Slavery Essay -- Slavery Essays

Servitude Servitude in America achieved an effective south yet additionally end up being one of the most horrible things done by people to people. Subjection turned into a lifestyle in early America. Eight out of the initial twelve presidents claimed slaves. Individuals in the south profited by slaves the most. Reaping those enormous cotton fields took numerous hands. That’s were the slaves got key to the accomplishment of the south. Slaves were predominately dark Africans. Africans made up the lion's share however they were by all account not the only ones. Local Americans and even English obligated workers made up the remainder of the individuals put into servitude. There are two various types of slaves. There are slaves that remained in the house and dealt with the families, and there were the slaves that worked the land. Local slaves were generally ladies and kids. Mean and little youngsters made up the ranch hands. These men worked from dawn to dusk. Working outside was by a long shot the most noticeably awful of the two. A few slaves didn’t fall under these to types there were slaves that filled in as aides, trappers, make laborers and medical caretakers. Occupations that individuals don't relate slaves with. Slaves had various employments relying upon what of the nation they were sent to. Slaves in the north by and large worked in the factories and clearing backwoods. Slaves in the south worked the homesteads all year. Up north slaves just needed to work the homesteads in the late spring months in view of the thorough winters they experienced. Residential slaves remained in the house got after the family, prepared and served suppers, tidied and stayed aware of the day by day errands of the house. It was simpler than working outside. Slaves were treated as property. Proprietors reserved the option to do anything they desired to them. They were property, not individuals. Proprietors would have the white ranch hands remain in the fields and ensure the slaves were functioning as quick and hard as they could. In the event that they weren’t functioning as hard as could be expected under the circumstances and a white farmhand saw it. The slaves would be beaten, and here and there in serious cases murdered. At the point when the proprietor wasn’t around slaves could collaborate with one another. Families that came over on the vessels were torn separated at the closeout squares. They were put together not knowing one another and needed to shape a structure to their own lives. More youthful people and youngsters looked into the more established people as guardians. Slaves would be placed in... ...cap commanders could get their hands on. The proprietors of the boats needed to keep the slaves fit as a fiddle to get as much as possible for them. The white deck hands would welcome the slaves at hand and experience and exercise they called â€Å"dance.† The men had to bounce until the shackles broke they skin on their lower legs. The ladies and youngsters who were not shackled could move to a beat. Slaves making the most of their activity since it was the main time they were out loud to move around. In the event that the slaves would not move they were beaten with whips. The whips were called â€Å"cat-o-nine-tails† they were comprised of nine strings secured with tar; each rope had a bunch toward the end. At the point when awful climate hit it turned out to be harsh for the slaves. The slaves were not so anyone might hear to come up on the deck. This is the place ailment and foulness went through the slaves. Taking everything into account, bondage in spite of the fact that was a major piece of the ascent of this nation. It was thinking back, one of the most awful things done by people to different people. Gaining from our slip-ups took quite a while. The Civil War was the point in our history where everybody understood that you were unable to treat individuals like creatures. That everybody is viewed as equivalents.

Pygmies Essays - African Pygmies, Mbuti People, Ef People

Dwarfs Dwarf bunches are dissipated all through central Africa, from Cameroon in the west to Zambia in the southeast. In Zaire, there are three principle gatherings of Pygmies: the Tswa in the west, the Twa between Lake Kivu and Lake Tanganyika, and the Mbuti (additionally alluded to as Bambuti or on the other hand BaMbuti) of the Ituri Forest. As per Schebesta, the creator of the most punctual solid reports, just the Mbuti are genuine Pygmies, i.e., under 150 cm. in stature and generally unmixed with neighboring people groups. Different gatherings are alluded to as Pygmoids, being profoundly intermixed with different people groups both truly and socially (Turnbull 1965A: 159-B). The accompanying rundown alludes just to the Mbuti Pgymies of the Ituri Forest in Zaire. The Mbuti are situated at lat. 0 degrees-3 degrees N and long. 26 degrees-30 degrees E. Their domain is an essential downpour woodland. The Mbuti have routinely been isolated into three gatherings, which are unmistakable from one another phonetically, monetarily, and topographically. Every one of the three gatherings communicates in an alternate language (which relates to the language expressed by neighboring locals), rehearses unique chasing strategies, and is regionally unmistakable. The Aka talk the Mangbetu language (Sudanic family), chase fundamentally with lances, and live in the north. These lance trackers have not been broadly considered. The Efe communicate in the Lese language (Sudanic family), are toxophilite, and are situated in the east. The Efe were concentrated by Schebesta. The Sua communicate in the Bira language (Bantu part of the Benue-Congo family), chase with nets, and live toward the south. They were concentrated by Putnam what's more, Turnbull. The most significant distinction between the three gatherings, the phonetic distinction, is, as indicated by Turnbull, of late beginning and is absolutely unintentional (Turnbull 1965B 22-23). Moreover, regardless of the certainty that the three dialects are altogether different, there are sufficient similitudes in inflection to make it workable for Pygmies to perceive, if not fathom, one another. The entirety of the Pygmies of the Ituri Forest perceive themselves by the term Mbuti, and the main political character they have is in restriction to the town cultivators. The Mbuti all in all are plainly unmistakable from these town neighbors both racially and socially, and, Turnbull says, the financial contrasts between the three Mbuti bunches cover an essential basic solidarity (Turnbull 1965B: 22-23). Since there has never been an official segment statistics, it is incomprehensible to give a precise gauge of the complete Mbuti populace. From conversation with ministers and managers and from his own understanding, nonetheless, Turnbull speculated that the populace was around 40,000 in 1958 (Turnbull 1965B: 26). The Mbuti live in regionally characterized itinerant groups. The participation of these groups is liquid. Groups have no formal political structure; there are no boss, and there is no gathering. A casual agreement among old regarded men is the premise of choices influencing the whole camp. Regardless of Turnbull's emphasis on essential basic solidarity, the contrasts in chasing strategies aqppear to have significant impact upon the idea of the band association. Net chasing is an agreeable adventure, requiring the participation of the entire band, including the ladies and youngsters. Arrow based weaponry, then again, is fundamentally a family adventure, requiring just a few men. The most evident qualification coming about because of the financial contrasts is that of band size. Bowman groups normal around 6 cabins for each band, while net-chasing groups normal around 15 hovels. The Mbuti keep up associations with encompassing town cultivators whose dialects the Mbuti have received. Numerous records demonstrate that the Mbuti are exceptionally acculturated and have embraced numerous highlights of resident way of life past language, for example, the family framework and certain strict observances. Turnbull feels that these highlights are very shallow, be that as it may. The connection between the Mbuti and the townspeople is kept up on a few unique levels, revolving around exchange. The Pygmies bring the townspeople nectar and meat as a byproduct of ranch items. This financial trade can happen on a few levels: between the band and the town all in all (capita/boss), among ancestry and heredity (genealogy senior/Kpara), or between people (kare/kare). The first kind of relationship doesn't happen frequently, trades being more effectively led on a relational premise. The ancestry relationship is genetic on the two sides. The kare fellowship is set up in nkumbi commencements. In the nkumbi inception, male residents and Mbuti are circumcised. The relationship set up in the inception is proceeded all through life and bases on financial trade. The strict existence of the Mbuti isn't at all reasonable. Early reports express that they had no religion by any means, and later reports harp on regardless of whether the Mbuti relationship to the powerful basically establishes religion (typically characterized by faith in one incomparable being) or then again enchantment. In

Hypersensitivity Case Study Essay

*Poison Ivy-The body’s safe framework is typically in the businessâ ­ of shielding us from microbes, infections, and other outside trespassers that can make us wiped out. Be that as it may, when urushiol from the toxic substance ivy plant contacts the skin, it prompts an invulnerable reaction, called dermatitis, to what might some way or another be an innocuous substance. Feed fever is another case of this sort of reaction; on account of feed fever, the resistant framework goes overboard to dust, or another plant-created substance. Here’s how the toxin ivy reaction happens. Urushiol advances down through the skin, where it is utilized, or separated. Invulnerable cells called T lymphocytes (or T-cells) perceive the urushiol subsidiaries as an outside substance, or antigen. They convey fiery signs called cytokines, which acquire white platelets. Compelled from the cytokines, these white platelets transform into macrophages. The macrophages eat outside substances, however in doing so they additionally harm typical tissue, bringing about the skin aggravation that happens with poison ivy. Â ­ The unfavorably susceptible response to harm ivy is known as deferred extreme touchiness. In contrast to quick excessive touchiness, which makes an unfavorably susceptible response close to presentation an antigen, deferred extreme touchiness responses don’t rise for a few hours or even days after the introduction. A great many people don’t have a response the first occasion when they contact poison ivy, however build up an unfavorably susceptible response after rehashed presentation. Everybody has an alternate affectability, and accordingly a marginally unique response, to harm ivy. Affectability as a rule diminishes with age and with rehash exposures to the plant. *Transfusing an individual of Type A Blood with Type B Blood-ABO blood classification framework The ABO framework comprises of A, B, AB, and O blood classifications. Individuals with type A have antibodies in the blood against type B. Individuals with type B have antibodies in the blood against type A. Individuals with AB have no enemy of An or hostile to B antibodies. Individuals with type O have both enemy of An and hostile to B antibodies. Individuals with type AB blood are called all inclusive beneficiaries, since they can get any of the ABO types. Individuals with type O blood are called all inclusive contributors, on the grounds that their blood can be given to individuals with any of the ABO types. Befuddles with the ABO and Rh blood classifications are responsibleâ for the most genuine, some of the time perilous, transfusion responses. So except if the individual is RH-there as a rule isn’t that enormous of a response when A Type An is given Type B blood. These responses might be gentle or extreme. Most mellow responses are not hazardous when rewarded rapidly. Indeed, even gentle responses, however, can be startling. Serious transfusion responses can be perilous, however this is exceptionally uncommon. Gentle unfavorably susceptible responses may include tingling, hives, wheezing, and fever. Extreme responses may cause anaphylactic stun. Introduction to a field of Ragweed-Ragweed sensitivity, like other dust hypersensitivities, may incorporate side effects of unfavorably susceptible rhinitis, unfavorably susceptible conjunctivitis and unfavorably susceptible asthma. Side effects brought about by ragweed dust sensitivity would be required to begin during August and September and last until October or November, contingent upon the atmosphere. So avoid a field of Ragweed during those times each year in the event that you experience sensitivity or excessive touchiness around ragweed. *Unsuccessful Kidney Transplant-Transplant dismissal is when transplanted tissue is dismissed by the recipient’s safe framework, which obliterates the transplanted tissue. Transplant dismissal can be reduced by deciding the atomic comparability among giver and beneficiary and by utilization of immunosuppressant tranquilizes after transplant. Hyper-intense dismissal happens a couple of moments after the transplant when the antigens are totally unparalleled. The tissue must be evacuated immediately so the beneficiary doesn't kick the bucket. This sort of dismissal is seen when a beneficiary is given an inappropriate kind of blood. For instance, an individual given sort A blood when the person in question is type B.

Anthropological Observations Free Essays

Tyler Adams Anthropology 2 seventeenth November 2012 Research Paper Outline I. Presentation A. The motivation behind this paper is to watch and comprehend the practices and parts of culture in Starbuck’s Coffee. We will compose a custom paper test on Anthropological Observations or on the other hand any comparative theme just for you Request Now B. To assess this difficult I utilized member perception, breaking down and watching individuals without predisposition while taking part in the earth. In member perception one must not make it realized that the person in question is breaking down individuals so as not to change their practices, one should likewise make certain to stay fair-minded all through the procedure. C. I contend that there are a few unique intentions in going to Starbuck’s however it is a focal gathering place for societies to cooperate and appreciate. D. The accompanying paper will give models and evidence that I found in my exploration about this circumstance and incorporates realities I saw at Starbuck’s Coffee. II. One factor about the issue: A. What number of individuals were there at various occasions? B. A lot of various sizes of gatherings came into Starbuck’s. C. Gaiety in Catalina III. Another factor of the issue: A. What are the various subjects individuals are talking about? B. Contemplating, tests, inquire about, public activity, sporting events, legislative issues. C. Reference for second factor IV. Another factor of the issue: A. What are the functionalities of Starbuck’s other than food and drink? B. Party, examining, meeting new individuals. C. Reference for third factor V. Decisions A. I infer that Starbuck’s Coffee is a focal social gathering place where numerous individuals want a few unique reasons, various measures of individuals and diverse conversational topics were available in the café at different occasions. The most effective method to refer to Anthropological Observations, Essays

Lideship 3 Essay Example | Topics and Well Written Essays - 500 words

Lideship 3 - Essay Example It is essential to pick a vocation that fits one’s aptitudes, abilities, character and inspirational core interest. Says Heidi Grant Halvorson, â€Å"More than a time of research shows that when individuals experience a fit between their own inspiration and the manner in which they work, they are progressively successful, however they additionally discover their work all the more intriguing and drawing in, and esteem it more.† (Halvorson, 2013) Motivational center is the total of the qualities and shortcomings that each one’s character is comprised of. Notwithstanding persuasive center, one needs to test the open doors that exist for the profession one picks just as the instructive and preparing needs included. Having inquired about these things altogether, I have reached the resolution that the vocation that I might want and one that fits me best would be that of a cop. It is so natural to state pick something that you like. Anyway this is more effortlessly said than done. It is critical to explore each part of the profession and compare it with what one’s own needs and capacities are. To pick the correct profession one needs to contribute some time on self-evaluation. It is important to introspect on one’s qualities and shortcomings just as the aptitudes one has and what one truly expects out of the vocation. I have done a careful self-examination with the assistance of different devices to discover where my center falsehoods. I am additionally ready to put resources into further preparing. In this setting specialists concur that individuals can be comprehensively separated into two classes. Albeit we all have both the advancement just as the avoidance center in some degree, while picking a profession one needs to discover which one is the more predominant one to empower one to settle on the correct decision. Each of these centers have particular qualities and shortcomings, consequently the activity of discovering which class one has a place with empowers one to check the sort of profession that would suit him/her best. The advancement centered individual

Signs and Symptoms of Stress in Men

Signs and Symptoms of Stress in Men Stress Management Print How Recognize the Stress Symptoms in Men By Jerry Kennard Jerry Kennard, PhD, is a psychologist and associate fellow of the British Psychological Society. Learn about our editorial policy Jerry Kennard Medically reviewed by Medically reviewed by Daniel B. Block, MD on November 23, 2019 twitter linkedin Daniel B. Block, MD, is an award-winning, board-certified psychiatrist who operates a private practice in Pennsylvania. Learn about our Medical Review Board Daniel B. Block, MD Updated on February 05, 2020 How Stress Impacts Your Health Overview Signs of Burnout Stress and Weight Gain Benefits of Exercise Stress Reduction Tips Self-Care Practices Mindful Living Robert Daly/Caiaimage/Getty Images When the pressures around a person outstrip their ability to cope with them, we call this stress. What we really mean is distress, because there are two kinds of stress: eustress, or helpful stress, and distress, which is unhelpful and damaging stress. Without some stress, we would not have the motivation to win races, solve problems, take exams and make important changes. Stress is a protector in that it gives us a mechanism for dealing with threats. It prompts us to confront threats or avoid themâ€"the so-called fight or flight mechanism. But stress, particularly long-term stress, can be a factor in the onset or worsening of ill health and a shortened lifespan.?? Men may not always good at recognizing stress in themselves, and stress is clearly an individual experience. What one man finds stressful, another will not. What can be stressful at one time may not cause stress during another time. And the signs and symptoms of stress can also vary from person to person and from year to year. Measuring Stress in Men Stress can be measured in different ways, but testing usually takes the form of a self-report in which a person rates particular experiences, events, or feelings on a defined scale. Perhaps the most well known of these is the SRRS (Social Readjustment Ratings Scale), developed in 1967 by the American psychiatrists Thomas H. Holmes and Richard Rahe.?? The SRRS lists a number of life events assumed to be stressful, such as moving or the death of a spouse or other close loved one. Holmes and Rahe assigned a numerical value to each of these events based on the intensity of the stress. The death of a spouse, for example, was rated the most stressful, at 100, whereas a minor violation of the law was assigned a value of 11. What Stress in Men Looks Like Broadly speaking, stress can be experienced in two ways, physically and psychologically, but the two are interrelated. For example, research has shown that chronic stress can lead to decreased immune function.?? This included an increased risk of infection and decreased ability to fight infection or repair tissue. One study found that stress not only slowed wound healing, it often also led to behaviors that slowed recovery from injury or surgery such as heavy alcohol use or poor self-care.?? Physical Symptoms Remember that stress is an individual experience and that symptoms are too. Signs of disease should not be ignored just because you believe they are stress-related. Get serious  symptoms checked by your doctor. Some potential effects of stress include:?? Chest painPounding heartHigh blood pressureShortness of breathFatigueDiminished or increased sex driveMuscle aches, such as back and neck painHeadachesDizzinessClenched jaws and  grinding teethTightness, dryness or a feeling of a having lump in your throatIndigestionConstipation or diarrheaIncreased perspirationStomach crampsWeight gain  or lossSkin problems Psychological Symptoms If these effects of stress are interfering with your daily life, consult your doctor for advice on how to find relief. Stress management is essential to well-being and something we should practice every day. SadnessDepression??CryingWithdrawal or isolationInsomniaMood swingsWorryRestless anxietyIrritability, anger or decreased anger controlOvereating or anorexiaFeelings of insecurityDecreased productivityJob dissatisfactionChanges in close relationshipsIncreased smokingIncreased use of alcohol and drugs 17 Highly Effective Stress Relievers

4 Super Fast Ways of Writing a Book Review

4 Super Fast Ways of Writing a Book Review If you search for writing book review  in Google, you will undoubtedly find tons of materials on how to write a book review competently. However, do you know how to write one quickly, especially if you have a fast-approaching deadline? Most articles on book reviews don’t discuss thisand if they do, it is not in length. Here are four ways to write book reviews speedily: Don’t wait to write stuff down while reading your book. Have note cards handy at all times while reading the book, and note important facts, ideas, passages, and your own interpretations down. Organize your notes properly in either alphabetical order or by category. As soon as something strikes you about the book, write it down. Most likely, you will forget what struck you if you wait to write it down. Our attention spans are not that long. Create a format for the review that is a standard for you. It is kind of like a fill-in sheet that you can use to keep you on track. This makes the process of drafting smoother and more organized. Before reading the book, create an outline of the format that you want your reviews to be in. Try to keep to this format as much as you can, but if you feel leeway should be given, then you can break your rules at times. If you are confused about how to format a review, usually reviews begin with introductory information about the book, move onto to giving a summary of the book, and then analyze the strengths and weaknesses of the book in terms of its style, pace, voice, and other characteristics of storytelling. Do automatic writing. Let your inner editor be silent and let the words rip! When writing, write fast without looking back. Remember: you have time to edit later. The first draft is done to get your ideas down according to your pre-designed format. The finer points come later. A good practice is to set a timer. Usually 5 minutes of free writing, taking a break, and doing 5 minutes of free writing again does the trick. Don’t care that your writing sounds crazy, off, inappropriate, or whimsical. No will see this draft besides you. Like Hemingway said, â€Å"Write drunk, edit sober.† You don’t have to drink alcohol to be drunk. Simply write without inner your editor and you are â€Å"drunk† on writing. If you hit a block and can’t seem to get through the review, move onto doing another review. There is no harm in doing two reviews simultaneously. It is better than sitting and doing nothing, being frustrated at yourself and the book you have to review. You can also take a short walk outside or watch a comedy video for 5 minutes. Usually these two things refresh us and make us feel like we can do our work again. Besides these 4 hints, you can always make some coffee, eat some chocolate, or drink some strong tea, and your work will be faster. Having a comfortable space to write that is quiet is also beneficial. At AdvancedWriters writing company you can get professional book review help from top-rated academic experts. Just fill in the order form online!

Blue Tang Facts Habitat, Diet, Behavior

The blue tang is among the most common aquarium fish species. Its popularity soared after the release of the 2003 movie Finding Nemo and the 2016 sequel Finding Dory. These colorful animals are native to the Indo-Pacific, where they can be found living in pairs or small schools in the reefs of Australia, the Philippines, Indonesia, Sri Lanka, and East Africa. Fast Facts: Blue Tang Common Name: Blue tangOther Names: Pacific blue tang, regal blue tang, palette surgeonfish, hippo tang, blue surgeonfish, flagtail surgeonfishScientific Name: Paracanthurus hepatusDistinguishing Features: Flat, royal blue body with black palette design and a yellow tailSize: 30 cm (12 in)Mass: 600 g (1.3 lbs)Diet: Plankton (juvenile); plankton and algae (adult)Lifespan: 8 to 20 years in captivity, 30 years in the wildHabitat: Indo-Pacific reefsConservation Status: Least ConcernKingdom: AnimaliaPhylum: ChordataClass: ActinopterygiiFamily: AcanthuridaeFun Fact: At present, all blue tangs found in aquaria are fish captured in the wild. While children may know the blue tang as Dory, the fish has many other names. The animals scientific name is Paracanthurus hepatus. It is also known as the regal blue tang, hippo tang, palette surgeonfish, royal blue tang, flagtail tang, blue surgeonfish, and Pacific blue tang. Simply calling it a blue tang can lead to confusion with Acanthurus coeruleus, the Atlantic blue tang (which, incidentally, also has many other names). A Fish with Many Names Humberto Ramirez / Getty Images Appearance Surprisingly, the blue tang isnt always blue. An adult regal blue tang is a flat-bodied, round-shaped fish with a royal blue body, black palette design, and a yellow tail. It reaches 30 cm (12 inches) in length and weighs around 600 g (1.3 lbs), with males typically growing larger than females. Humberto Ramirez / Getty Images However, the juvenile fish is bright yellow, with blue spots near its eyes. At night, the adult fishs coloring turns from blue to violet-tinged white, probably due to changes in its nervous system activity. During spawning, adults change color from dark blue to pale blue. The Atlantic blue tang has yet another color-change trick: Its biofluorescent, glowing green under blue and ultraviolet light. Diet and Reproduction Juvenile blue tangs eat plankton. Adults are omnivorous, feeding on some plankton as well as algae. Blue tangs are important for reef health because they eat the algae that could otherwise cover the coral. During spawning, mature blue tangs form a school. The fish suddenly swim upward, with females expelling eggs above the coral while males release sperm. Around 40,000 eggs may be released during a spawning session. Afterward, the adult fish swim away, leaving tiny 0.8-mm eggs, each containing a single drop of oil to keep it buoyant in the water. The eggs hatch in 24 hours. Fish reach maturity between nine to 12 months of age and may live up to 30 years in the wild. Sword Fights and Playing Dead Blue tang fins contain spines sharp enough to be comparable to a surgeons scalpel. There are nine dorsal spines, 26 to 28 soft dorsal rays, three anal spines, and 24 to 26 soft anal rays. Humans or predators foolish enough to grab a regal blue tang can expect a painful and sometimes venomous stab. Male blue tangs establish dominance by fencing with their caudal spines. Although they are armed with sharp spines, blue tangs play dead to deter predators. To do this, the fish lie down on their side and stay motionless until the threat has passed. Ciguatera Poisoning Risk Eating a blue tang or any reef fish carries the risk of ciguatera poisoning. Ciguatera is a type of food poisoning caused by ciguatoxin and maitotoxin. The toxins are produced by a small organism, Gambierdiscus toxicus, which is eaten by herbivorous and omnivorous fish (such as tangs), which in turn may be eaten by carnivorous fish. Symptoms may appear anywhere from a half-hour to two days after eating an affected fish and include diarrhea, low blood pressure, and reduced heart rate. Death is possible, but uncommon, occurring in one in 1,000 cases. Regal blue tangs are strong-smelling fish, so its unlikely a person would attempt to eat one but fishermen use them as baitfish. Conservation Status The regal blue tang is not endangered, classified as least concern by the IUCN. However, the species faces serious threats from habitat destruction of coral reefs, exploitation for the aquarium trade, and use as bait for fishing. To catch fish for aquaria, the fish are stunned with cyanide, which also damages the reef. In 2016, researchers at the University of Florida bred blue tangs in captivity for the first time, which raised the hope that captive-bred fish may soon be available. Sources Debelius, Helmut (1993). Indian Ocean Tropical Fish Guide: Maledives [i.e. Maldives], Sri Lanka, Mauritius, Madagascar, East Africa, Seychelles, Arabian Sea, Red Sea. Aquaprint. ISBN 3-927991-01-5.Lee, Jane L. (July 18, 2014). Do You Know Where Your Aquarium Fish Come From? National Geographic.McIlwain, J., Choat, J.H., Abesamis, R., Clements, K.D., Myers, R., Nanola, C., Rocha, L.A., Russell, B. Stockwell, B. (2012). Paracanthurus hepatus. IUCN Red List of Threatened Species. IUCN.

Planning an Advertising Campaign - 671 Words

The Flamingo Grill is an upscale restaurant located in St. Petersburg, Florida. To help plan an advertising campaign for the coming season, Flamingos management team hired the advertising firm of Haskell Johnson (HJ). The management team requested HJs recommendation concerning how the advertising budget should be distributed across television, radio, and newspaper advertisements. The budget has been set at $279,000. In a meeting with Flamingos management team, HJ consultants provided the following information about the industry exposure effectiveness rating per ad, their estimate of the number of potential new customers reached per ad, and the cost for each ad. Advertising Media Exposure Rating / Ad New Customers / Ad Cost / Ad†¦show more content†¦Flamingos management team accepted maximizing the total exposure rating, across all media, as the objective of the advertising campaign. Because of managements concern with attracting new customers, management stated that the advertising campaign must reach at least 100,000 new customers. To balance the advertising campaign and make use of all advertising media, Flamingos management team also adopted the following guidelines. †¢ Use at least twice as many radio advertisements as television advertisements. †¢ Use no more than 20 television advertisements. †¢ The television budget should be at least $140,000. †¢ The radio advertising budget is restricted to a maximum of $99,000. †¢ The newspaper budget is to be at least $30,000. HJ agreed to work with these guidelines and provide a recommendation as to how the $279,000 advertising budget should be allocated among television, radio, and newspaper advertising. Managerial Report Develop a model that can be used to determine the advertising budget allocation for the Flamingo Grill. Include a discussion of the following in your report. 1. A schedule showing the recommended number of television, radio, and newspaper advertisements and the budget allocation for each media. Show the total exposure and indicate the total number of potential new customers reached. 2. How would the total exposure change if an additional $10,000 were added to the advertising budget? 3. A discussion of the ranges for theShow MoreRelatedMarketing At Hardees Food Systems, Marketing Department From 1978-19891320 Words   |  6 Pagesin the strategic development and execution of advertising and promotional campaigns. Our field marketing structure divided the system into seven regions, and deployed a full complement of personnel in each region. I was Regional Director of Marketing, with six Marketing managers, and a regional advertising agency, Advertising Communications Incorporated (ACI). Our national agency, Benton Bowles (BB) supplied strategic direction, television planning and buying, and creative development. 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Regardless of which option you select, the length and timing of the campaign will be determined by the targets set by the original briefRead MoreHow to Create a Persuasive Advertising Campaign998 Words   |  4 Pagessupport you to accomplish the best proposal for creating a persuasive advertising campaign for your organisation. Situation Assessment As you hold, a solid customer vision from instant knowledge for the potential target market and also the significance of your services, it is vibrant that you encirclement the essential resources to make your company blossom. This is because; you have the inner understanding of your campaign, which reimburses towards the amenities, provided by you to the market

The Stress Level Among Employees - 1035 Words

rest of the group. Employees who are silent about important issues may also experience psychological stress. (Robbins, S and Judge, T, 2014). Below chart shows some other major causes of stress when working in groups in an organization. Fig 6 - Working with Others Is Often Irritating. (Robbins, S and Judge, T, 2014). At any stage, if the managers and team members disagree about perceptions of organizational support, stress level among employees increases. The employees are unsure about how to proceed with the task in hand, if they don’t know what management is expected of the task or what management see as the project output. This scenario combined with increased job demand causes employees to stress out more as there is no clear guidance on how proceed here. Organizational culture with less support and encouragement for innovations, motivation and which supports risk taking causes employees to take less interest in those innovative projects. If the task expects improved quality while not equipping employees with any additional tools to improve delivery efforts also cause the stress levels to be impacted. In an organization culture where employees are expected to finish tasks very quickly and more efficiently than in the past cause employees to stress more as new projects are assigned to t hem from time to time. This comes under how the aggressiveness and outcome orientations factors are perceived. Also, some organizational culture it is expected that employees workShow MoreRelatedWorkplace Stress Among The Employee951 Words   |  4 PagesWorkplace Stress among the Employee in Insurance sector: A study 1. Introduction Stress is a part of daily living. It is an adaptive response. Stress occurs at the workplace when there is a mismatch between the expectations of the employee and demand of the employer. Stress basically reduces a person’s ability to perform and think differently which is bad for everyRead MoreThe Effects Of Substance Hormones On The Body And Brain Essay1296 Words   |  6 PagesLet’s face it! Stress is†¦ well, stressful! Stress is also a part of life. So, life is stressful†¦ some parts of life are more stressful than others. What is stress? â€Å"Stress refers to a physiological reaction to the body that overstimulates the adrenal glands, resulting in the overproduction of body stress steroid hormones such as cortisol and stress neurochemicals such as adrenaline. 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Customer service - Business is usually done with a company because of the relationship the client has with an employee of the company. When this employee leaves, this relationship is severed thus leading to potential client loss. Turnover results in more turnovers - When an employee leaves, the mood in the office changes. ThisRead MoreZyx Incorporated Essay694 Words   |  3 Pageswhat is causing the increase in absenteeism and sick leaves. ZYX’s employees’ job satisfaction will be measured by using different types of tests in which one will be able to find out the variables that impact their satisfaction. In this study one will be able to understand why there are attendance problems, as well as the factors that interfere with such problems and what needs to be done to improve job satisfaction among the employees. All variables used in this study are important because each variableRead MoreStress in the Workplace Essay1426 Words   |  6 PagesStress in the workplace Stress in the workplace has become one of the increasingly popular topics of discussion over the last couple of decades. It has become a major concern among various organizations creating an impact on the management and operations of the organization. This paper will give a detailed definition of what stress in the workplace is and the most common causes of stress amongst both employers and employees. In the midst of investigating the causes of stress, I will give an outlineRead MoreJob Satisfaction wth Different Variables1258 Words   |  5 Pagesmeasure the reliance of dependent variable i.e. job satisfaction on several manipulated variables (motivation, stress, working conditions, etc.). Job satisfaction describes how content an individual is with his or her job. There are several factors that influence person’s level of job satisfaction. Some of these factors include the fairness of the promotion system within an organization, stress factor, the quality of the working conditions, leadership and social relationships, the job itself (the varietyRead MoreTaking a Look at Stress1745 Words   |  7 PagesStress is said to have existed throughout evolution. In most cases stress is debated with the perception that it is only associated with human beings. If we look at geography, the formation of the planets and everything existing in them is a result of stress in the form of meltdown which happened over millions of years. Rivers are formed as a result of soil erosion when the earth’s surface is subject to stress by wind or running water. History talks of the transformations from the Stone Age to theRead MoreJobs in The Service Industry: Calling Center Essay1442 Words   |  6 PagesIn the current world, workplace can be either a beneficial place or the worst place to be for employees. The worst case happens especially in the service industry, such as the call centre, where there is a high level of control and job demands among employees (Casta nheira and Chambel 2010). This eventually leads to employee burnout which is a major problem in the workplace. The purpose of this essay is to discuss how job demands contribute to employee burnout based on different findings by severalRead MoreIntroduction . Moral Stress. Moral Stress. Moral Distress1701 Words   |  7 PagesIntroduction Moral Stress. Moral Stress. Moral distress according to Detienne et al. (2012) is referred to a commix of ethics and moral conflicts; paying close attention to moral distress as it relates to intensity and frequency. Moral distress has no formal definition, but encompasses perspectives, internal and external constraints, values, etc. that can impact workplace performance and outcomes. Detienne et al. (2012) assess the relationship between moral stress as a consequential soothsayer of

My Best Friend Is My Friend - 847 Words

Everyone has a best friend. Most people have been through multiple best friends within their lifetime. A best friend is your closest friend, someone to talk to, the first person you think about when you want to do something, someone to help you with things and they are so much more than just those qualities. In my case my best friend has helped me become a better person, helped me to understand certain situations from a different point of view rather than just my own. She has taught me how to be nicer to people, even people who are not nice to me. She is there for when I need her and I am there for her when she needs me. It’s what best friends do for each other. I believe that people have best friend soulmates. And I have mine. My best friend, Natalie, has an incredible impact on my life. Natalie’s importance in my life is at a very high level. I don’t know what I would do without her. We have only been friends for a short period of time compared to my other clo se friends. We’ve only been friends for one year and ten months, although it feels like it has been centuries. I absolutely adore her. She is one of my favorite people in my life. She has helped me through some of the worst times in my life and I am so thankful for her friendship. I would do anything I possibly could to keep her happy. I promised to love her, advise her, protect her and be there for her when she needs me. When most people say â€Å"best friends forever† they hardly stay best friends forever. But when IShow MoreRelatedMy Best Friend : My Friend1417 Words   |  6 PagesMy Best Friend I didn’t have the most normal childhood that there was to have. I had more family issues than a child under the age of 5 should probably have for proper development. My biological mother couldn t ever behave like a responsible adult and most of the time couldn t afford to feed me and take care of me, so she would drop me off with my different family members and I would bounce around from place to place, week to week; Because of this, I moved from Medford, Oregon to Colby, KansasRead MoreMy Best Friend : My Friend1292 Words   |  6 PagesMy best friend. My biggest supporter. My brother. For those of us with brothers, we can easily say that they tend to be aggravating at times, but at the same time they can be one of the most positive influences in our lives. This describes my older brother Abraham, or Abe for short. All through my life, having him next to my side has been one of the greatest things that has ever happened to me. From the headaches of school, to the carelessne ss of child play, to now living in his house; Abraham hasRead MoreFriends : My Best Friend744 Words   |  3 PagesWe have always been close friends but at lunch, everything changed. We didn’t have any classes together so we enjoyed every minute we saw each other at school. We always had something to talk about and secrets to spill, but one day I had a huge secret that I could never tell. My feelings started to change rapidly, everything was different about them. They were no longer that quirky friend of mine with glasses that were way too big for their face. They became that friend that had curls that bouncedRead MoreMy Best Friend809 Words   |  4 Pageshappened yesterday, I’ll try my best to tell you about my life and how it made me who I am today. I never thought this would happen I always thought we would be best friends forever but in the next couple years that was not how it was. This friend was very sad and was getting bitter which was understandable but I tried my best to be there. Time passes a bit and we both start going to Crestwood in 5th grade. It was starting off to be a great year and I even made a new friend, she was awesome, we startedRead MoreMy Best Friend Who Is My Friend978 Words   |  4 PagesJimmy my best friend who is always with me where I go and when I need him. Jimmy support me in many ways, He is always there for me. He is a unique best friend I have in my life. Jimmy become my friend in July 2008, when I was in need of somebody for support, guide, I find Jimmy. To help me out. Without jimmy I would not be able to do things by myself. Living is free, we have free air, and we can live our lives however we want because we have everything we need to make it happen. We have hands toRead MoreArchenemy And My Friend : The Best Friend And Their Best Friend983 Words   |  4 Pages During a person’s lifetime they have a best friend along with an arch enemy. Their best friend and their arch enemy are two different people. A best friend there for them no matter what, her an arch enemy like a friend but secretly does not like her. Their arch enemy could be a friend of her best friends and is mad due to the fact that they are mad that she is someone else’s best friend. An archenemy could be a friend of theirs consequently, could become upset considering they spend more time withRead MoreMy Best Friend764 Words   |  4 Pagesall my friends everyday. My best friends however, don’t go to Paul Revere, my best friends are my neighbors. My favorite neighbor is my best friend Theo, he would say I’m very funny, but he is even funnier. My family and friends would probably describe me as kind, funny, helpful, easy-going, and laid back. I would describe myself as outgoing and helpful. I like to put other peoples needs before my own. Around people I don’t know very well I am usually quiet. I am good at getting my friends to laughRead MoreMy Best Friend750 Words   |  3 PagesThe day I meet my best friend was when I was fifteen, and I met him while visiting my uncle. Even though I had seen him in school, I had never talked to him. Surprisingly after we started talking, it only took us three months to start dating. After two years, we are now engaged. This wonderful man has shown me that getting abused is not what every man does, and that you can’t show love that way. 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Now all I have of him is very little, but the gold chain, the pictures, the memories are incredible. His love for the Miami Hurricanes rubbed off on me in the last few years, but was hard watching them play their rival Florida State with the family we managed to make it work though. We have shared countless hours

Short Stories Free Essays

In many of the works we have read thus far, a character is isolated or alienated from or in conflict with his or her culture and/or environment. Two prime examples of this dilemma include Leonard Mead in â€Å"The Pedestrian,† and Miss Brill in â€Å"Miss Brill. † Labeled as outcasts whether willingly or unwillingly, the main characters struggle to identify with their current environment. We will write a custom essay sample on Short Stories or any similar topic only for you Order Now Throughout these short stories it is evident they become more and more detached from their surroundings.Throughout Ray Bradbury’s â€Å"The Pedestrian† the main character Leonard Mead is at odds with the brain-dead society he lives in. Everyone in society is the same in how they live their lives; they go to work during the day, stay inside and sit in front of the television every night. Leonard Mead, however, as a true individualist does not do any of these things. In the evening Leonard walks purely for enjoyment, unlike the rest of the 3 million civilians in his city who watch television at nighttime.He considers himself a writer, as he identified to the lone unmanned police cruiser, even in a world where literature no longer exists. The culmination of his desire to stay outside the norm and go for walks, in addition to his non-profession, makes Leonard Mead an outsider in the world he lives in. In Katherine Mansfield’s â€Å"Miss Brill† the isolation of Miss Brill from her environment is evident all throughout her public Sunday afternoon in the park.Miss Brill, a middle-aged English teacher in a French vacation town, imagines her daily routine as if it were a stage. In her reality Miss Brill, along with the rest of the people around her, are actors and actresses going about their weekly performances. She identifies each onlooker and walker-bye with a back-story as to what their role plays in the act. In addition to her vicarious living, Miss Brill personifies her fur.These allusions of Miss Brill and her fantasy come crashing down when she’s forced back to reality, and realizes her true role or lack thereof in the world she lives in. These characters struggle to find their place within the society and world they live in. Their conflicts with isolation ultimately lead to their downfall. Leonard Mead, an individual amongst conformity, is punished for his seemingly abnormal way of life. Likewise, Miss Brill is punished with her own reality when her allusions and fantasy world cease to exist. How to cite Short Stories, Papers

Molecular Biology of the Cell Garland Science

Question: Describe about the Molecular Biology of the Cell for Garland Science? Answer: Cell is structural, functional and biological unit of all the living organism. They are small unit of life of organisms. The replication process is independent and are known as building block of life. There are two type of cells found in all organisms. Prokaryotic cell that are made up from a single cell and Eukaryotic cell that are made up from two or more than two cells (Lodish et al, 2004). In the later paragraphs the structure and function of both eukaryotic and prokaryotic cells are explained in detail. Prokaryotic cells are simple cells. They lack cell membrane and organelles. They reproduce by binary fission. They have a cell envelope known as capsule made from polysaccharides. They also have plasma membrane made up of proteins, phospholipids, carbohydrates. Inner to it is cytoplasm, it contains ribosome, mesosomes and plasmids (Whiteman, 1998). The ribosomes exist freely inside the cytoplasm and the mesosomes are folding in the plasma membrane. In Bacteria small Pilli and flagella are present. Eukaryotic cell are complex. They have membrane bound nucleus. They have a cell wall, inner to it is plasma membrane which is a double layered wall. Inner to it cytoplasm is present which is a jelly like substance in which all other organelles are present. Nucleus is present in the center with a nucleolus inside and covered by nuclear membrane (Raven, 1987). The other organelles that are present include mitochondria, chloroplast, endoplasmic reticulum, ribosome, golgi bodies, lysosomes, vacuoles and all these organelles are present inside the cytoplasm. It also consists of chromosome e present in the nucleolus of the cells. There are many eukaryotic cells. Among these most important are plant cells and the animal cells. Plant cells: These are eukaryotic cells which has nucleus that is membrane bound. They are larger in size than to animal cells. They are rectangular or cuboidal in shape. The cell wall is present outside the plasma membrane and is made of cellulose and functions to support and provide rigidity. They have membrane bound cell structures (Albert et al, 2002). The organelles carry out functions like producing hormone, enzyme and carrying out metabolic activities. Animal cells: The animals are multicellular so eukaryotic cells. They are covered by cell membrane but do not have a cell wall. The animal cells consists of are centrioles, cilia and flagella, endoplasmic reticulum, Golgi apparatus, lysosomes, microfilaments, microtubules, mitochondria, nucleus, peroxisomes, plasma membrane and ribosomes (Margulis, 2000). The part of plant and animal cells cell along with their structure and function are explained below: Cell wall: The outermost covering meant for support, rigidity and protection. Cell membrane: Inner to cell wall made up of phospholipid Cytoplasm: All the organelles reside in this Nucleus: inside the cytoplasm and contains hereditary information of the cell that is inside the DNA. Chloroplast: Plastid containing chlorophyll meant for trapping light energy and carrying out photosynthesis. Mitochondria: Power house of the cell. They are present inside the cytoplasm. Vacuoles: Temporary storage unit of cell Golgi complex: Proteins are sorted and packed in it. Ribosomes: Meant for assembling proteins Endoplasmic reticulum: Meant for transporting material The cell membrane present is a semi permeable membrane. It is double layered made up of phospholipids with proteins embedded inside it. The major function of cell membrane are as follows: Isolating the cytoplasm from the outside environment Regulating the exchange of substances in to and out of the cell Communicating with other cells The substance move across the membrane in a passive that is coming in absence of input of cells energy or active which expands the cell energy and than transport it. It also make up the cell potential. Thus making the cell membrane a filter and allowing a specific amount of things to go out and come inside the cell. Phospholipids are made up of a hydrophilic head and a tail that is hydrophobic and forms a barrier. The small particle which does not have charge easily passess through the membrane bilayer like carbon dioxide and oxygen. The water molecules are charged so does not pass easily, and requires a channel protein known as Aquaporin to pass through the membrane (Jesse et al, 2007). The transport mechanism is passive which takes place by simple diffusion, facilitated diffusion by help of proteins, osmosis and with the help of contractile vacuoles or central vacuoles. The transport mechanism which is active involving the movement of molecule uphill that is going against the conce ntration gradient is carried up with the help of ATP molecules. It involves three processes of endocytosis, exocytosis or by the aid of sodium and potassium pump. Explain the terms active and passive transport of substances across a membrane? Active transport is the movement of biomolecules from the region of low concentration to the region of high concentration with the help of chemical energy (Nelson, 2005). The types of active transport are Endocytosis, exocytosis and sodium-potassium pump. The Passive transport is movement of biomolecules from the region of high concentration to the region of low concentration and without the help of any kind of chemical energy. The type of passive transport are diffusion, facilitated diffusion and osmosis. Name a substance that moves by each mechanism The proteins and ions move via the active transport process (Wchtershuser, 2003). The water and oxygen molecules move up by the passive process. Explain why the process of mitosis is important in cells Mitosis is necessary because by it the division of parent genome takes place and it is divided in to two same copies of the two daughter genome. In both the animal and plant cell mitosis helps the tissues to grow, body parts to grow and repair any abnormalities. Describe the key stages in the process of mitosis Mitosis is the division of cell in to two identical daughter cells. It consists of four stages: Prophase: Duplication of DNA takes place and cell is prepared for dividing. The nuclear membrane disrupts in this phase (Morgan David, 2007). Metaphase: The chromosomes along with their chromatids are aligned aloe equator or the metaphasic plate. The spindle fibre formation begins. Anaphase: The two sister chromatids separate and try to move to the end of the poles of spindle Telophase: The cell membrane closes up and split the cell in to two halfs. It gives two daughter cells with same genome. Name the process in animals which require meiosis to take place Reproductive cells known as germ cells requires meiosis to take place. Outline the stages of meiosis describing the key chromosome movements which occur The stages of meiosis in which the chromosome movement occurs during the prophase I of meiosis I. These are: Leptotene Zygotene Pachytene Diplotene Diakinesis Explain the biological importance of meiosis? The biological importance of meiosis is that by this the haploid gametes are formed which carry out sexual reproduction(Freeman, 2002). It also results in maternal and paternal genes being exchanged during crossing over and allowing variations to occur in the offsprings. It also maintains the same chromosome number that is n in all the daughter chromosomes. References Alberts B, Johnson A, Lewis J et al. (2002). Molecular Biology of the Cell (4th ed.). New York: Garland Science. Freeman, S (2002). "Cell Division". Biological Science. Upper Saddle River, NJ: Prentice Hall. pp. 155174. Jesse Gray, Shana Groeschler, Tony Le, Zara Gonzalez (2002). "Membrane Structure" (SWF). Davidson College. Retrieved 2007-01-11. Lodish H, Berk A, Zipursky LS et al. (2004). Molecular Cell Biology (4th ed.). New York: Scientific American Books Margulis, L. (2000). Origin of Eukaryotic Cells. New Haven, London: Yale University Press Morgan, David L. (2007). The cell cycle: principles of control. London: Published by New Science Press in association with Oxford University Press. Nelson, David L.; Cox, Michael M. (2005). Lehninger Principles of Biochemistry (4th ed.). New York: W.H. Freeman Raven, J. A. (1987). "The role of vacuoles". New Phytologist 106: 357422. Wchtershuser G (January 2003). "From pre-cells to Eukaryaa tale of two lipids". Mol. Microbiol. 47 (1): 1322 Whitman; Coleman; Wiebe (1998). "Prokaryotes: The unseen majority" (PDF). Proc. Natl. Acad. Sci. USA 95 (12): 65786583

Sirtris Pharmaceuticals Living Healthier, Longer Essay Example For Students

Sirtris Pharmaceuticals: Living Healthier, Longer Essay N9-808-112 MARCH 18, 2008 TOBY STUART DAVID KIRON Sirtris Pharmaceuticals: Living Healthier, Longer You can live to be a hundred if you give up all the things that make you want to live to be a hundred. Woody Allen One Saturday in February 2007, Dr. David Sinclair and Dr. Christoph Westphal co-founders of Sirtris Pharmaceuticals, a Cambridge, MA-based life sciences firm, navigated the company’s narrow hallways and cramped offices to a conference room for their regular weekend strategy planning session. When they reached the conference room, Sinclair and Westphal reviewed their activities during the past week. Sinclair, who was an associate professor of pathology at Harvard Medical School and co-chair of Sirtris’s Scientific Advisory Board, had had interviews with Charlie Rose, the Wall Street Journal, and Newsweek. Westphal, who was Sirtris’s CEO and vice chairman, had closed a $39 million round of financing, bringing the total amount of invested capital in the company to $103 million. Sinclair and Westphal were riding a wave of interest generated, in part, by their company’s promising research into age-related diseases, such as diabetes, cancer, and Alzheimer’s. The company’s research into disease, however, only partly explained its appearance on the covers of Scientific American, Fortune, and the Wall Street Journal. According to their suggestive headlines – â€Å"Can DNA Stop Time: Unlocking the Secrets of Longevity Genes† (Scientific American), â€Å"Drink wine and live longer: The exclusive story of the biotech startup searching for anti-aging miracle drugs† (Fortune) and â€Å"Youthful Pursuit: Researchers seek key to Antiaging in Calorie Cutback† (Wall Street Journal) – Sirtris was hoping to develop drugs that could treat diseases of aging, and in so doing had the potential to extend the lifespan of human beings. The Sirtris team had, in fact, established a link between resveratrol, a compound found in red wine-producing grapes, and sirtuins, a newly discovered family of enzymes with links to improved longevity, metabolism and health in living things as diverse as yeast, mice and humans. Sinclair and Westphal were building Sirtris around the development of sirtuin-activating drugs for the diabetes market. The Sirtris team had developed its own proprietary f ormulation of resveratrol, called SRT501, and was developing new chemical entities (NCEs) that were up to 1000x more potent activators of sirtuins than resveratrol. Leonard Guarente and David Sinclair, â€Å"Can DNA Stop Time: Unlocking the Secrets of Longevity Genes,† Scientific American, March 2006; David Stipp, â€Å"Researchers seek key to antiaging in calorie cutback,† Wall Street Journal, October 30, 2006. David Stipp, â€Å"Drink wine and Live Longer: The exclusive story of the biotech startup searching for anti-aging miracle drugs,† Fortune, February 12, 2007. See Appendix for pictures of the covers of the Wall Street Journal and Fortune. ____________________________________________________________ ____________________________________________________ Professor Toby Stuart and Senior Researcher David Kiron, Global Research Group, prepared this case, with advice and contributions from Alexander Crisses (MBA 2008). HBS cases are developed solely as the basis for class discussion. Cases are not intended to serve as endorsements, sources of primary data, or illustrations of effective or ineffective management. Copyright  © 2008 President and Fellows of Harvard College. To order copies or request permission to reproduce materials, call 1-800-545-7685, write Harvard Business School Publishing, Boston, MA 02163, or go to http://www. bsp. harvard. edu. No part of this publication may be reproduced, stored in a retrieval system, used in a spreadsheet, or transmitted in any form or by any means—electronic, mechanical, photocopying, recording, or otherwise—without the permission of Harvard Business School. 808-112 Sirtris Pharmaceuticals: Living Large, Longer In today’s strategy session, which included Dr. Michelle Dip p, Sirtris’s senior director of corporate development and Garen Bohlin, the company’s chief operating officer, the team was discussing their upcoming move to new aboratory space in another part of Cambridge, and three of the more pressing strategic issues facing the firm. †¢ In-licensing. One issue was whether to in-license compounds from a biotech company to diversify Sirtris’s drug development platform beyond its narrow focus on SIRT1, one of seven sirtuin variants in the human body. Several members of the Sirtris executive team were advocating a more balanced risk portfolio as the company started to increase investment in its drug development efforts. Partnership with Pharma. As is almost always the case in biotech, the team was in discussions about a partnership with a few large pharmaceutical firms. They were considering (a) what it would mean for the organization to become tied to a pharmaceutical company at this stage of its development and (b) whether to postpone a deal until Sirtris had more clinical data. Was this the right point in the company’s history to do a deal? Nutraceuticals. Sinclair received a near-constant stream of emails and phone calls from the public requesting Sirtris’s proprietary version of resveratrol, SRT501. For some time, he had contemplated selling SRT501 as a nutraceutical, an off-the-shelf health supplement that would not require FDA approval. This idea raised many questions about market opportunity, commercialization strategies, and the potential impact of a nutraceuticals offering on the Sirtris brand and the all-star group of scientists that had allied themselves with the organization. †¢ †¢ Anti-Aging Science The quest for long life has spurred the imagination of people in virtually every era in human history. Ancient Greeks imagined immortal gods, the sixteenth century Spanish adventurer Ponce de Leon searched for the fountain of youth, and twenty-first-century scientists test rodents for lifeextending biological compounds. Until the 1990s, the only proven means of increasing life-span in any animal was to reduce its calorie intake. In 1935, Cornell University researchers discovered that reducing calorie intake in rodents by 40% increased their lifespan by an average of 30-40%. Conventional wisdom ecame that calorie reduction (CR) activates an evolutionary adaptive process that lowers metabolism to help animals through periods of food shortages or droughts. Decades passed before scientists could shed light on the biological mechanism triggered by CR. When new information arrived in the 1980s and early 1990s, it contradicted what had become the conventional wisdom. The new work indicated that instead of lowering metabolism, calorie reduction is a biological stressor that activates a defens ive metabolic response. Few scientists paid much attention to the shift in view, as few serious scientists focused their academic careers on antiaging studies. Longevity research began to gain traction as an academically credible field of study in the early 1990s, after MIT professor Leonard Guarente and his laboratory traced the molecular pathway of calorie reduction in yeast to sirtuins (silent information regulators), which are proteins (enzymes) that are found in all cells. (See Exhibit 1 for timeline of scientific milestones in longevity research. ) In humans, there are seven types of sirtuins in different parts of cells and in different parts of the body. Sirtris Pharmaceuticals: Living Large, Longer 808-112 Sirtris was focusing 90% of its RD on one sirtuin, called SIRT1 in humans. For simplicity, any reference to sirtuins, unless otherwise noted, is to the family of sirtuins or SIRT1. David Sinclair In 1993 while sightseeing in Sydney, Australia, Guarente was taken to dinner by some local yeast resea rchers, a group that included David Sinclair, then a young doctoral candidate at the University of New South Wales. During the dinner, Guarente mentioned that he had two students working on aging in yeast. I was incredibly excited by Lenny’s work,† said Sinclair. â€Å"I asked him why the longevity field was so pre-occupied with looking for genes that ended life, rather than genes that could extend it. By the time we finished dinner, I told him I was going to work with him at MIT. † Sinclair grew up in St. Ives, near Sydney Australia, the eldest son of parents who both worked in the medical diagnostics industry. In high school, he was known as a talented class clown and risktaker, a young man who aced science classes but could not resist setting off minor explosions in chemistry lab. Two years after their first meeting, Sinclair made good on his promise and joined Guarente’s MIT lab as a postdoctoral fellow. Sinclair quickly established himself as a creati ve and productive researcher, publishing a 1997 article in Cell with Guarente that described how the yeast equivalent of SIRT1 increased the longevity of yeast. When yeast cells divide (a sign of aging in yeast cells), they spin off extra copies of genetic material called extrachromosomal rDNA circles (or ERCs). With each successive cell division, ERC copies accumulate in the nucleus. The original cell, faced with copying both its original genetic material and an increasing number of ERCs, soon runs out of energy and eventually dies. But when an extra copy of the sirtuin gene was added to the cell nucleus, the formation of ERCs was repressed and the cell’s life span was extended by 30 percent. In 1999, Sinclair left Guarente’s lab for a tenure track position at Harvard Medical School, but continued to collaborate with Guarente. 3 They found that extra copies of the sirtuin gene extended the life span of roundworms by as much as 50 percent. We were surprised not only by this commonality in organisms separated by a vast evolutionary distance but by the fact that the adult worm body contains only non-dividing cells,† wrote Guarente and Sinclair in their 2006 Scientific American article. 4 The search was on for sirtuin activating compounds, or STACs. This was a high-stakes search. â€Å"No chemical or drug had ever increased the activity of sirtru ins† said Dr. Dipp, affectionately 2 David Stipp, â€Å"Drink wine and Live Longer,† Fortune, February 12, 2007. 3 Dr. Sinclair obtained a BS with first-class honors at the University of New South Wales, Sydney, and received the Commonwealth Prize for his research. In 1995, he received a Ph. D. in Molecular Genetics and was awarded the Thompson Prize for best thesis work. He worked as a postdoctoral researcher with Dr. Leonard Guarente at M. I. T. being recruited to Harvard Medical School at the age of 29. Dr. Sinclair has received several additional awards including a Helen Hay Whitney Postdoctoral Award, and a Special Fellowship from the Leukemia Society, a Ludwig Scholarship, a Harvard-Armenise Fellowship, an American Association for Aging Research Fellowship, and is currently a New Scholar of the Ellison Medical Foundation. He won the Genzyme Outstanding Achievement in Biomedical Science Award for 2004. http://medapps. med. harvard. edu/agingresearch/pages/faculty. htm, Accessed 1. 4. 07. 4 Leonard Guarente and David Sinclair, â€Å"Can DNA Stop Time: Unlocking the Secrets of Longevity Genes,† Scientific American, March 2006. 3 808-112 Sirtris Pharmaceuticals: Living Large, Longer known within the firm as â€Å"The General†. â€Å"A compound that could activate sirtuins would increase the speed of cellular metabolism. It could have far reaching implications for human healthcare. In 2003, Sinclair discovered that resveratrol, a compound found in red wine, activated sirtuins in yeast cells, a discovery which indicated that in fact it might be possible to develop a drug that could activate the sirtuin enzyme. One way to activate the sirtuin enzyme was to optimize the effects of resveratrol by giving it in highly purified form. Another was to mimic the effects of resveratrol using an entirely new, more potent chemical structure. Sirtris was pursuing both approaches through its SRT501 and new chemical entity drug development projects. When Sinclair’s Nature article was published September 11, 2003, it was hailed by many scientists as a seminal paper, but it also drew criticism from members of the scientific community, including former colleagues from Guarente’s MIT laboratory. The article also drew the attention of Dr. Christoph Westphal, who had recently been promoted to general partner at Polaris Venture Partners, one of the larger Boston-area venture capital funds. Christoph Westphal In his four years at Polaris, Westphal had had several successful investments and stints as founding CEO. Between 2000 and 2004, Westphal co-founded five companies and served as the original CEO at four of them. In all cases, Westphal recruited a CEO to replace him and remained on the board as lead investor once he got the company off the starting blocks. Two went public – Alnylam and Momenta – and had a combined market value of $1. 4 billion in early 2007. Philip Sharp, a Nobel Prize winning biologist and Sirtris advisor, described Westphal’s business and science acumen: Christophs combination of skills is very rare. I havent seen his equivalent in 30 years of working in biotech. 5 In 2002, MIT’s Technology Review recognized Westphal as one of the country’s top 100 Young Innovators under 35. The son of two doctors, Westphal was a former McKinsey consultant and physician, who sped through an MD/Ph. D. program at the Harvard Medical School in less than six years. A polyglot (English, French, German, and Spanish) and accomplished musician (cello), Westpha l was described by several Sirtris board members as having â€Å"extraordinary energy† and a reputation as a â€Å"rock star† in the biotechnology world. He has an unusual combination of abilitiesto understand the science and its commercial potential, and explain it all clearly in an understated way that resonates with investors,† said John Freund, Managing Director and cofounder of Skyline Ventures as well as a Sirtris director at the time of the case. Westphal had a distinctive approach to building biotech companies—his own mode of operation. Westphal’s major successes, Alnylam and Momenta, both went public before many market watchers believed them to be ready for an IPO. In both cases, Westphal teamed with world-renowned authorities (Alnylam with Paul Schimmel, a prominent scientist at the Scripps Institute and biologist Philip Sharp; Momenta with Robert Langer, an MIT Institute Professor and one of the world’s most prolific scientist/entrepreneurs). Westphal described the elements he looked for and the approach he took in starting and building companies: 5 David Stipp, â€Å"Drink wine and Live Longer,† Fortune, February 12, 2007. 4 Sirtris Pharmaceuticals: Living Large, Longer 808-112 You need fantastic science. Second, you need a great story. Third, you need great venture capital support and lots of money. I am a big believer in raising as much money up front as possible. Applying this model and exploiting an ever-growing network among the biotech industry’s prominent players, Westphal had clearly developed a successful approach to launching early stage companies and then passing the CEO’s baton to a different leader. In 2003, Westphal was looking for his next investment opportunity, when he encountered Sinclair’s paper in Nature. Westphal quickly realized that this was a novel and possibly watershed discovery if it could be extended to humans. Westphal phoned Sinclair to discuss the prospects of commercializing his discovery. Launching Sirtris At the time, Sinclair had been thinking of commercializing his work for many years. In 1999, he almost joined his mentor, Guarente, in launching Elixir Pharmaceuticals, a longevity-oriented biotech company. Several years later, as Sinclair finalized the 2003 Nature paper, he began exploring opportunities to form a company of his own. Sinclair described his initial meeting with Westphal, â€Å"He came in and refused to sign a nondisclosure agreement. So, I told him I wouldn’t talk to him. And he said, ‘David, if I walk out of this office, I’m not coming back. So I suggest you tell me as much as you can. ’† I wound up telling him more than I normally would have. It soon became apparent that he’s one of the smartest people I’d ever met. But it took me months to realize that he’s also a nice guy. †6 After their initial meeting, Westphal expressed an interest in starting a company with Sinclair, but could not do so until he found someone to replace him as CEO of Acceleron, one of the companies he had launched while at Polaris. Meanwhile, Sinclair continued discussions with other investors. Westphal re-entered the picture six months later, expressing a readiness to invest and pull the venture together. Sinclair and Harvard (the owner of several pieces of intellectual property that would be licensed by Sirtris) decided to move forward with Westphal as the founding CEO. After an agonizing decision process, Westphal chose to join Sirtris as its full-time CEO. Unlike his other start-ups, his plan this time was to remain with the company, which meant that he would be leaving behind the venture capital life and a high six-figure salary. Westphal explained his decision: Many people thought it was too risky to leave a successful VC career. I was taking a $500,000 paycut and my wife and I had just purchased an expensive house in Brookline close to Fenway Park. At the time, David had no data that showed resveratrol activated sirtuins in mammals or could affect mammalian glucose levels or insulin, although we hoped all that would prove true. My VC friends were telling me that I was not being rational. In some ways they were right, but I was excited about Sirtris in a way I had not yet been at my other companies. Scientific Advisory Board Westphal set out to attract a world-class Scientific Advisory Board (see Exhibit 2 for details on the SAB). Virtually all early-stage biomedical companies create boards of scientific advisors. Among 6 David Stipp, â€Å"Drink wine and Live Longer,† Fortune, February 12, 2007. 5 808-112 Sirtris Pharmaceuticals: Living Large, Longer other roles, SAB members advise the company on matters related to scientific and experimental strategies; they sometimes assist in securing access to intellectual property produced by SAB members; and they serve as portals that keep the company abreast of developments in the broader scientific community. Sirtris’s goal was to collect the brightest scientists in the field of sirtuin research, including those who would generate IP for Sirtris and be the â€Å"eyes and ears† of the company. Sinclair explained the formation of the Sirtris SAB: â€Å"Christoph said, ‘Give me a list of the top 10 people in your field. ’ Within a week or two, we were having conference calls with all of these people. In one case, an academic was going to start a rival company, and Christoph flew out to St. Louis and convinced him to join us instead. One observer described the Sirtris SAB and board of directors in the following terms (see Exhibit 3 for Sirtris Board of Directors): Since combining forces with Sinclair, Westphal has organized what is arguably the most pedigree-rich scientific advisory board in biotech, including MIT’s Sharp; Robert Langer, one of medicine’s most prolific inventors, also of MIT; Harvard gene-cloning pioneer Thomas Maniatis; and Thomas Sa lzmann, formerly executive vice president of Merck’s research arm. The group now numbers 27, among them many of the world’s leading experts on sirtuins. Edward Weston EssayPartnering with a large pharmaceutical company would require out-licensing these new compounds without knowing their full value. If Sirtris waited for new NCE data to arrive, it might be able to arrange a more lucrative deal than what might have been doable in early 2007. Of course, if the NCE data came in and it did not produce the results Sirtris was expecting, the pharma deal terms would be substantially worse, assuming that the pharmaceutical companies remained interested at that point. In-Licensing or Expanding the Scientific Base From the very beginning of the company, Sirtris executives had had an internal debate over how much of the company’s resources to focus on SIRT1 versus alternative sirtuin targets. The biotechnology industry was littered with companies and drug development projects that had stalled in moving from mouse studies and toxicity screens to human trials. Several board members were advocating that the firm diversify its product development platform. There were two main alternatives. One was to investigate the six other human sirtuins. The other was to in-license from another biotechnology firm a compound that had a better known mechanism of operation. The study of sirtuins was still in its infancy, so investigating the clinical possibilities of other sirtuins would require a great deal of basic research, financing and time. (See Exhibit 11 for Sirtris financial data, 2004-2006. ) Even so, the clinical role of the other human sirtuins offered tantalizing commercial options. SIRT3, for instance, was found in mitochondria and was considered a potential drug target, but little was currently known about its functional role. Developing a research platform based on SIRT3 might complement the company’s own drug development efforts in other mitochondrial disorders, including diabetes and MELAS. Several members of the SAB and the board of directors considered the in-licensing option to be an appealing alternative, although others disagreed. It would balance their investment in SIRT1, which was absorbing 90% of the firm’s RD expenditures. Dr. Dipp explained that, after investigating more than one hundred potential compounds to in-license, Sirtris had found a few anti-diabetic compounds that had better characterized effects than sirtuin-activating compounds. It would be what we call â€Å"me-too† drugs. We know how they work, and if we could get them on the market they would get at least a small percentage of market share. It’s something to have in your back pocket. † When the firm launched in 2004, Sinclair and Westphal debated whether to in-license a compound and decided aga inst doing so. â€Å"I was the only person at the company,† said Sinclair, â€Å"who thought that SIRT1 activation was the right bet to make. I told Christoph, ‘dont stop it until you know its wrong. ’ If Im wrong, find out sooner than later, and then in-license something. Westphal offered another view, â€Å"For the first eight months of this company, I was sitting there like a venture guy thinking that resveratrol will not be a great drug. Its a great story, but well have to bring in other stuff to build the company around. † Even though new experimental data seemed to confirm that resveratrol activated SIRT1, and that SIRT1 activation could be clinically important, Sinclair, Westphal, Bohlin and Dipp continued to debate whether to focus the firm’s time, money, and other resources on that one target or divert more 11 808-112 Sirtris Pharmaceuticals: Living Large, Longer of the firm’s resources to additional targets, including non-sirtuins. They still did not have evidence that SIRT1 had the effects in humans that Sinclair believed they would one day see. Conclusion After discussing these three issues for several hours, Sinclair and Westphal decided to summarize their views on the decisions they needed to make. At a general level, they remained convinced that sirtuin-activating drugs, if they could be successfully developed, would have a revolutionary impact on human disease. However, they recognized that Sirtris was still many years from completing development of these drugs, much less manufacturing and selling them. To reach that distant point would require successfully navigating technical and regulatory hurdles that had stymied the majority of other biotechnology companies at similar points in their history. According to a pharmaceutical industry association report, only one in five compounds entering clinical trials gained FDA approval. 11 And, only 30% of approved drugs recovered the average development cost of a new medicine. 2 Given all of the unknowns about what could happen Sinclair and Westphal described several options for addressing the risks they faced: One approach would be to fully â€Å"hedge their bets:† Sirtris could try to complete a pharmaceutical deal, in-license a compound with better known effects, and consider a nutraceuticals business around SRT501. Another approach would be to â€Å"swing for the fences† (or, in a frequently used metaphor in the industry, â€Å"one shot at gold†). This would continue the firm’s focus on a sirtuin-activating drug development platform. If successful, Sirtris could become, as one pharmaceutical executive suggested, â€Å"the Google of biotech. † However, an IPO would be less likely in the interim, since markets often prefer that biotech firms have a validating deal with a large pharmaceutical company. A third approach would be a â€Å"middle of the road† path that incorporated some hedging, such as pursuing an in-licensing deal, but also accepted some risk, e. g. , deferring a potential pharmaceutical deal. Alternatively, Sirtris could try to complete a pharmaceutical deal now, but forego in-licensing and the nutraceuticals project. ******** The company seemed to have arrived at a critical juncture in its development. What approach should Sinclair and Westphal take? And why? 11 PhRMA Pharmaceutical Profile Industry Report, 2007. http://www. phrma. org/files/Profile%202007. pdf, Accessed February 28, 2008. 12 PhRMA Pharmaceutical Profile Industry Report, 2007. http://www. phrma. org/files/Profile%202007 . pdf, Accessed February 28, 2008. 12 Sirtris Pharmaceuticals: Living Large, Longer 808-112 Exhibit 1 1884: 1934 1986 Anti-Aging Science Timeline William Jones MD reports that a fasting spider lives unusually long, 204 days. Longevity in a fasting spider, Science 3: 4, Jan. 4, 1884] Clive McCay and Mary Crowell of Cornell University report delayed aging in rats on limited calorie diets. Roy Walford and Richard Weindruch show limited-calorie diet produces â€Å"youthful† old mice. Leonard Guarente of MIT mimics calorie restriction’s prolonged lifespan effects in yeast cells. David Sinclair of Harvard extends life of yeast cells with resveratrol. Marc Tatar of Brown University and David Sinclair of Harvard report resveratrol extends life of roundworms. Italian researchers are first to report resveratrol prolongs the lifespan of a vertebral animal (cold-water fish). David Sinclair and colleagues demonstrate resveratrol extends life of warm-blood mammal (mice) and ov ercomes deleterious effects of a high-fat diet. JAMA. 2006 Apr 5;295(13):1539-48. Lagouge, M. et al. , Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha. Cell. 2006 Dec 15;127(6):1109-22. Civitarese, A. E. et al. , Calorie Restriction Increases Muscle Mitochondrial Biogenesis in Healthy Humans. PLoS Med. 2007 Mar 6;4(3). Adapted from http://www. longevinex. com/article. asp? story=Time%20Of%20Research%20Involving%20Calorie %20Restriction%20and%20Longevity, accessed February 25, 2008; and Sirtris documents. 2000: 2003 2004 2006: 2006 2006 2006 2007 Source: 13 808-112 Sirtris Pharmaceuticals: Living Large, Longer Exhibit 2 Sirtris Scientific Advisory Board BioPharma Expertise Tom Salzmann, Co-Chair SAB Former EVP Merck Julian Adams President and CSO, Infinity Peter Hutt Former FDA General Counsel Sirtuin Expertise Biochemistry John Denu, Wisconsin Anthony Sauve, Cornell Vern Schramm, AECOM David Sinclair, Co-Chair SAB, HMS Eric Verdin, UCSF Mouse Genetics, Phenotypes Fred Alt, HMS, NAS, HHMI Johan Auwerx, ICB Structural Biology Cynthia Wolberger, JHU, HHMI Links to Disease Ron Kahn, Joslin, NAS Jeff Milbrandt, Washington University Jerrold Olefsky, UCSD Pere Pulgserver, HMS Eric Ravussin, Pennington Institute Li-Huei Tsai, MIT, HHMI Bob Langer MIT, NAS, NAE, IOM, Co-Founder Momenta, AIR Tom Maniatis Harvard, NAS, Co-Founder GI, Acceleron Phil Sharp Co-Founder Biogen and Alnylam, NAS, Nobel Prize Ted Sybertz SVP Genzyme, Schering (Zetia) Eric Gordon Former head of Medicinal Chemistry at BristolMyers, Founder of Vicuron Pharmaceuticals Chris Walsh Harvard, NAS, IOM, Genzyme, Vicuron Source: Company. HHMI = Howard Hughes Medical Institute ICB = Mouse Clinical Institute in Strasburg, France NAS = National Academy of Sciences NAE = National Academy of Engineers AECOM = Albert Einstein College of Medicine 4 Sirtris Pharmaceuticals: Living Large, Longer 808-112 Exhibit 3 Sirtris Board of Directors (as of February 2007) Name Richard Aldrich (F) John Clarke Alan Crane John Freund Stephen Hoffman, Ph. D. , M. D. Wilf Jaeger Stephen Kraus Richard Pops (F) Paul Schimmel, Ph. D. (F) David Sinclair, Ph. D. (F) Christoph Westphal, M. D. , Ph. D. (F) Source: Company. Background Founder, RA Capital. Managing General Partner, Car dinal Partners Momenta Managing Director, Skyline Ventures Managing Director, TVM Capital Three Arch Partners Bessemer Venture Partners Chairman, Alkermes Professor, The Scripps Research Institute Associate Professor, Harvard Medical School CEO and Vice Chair, Sirtris Pharmaceuticals, Inc. F = Founder 15 808-112 Sirtris Pharmaceuticals: Living Large, Longer Exhibit 4 Sirtris Investors and Investment Rounds Round Date Investors Investment Pre-$ Valuation $2. 8 M (A) Aug. 2004 Polaris Venture Partners, Cardinal Partners, Skyline Ventures and TVM $5 M A1 Oct. 2004 Polaris Venture Partners, Cardinal Partners, Skyline Ventures, TVM and The Wellcome Trust $13M $10. 9M B Mar 2005 Three Arch Partners, Cargill Ventures, Novartis Bioventures Fund, Polaris Venture Partners, TVM, Cardinal Partners, Skyline Ventures, and The Wellcome Trust $27 M $32. 5M C Apr 2006 Bessemer Venture Partners, Genzyme Ventures, QVT Fund LP, Alexandria Real Estate Equities, Inc. Polaris Venture Partners, TVM Capital, Cardinal Partners, Skyline Ventures, Three Arch Partners, The Wellcome Trust, Novartis Bioventures Fund, Cargill Ventures, Cycad Group, Hunt Ventures, and Red Abbey $22 M ($22 million in Series C-equity placement, plus $15 million in venture debt financing from Hercules Technology Growth Capital) 95. 4M C1 Feb. 2007 John Henry Trust, Peter Lynch and several investors from previous rounds $35. 9 million $184M Source: Company. 16 Sirtris Pharmaceuticals: Living Large, Longer 808-112 Exhibit 5 Pre-IPO Financing of Comparable Biotechnology Companies Company Anesiva (IPO 2004) Round/Date 2Q2001 Investors InterWest Partners, Alta Partners, J. P. Morgan Partners Investment $13 mi llion 2Q/2002 Bear Stearns Health Innoventures, Alta Partners, HBM BioVentures, J. P. Morgan Partners, InterWest Partners, MIC Capital, China Development Industrial Bank (CDIB Ventures) Bristol Myers Squibb $50 million 4Q/2003 45 million Cytokinetics (IPO 2004) 2Q/1998 Mayfield, Sevin Rosen Funds, Individual Investors $5. 3 million 3Q/1999 International BM Biomedicine Holdings, Vulcan Capital, Mayfield, Sevin Rosen Funds, NMT New Medical Technologies, Duke University, Individual Investors Credit Suisse, Alta Partners, Lombard Odier Darier Hentsch, Mayfield, Sevin Rosen Funds, Vulcan Capital, NMT New Medical Technologies, Duke University, Individual Investors GlaxoSmithKline $20 million 4Q/2000 $50 million 2Q/2001 $14 million Momenta 2Q/2002 Cardinal Partners, Polaris Venture Partners $4. 4 million (IPO 2004) 2Q2003 1Q2004 Atlas Venture, MVM Limited, Polaris Venture Partners, Cardinal Partners Mithra Group, Polaris Venture Partners, Atlas Venture, MVM Limited, Cardinal Partners $19 million $20 million Source: Growthink Research. 17 808-112 Sirtris Pharmaceuticals: Living Large, Longer Exhibit 6 Diabetes Market Data Incidence  of  diabetes  in  the  U. S. Millions 15. 4 14. 7 13. 6 2002 2004 2006 Worldwide  market  for  diabetes/metabolic  drugs  by  class   ($  millions) 2005 2010p Insulins Glitazones DPP? IV  Inhibitors Anti? Obesity GLP? 1  Analogs Sulfonylureas Thyroid  Drugs Other  Oral  Agents $0 $714 $75 $2,875 $2,118 $2,039 $2,099 $1,573 $659 $493 $1,718 $2,026 $5,214 7,831 $16,033 $9,393 †¢ †¢ 90% of the total diabetic population has Type 2 Diabetes Total direct and indirect costs associated with diabetes were over $100 billion in 2002 Source: Company. 18 Sirtris Pharmaceuticals: Living Large, Longer 808-112 Exhibit 7 Proof of Principle for SIRT1 Ac tivators Pre-clinical Therapeutic Nature 2006 Nov 16:444(7117):337-42. Cell. 2006 Dec. 15; 127(6):1109-22. Unpublished PLoS Medicine. 2007 Mar 6:4(3). JAMA. 2006 Apr 5;295(13) 1539-48. Cell. 2006 Dec 15;127(6):1109-22. Human Physiological Human Genetic Source: Company. Exhibit 8 Effects of High Doses of Resveratrol in Mice Two mice fed the same high-calorie diet in a Sirtris-sponsored study: The svelte one on the left received high doses of resveratrol. Source: Company. 19 808-112 Sirtris Pharmaceuticals: Living Large, Longer Exhibit 9 Potential Sirtris Pharma Deal Terms †¢ Five year term. †¢ †¢ †¢ †¢ 19. 9% OR 51% equity stake at a 50% premium to most recent share price. a $20 million upfront for an exclusive option to join Sirtris in developing and marketing compounds from its SIRT1 Activator Program. 5 years of guaranteed R support totaling $100 million. Payments to step up over time. $10 million in year one. A combination of royalties, possibly manufacturing profits, and co-promotion fees that equate to approximately a 50/50 split of profits in the U. S. This is a significant point for Sirtris since the SIRT 1 activator program is a core program, and the one that represents 90% plus of the firm’s value. The pharmaceutical company will lead marketing and country specific development ex-U. S. , Sirtris to receive substantial, double digit royalties on ex-U. S. sales. Roughly $200 million in milestones concurrent with risk reducing progress. Roughly 15% upon successful completion of safety/PK of a SIRT 1 activator NCE in humans; Roughly 25% based on observation of glucose effects in phase 1b of NCE in man; Roughly 30% upon successful completion of a phase 2a efficacy study for an NCE in man; and roughly 30% upon completion of phase 2b studies. †¢ †¢ a: Two different equity stakes were under discussion—19. 9% or 51% of Sirtris’s equity. All other terms would remain the same in both scenarios. Source: Company. 20 808-112 -21- Exhibit 10 Comparison Agreements between Comparable Biotechnology Start-ups and Large Pharmaceutical Companies Company Anesiva is a late-stage biopharmaceutical company that seeks to be the leader in the development and commercialization of novel therapeutic treatments for pain. The Company has four drug candidates in clinical development for multiple potential indications. IPO in 2004 (formerly called Corgentech—this was the name when it went public). Cytokinetics is a biopharmaceutical company dedicated to the discovery, development and commercialization of novel classes of smallmolecule therapeutics, particularly in the field of cytoskeletal pharmacology. IPO in April 2004 Deal Partner Bristol-Myers Squibb Company Agreement Jointly develop and commercialize Corgentechs E2F Decoy (edifoligide sodium), a first-of-its-kind E2F Decoy treatment currently in Phase III development for the prevention of vein graft failure following coronary artery bypass graft (CABG) and peripheral artery (i. e. , leg) bypass graft surgery. Terms Bristol-Myers Squibb will make an initial payment to Corgentech of $45 million comprising cash and an equity investment in Corgentech, with the potential for an additional $205 million in clinical and regulatory milestone payments. BristolMyers Squibb and Corgentech will share development costs in the U. S. and Europe based on a pre-agreed percentage allocation. GSK has committed funding of approximately $50 million over the minimum 5-year research term, including a $14 million upfront cash payment and a $14 million purchase of Cytokinetics preferred stock. In addition, GSK could make milestone payments to Cytokinetics ranging from $30-50 million per target for products directed to each of over 10 mitotic kinesins that will be the subject of collaborative activities. Sandoz has committed $600,000 in an upfront cash payment and has the right to purchase $5-10 million in Momenta equity. RD payments estimated to be $12 million and up to $50 million in contingent payments to accompany development milestones. GlaxoSmithKline A broad strategic collaboration to discover, develop and commercialize novel smallmolecule therapeutics targeting mitotic kinesins for applications in the treatment of cancer and other diseases. Momenta Pharmaceuticals was founded based on proprietary technology developed at MIT that enables high throughput, detailed characterization and engineering of sugars. IPO in June 2004 Sandoz/Novartis A strategic alliance covering joint product development and commercialization in the area of complex pharmaceutical products. The collaboration will apply Momenta’s novel technological capabilities related to complex sugars and the leadership of Sandoz in the generic pharmaceuticals industry to pursue the joint goal of commercializing products. Under the terms of the agreement, Sandoz and Momenta will jointly manage product development and commercialization. Source: Recombinant Capital. NOTE: All deals inked when biotech was still private. 808-112 Sirtris Pharmaceuticals: Living Large, Longer Exhibit 11 Sirtris Financial data 2004-2006 (in thousands, except share and per share amounts) Period from March 28, 2004 (date of inception) through December 31, 2004 Period from March 25, 2004 (date of inception) through December 31, 2006 Year Ended December 31, 2005 2006 Statement of operations data: Revenue Operating expenses: Research and development General and administrative Total operating expenses Loss from perations Interest income Interest expense Net loss Net loss per share—basic and diluted Weighted average number of common shares used in net loss per share— basic and diluted Pro forma net loss per share—basic and diluted Shares used in computing pro forma net loss per share—basic and diluted Source: Company. $ — $ 68 $ — 14,242 4,340 18,582 $ 68 22,494 8,904 31,398 (31,330) 3,635 (878 $(28,573) 1,190 699 1,889 (1,889) 45 à ¢â‚¬â€ $(1,844) $ (0. 93) 7,062 3,865 10,927 (10,859) 1,143 — $(9,716) $ (3. 16) 18,582) 2,447 (878 $(17,013) $ (3. 52) 1,995,468 3,087,716 4,854,646 $ (0. 20) 85,603,228 22 Sirtris Pharmaceuticals: Living Large, Longer 808-112 Appendix Fortune and Wall Street Journal Covers Source: David Stipp, â€Å"Drink wine and Live Longer: The exclusive story of the biotech startup searching for anti-aging miracle drugs,† Fortune, February 12, 2007. 23 808-112 Sirtris Pharmaceuticals: Living Large, Longer Source: David Stipp, â€Å"Researchers seek key to antiaging in calorie cutback,† Wall Street Journal, October 30, 2006. 24