Xbox 360

Microsoft placed kiosks for demonstration in some stores and the error began appearing. On the other hand, at least one Democratic Senator has criticized Bush for not planning to buy enough anti-viral drugs [21]. It was discovered in Wal-Mart stores days before the official console launch. Previously, Rumsfeld has been implicated in a racketeering lawsuit involving the FDA approval of the artificial sweetner aspartame [20]. The Xbox 360 screen of death is an error screen displayed by the Xbox 360 game console. The rise in Gilead's share prices from $35 to $57 per share will have added between $2.5 million to $15.5 million to Rumsfeld's net worth. [41]. Rumsfeld is a former chairman of Gilead, and federal disclosure forms indicate that he owns between $5 million and $25 million in Gilead stock (Schwartz 2005 [19]).

On January 26, 2006, Microsoft released Q2 2006 earning report, stating the Xbox 360 has reached 1.5 million units in 2005, 0.9 million units in North America, 0.5 million units in Europe, and 0.1 million units in Japan. government's endorsement and planned purchase of oseltamivir, noting Secretary of State Donald Rumsfeld's close ties to Gilead Sciences, rightsholder to the Tamiflu patent. Purchased separately, the price of the items would be AU$209.95. Some commentators (e.g., [18]) question the motives of the U.S. To compensate for the Late Xbox 360 release to Australia and New Zealand, Microsoft released a VIP pack priced AU$149.95, containing the items below. Bush's plan included $1.4 billion for government purchases of anti-viral drugs[17]. The Xbox 360 is scheduled to be released in Australia and New Zealand on March 23, 2006, delayed for 3 weeks from the original March 2 launch date. Bush requested Congress to fund $7.1 billion in emergency spending for flu pandemic prepardness (the Senate had already passed an $8.1 billion bill)[16].

In Hong Kong, there are promotions include: free PGR3 faceplate with purchase of selected titles, DOA4 collectibles with purchase of a extra game, and reduced price when purchased with cross-promotional items. president George W. The launch date for Hong Kong and Singapore is March 16, 2006, delayed from original March 2 launch date. In November, 2005, U.S. Promotions include one free limited edition PGR3 faceplate bundled for the initial shipment, and a gamepad-game combo pack containing Kameo and a wireless gamepad. The week before, Thai authorities said they would begin producing oseltamivir by February 2006, claiming that Roche had not patented Tamiflu in Thailand[15]. It will be released in Taiwan on March 2, 2006. On November 9, 2005, Vietnam became the first country to be granted permission by Roche to produce a generic version of oseltamivir[14].

The Xbox 360 is scheduled to be released in South Korea on February 24, 2006. Roche said it would instead send all supplies to China's health ministry[13]. In Mexico retailers such as the Liverpool, CompuDabo, Game Planet, gdGames, Cyberbox, and Camelot Games have started selling the console, games, and accessories. [10][11][12] Sales were suspended in Hong Kong as well, and on November 8, also in China. The Xbox 360 was released in Mexico and Colombia on February 2, 2006. It said that, when distribution resumes in Canada, the remaining available drug will be saved for use in high-risk settings like long-term care facilities and hospitals. Sony has a substantial amount of Japanese third party developers. In late-October 2005, Roche announced that it was suspending shipments to pharmacies in the United States and Canada until the North American seasonal flu outbreak began, to address concerns about private stockpiling and to preserve supplies for seasonal influenza.

Recent surveys in Japan have confirmed that the majority of Japanese 'gamers' are strong supporters of Sony. Also in October, it was announced that Roche was in discussions with four generic drug manufacturers about possibly issuing sublicenses to increase production. On the day of the launch, Capcom unveiled their Xbox 360-exclusive sci-fi game Lost Planet, which features South Korean actor Lee Byung Hun in the lead role. Cipla argues that it can legally sell oseltamivir to India and 49 other less-developed countries, possibly as early as January 2006. On December 17, Rakuten's website announced a special five-day sale starting on December 22 selling 10 Xbox 360s at 24,900 yen.[40]. Most patent laws allow governments to authorize supply from generic companies, subject to remuneration to patent owners to address public health problems, including emergencies, although Roche has annouced its intention to remain the sole supplier of the drug. To entice people into buying the Xbox 360 some retailers are offering discounts on the system if they sign up for a 2 year broadband contract, similar to cell phone deals in the US. In October 2005, the Indian drug company Cipla announced their plan to begin manufacture of generic oseltamivir without license from Roche.

Maruyama is widely credited for attracting support from Japanese game developers. Though significant, the quantities stockpiled would not have been sufficient to protect the entire population of these countries. Microsoft Japan executive Yoshihiro Maruyama stated that he expects sales of Xbox 360 in Japan to hit one million units sometime next year. In response to the epidemic, various governments – including those of the United Kingdom, Canada, United States and Australia – stockpiled quantities of oseltamivir in preparation for a possible pandemic. It should be noted that this number is roughly equal to the number of Xbox units sold in Japan by November of 2005. Oseltamivir, otherwise known as Tamiflu, was widely used during the H5N1 avian influenza epidemic in Southeast Asia in 2005. Namco expects to sell 500,000 copies of Ridge Racer 6 in Japan. Veterinary investigation of its use for canine parvo [8] and canine flu [9]is ongoing, but many shelters and rescue groups have reported great success employing Tamiflu in the early stages of these illnesses.

Initial predictions were highly optimistic as the highest rating launch game reviewed by Famitsu, Namco's Ridge Racer 6, scored 35 out of 40 stars. Tamiflu appears to be active against canine parvovirus, feline panleukopenia, the canine respiratory complex known as "kennel cough," and the emerging disease dubbed "canine flu", an equine virus that began affecting dogs in 2005. Matsui predicts however that the Xbox 360 will likely gain momentum coming into January 2006 when new titles come out which includes Ninety-Nine Nights. In addition, quinic acid, derived from the bark of the cinchona tree of Zaire, is a potential alternative base material for the production of oseltamivir. The 2-day 62,135 sales figure of the Xbox 360 is a little past half of the 123,334 units of the old Xbox that Microsoft sold in the first 3 days in Japan in February 2002. Other potential sources of shikimic acid include the ginko tree. He even added information that over 60% of his readers had planned to buy the much anticipated Tecmo fighting game which is set for a December 29 release. An alternative method for production of the acid involves fermentation of genetically-modified bacteria.

For his part, Famitsu Xbox 360 editor-in-chief Munetatsu Matsui pointed to DOA4's absence as the main factor behind the slow start. Some academic experts and other drug companies are disputing the difficulty of producing shikimic acid by means other than star anise extraction. Others have also attributed this slow start to titles such as Dead or Alive 4 and Enchant Arm missing the launch date while others point to the marketing strategy that focused on selling the Xbox 360 as a fashionable item when customers were looking for an affordable or a high performance gaming console. The northern Vietnamese province of Lang Son has 80 km² of star anise.[7]. Some believe this is mainly due to the other popular and prospective video game handheld consoles like the Game Boy Advance, Nintendo DS, and PlayStation Portable, all of which have sold far more than the Xbox 360. Ninety percent of the harvest is already used by Roche in making Tamiflu. [38][39]. Thirteen grams of star anise make 1.3 grams of shikimic acid, which can be made into 10 Tamiflu capsules.

While other regions such as the United States or Europe enjoyed successful launches, sales in Japan have trailed the other regions, totalling 100,000 by the end of 2005. The shikimic acid is extracted from the seeds in a ten-stage manufacturing process. [37]. Star anise is grown in four provinces in China and harvested between March and May. Three North American titles (Ridge Racer 6, NBA 2K6, and NHL 2K6) were not available for the Europe launch. A shortage of star anise is one of the key reasons why there is a worldwide shortage of Tamiflu (as at 2005). [36]. According to Roche, the major bottleneck in oseltamivir production is the availability of shikimic acid, which cannot be economically synthesized and is only effectively isolated from Chinese star anise, an ancient cooking spice; although most autotrophic organisms produce shikimic acid, the isolation yield is low.

A total of 15 games were available for launch, including critical hits Call of Duty 2, Project Gotham Racing 3 and Perfect Dark Zero. (See Pandemic Fears, below). [34][35]. In early-2005, Roche announced a production shortage. [33] By the end of 2005, Microsoft sold 500,000 consoles in the region. (2004) all appeared within individual children after treatment with oseltamivir - the children did not catch the resistant strains in human-to-human transmission. [32] In turn, some retailers blamed Microsoft for failing to provide enough consoles in the Christmas period. It is worth noting that the oseltamivir-resistant strains detected by Kiso et al.

[31] The shortages led to some consumers criticising retailers, and others attacking Microsoft itself for failing to fill demand. Second, the development of a robust, resistant virus strain appears to be less likely (Ward et al., 2005). [30] As in North America, thousands of Xbox 360 appeared on auction websites like eBay, selling for more than twice their retail price. First, these drugs work on a broader spectrum of influenza strains. Microsoft confirmed that 300,000 units were available for the European launch. The lack of variation in neuraminidase gives two advantages to oseltamivir and zanamivir, the drugs that target that enzyme. [27], and Microsoft has revised their initial 90 day estimate down to 2.5 million units, though their 6 month sales estimate remains unchanged at 4.5 to 5.5 million consoles.[28][29]. This means that there are relatively few variations, and there is also evidence that variations that do occur tend to be less "fit." Thus, mutations that convey resistance to oseltamivir may also tend to cripple the virus by giving it an otherwise less-functional enzyme.

Analysts believe Microsoft will not meet the original worldwide target of 2.75-3 million units sold in the first 90 days after launch. The genetic sequence for the neuraminidase enzyme is highly conserved across virus strains. [25][26]. Kiso et al. (2004) suggest that "a higher prevalence of resistant viruses should be expected" during a pandemic. By the end of 2005, Microsoft sold roughly 900,000 units. Resistance is of concern in the scenario of an influenza pandemic, since resistance is more likely to develop due to the potentially longer duration of infection by novel viruses. [24] In Canada, all 32,100 units available for launch were sold. Moscona (2005) gives a good overview of the resistance issue, and says that personal stockpiles of Tamiflu could lead to under-dosage and thus the emergence of resistant strains of H5N1.

According to the NDP Group, North American sales totaled 326,000 units in November. They also note that the recommended dosage of oseltamivir does not always completely suppress viral replication, a situation that could favor the emergence of resistant strains. As of January 26, 2006 at 4:59 EST, major online retailers are sold-out of both Xbox 360 packages (including Amazon.com, circuitcity.com and buy.com). They suggest that the emergence of a resistant strain may be associated with a patient's clinical deterioration. It was reported [23] that 40,000 units appeared on eBay during the initial month of release, which would mean that 10% of the total supply was resold. (2005) describe resistance development in two more Vietnamese patients suffering from H5N1, and compare their cases with six others. eBay in particular was a popular location for such offers with thousands of consoles going up for auction, some selling for many times the original retail price. de Jong et al.

The high demand for the Xbox 360 led to some owners almost immediately re-selling their console for vastly inflated prices. She was being treated with oseltamivir at time of detection (Le et al., 2005; World Health Organization, 2005). Microsoft has stated that they will look into the reports and have offered assistance reachable by phone. High-level resistance has been detected in one girl suffering from H5N1 avian influenza in Vietnam. Microsoft claims that these problems are to be expected on a large scale release for a console and the number of reports versus the number of consoles released was very minimal. Third, the dosage regimen in Japan is different from that of other nations, and some children may have been given a suboptimal dosage of oseltamivir. [22] The manual contains warnings about not placing the Xbox 360 on soft surfaces or in enclosed spaces to avoid heating problems. Second, Kiso et al. (2004) claim to have used more rigorous detection techniques than previous studies.

Some reported the Xbox 360 crashing with errors, some reported the hard drive does not respond in certain situations while others report error messages during various games or unusually fast overheating. First, children typically have a longer infection period, giving a longer time for resistance to develop. Immediately after the launch, reports about the new machine's technical glitches started coming out. Several explanations were proposed by the authors of the studies for the higher-than-expected resistance rate detected. [21]. This rate was similar to another study where resistant isolates of H1N1 influenza virus were found in 16.3% of another cohort of Japanese children (Ward et al., 2005). Peter Moore, Microsoft corporate vice president, predicts that shipments will reach 10 million units worldwide by the end of 2006. Mutant H3N2 influenza A virus isolates resistant to oseltamivir were found in 18% of a group of 50 Japanese children treated with oseltamivir (Kiso et al., 2004).

This allowed them to launch several months earlier than would otherwise be possible, but also led to shortages. Mutations conferring resistance are single amino acid residue substitutions in the neuraminidase enzyme (Ward et al., 2005). They did not, however, build up a sufficient supply of consoles to satisfy the entire demand at launch. The resistance rate reported during clinical trials up to July 2004 was 0.33% in adults, 4.0% in children, and 1.26% overall. they did not withhold produced consoles). As with other antivirals, resistance to the agent was expected with widespread use of oseltamivir, though the emergence of resistant viruses was expected to be less frequent than with amantadine or rimantadine. Evidence indicates that Microsoft launched with all consoles available at the time, and operating at maximum production capability (i.e. Roche has other routes to Tamiflu that do not involve the use of (−)-shikimic acid as a chiral pool starting material, such as a Diels-Alder route involving furan and ethyl acrylate or an isophthalic acid route, which involves catalytic hydrogenation and enzymatic desymmetrization.

Prelaunch reports assume that Microsoft intentionally restricted supply [18], although there is no evidence to support this and Microsoft has said they are releasing all units into supply chains as quickly as possible [19] [20]. It is noted that the synthesis avoids the use of potentially explosive azide reagents and intermediates; however, the synthesis actually used by Roche uses azides. contest that offered participants a chance to win one of three hundred and sixty Xbox 360 console bundles six days before the official launch.[17]. The final product is obtained in high purity (99.7%) and an overall yield of 17-22% from (−)-shikimic acid. The campaign was later revealed to be a U.S. Finally, deallylation as above, yielded the freebase of oseltamivir, which was converted to the desired oseltamivir phosphate by treatment with phosphoric acid. [16] This website hosted a number of images that appeared to perpetuate obscure conspiracy theories, but sometimes contained obtuse references to Xbox 360. Selective acylation with acetic anhydride (under buffered conditions, the 5-amino group is protonated owing to a considerable difference in pK_a, 4.2 vs 7.9, preventing acetylation) yields the desired N-acetylated product in crystalline form upon extractive workup.

On October 13, 2005, members of the TeamXbox forums were directed to the Hex168.com website through mysterious messages posted by someone called "Lutz". Acidic hydrolysis then removed the imine. October 2005 saw the launch of "Hex168", another viral marketing campaign commissioned by Microsoft and executed by the Marden-Kane advertising agency. With the librated methanesulfonic acid, the aziridine opens cleanly to yield a diamine that immediately undergoes a second transimination. Design for the website employs flash animation of a Bonsai tree and bland elevator music to create a serene environment that is punctuated by visually intense psychedelic episodes involving the host rabbits. Mesylation, followed by removal of the solid byproduct triethylamine hydrochloride, results in an intermediate that was poised to undergo aziridination upon transimination with another equivalent of allylamine. New contests include a Halo 2 tournament and a competition to design a "Gamertile" (an avatar icon). The aminoalcohol was converted directly to the corresponding allyl-diamine in an interesting cascade sequence that commences with the unselective imination of benzaldehyde with azeotropic water removal in methyl tert-butyl ether.

The initial contest was a raffle that required participants to answer three trivia questions regarding the Xbox 360 for a chance to attend a promotional pre-launch event. Reduction on palladium, promoted by ethanolamine, followed by acidic workup yielded the deprotected 1,2-aminoalcohol. Unveiled on September 27, 2005 the website, hosted by talking rabbits Boss and Didier offers visitors an opportunity to enter in various contests. The water-immiscible solvents methyl tert-butyl ether and acetonitrile are used to simplify the workup procedure, which involved stirring with 1 M aqueous ammonium sulfate. OrigenXbox360.com was the next viral marketing campaign from Microsoft. Using the inexpensive Lewis acid magnesium bromide diethyl etherate (commonly prepared fresh by the addition of magnesium turnings to 1,2-dibromoethane in benzene:diethyl ether), the epoxide is opened with allyl amine to yield the corresponding 1,2-amino alcohol. Allard. The corresponding epoxide is formed under basic conditions with potassium bicarbonate.

On May 12 the ARG section of OurColony closed, visitors were instead greeted with a promotional video hosted by J. Reductive opening of the ketal under modified Hunter conditions (JOC 1993, 58, 6756) in dichloromethane yields an inseparable mixture of isomeric mesylates. Throughout March and April OurColony.net offered challenges to its community, rewarding solutions with cropped pictures of the console and game screenshots. The 3,4-pentylidene acetal mesylate is prepared in three steps: esterification with ethanol and thionyl chloride; ketalization with para-toluenesulfonic acid and 3-pentanone; and mesylation with triethylamine and methanesulfonyl chloride. The promotional campaign for Xbox 360 began on March 14, 2005 with the opening of an alternate reality game called OurColony. The synthesis commences from naturally available (−)-shikimic acid. EB Games locations received the Xbox 360 kiosks in their stores just over a week prior to its release. The reported azide-free Roche synthesis of tamiflu is summarized graphically below:.

The system, along with some playable games, were shown off at E3 2005. On November 18, 2005, a previously-scheduled Advisory Committee to the United States Food and Drug Administration (FDA) met to reconsider the pediatric safety of Tamiflu; a six-page report was issued: Pediatric Safety Update for Tamiflu. In the article he says "It's perfect...The day Sony launches [the new PlayStation], and they walk right into Halo 3." [13] Read more at wikiquote. Microsoft executive Robbie Bach later clarified this statement, saying "Philosophically the point Bill was trying to make is that we're not just going to ship and not have great stuff coming up."[14] Gates himself later clarified that "Halo 3 will ship when Bungie is ready." [15]. Roche points out that 32 million doses have been prescribed worldwide, most of them in Japan, and emphasizes the drug's safety. The Xbox 360 was also featured on the cover of Time magazine's May 23, 2005 issue with Microsoft chairman Bill Gates holding up one of the units. The two deaths were reported to the Japanese health ministry by Chugai Pharmaceutical Co., a corporation half-owned by Roche, which distributes Tamiflu in Japan (Japan Times November 13, 2005; Reuters Nov 14, 2005). The official unveiling of the system occurred on Thursday, May 12, 2005 on MTV in a program called MTV Presents: The Next Generation Xbox Revealed hosted by actor Elijah Wood with a musical performance by the band The Killers. A third teen reportedly attempted to jump from the window of a building.

See Xbox Live Arcade, Xbox Live Marketplace, and Microsoft Points. In February 2005, a 14-year-old male died after falling nine stories from his condominium building. Points can be purchased directly through Live or via game cards sold at retails shops such as Target. In February 2004, a 17-year-old male jumped in front of a truck and died after taking one capsule of Tamiflu. While game demos and trailers are free, full versions of games must be purchased using a system called Microsoft Points. According to Japan's Pharmaceuticals and Medical Devices Agency, there were 64 cases of psychological disorders linked to the drug between fiscal years 2000 and 2004. By far one of the most interesting features of the Xbox 360 Live is the capability to download arcade-style games through Xbox Live Arcade, as well as game demos and other content through Xbox Live Marketplace. In May 2004, the safety division of Japan's health ministry ordered changes to the literature accompanying oseltamivir to add neurological and psychological disorders as possible side effects, including: impaired consciousness, abnormal behavior, and hallucinations.

It offers the following selections:. The number of adverse reaction reports may be a clue, but these number are not reported by Roche in this document. The Xbox Game Guide is a tabbed user interface that can be accessed instantly by pressing the Guide Button on any Xbox 360 controller. However, given that forms are voluntary, it may be difficult to determine prevalency rates or whether an actual causal relation exists. An Xbox Live Gold account costs $49.99 USD, £39.99 Pounds Sterling, €59.99 per year (or, in the UK, a 3-month Gold membership is available for £11.99). Postmarketing studies are advantageous because the drug is effectively "tested" on a larger population, and previously missed adverse reactions may be discovered. Then when the user goes to add a Xbox Live enabled profile to their console, the user just needs to provide the console with their passport account information. According to Roche, in the postmarketing period, voluntary reports have possibly linked oseltamivir to the following other adverse reactions:.

To transition an Xbox Live account to the new system the user needs to link a Microsoft Passport account to their gamer tag on Xbox.com. Other adverse reactions were not reported by Tamiflu-treated patients at a markedly higher rate than those treated with placebo. Microsoft has allowed for previous Xbox Live subscribers to maintain their profile information, buddy lists, and games history when they make the transition to Xbox Live Gold. In the clinical trials performed by Roche (comparing roughly 2,700 individuals given Tamiflu with 2,650 given placebo), nausea and vomiting were the most frequent adverse reactions reported. However, video conferencing was not available when the console was first released. The following information (but not its interpretation) comes from Roche's "Complete Product Information" publication for Tamiflu (intended for the United States). Xbox Live Gold has the same features as Silver plus online game playing capabilities and video conferencing. 2002)[4], but was publicized only in October 2005 by a doctor who had reviewed the data (Butler 2005)[5].

Microsoft has also announced there will be trial weekends for Silver members to access the full features of Gold service temporarily. The evidence for this interaction comes from a 2002 study by Roche (Hill et al. Silver members are not allowed to play any games online. Probenecid was used in similar fashion during World War II to extend limited supplies of penicillin. Xbox Live Silver is free of charge and allows users to create a profile, join on message boards, access to Microsoft's Xbox Live Arcade, and talk to other members. 500 mg of probenecid given every six hours doubles oseltamivir's maximum blood concentration and also doubles the time that oseltamivir stays in the blood, multiplying a patient's overall exposure to the drug 2.5-fold. With the launch of the Xbox 360, Microsoft's online gaming service, Xbox Live went through a major upgrade adding a basic non-subscription service (Silver) to its already established premium subscription-based service (Gold). Probenecid reduces excretion of oseltamivir's active metabolite.

Microsoft has changed the content of several Xbox games when running under the 360's emulator, such as when they blocked the Halo 2 trailers from running off of later copies of Halo: Combat Evolved discs, presumably because the advertisements promoted a very different game than what ended up being released. It has been suggested that co-administration of oseltamivir with another drug called probenecid could dramatically extend the world's limited supply of oseltamivir. [12]. 2005). Microsoft states that they will be adding more emulation profiles as they become available, with the intended goal of making the entire Xbox library playable on the Xbox 360. (de Jong et al. As of January 10, 2006, the Japanese Xbox site shows only 30 [11]. Besides allowing the infection to proceed, such incomplete suppression provides opportunities for drug resistance to develop.

list includes over 200 games, fewer games are listed as backward compatible in the European markets. [A]t least in some patients with influenza A (H5N1) virus infection, treatment with the recommended dose of oseltamivir incompletely suppresses viral replication. Although the U.S. Doctors in Vietnam concur, noting that. market was released on November 11, 2005 and is maintained at Xbox.com. Peter Hobby (of the World Health Organization) has suggested that Vietnam should investigate and test a higher dosage and longer treatment with Tamiflu for patients with avian influenza[2][3]. The list of backward-compatible games for the U.S. The above treatment regimes are based upon studies of normal human influenza.

[10]. According to prescription information by Roche for the United States[1], Tamiflu usage is indicated for both the treatment and prophylaxis of influenza at the following dosages. Updated emulation profiles can be obtained through Xbox Live, by burning a CD with content downloaded from Xbox.com, or by ordering an update disc from Microsoft at a small charge for shipping. Tamiflu is available from Roche in 75mg capsules and as a powder for aqueous suspension of 12 mg/mL. Hard drives purchased separately or as part of the console package will include a certain number of "emulation profiles" for games, including Halo and Halo 2. . A hard drive is required to enable backward compatibility. Production capacity is limited, and governments are stockpiling the drug.

Software emulation is far from perfect, as significant drops in framerate are observable in some titles.[9]. With increasing fears about the potential for a new influenza pandemic, oseltamivir has received substantial media attention. Some games have slightly improved draw distance, possibly due to the system's greater memory bandwidth. Oseltamivir was developed by Gilead Sciences and is currently marketed by Hoffmann-La Roche (Roche) under the trade name Tamiflu®. Games have minor graphical enhancements due to being rendered in 720p resolutions with Anti-Aliasing enabled. Oseltamivir is a prodrug (usually administered as phosphate); it is hydrolysed hepatically to the active metabolite, the free carboxylate of oseltamivir (GS4071). The Xbox 360 achieves backward compatibility through software emulation of the original Xbox hardware. Oseltamivir was the first orally active neuraminidase inhibitor commercially developed.

The Playstation 3 also has impressive procedural synthesis capabilities, but the technical implementation differs significantly. Like zanamivir, oseltamivir is a neuraminidase inhibitor, acting as a transition-state analogue inhibitor of influenza neuraminidase and thereby preventing new viruses from emerging from infected cells. Other interesting examples of procedural synthesis are shown in various demoscene demos. Oseltamivir (pronounced ah sell TAH mih veer) is an antiviral drug used in the treatment and prophylaxis of both Influenzavirus A and Influenzavirus B. Procedural synthesis is also found outside of the Xbox 360 in the advanced freeware FPS game .kkrieger, where such techniques have reduced the size of the visually stunning game to a mere 96 kilobytes. Chimia 2004, 58, 621. The downside to this approach is that when part of the L2 cache is locked, there is even less data immediately available to keep the 3 symmetric cores in the Xenon CPU running at full efficiency (1 MB of shared L2 is already a rather small amount of cache for 3 symmetric cores to share, especially considering that the Xenon CPU does not support out-of-order execution to more efficiently use available clock cycles). Synthesis of Tamiflu.

A newer approach to generating content is utilised for Xbox 360 titles, a method referred to by Microsoft as procedural synthesis. WHO inter-country-consultation: influenza A/H5N1 in humans in Asia: Manila, Philippines, 6-7 May 2005. As complexity in each rises, the demand for storage rises as well. World Health Organization. In traditional games, all content is statically stored and generally immutable; that is, textures, meshes, and other game content is stored on a storage medium. PMID 15709056. For the Xbox 360, Microsoft has drawn on recent research in computer graphics to enable a new method for game programming. J Antimicrob Chemother 2005;55(Suppl 1): i5-i21.

For example, John Carmack stated at QuakeCon 2005 that the Xbox 360 had "the best development environment" he has seen for a console. Oseltamivir (Tamiflu) and its potential for use in the event of an influenza pandemic. To date, some developers have endorsed XNA Studio. Ward P, Small I, Smith J, Suter P, Dutkowski R. Microsoft believes that this will give developers more time to generate unique content and reduce time running the content process. New England Journal of Medicine 2005;353(25):2633-2636. XNA Studio will allow team members to collaborate using familiar techniques and tools, even when elements of the team are distributed geographically, an increasing trend in game development. Oseltamivir Resistance - Disabling Our Influenza Defenses [Perspective].

These tools are designed to work together to automate common development tasks and present interfaces tailored to the different functions within the team. Moscona, Anne. XNA Studio will provide versions of key production tools such as asset management, defect tracking, project automation and work lists. Nature 2005;437(7062):1108. Based on Microsoft's Visual Studio 2005 Team System, the XNA Studio is the Visual Studio for game development; an integrated, team-based development environment tailored for game production. Avian flu: Isolation of drug-resistant H5N1 virus. XNA Studio will enable collaboration between content creators, programmers, management and QA staff to speed the game production process. Le Q M, Kiso M, Someya K, Sakai Y T, Nguyen T H, Nguyen K H L, Pham N D, Ngyen H H, Yamada S, Muramoto Y, Horimoto T, Takada A, Goto H, Suzuki T, Suzuki Y, Kawaoka Y.

XNA Studio covers three areas: Content Creation, Production Processes and Game Technologies. PMID 15337401. The Xbox 360 game development will be centered around the XNA Studio game development platform. Lancet 2004;364(9436):759-65. In March 2004, Microsoft announced a new game development software strategy dubbed "XNA", which Microsoft claims would enable game studios to cut development times by up to a third if developing across multiple Microsoft platforms, by means of tools created with the increasing difficulty of programming for a machine with three processor cores in mind. Resistant influenza A viruses in children treated with oseltamivir: descriptive study. During early development the Xbox 360 was referred to as "Xenon", "Xbox 2", and "Xbox Next". Kiso M, Mitamura K, Sakai-Tagawa Y, Shiraishi K, Kawakami C, Kimura K, et al.

[7]. (Online at: http://dmd.aspetjournals.org/cgi/content/abstract/30/1/13). By using a program "mceDivX360" on the PC, the Xbox 360 is able to receive streamed films which are converted to WMV format from DivX by Windows Media Encoder. Drug Metabolism and Disposition 2002;30(1):13-19. The Xbox 360 is able to stream movies from a PC running Windows XP Media Center Edition, although it is unable to stream movies in DivX format. The anti-influenza drug oseltamivir exhibits low potential to induce pharmacokinetic drug interactions via renal secretion--correlation of in vivo and in vitro studies. Windows Media Connect allows users to stream their favorite music collection through the Xbox 360 Dashboard, and allows users to play their music via the Xbox 360 Guide in place of the game's original soundtrack. Hill G, Cihlar T, Oo C, Ho E S, Prior K, Wiltshire H, Barrett J, Liu B, Ward P.

After installation the computer and the and Xbox 360 will automatically detect one other. (Online at http://content.nejm.org/cgi/content/full/353/25/2667#F1). To connect the Xbox 360 to a computer the user will need to download Windows Media Connect. New England Journal of Medicine 2005;353(25):2667-2672. The Xbox 360 has the ability to connect to Windows XP based computers over a home network to stream music and pictures right to a TV. Oseltamivir Resistance during Treatment of Influenza A (H5N1) Infection. The main dashboard is divided into 4 main sections:. Malik; Hien, Tran Tinh; and Farrar, Jeremy.

From there, the full Dashboard can be run, exiting the current game. de Jong, Menno D.; Thanh, Tran Tan; Khanh, Truong Huu; Hien, Vo Minh; Smith, Gavin J.D.; Chau, Nguyen Vinh; Cam, Bach Van; Qui, Phan Tu; Ha, Do Quang; Guan, Yi; Peiris, J.S. The Dashboard can also be accessed via the Xbox Guide button on the controller at any time to open a player specific blade. (Accessed on November 2, 2005, at http://www.nature.com/nature/journal/v438/n7064/full/438006a.html). The Dashboard will launch automaticially at boot if no game disc is inserted into the console. Nature 2005;438(7064):6. The Dashboard is the main interface to the Xbox 360, governed by a series of "blades" to subdivide categories. Wartime tactic doubles power of scarce bird-flu drug [News article].

Due to the limited space of standard DVDs, some games made for the system may span multiple discs, although procedural generation of textures and models (as seen in the PC game .kkrieger) may reduce the need for multiple discs. Butler, D. Xbox 360 games are set to the standard 7.95GB of storage available on a dual-layer DVD. The New York Times (Accessed on November 5, 2005 at http://www.nytimes.com/2005/11/05/business/05tamiflu.html). Bill Gates has confirmed during his keynote speech at CES 2006 that an external HD-DVD drive will be released for the 360 this year.[5] However, Peter Moore has stated that if HD-DVD loses the format war, Microsoft may release an external Blu-Ray drive.[6]. Is Bird Flu Drug Really So Vexing? Debating the Difficulty of Tamiflu [News article]. [4]. Pollack, Andrew.

It has been confirmed by Yoshihiro Maruyama, Japan's chief of Xbox operations, that Microsoft will never release games for Xbox 360 in a format other than DVD. Fortune (Accessed on Nov 28, 2005 at http://money.cnn.com/2005/10/31/news/newsmakers/fortune_rumsfeld/?cnn=yes). The other supported formats are: CD-DA, CD-ROM, CD-R/RW, WMACD, MP3CD, and JPEG Photo CD. Rumsfeld's growing stake in Tamiflu: Defense Secretary, ex-chairman of flu treatment rights holder, sees portfolio value growing. A 12X DVD-ROM SATA drive, capable of reading DVD+R/RW discs and DVD-R/RW, is part of the console, with game titles shipping on single or dual-layer DVDs. Oct 31, 2005. The system bandwidth comprises:. Schwartz, Nelson .

The graphics processing unit (GPU) is a custom ATI R500-based "Xenos". Metabolic: Aggravation of diabetes. ^[3]. Neurologic: Seizure, confusion. The central processing unit (CPU), named Xenon (Microsoft) or Waternoose (IBM) is a custom IBM triple-core PowerPC-based design. Cardiac: Arrhythmia. Specifications are also available at the official Xbox website. Digestive: Hepatitis, liver function tests abnormal.

The price of these custom designs are around $20 with more to be released by third party manufacturers. General: Rash, swelling of face or tongue, toxic epidermal necrolysis. Microsoft has also distributed two promotional faceplates, one for those present at the E3 2005 unveiling and one for VIP X05 attendees. Safety and efficacy for prophylaxis has not been established for patients under 13 years old. The default faceplate (Xbox 360's Chrome or Core System's Chill) can be replaced with a range of custom designs, each to be sold separately. Standard dosage is 75 mg once daily for patients aged 13 and older, which has been shown to be safe and effective for up to six weeks. According to J Allard, the chief of Microsoft's Xbox division, Microsoft may sell larger capacity detachable hard drives for the Xbox 360 in the future, and territories outside of North America may have a differently sized hard drive in the retail unit. Tamiflu is indicated for prophylaxis of influenza either during a community outbreak or following close contact with an infected individual.

This drive will not be included in the Core System bundle at launch, and also will not be sold separately in Japan. Dosage for children is by weight. This content will be included on both the bundled hard drive and the stand alone product. For influenza treatment, the standard dosage for patients 13 years and older is 75 mg twice daily for five days. The individual drives will come pre-loaded with a promotional video about the making of the Xbox 360, the "XBOX 360 Custom Mix" (A collection of music), additional Dashboard skins, songs, additional Xbox Live Gamertag images, and Hexic HD, an Xbox Live Arcade game from Tetris creator Alexey Pajitnov. Tamiflu is indicated for the treatment of influenza in patients 1 year and older who have had symptoms for no more than two days. A hard drive is also required for the user to be able to play backward compatible Xbox games.

Only 13 GB of this hard drive are available to the user; the rest is reserved for the system and games. A detachable SATA 20 GB hard drive is used for the storage of games, music, downloaded trailers, levels, demos, player preferences, and community-created content from Xbox Live Marketplace; it may also be used to transfer such content between Xbox 360 units. This port replaces the two proprietary USB connectors on the front of the Xbox controller. The rear of the controller includes a port where the player can connect a headset.

The black and white buttons have been redesigned as shoulder buttons, now referred to as bumper buttons, located above the left and right triggers. The ring of light lights up the quadrant (on the controller as well as the console) that represents the player number assigned to that controller (starting with the top left quadrant as player one, and proceeding clockwise to player 4 in the bottom left). Pressing the Xbox guide button will bring the Xbox 360 out of sleep mode, turn the console on or off, and bring up the "Xbox Guide" for access to digital movies, music and games libraries. The Xbox 360 controller adds an Xbox guide button, which has the appearance of the Xbox 360 emblem and is surrounded by a ring of green LEDs.

The controller for the Xbox 360 is a similar version of the Type-S gamepad for the original Xbox. The wireless controller has a battery life of up to 25 hours on the NiMH rechargeable battery pack (optional and recommended) and a recommended range of up to 30 feet (9.14 m). The controllers have two digital Touch-sensitive trigger buttons.The rest of the buttons are not Touch-sensitive. The wired controller has a nine foot (2.74 m) long cord with a break-away feature.

Since the controller has a USB cable, it is also usable in Windows PCs. Alternately it can support two wired controllers through the use of its USB ports at the front, the USB port on the back will support a third controller. The Xbox 360 has the ability to support up to four wireless controllers.
.

This discrepancy is partially accounted for by the time needed to localize the games. Japanese customers, however, only had six titles to choose from by the time the Xbox 360 was released on December 10, 2005. The European countries had fifteen titles available for the launch date of December 2, 2005. Eighteen launch titles were available for customers in the United States, Canada and Puerto Rico on November 22, 2005.

For full details see Console Launch. Without it the Xbox 360 numbers sold were less than originally anticipated. The main reason for this may have been the delaying of Dead Or Alive 4 which remains an extremely popular Xbox 360 Japanese game. In Japan, it was received far less enthusiastically, despite the low price and bonus features.

Many stores sold out on the first day, and as of mid-January consumers had to hunt across many stores to find one in stock. The Xbox 360 has been released in North America, Puerto Rico, Europe and Japan. They have also stated that they may release a similar Blu-ray attachment, depending on which format (HD-DVD or Blu-ray) becomes standard, though there is currently no plan except the support for HD-DVD. Microsoft plans to release an external HD-DVD attachment to play high-definition movies.

Xbox 360 is compatible with DVD movies, but not HD-DVD nor Blu-Ray. Microsoft hopes to avoid such a predicament with its new console, the company is predicting that a greater market share and falling hardware costs will make the Xbox 360 a profitable item. Microsoft's home entertainment division posted a loss through nearly every quarter of the console's lifecycle as a result. Because of these chips and the added expense of a hard drive component, Microsoft was never able to reduce the cost of manufacturing an Xbox below the break-even point.

Both of these were very similar to "off the shelf" PC hardware and were therefore sold to Microsoft at inflated market prices. This flexibility stands in contrast to the situation faced by the original Xbox, which contained a processor from Intel (a slightly modified Pentium III) and a GPU from NVidia (a modified GeForce 3). Also, since Microsoft owns the patents or licenses thereunder for all custom hardware used in the Xbox 360, they can easily switch to new fabrication processes or change suppliers in the future in order to reduce manufacturing costs. The strategy of selling a console at a loss or near-loss is common in the console games industry, as console makers can usually expect to make up the investment with revenue from game licensing.

BusinessWeek magazine compiled a report which estimates that the total cost of all of the components in the "premium" bundle is $525 USD, aside from additional manufacturing costs, meaning that Microsoft is losing at least $126 on every Xbox 360 system sold in the US, and at least as much in Japan. However because of the existence of a Core System edition, many games do not require a hard drive. Microsoft's decision has also allowed Japanese developers to fully utilize the hard drive to optimize game performance, since it is part of the default system configuration in their market. Japanese pricing of the console has drawn some criticism, as customers there will be able to purchase the Xbox 360 full package, albeit one region-coded for Japan, for a lower price than in other countries.

The Xbox 360 Premium Edition is being sold in America for $399.99. The Core System is not available in Japan, instead Microsoft offers a package identical to the Xbox 360 SKU for ¥37,900 ($323.90 as of 21 December 05 8:09 UTC, [1]). In United Kingdom and Europe, the console is available in two versions: an Xbox 360 SKU, frequently referred to as the "Xbox 360 Premium Package"; and an Xbox 360 Core System SKU. Microsoft's current retail strategy involves two different configurations of the Xbox 360 in most countries.

. Australia and New Zealand, after being delayed, have been set-back from March 2 to March 23. It will be released February 24 in South Korea, March 16, 2006 in Hong Kong, Singapore, and Taiwan (Delayed from original March 2 launch date). The Xbox 360 was released on November 22, 2005 in United States, Canada, and Puerto Rico, December 2 in Europe, December 10 in Japan, February 2, 2006 in Mexico and Colombia.

It is equipped with 512 MB of RAM and uses the DVD-ROM storage medium for Xbox 360 game software. The console hardware is based on a custom IBM PowerPC-based "Xenon" central processing unit (CPU) and a custom ATI R500-based "Xenos" graphics processing unit (GPU). The Xbox 360 configuration, often referred to as the "Premium Edition", includes a hard drive (required for backwards compatibility with original Xbox games), a wireless controller, a headset, an Ethernet cable, an Xbox Live silver subscription, and a component HD AV cable (which can also be used on non-HD TVs). In all countries except Japan the console is sold in two different configurations: the "Xbox 360" and the "Xbox 360 Core System".

The Xbox 360 will compete amongst the upcoming generation of consoles, including the Sony PlayStation 3 and Nintendo Revolution, and was officially unveiled on MTV on May 12, 2005, a week before the E3 trade show. The Xbox 360 is Microsoft's second video game console, the successor to their original Xbox. Membership to the Xbox 360 VIP website. One Xbox 360 Preview DVD.

One Wireless Controller. Perfect Dark Zero. Xbox 360 Faceplate. Friends Lists.

Custom Playlists. Favorites List. Marketplace. Xbox Live.

Initial Setup - Runs the system setup that executes the first time the Xbox 360 is used. Computers - Manage connections to other computers over network. Network Settings - Create and manage internet connections, set up wireless connections. Memory - Manage things on the harddrive such as game saves, profiles, and downloaded content.

Family Settings - Toggle parental controls, adjust profile levels. Console Settings - Edit Xbox 360 settings such as display, audio, and language. Media Center - Activate Media Center extender. Video - Watch videos stored on the HD.

Pictures - View pictures stored on a camera, a computer or other portable devices. Music - Listen to music from the hard drive, computer or other USB-connected devices. Trailers - Watch downloaded movie/game trailers. Demos - Play downloaded game demos.

Xbox Live Arcade - Allows the user to play games they have downloaded from the Xbox Live Marketplace. Played Games - Displays a list of all the games the user has played. Achievements - Allows the user to view all of their unlocked achievements from games they have played. Xbox Live Marketplace - Download a wide variety of content such as avatars, trailers, even game demos.

Friends - Displays the user's Xbox Live friend list. Messages - View messages, friend requests or game invites sent by other Xbox Live members. Connect to Xbox Live - If offline, allows the user to connect to Xbox Live. There are several ways to utilize the custom soundtrack option: by ripping music from audio CD's, by streaming music directly from a PC, plugging in a USB Flash Drive, or by plugging in a USB-capable portable music player.

Microsoft claims all games will support custom music. 3 USB 2.0 ports. Some games will optionally support native 1080i and 480p video resolutions as well. The GPU can downsample 720p to lower display resolutions (including 480i SDTV and 480p) and dynamically crop or scale 16:9 to fit 4:3 screens.

All games must support a 16:9 aspect ratio, and a minimum of 720p HD resolution with 2x full-scene anti-aliasing enabled. DVD playback on the console has similar lockouts. Games bought for the console in a specific region can only be played in a console from the same region, though some games are region-free. The console makes use of regional lockout.

Media Center Extender capability. Support for WMV HD and progressive or interlaced DVD video playback. 45.9 cm (L) x 35.8 cm (W) x 18.3 cm (H) (22.15 x 20.15 x 13.27 in). Weight 3.5 kg (7.7 lb).

additional MPEG2 decoder for DVD video playback. Bink Video is licensed for games like Project Gotham Racing 3. VC-1 supports DVD quality and high definition quality video. VC-1 or WMV will be used for streaming video.

VC-1 at non-HD NTSC and PAL resolutions. Uses XMA codec (advanced audio technology from Microsoft). Voice communication except during games or applications that do not support voice. No voice echo to game players on the same Xbox console; voice goes only to remote consoles.

256+ audio channels. 32 bit processing. 320 independent decompression channels. Supports 48 kHz 16-bit audio.

All games support at least six channel (5.1) Dolby Digital surround sound. 1 TFLOPS theoretical peak performance of CPU and GPU combined. 115 GFLOPS theoretical peak performance for CPU. 1 GB/s southbridge bandwidth (aggregated 500 MB/s upstream and downstream).

21.6 GB/s front side bus (aggregated 10.8 GB/s upstream and downstream). 32 GB/s GPU to eDRAM bandwidth (2 GHz × 2 accesses per clock cycle on a 64 bit DDR bus). 256 GB/s eDRAM internal logic to eDRAM internal memory bandwidth. 22.4 GB/s memory interface bus bandwidth (700 MHz × 2 accesses per clock cycle (one per edge) on a 128 bit bus).

512 MB 700 MHz GDDR3 (1400MHz effective) RAM (Total system memory is shared with the GPU via the unified memory architecture.). Dot product operations: 24 billion per second or 33.6 billion per second theoretical maximum when summed with CPU operations. Pixel fillrate: 16 gigasamples per second fillrate using 4X multisample anti aliasing (MSAA) or 4 gigapixel per second without multisample anti aliasing (8 ROPs x 500MHz). Texel fillrate: 8 gigatexel per second fillrate (16 textures x 500MHz).

Maximum polygon performance: 500 million triangles per second. 16 Filtered & 16 unfiltered texture samples per clock. 8 ROPs in daughter die. Shader performance: 48 billion (48,000 million) shader operations per second (96 shader operations x 500MHz).

96 Shader operations per cycle across the entire shader array. 2 Shader operations per pipe per cycle. Support for DirectX 9.0 Shader Model 3.0, limited support for future DirectX 10 shader models. Unified shader architecture (This means that each pipeline is capable of running either pixel or vertex shaders.).

1 ALU per fragmentpipe for vertex or pixel shader processing. 3 groups of 16 arithmetic logic units. 48-way parallel floating-point dynamically-scheduled shader pipelines