fat, hair loss and aged skin, alongside tissue and organ degeneration. Average lifespan for sufferers of HGPS is thirteen years and cause of death is invariably due to heart failure. Due to the nature of these symptoms, HGPS is referred to as an accelerated aging disorder. Currently, only 100 cases of HGPS have been formally documented, around 50 of which are children who are alive today; however it is estimated that a further 150 children worldwide currently suffer from HGPS, but have not yet been formally diagnosed. The identification of the HGPS mutation has only recently been identified and located on codon 608 of the LMNA gene, which codes for four types of lamin proteins: lamin A, lamin C, lamin Aà ¢Ã‹â€ Ã¢â‚¬  10 and lamin Cà ¢Ã‹â€ Ã¢â‚¬  2. These, along with the B-type lamin are responsible for keeping the structure of the nucleus together by forming a scaffold which lines and interacts with the nuclear membrane. The LMNA mutation leads to the expression of progerin, rather than lamin A, altering the structure of the nuclear membrane and leading to loss of nuclear integrity, DNA damage and a compromised DNA double-strand-break repair mechanism. This causes a variety of problems relating to normal cellular function as well as resulting in increased apoptosis and significantly decreased proliferation rates. Until recently, medical assistance for children with HGPS only involved treating the symptoms which accompany the disease, rather than the effects of the HGPS mutation; however in August 2009, clinical trials began testing the effects of farnesyltransferase inhibitors (FTIs) on HGPS patients. This was following experimental evidence from Toth et al (2005) who showed that human fibroblast cells expressing progerin had reversed nuclear alterations when treated with farnesyltransferase inhibitors in vitro. Introduction Aging is a normal and natural physiological process which all living things must experience, unless death should occur prematurely. Aging impairs verve and mobility, causes hair loss, weakens bones and inevitably will ultimately lead to death. As humans, the price that must be paid for our unique self-awareness is the knowledge that we will eventually age and die, forcing us to come to terms with our own mortality and compelling us to value youth. Patients suffering from HGPS are not given the opportunity to experience their youth in the same way as most. By 18-24 months their bodies are already showing signs of physiological aging and by 5 years old they will show more signs of age-related disease than many adults in their 70s. In young, healthy humans, cells are able to cope with the assault of DNA damage which all livings organisms will unavoidably encounter over time. Over time, the ability to deal with this damage lessens and the physiological process of aging will gradually occ ur. HGPS cells are not capable of dealing with this DNA damage to the same extent and so aging happens quickly and prematurely. Despite this, intelligence and cognitive function in children with HGPS are often above average compared to other children within their age bracket (Progeria Research Foundation, 2006). To understand the cellular and molecular mechanisms of HGPS, it is first important to understand the process of normal aging in healthy humans. Normal Physiological aging Aging on an evolutionary level may be described as a progressive decline in fitness (the ability to survive and reproduce) due to a decline in tissue functionality with increasing age (Partridge Gems, 2002). On a cellular level it may be described as a progressive functional decline and increase in cell mortality (Lombard et al., 2005). Although many theories have been proposed, no conclusive theory has been agreed upon to explain how or why we age. Aging is thought to be caused by various genetic and environmental factors. At the cellular level this progressive malfunction of tissue is thought to be due to accumulation of damage by various biomolecules which leads to cell loss or damage (Vijg, 2000). Usually the body has the ability to regenerate these damaged or lost cells through pools of stem cells, however the body does not have the ability to regenerate infinitely and over time this causes a decline in tissue functions typical of aging. This is consistent with the disposable soma theory of aging (Kirkwood Holliday, 1979), which states that cell repair and maintenance (including DNA repair, defence against oxidants, etc) are costly activities. To work to extend life indefinitely would make little sense, as in the wild many organisms have an extremely high mortality rate. Therefore, animals have evolved in such a way that energy invested in maintaining the soma is limited, so that the animal is kept alive long enough for it to reproduce, but not to keep it alive indefinitely. Past this point, the bodys regeneration mechanisms fail and physiological aging becomes apparent. From an evolutionary point of view, this theory makes more sense than others which are based around aging being a genetically inbuilt process, as this would provide no benefit whatsoever to the individual animal or the species as a whole. Aging may involve damage to a variety of cellular components; however damage to various DNA and RNA molecules is likely to be a major contributing factor. Despite the cells inbuilt mechanisms designed to repair damage, damaged DNA which has not been restored perfectly can lead to mutations with detrimental consequences. Balaban et al. (2005) outlines the potential role for damaged mitochondria DNA in the process of aging, however nuclear DNA is a more likely culprit. Mitochrondial DNA has thousands of copies present within the cell which can be replaced if damaged, whereas there are only two copies of nuclear DNA. Several studies have shown that as age increases, so does the risk of mutation (Martin et al., 1996) and there is substantial evidence to suggest a causal link between damage to nuclear DNA and physiological aging. Sedelnikova et al. (2008) showed that the level of double strand breaks (DSBs) that take place increase with age and older cells are less able to repair these DS Bs. Finally, there is the observation that symptoms of progeria are caused by defined mutations in DNA maintenance proteins, which leads to impaired DNA repair mechanisms (Musich Zou, 2009). HGPS belongs to a group of disorders known as segmental progeroid syndromes, characterised by early manifestation of features usually associated with normal physiological aging. They are consequently referred to as accelerated aging disorders. HGPS Background HGPS was first described over 120 years ago by Hutchinson (1886) and again later by Gilford (1904). Since its original classification in 1886, just over 100 cases of the disease have been documented. It affects around 1 in 4-8 million newborns all over the world with no preference for gender. Figure 1 Locations of children around the world who have been diagnosed with HGPG. There are currently 50 living children diagnosed with HGPS, most of whom reside in affluent Western countries. It is estimated that a further 150 children worldwide suffer from progeria but have not yet been identified due to insufficient means to diagnose in less prosperous countries as well as the rarity and complexity of the disease and the fact that the HGPS gene has only recently been identified. (Adapted from the Progeria Research Foundation, 2006) Children with progeria are often born appearing healthy, however shortly after birth it becomes apparent that weight and height gain are below that of which is expected of healthy children (Merideth et al., 2008). By 18-24 months of age they begin to display signs of premature aging, which can be seen in figure 2 below. Figure 2: A 3 and a half year old boy with HGPS showing typical progeroid symptoms. These include stunted growth, loss of hair and body fat, aged skin and unusually prominent eyes. Non-visible symptoms include stiff joints, atherosclerosis., osteoporosis and fatigue. Impaired growth does not seem to be due to any hormone inbalance/resistance or malnutrition. Cardiovascular problems are generally thought to be caused by loss of smooth muscle cells, disruption of the extracellular matrix and other irregularities in vascular structure. Life span ranges from 8 21 years with the average being around 13 years old. Death is almost invariably caused by atherosclerosis (Progeria Research Foundation, 2006). HGPS has recently been acknowledged as part of a family of diseases known as laminopathies, as it is caused by a dominant mutation on the LMNA gene. Before the identification of the gene responsible for progeria, diagnosis was carried out solely on the symptoms that have been mentioned. Thanks to the recent discovery of the mutated gene (Eriksson et al., 2003), diagnosis can be carried out based on the appearance of this mutation. HGSP is caused by a de novo mutation on the LMNA gene, although other progeroid syndromes may be hereditary. The lamins The LMNA gene codes for the nuclear A-type lamin proteins: lamin A, lamin C, lamin Aà ¢Ã‹â€ Ã¢â‚¬  10 and lamin Cà ¢Ã‹â€ Ã¢â‚¬  2 (Fisher et al., 1986). These, along with the B-type lamins are responsible for keeping the structure of the nucleus together by forming a scaffold which lines and interacts with the nuclear membrane. The structure of the nuclear lamina within the nuclear envelope is shown in figure 3. Figure 3: Structure and function of the nuclear lamina The lamina exists on the inner nuclear membrane (INM), providing structural support and helping with chromatin organisation as well as binding nuclear pore complexes (NPCs), nuclear proteins (purple) and transcription factors (pink). Barrier to auto integration factor (BAF) is a chromatin-associated protein which binds to the lamina and various nuclear envelope proteins (Coutinho et al. 2009) Fawcett (1966) deduced that the lamins are components of the nuclear lamina, a layer found between the chromatin and the nuclear envelope initially thought to provide structural support for the nuclear membrane and a location for the chromatin to attach. Recently, further roles of nuclear lamins have been proposed, including DNA synthesis, transcription, apoptosis and assembly of the nuclear envelope. It has been determined that several isoforms of lamins are encoded by three different genes: The LMNA gene encodes lamin A, lamin C, lamin Aà ¢Ã‹â€ Ã¢â‚¬  10 and lamin Cà ¢Ã‹â€ Ã¢â‚¬  2 and the LMNB1 gene encodes lamin B1 and LMNB2 encodes B2 and B3 lamins (Stuurman et al., 1998). Whilst every vertebrate cell expresses at least one type of B lamin, lamins encoded by the LMNA gene are only expressed in differentiated tissue. This observations suggest that lamin encoded by LMNA may have specific roles within certain cells. It is possible that the role of these lamins is in fact to induce or maintain differentiation within these cells, although no conclusive evidence has been presented to support this. It is likely, however, that A type lamins have roles related to and dependant on correct chromatin organisation and nuclear structure. This includes reformation of the nuclear envelope post-mitosis, transcription, DNA replication and nuclear positioning (Holaska et al., 2003; Spann., 20 02; Moir et al., 2000; Haque et al., 2006). Although studies have shown that LMNA deficient mice develop normally, shortly after birth growth problems occur (Sullivan et al., 1999). Shortly before cell division in the late prophase stage of the cell cycle, the phosphorylation of lamin subunits takes place, causing the nuclear envelope to break down. A-type lamins are the first to be disassembled, occurring during early prophase, whilst B-type lamins are disassembled during prometaphase (Georgatos et al., 1997). This course of action is thought to be a necessary requirement for the reassembly of the nuclear envelope after cell division have taken place (Burke and Gerace, 1986). However, studies such as those by Newport et al. (1990) have provided evidence against these theories, stating that when these disassembled lamin subunits are imported, they are done so into a formed nuclear envelope with fully functional pores. Perhaps is it possible that a finite number of lamin monomers are used in the reassembly of the nuclear envelope and the rest are transported in at a later stage. The role of lamins in DNA replication is unclear, however several studies have suggested that Xenopus interphase extracts were depleted of Lamin B3 which resulted in a lack of DNA replication (Newport et al., 1990), however it remained unclear whether this was entirely due to the absence of lamins or if other factors, such as a smaller and more fragile nuclear envelope, contributed. A later study by Moir et al. (2000) provided evidence to suggest that normal nuclear lamin organisation is required for DNA synthesis and that this dependency is completely unrelated to the insufficient formation of the nuclear envelope. It appears that when nuclear lamin organisation is incorrect, the elongation phase of replication fails to take place, probably due to an alteration in distribution of elongation factors, Replication Factor Complex and Proliferating Cell Nuclear Antigen. The potential role of nuclear lamins in transcription has been put forward by Spann et al. (2002), who disrupted the normal nuclear organisation of nuclear lamins using a dominant negative mutant lamin lacking the NH2- domain. This resulted in the inhibition of RNA polymerase II activity in both mammalian and embryonic Xenopus cells. Notably, RNA polymerases I and III were not affected. The role of lamins in apoptosis is directly related to the state of the nuclear envelope. Apoptosis is a very precise physiological mechanism for effective destruction of unwanted cells without causing inflammation or distress to other cells, as would occur in necrosis. Lamin degradation is one of the processes that occur during apoptosis, however several studies have suggested nuclear lamins play a role in the induction of apoptosis (Rao et al, 1996; Di Matola et al., 2001). Post mitosis, protein phosphatise 1 (PP1) is dispatched to the nuclear envelope to initiate lamin B reformation. If this process is abolished, lamin B is degraded and apoptotic signals take place. As previously mentioned, expression of lamins A/C is limited to differentiated cells. Due to their role in DNA replication and transcription, several researchers have hypothesised that they play a role in gene expression as well. Gupta and Saumyaa (2008) propose that specialised A/C lamin expression regulates gene expr ession in such a way which may prevent cell division and cause the cell to undergo terminal differentiation a form of programmed cell death. Lamins are also used for chromatin organisation and positioning within the nucleus, so cells with LMNA mutations exhibit a range of problems involving abnormal chromosome organisation. Glass et al (1993) showed that A lamins interact with chromatin by binding histones as well as indirectly through lamin-binding proteins such as LAP2ÃŽÂ ± and barrier-ro-autointegration (BAF) (Holaska et al., 2003). Cellular and molecular mechanisms of HGPS The most commonly reported mutation responsible for causing HGPS is LMNA  codon 608 in exon 11 (c. 1824 C>T). Although the LMNA gene encodes both A and C type lamins, only A lamins are affected as exon 11 is not present in lamin Cs. Whilst this point substitution does not result in an amino acid change (G608G ) it partially activates a cryptic splice site, resulting in the deletion of ~50 amino acids near the carboxyl terminal in lamin A (LAà ¢Ã‹â€ Ã¢â‚¬  50) but maintaining the CAAX site. Amongst the deleted amino acids is the ZMPSTE24 cleavage site, which is necessary for the maturation of lamin A. This results in farnesylation and carboxymethylation of lamin A, resulting in progerin (Capell et al., 2005). This cryptic splice site is only partially activated and it is estimated that only 10-50% of splices mRNA in transcribed. Since the second LMNA allele is normal, there is still some presence of wild-type lamin A although it is present in much lower levels. Whilst most HGPA pat ients are heterozygous for LMNA p.G608G, mutations have been reported on other location on the LMNA gene, such as one patient with a p. E145K mutation and another with 471C and R527C mutations (Goldman et al., 2002). These mutations have lead to various laminopathies very similar to HGPS (often referred to as atypical HGPS) however the pathophysiological manifestation of these diseases is probably different as they do not result in the production of progerin. HGPS cells are significantly larger than normal cells and usually have large cytoplasmic vacuoles, an abnormally shaped and sized nucleus, often distorted with chromatin extrusion (De Sandreà ¢Ã¢â€š ¬Ã‚ Giovannoli et al., 2003). Goldman et al. (2004) also report evidence of misshapen nuclear envelopes and abnormally thick lamina, both of which are associated with other mutations on the LMNA gene. Not surprisingly, these structural abnormalities cause a variety of cellular dysfunctions including loss of structural nuclear integrity and certain mitotic problems such as irregular chromosome separation, delays in cytokinesis and nuclear assembly and binucleation (Dechat et al., 2007). The loss of nuclear integrity can have a detrimental effect of the function of the cell, however it does not remove all structural ability of the nucleus and cell, it only reduces it. This means that the tissues most likely to be affected by a comprised nucleus are those which are consistently subjected t o mechanical stress, such as blood vessels. Indeed, vasculature in HGPS patients is often severely compromised and death is almost always caused by heart failure. HGPS cells have abnormal chromosome organization in interphase nuclei and can show a loss of peripheral heterochromatin, possibly due to various epigenetic changes. These include upregulation of genes such as H3K9me3 and H4K20me3, both of which are involved in the definition of constitutive heterochromatin (Columbaro, 2005). The H3K27me3, responsible for the definition of facultative heterochromatin, is downregulated, possible due to a reduction in the expression of the histone methyltransferase enhancer EZH2 used for H3K27 trimethylation (Schumaker et al., 2006). Evidence has suggested that these changes in heterochromatin due to altered gene expression may often result in further changes in gene expression. An interesting line of investigation to follow would be to monitor the expression of various other genes in HGPS cells. It is important to understand if HGPS enhances or inhibits the expression of various other genes and, if so, what these genes are and whether these genes play a part in the HGPS phenotype. Since lamin A only appears in differentiated cells, it is possible that one of the roles of lamin A is to maintain differentiation of the cells by securing tissue-specific gene expression. This could mean that the premature aging phenotype is not actually related to normal physiological ageing, but occurs due to certain tissues being unable to perform their designated function due to incorrect gene expression, leading to cell death, tissue degeneration and organ failure. Several studies have indicated that HGPS cells show increased damage to DNA. This was demonstrated by Bridger and Kill (2004) whose experiments showed that HGPS cells were unable to proliferate sufficiently when kept in culture and showed increased rates of apoptosis as well as demonstrating early signs of cellular aging. All of these afflictions are caused by damage to nuclear DNA. Liu et al (2006) also demonstrated that HGPS cells have increased activity in their DNA repair pathways, strongly implying that DNA damage has occurred. The most compelling evidence to suggest DNA damage as a likely culprit for progeroid symptoms is presented in a study by Liu et al. (2005), which showed that HGPS cells have a double strand break (DSB) repair defect. These cells show less concentrated levels of DSB repair factors such as Rad50 and Rad51 as well as damage signaling molecules such as 53BP1. With this evidence, the conclusion can be drawn that Lamin A in necessary for complete DNA repair to take place when necessary, and also that DSB repair is diminished in HGPS cells. DSBs are the most dangerous type of DNA damage that can potentially occur as a result of the constant attack from various agents, as they can potentially result in loss or confusion of genetic information or cell death. To some extent, DSBs occur naturally within the body during normal processes such as meiosis (Keeney Neale, 2006), or during replication when the separated stands encounter blocking lesions. The level of DSBs that occur during these processes can be increased by UV radiation, ionizing radiation, various chemical agents and the presence of free radicals. When a DSB occurs, the cells defense mechanisms commands that the cell cycle halts and DSB repair mechanisms activate. DNA DSB repair mechanisms are thought to occur as one of two processes: Non-homologous end joining (NHEJ) and homologous recombination (HR). Although HR is thought to be considerably more accurate than NHEJ, neither mech anism will produce perfect results. Evidence has been presented to imply that as we age we become increasingly dependent on HR to repair DSBs as activity of NHEJ and all other mechanisms gradually decrease (Johnson-Schlitz Engels, 2006). Many of the changes to the nuclear membrane are not a direct result of insufficient lamin A, but instead are caused by the presence of Progerin, an abridged version of lamin A, and its accumulation of the INM. This accumulation results in alterations in the structure of the nuclear lamina. Liu et al. (2005) suggests that the inefficient DNA repair mechanisms which occur in HGPS cells are in fact due to raised levels of Progerin at the INM. Fitting with this theory, experiments designed to reduce the levels of Progerin have successfully managed improve the cellular phenotype of HGPS cells. Scaffidi and Mistelli (2005) proposed inhibiting the production of Progerin whilst leaving lamin A unaffected by using specific antisense morpholinos which inhibit splicing at the deviant site. Another approach is to treat HGPS cells with farnesly transferase inhibitors (FTIs) which, as the name suggests, inhibit farnesyl transferase, so preventing the modification of Progerin to the farnseylated ki nd seen in HGPS cells. Liu et al., (2006) have shown that this approach does not only improve the cellular and nuclear abnormalities of HGPS cells, but can actually improve the health of HGPS mice. However, FTIs are not specific to Progerin as antisense morpolinos are, and lamin A is likely to be inhibited as well as the modification of Progerin. It is also possible that several other unrelated proteins would be affected by this approach; however these negative side-effects have not yet been documented. Several potential cellular and molecular mechanisms which may contribute to the HGPS phenotype are described below in figure 4. Figure 4 Various cellular and molecular mechanisms which may contribute to the HGPS phenotype. Progerin becomes trapped within the nuclear membrane as a result of permanent farnesylation. Alteration of the normal lamina structure causes vulnerability to mechanical stress and some nuclear blebbing. Other consequences involve disruption of protein interactions, disorganization/loss of heterochromatin and disrupted interactions with RNA polymerase II, RNA splicing factors and transcription factors, causing misregulation of gene expression. (Coutinho et al. 2009) The way these cellular abnormalities cause the general HGPS phenotype are not yet understood and currently can only be speculated on. As further research is carried out regarding HGPS, the cause of premature aging throughout the whole body may become more transparent. Treatment Due to the rarity and complexity of HGPS, there is currently no known cure; however, there are a variety of treatments aimed at alleviating the symptoms which are associated with this disease (Progeria Research Foundation, 2006). It is recommended that patients suffering from HGPS have a regular and nutritional diet as well as supplementary vitamin tablets (in normal doses). Dental problems which occur as a result of HGPS are treated with fluoride supplements, and aspirin should be administered on occasion in order to reduce the risk of heart attacks and strokes, which are invariably the main causes of death in HGPS children. In the case of heart-related problems such as angina, drugs like nitroglycerin may be used, although the dose should be measured carefully based on weight and height as use of anesthetics on children can be potentially dangerous. There is little that can be done to reduce the effect of reduced bone mass except for vitamin and calcium supplements, so children sho uld be accompanied at all times as they are at significantly greater risk of fracturing bones. The hip bones are particularly susceptible to dislocation due to coxa valga. Certain surgical procedures can take place to reduce the risk of this, as well as physical therapy in order to keep all joints as mobile as possible. The use of growth hormones has been suggested as a potential treatment for HGPS children; however the long term effects of this have not been shown to be significant. Currently there are several areas of research into possible clinical therapeutic treatments for progeria. Wang et al. (2008) and Liu et al (2006) demonstrated the use of farnesyltransferase inhibitors (FTIs) which appear to reduce the nuclear abnormalities present in HGPS cells, reducing the severity of symptoms on HGPS mice, improving their general health. Subjects showed improved cardiovascular health, a reduction in the number of bone fractures and improved survival and growth rates. This has been substantiated with evidence from Toth et al (2005) who showed that human fibroblast cells expressing progerin had reversed nuclear alterations when treated with FTIs in vitro. Clinical trials testing the effect of FTIs in children with HGPS began in August 2009 and ended the following December. Results from these trials are still being awaited. Summary Most of the breakthrough discoveries regarding HGPS have been made within the last few years. These include the location of the HGPS mutation, the nature of the disease and potential clinical therapies which are aimed at preventing the HGPS phenotype on a cellular and molecular level instead of simply treating the symptoms. There are several ways that the effects of the point mutation on the LMNA gene on chromosome 1 could lead to the pathogenesis of HGPS and it is likely that the combined affects of this mutation results in the HGPS phenotype. Compromised nuclear integrity may lead to reduced structural support for the cell, so those tissues under constant mechanical pressure such as the vasculature will suffer more greatly than other tissues. Another possible cause of the HGPS phenotype is the accumulation of DNA damage. This is a logical conclusion to draw, as the mechanism of normal human aging is thought to occur in this way. HGPS cells have insufficient DNA DSB repair mechanisms and so the phenotype of premature ageing in children with progeria is simply due to the magnification of one of the factors that causes aging in healthy humans. The pool of stem cells that healthy humans rely upon to counter increased apoptosis as a result of DNA damage would be under more pressure to proliferate in HGPS children, perhaps exhausting supplies and causing tissue degeneration. It is also possible that the stem cells themselves are affected by the HGPS mutation, causing a decline in proliferative ability. The possibility that the HGPS mutation may lead to up or down regulation of other genes is not one that should be ignored. If this is the case, the vast variety of symptoms which accompany HGPS may be explained by the altered lev els of expression of other genes. Until more is understood about Hutchinson-Gilford progeria syndrome, it is impossible to conclusively explain the extraordinary symptoms of this disease. Perhaps the results of the recent clinical trials will shed more light on how the alteration of two proteins due to a single point mutation can cause a child to show such drastic physiological aging. Experimental data analysis Programmed cell death (PCD or apoptosis) is a necessary part of complex life in all sorts of multicellular organisms. In humans, it is not only essential during embryonic development (preventing all manner of deformities) but also consistently through life. Efficient apoptosis prevents a vast number of diseases by ensuring that any unnecessary or potentially harmful cells are destroyed safely, without harmful effects on neighbouring cells, which happens in necrosis. Apoptosis only causes a diseased state when its rate of action exceeds or falls short of that which is necessary to keep an individual healthy. Insufficient apoptosis is well known culprit for the development of cancers, when tumorous cells which should have been erased are allowed to proliferate and develop into tumours. Another well known example of diseases due to lack of apoptosis is the vast number of immunodeficiency diseases caused by self-targeting T and B lymphocytes. These cells should have been removed through apoptotic signals, but when these signals fail these self-targeting lymphocytes are allowed to survive and will target the bodys own tissues. Increased rates of apoptosis throughout the body are commonly observed in many diseases, for example, HGPS. Abnormalities either within or external to the cell cause apoptotic signals to occur, resulting in PCD of cells which would otherwise not have been destroyed. PLAC8 (placenta-specific 8) is a gene which encodes a small, highly conserved protein known as onzin. Experimental evidence has been presented to demonstrate that under expression of endogenous onzin results in reduced cell proliferation, whilst over expression results in an increased cell count (Rogulski et al, 2005). This data suggests that onzin has a negative effect on the rate of apoptosis. Li et al. (2006) suggest that expression of onzin within a cell protects it from apoptotic signals and that when onzin levels are depleted the cell becomes sensitive to apoptotic assault. To test the effects of onzin on the rate of apoptosis, CEM-C7 T-leukemic cells were transfected with either an expression construct containing PLAC8 or pcDNA3, where the pcDNA3 vector acted as the control. Cultures of these cells where then exposed to a range of apoptosis-inducing agents: Fas, Dexamethasone (dex), cisplatin, butyric acid, okadaic acid and UV exposure. This was in order to determine whether expression of the PLAC8 gene effectively reduces the rate of induced apoptosis. Cell counts were taken after 24, 48 and 72 hours. The significance of the difference between cell counts in PLAC8 and pcDNA3 cultures when exposed to all apoptosis inducing agents was determined using a two-sample T-test. The samples used in each test were the apoptosis-inducing agent transfected with PLAC8 and the same apoptosis-inducing agent transfected with pcDNA3. The results from these two-sample T-tests are shown below in table I. Table I. Apoptosis inducer p-value (24 hours) p-value (48 hours) p-value (72 hours) Dex 0.023 0.069 Cisplatin 0.026 0.045 0.042 Butyric acid 0.003 Okadaic acid 0.03