document_title: MacBook Air

question_text: what kind of ports does a macbook air have

text: MacBook Air

text: History[edit]

text: Steve Jobs introduced the first MacBook Air during a speech at his keynote at the 2008 Macworld conference on January 15, 2008.[6] The first-generation MacBook Air was a 13.3"-only model, initially promoted as the world's thinnest notebook.[7] It featured a custom[8] Intel Merom CPU and Intel GMA graphics. In late 2008, the CPU was updated to a faster, non-custom Penryn CPU and integrated Nvidia GeForce graphics while the hard drive capacity was increased and the micro-DVI video port was replaced by the Mini DisplayPort.[9] A mid-2009 refresh, introduced alongside the MacBook Pro family, featured a slightly higher-capacity battery, and a faster Penryn CPU.[10]

text: On October 20, 2010, Apple released a redesigned 13.69" model, with improved enclosure, screen resolution, battery, and flash storage instead of a hard drive. In addition, a new 11.6" model was introduced, offering reduced cost, weight, battery life, and performance relative to the 13.3" model, but better performance than typical netbooks of the time.[11][12][13][14]

text: On July 20, 2011, Apple released updates to the 11.6" and 13.3" models of the MacBook Air, which also became Apple's entry-level laptops due to lowered prices and the discontinuation of the white MacBook around the same time.[5] The mid-2011 MacBook Airs were powered by the new Sandy Bridge 1.6 or 1.7 GHz dual-core Intel Core i5, or 1.8 GHz dual-core Intel Core i7 processors, that came with an Intel HD Graphics 3000 processor, and with a backlit keyboard, two USB 2.0 ports, FaceTime camera, a standard of 2 GB of RAM (configurable up to 4 GB), Thunderbolt which shares function with Mini DisplayPort and Bluetooth was upgraded to v4.0.[15][16] Maximum SSD flash memory storage options were increased up to 256 GB. Both 11" and 13" models had an analog audio output/headphone minijack (that also supports an iPhone/iPod touch headset with microphone), but only the 13" model had an integrated SDXC-capable SD Card slot. These models use a less expensive "Eagle Ridge" Thunderbolt controller that provides two Thunderbolt channels (2 × 10 Gbit/s bidirectional), compared to the MacBook Pro which uses a "Light Ridge" controller that provides four Thunderbolt channels (4 × 10 Gbit/s bidirectional). A USB ethernet adapter was immediately available upon release and a Thunderbolt-to-Firewire 800 adapter became available in mid-year 2012.

text: On June 11, 2012, Apple released an updated model in the same form factor as the prior model. The new model is powered by the new Ivy Bridge dual-core Intel Core i5 and i7 processors, doubles the RAM and SSD speeds, has the new USB 3 ports (with USB 2 capability) in place of the USB 2 ports and the new MagSafe 2 charging port.[17] The camera was upgraded to 720p FaceTime HD.

text: On June 10, 2013, Apple released another update in the same form factor as the 2012 model during the company's Worldwide Developer Conference (WWDC). The 11" and 13" models have a minimum standard 4 GB RAM, with a maximum configuration of 8 GB. Both models are powered by the Haswell ULT 1.3 GHz dual-core Intel Core i5 processors, with Turbo Boost up to 2.6 GHz, while a 1.7 GHz Dual-Core i7, with Turbo Boost up to 3.3 GHz, option is also available. Each model's storage standard is 128 GB SSD, upgradeable to 256 GB and 512 GB SSD. Due to Haswell CPUs, battery life has considerably improved from the previous generation, and the mid-2013 models are capable of 9 hours on the 11" model and 12 hours on the 13" model; a team of reviewers exceeded expected battery life ratings during their test.[18]

text: While Apple's MacBook lines have been affected towards consumer trend to smartphones,[19] they still managed to ship 2.8M Macs in Q2 2012, notably Air, compared to 500K total Ultrabooks,[20][21] despite there being dozens of Ultrabooks from various manufacturers on the market while Apple only offered 11" and 13" models of it.[22] Through July 1, 2013, the MacBook Air took in 56% of all Ultrabook sales in the United States, despite being one of the higher-priced competitors. [23]

text: Design[edit]

text: The MacBook Air features an anti-glare LED backlit display and a full-size keyboard, as well as a large trackpad that responds to multi-touch gestures such as pinching, swiping, and rotating.[24] Since the release of Snow Leopard, the Air's trackpad has supported handwriting recognition of Chinese characters.[25]

text: On the 11" Air, the left side of the computer has a MagSafe power connector, a USB port, a headphone jack, and a microphone.[24] The right side of the computer has a USB port and a Mini DisplayPort, now sharing Thunderbolt function beginning with the 2011 model. On top of the screen bezel there is a webcam, first dubbed iSight and now the FaceTime camera.

text: The MacBook Air was the first subcompact laptop offered by Apple since the full-featured 12" PowerBook G4 was discontinued in 2006. It was also Apple's first computer with an optional solid-state drive.[26] ArsTechnica found "moderate" performance improvements of the 64GB[note 1] solid-state drive of the first-generation Air over the standard 80 GB hard drive in tests. On October 14, 2008, new models were announced with improved capacities of 128 GB SSD and 120 GB hard drive. For the late-2010 MacBook Air and later models, only flash storage is available, with the standard options currently being 128 GB and 256 GB.[27]

text: The CPU in the first-generation MacBook Air was a custom Intel Core 2 Duo Merom that was 40% of the size of the standard chip package.[28] For models of late 2008, the CPU was replaced with a low-voltage Penryn chip with 6MB of cache, running on a 1066 MHz bus.[29]

text: MacBook Air components are officially non-user-replaceable, though third-parties do sell upgrade kits for the SSDs. The flash memory and battery are enclosed within the casing, with RAM soldered onto the motherboard. The flash memory, difficult to access, has a 128MB cache[30] and a mSATA connection (updated to a proprietary PCIe interface) to the motherboard.[31]

text: Apple incorporated several features in the design of the MacBook Air, such as the reduction of lead to make it more environmentally friendly. The MacBook Air contains no BFRs and PVC wiring, meets Energy Star 5.0 requirements, has a recyclable enclosure, and is rated EPEAT Gold. Its display is made from arsenic-free glass, and contains no mercury.[7][32] To reduce the computer's size and weight, several features were sacrificed. It was Apple's first notebook since the PowerBook 2400c without a built-in removable media drive.[33] It also omits a FireWire port, Ethernet port, line-in, media card slots (except the 13" 2010 through 2015 models, which have an SD card slot), and a Kensington Security Slot.[34]

text: To gain optical drive features, users could either purchase an external USB SuperDrive or other brand, or the bundled Remote Disc software, only for browsing or software installation to access the drive of another computer wirelessly[35] that has the program installed.[36][37] It can also be used to reinstall the system software from the included installation DVD. Remote Disc supports NetBooting, so the Air can boot from its installation DVD in another computer's drive, which requires Remote Install Mac OS X to be running on that computer. The software does not allow playback or information of DVDs, CDs or installing Windows.[35] For these features, an external USB drive is required.[35] More recent versions of OS X replaced the installation DVD with a USB flash drive containing the software, eliminating remote installation.

text: The 2010 models include two speakers for stereo sound while earlier versions have one speaker located under the keyboard. The 2011 model replaces DisplayPort with a Thunderbolt 1 port, and also has a 1280×720 FaceTime HD Camera, replacing the previous 640×480 iSight camera. The 2012 model replaces USB 2 with USB 3, and uses the MagSafe 2 instead of the MagSafe connector for charging. The 2015 model updated the Thunderbolt port to Thunderbolt 2.

text: Specifications[edit]

text:
Discontinued

Current

text:
[hide]Table of models

Model
Early 2008
(February)[38]

Late 2008
(October)[9]

Mid 2009
(June)[39]

Late 2010
(October)[40][41]

Mid 2011
(July)[42][43]

Mid 2012
(June)[44][45]

Mid 2013
(June)[46][47]

Early 2014
(April)[48]

Early 2015
(March)[49]

Mid 2017
(June)[50]

Model identifier
MacBookAir1,1
MacBookAir2,1
MacBookAir3,1 (11"), MacBookAir3,2 (13")
MacBookAir4,1 (11"), MacBookAir4,2 (13")
MacBookAir5,1 (11"), MacBookAir5,2 (13")
MacBookAir6,1 (11"), MacBookAir6,2 (13")
MacBookAir7,1 (11"), MacBookAir7,2 (13")

Model number (on underside)
A1237
A1304
A1370 (11"), A1369 (13")
A1465 (11"), A1466 (13")
A1466 (13")

Part number (Order number)
MB003LL/A
MB543LL/A, MB940LL/A
MC233LL/A, MC234LL/A
MC504LL/A, MC505LL/A, MC506LL/A, MC503LL/A
MC968LL/A, MC969LL/A, MC965LL/A, MC966LL/A
MD223LL/A, MD224LL/A, MD231LL/A, MD232LL/A
MD711LL/A, MD712LL/A, MD760LL/A, MD761LL/A
MD711LL/B, MD712LL/B, MD760LL/B, MD761LL/B
MJVM2LL/A, MJVP2LL/A, MJVE2LL/A, MJVG2LL/A, MMGF2LL/A (2016, 8 GB, 128 GB SSD), MMGG2LL/A (2016, 8 GB, 256 GB SSD)
MQD32LL/A (128 GB SSD), MQD42LL/A (256 GB SSD)

Display
(glossy)
N/A
11.6", native 1366 × 768 (16:9). Lower resolutions supported
N/A

13.3", native 1280 × 800 pixels (16:10). Lower resolutions supported
13.3", native 1440 × 900 (16:10). Lower resolutions supported

Graphics
(Shared with system memory)
Intel GMA X3100 using 144 MB of DDR2 SDRAM with Micro-DVI output
Nvidia GeForce 9400M using 256 MB of DDR3 SDRAM with Mini DisplayPort output
Nvidia GeForce 320M using 256 MB of DDR3 SDRAM with Mini DisplayPort output
Intel HD Graphics 3000 processor using 256 MB (11" base model) or 384 MB (all other models) of DDR3 SDRAM
Intel HD Graphics 4000 processor with up to 1 GB DDR3 SDRAM shared from main memory
Intel HD Graphics 5000 processor with up to 1.5 GB LPDDR3 SDRAM shared from main memory
Intel HD Graphics 6000 processor with up to 1.5 GB LPDDR3 SDRAM shared from main memory

Front side bus/DMI
800 MHz
1066 MHz
800 MHz (11"), 1066 MHz (13")
Intel Direct Media Interface
2.5 GT/s
Intel Direct Media Interface
5.0 GT/s

Processor
1.6 GHz (L7500) or 1.8 GHz (L7700) Intel Core 2 Duo with 4 MB on-chip L2 cache
1.6 GHz (SL9300) or 1.86 GHz (SL9400) Intel Core 2 Duo with 6 MB on-chip L2 cache
1.86 GHz (SL9400) or 2.13 GHz (SL9600) Intel Core 2 Duo with 6 MB on-chip L2 cache
(11") 1.4 GHz (SU9400) Intel Core 2 Duo with 3 MB on-chip L2 cache
Optional 1.6 GHz (SU9600) Intel Core 2 Duo with 3 MB on-chip L2 cache
(13")1.86 GHz (SL9400) Intel Core 2 Duo with 6 MB on-chip L2 cache
Optional 2.13 GHz (SL9600) Intel Core 2 Duo with 6 MB on-chip L2 cache
(11") 1.6 GHz (i5-2467M) dual-core Intel Core i5 with 3 MB shared L3 cache
(13") 1.7 GHz (i5-2557M) dual-core Intel Core i5 with 3 MB shared L3 cache
(Higher-End 11" & 13") Optional 1.8 GHz (i7-2677M) dual-core Intel Core i7 with 4 MB shared L3 cache
(11") 1.7 GHz (i5-3317U) dual-core Intel Core i5 with 3 MB shared L3 cache
(13") 1.8 GHz (i5-3427U) dual-core Intel Core i5 with 3 MB shared L3 cache
(Higher-End 11" & 13") Optional 2.0 GHz (i7-3667U) dual-core Intel Core i7 with 4 MB shared L3 cache
1.3 GHz (i5-4250U) dual-core Intel Core i5 with 3 MB shared L3 cache
Optional 1.7 GHz (i7-4650U) dual-core Intel Core i7 with 4 MB shared L3 cache
1.4 GHz (i5-4260U) dual-core Intel Core i5 with 3 MB shared L3 cache
Optional 1.7 GHz (i7-4650U) dual-core Intel Core i7 with 4 MB shared L3 cache
1.6 GHz (i5-5250U) dual-core Intel Core i5 with 3 MB shared L3 cache
Optional 2.2 GHz (i7-5650U) dual-core Intel Core i7 with 4 MB shared L3 cache
1.8 GHz (i5-5350U) dual core Intel Core i5 with 3 MB shared L3 cache
Optional 2.2 GHz (i7-5650U) dual-core Intel Core i7 with 4 MB shared L3 cache

Memory
2 GB of 667 MHz DDR2 SDRAM
2 GB[note 2] of 1066 MHz DDR3 SDRAM
2 GB of 1066 MHz DDR3 SDRAM
Optional 4 GB
2 GB (11" base model; Optional 4 GB) or 4 GB of 1333 MHz DDR3 SDRAM (all other models)
4 GB of 1600 MHz DDR3L SDRAM Optional 8 GB
4 GB of 1600 MHz LPDDR3 SDRAM Optional 8 GB (8 GB standard for the 13" version since April 19, 2016)
8 GB of 1600 MHz LPDDR3 SDRAM

Storage
80 GB 4200-rpm 1.8-inch PATA HDD or 64 GB SSD
120 GB 4200-rpm 1.8-inch SATA HDD or 128 GB SSD
64 (MC505LL/A) or 128 GB (MC506LL/A) (11"), 128 (MC503LL/A) or 256 GB (MC504LL/A) (13") SSD
64 GB (11") SSD
128 GB (11") SSD Optional 256 GB upgrade128 or 256 GB (13") SSD
64 GB or 128 GB SSD (11") Optional 256 GB or 512 GB upgrade
128 or 256 GB SSD (13") Optional 512 GB upgrade
128 GB or 256 GB PCIe-based SSD Optional 512 GB upgrade

Video Camera
iSight (640 × 480)
FaceTime HD (720p)

Power Connector
MagSafe
MagSafe 2

Connectivity
Internal 802.11 a/b/g and draft-n
Internal 802.11 a/b/g/n (AirPort)
Internal Dual-Band 802.11 a/b/g/n (AirPort, Broadcom BCM43224 300 Mbit/s)
Internal 802.11ac a/b/g/n/ac compatible (AirPort, Broadcom BCM4360-based 867Mbit/s)

Bluetooth 2.1 + EDR
Bluetooth 4.0

Built-in infrared (IR) receiver for Apple Remote
N/A

Optional Apple USB Ethernet Adapter (Year 2008)
Optional Apple USB Ethernet 100 Mbit Adapter
Optional Apple USB Ethernet 100 Mbit Adapter Optional Apple Thunderbolt to Gigabit Ethernet Adapter
Optional Apple Thunderbolt to FireWire 800 Adapter

Latest possible OS X version
Mac OS X 10.7 "Lion"
(Unofficially, can run OS X 10.8 using MacPostFactor)
OS X 10.11 "El Capitan"
(Unofficially, can run macOS 10.12 "Sierra" without wi-fi using Sierra Patcher)
macOS 10.13 "High Sierra"

Battery
(removable lithium-ion polymer)
N/A
35-watt-hour (11")
38-watt-hour (11")
N/A

37-watt-hour (13")
40-watt-hour (13")
50-watt-hour (13")
54-watt-hour (13")

Battery cycle count [51]
300
500
1000

Unit weight
N/A
2.38 lb (1.08 kg) (11")
N/A

3.0 lb (1.36 kg)
2.96 lb (1.34 kg) (13")

Dimensions
N/A
11.8 in (30 cm) wide × 7.56 in (19.2 cm) deep × 0.11 in (0.3 cm) to 0.68 in (1.7 cm) high (11")
N/A

12.8 in (33 cm) wide × 8.94 in (23 cm) deep × 0.16 in (0.4 cm) to 0.76 in (1.9 cm) high (13")
12.8 in (33 cm) wide × 8.94 in (22.7 cm) deep × 0.11 in (0.3 cm) to 0.68 in (1.7 cm) high (13")

Peripheral connections
1× USB 2.0
2× USB 2.0
2× USB 3.0

1× 3.5 mm headphone jack

Micro-DVI video port
DVI-D/VGA adapter included
1× Mini DisplayPort video port
1× Thunderbolt port
1× Thunderbolt 2 port

N/A
1× SDXC card slot (13" only)

text: Reception[edit]

text: Comparison with iPad and netbooks[edit]

text: Although the 11" Air is only slightly lighter than the 13" Air, the biggest difference is the footprint which gives each model a distinct category; the 13” Air is much closer in size to most other conventional laptops, while the 11” Air is almost small enough to fit in a space that can hold an iPad.[52][53]

text: The 11" MacBook Air carried the desirable essential attributes of a netbook, but without the drawbacks of a slower processor and less capable operating system,[54] albeit at a higher price.[55][56][57][58][59] At the low end, Apple introduced the iPad—a different form factor than the netbook, but with improved computing capabilities and lower production cost. Both of these led to a decline in netbook sales, and most PC manufacturers have consequently discontinued their netbook lines in response.[60] Capitalizing on the success of the MacBook Air,[61] Intel promoted Ultrabook as a new high-mobility standard, which has been hailed by some analysts as succeeding where netbooks failed.[62][63][64]

text: Ultrabook competition[edit]

text: Intel developed a set of specifications for the Ultrabook, a higher-end type of subnotebook produced by various PC manufacturers and usually running Windows. Competing directly with the Air, the Ultrabook is intended to reduce size and weight, and extend battery life without compromising performance.[65][66][67]

text: Through July 1, 2013, the MacBook Air took in 56 percent of all Ultrabook sales in the United States, despite being one of the higher-priced competitors. [23] Apple had previously dominated the premium PC market, in 2009 having a 91 percent market share for PCs priced at more than $1,000, according to NPD, and Ultrabooks were an attempt by other PC manufacturers to move in on Apple's turf.[68] While Apple's MacBook lines were not immune to this consumer trend towards mobile devices,[19] they still managed to ship 2.8 million MacBooks in Q2 2012 (the majority of which were the MacBook Air) compared to 500,000 total Ultrabooks,[20][21] despite there being dozens of Ultrabooks from various manufacturers on the market while Apple only offered 11" and 13" models of the Macbook Air.[22] Forrester Research analyst Frank Gillett attributes Apple's increased success in the enterprise market to the 2010 MacBook Air and the iPad.[69]

text: While several Ultrabooks were able to claim individual distinctions such as being the lightest or thinnest, the MacBook Air was regarded by reviewers as the best all-around Ultrabook in regard to "OS X experience, full keyboard, superior trackpad, Thunderbolt connector and the higher-quality, all-aluminum unibody construction".[70]

text: The Microsoft Surface Pro has a similar size and price to the 11" MacBook Air;[71][72] Apple CEO Tim Cook has criticized the Surface Pro and other Ultrabook hybrids running the touch-based Windows 8, that attempt to combine laptop and tablet functionality in one device, saying that such devices were confusing like trying to "combine a fridge and a toaster".[73][74]

text: When released in October 2010, the 13" model's screen resolution was higher than the average 1366x768 screens of similar sized laptops. However, by mid-2013, with many premium Ultrabooks having high resolution screens (1080p or greater) as standard or upgrades, the MacBook Air has been increasingly criticized for sticking with a low-resolution screen. Many in the tech community had expected Apple to release a MacBook Air with Retina Display by mid-2013, similar to the MacBook Pro Retina which came out in 2012.[75] The October 2013 refresh of the 13" MacBook Pro Retina, with a slimmer chassis and a lower price point, was mentioned as a potential MacBook Air alternative as the battery life is not much shorter while not being considerably bulkier.[4][76] Apple released an entry-level version of the 13" MacBook Pro on October 27, 2016, which was specifically targeted towards MacBook Air users.[77]

text: "Thinnest laptop"[edit]

text: At the launch of the first MacBook Air in January 2008, Apple claimed it to be the thinnest laptop in the world. While this was true of laptops on sale at the time, the 2003 Sharp Actius MM10 Muramasas was thinner at some points than the Macbook Air, being 0.54 inches (14 mm) thick at its minimum.[78] It, like the MacBook Air, was a tapered design, with a maximum height of 0.78 inches (19.8 mm) —slightly thicker than the MacBook Air — shown above as 0.76 inches (19.3 mm).[79] The Sony Vaio X505, released in 2004, had a minimum thickness of 0.38 inches (10 mm) and a maximum of 0.8 inches (20.3 mm).[80]

text: Since the release of the first MacBook Air, other thinner laptops have been released, such as the Dell Adamo,[81] launched in March 2009, which is a constant 0.65 inches (17 mm) thick. Apple subsequently removed "The world's thinnest notebook" from their marketing materials.

text: The 11.6" MacBook Air, introduced in October 2010, is only slightly larger and heavier (when closed) than the iPad 2. The 11.6" Air has been regarded as thin and light compared to other ultraportables, such as the Sony VAIO Z and the 11" Samsung Series 9.[82]

text: As of 2013, several Ultrabooks such as the Sony VAIO Pro have managed smaller dimensions than the MacBook Air by using carbon fiber construction.[83][84][85]

text: Issues[edit]

text: Following its introduction, the MacBook Air was greeted with a mixed reception. The portability of the MacBook Air was praised in reviews, but the compromise in features was criticized.[86][87][88] The full-sized keyboard, weight, thinness, and Multi-Touch trackpad were appreciated in reviews, while the limited configuration options and ports, slow speed (in non-SSD models), non-user-replaceable battery, small hard drive, and price were criticized.[86][87] The flip-down hatch on the side of the original MacBook Air is a tight fit for some headphone plugs and USB devices, requiring users to purchase an extension cable. Apple removed the flip-down hatch on the late 2010 model in favor of open connection ports, as is the case with most other laptops.[89][90]

text: Most of these problems have been dismissed by now, following many revisions and speed enhancements, and with the addition of more portability and ports.[citation needed]

text: Since the release of the first-generation product, some MacBook Air users have complained of CPU lockup caused by overheating. Apple released a software update in early March 2008 to fix the problem with mixed results: the deactivation of one CPU core was corrected; however, the runaway kernel problem remained for some users.[91] The problem is aggravated by system-intensive tasks such as video playback or video chatting.[92]

text: Due to a more mature manufacturing process, the CPUs in the second-generation MacBook Air perform better under load, as the first generation chips ran at a higher temperature—the processor needed to be throttled to avoid overheating and this further degraded performance.[93]

text: On October 17, 2013, Apple announced a replacement program for the 64 GB and 128 GB MacBook Air flash storage drives that are installed in Air systems purchased between June 2012 and June 2013.[94]

text: Timeline of the MacBook family


document_title: Arsenal F.C.–Manchester United F.C. rivalry

question_text: when was the last time man u beat arsenal

root

text: History[edit]

text: Origins[edit]

text: A particularly memorable match between the two sides came on 1 February 1958, when they met in a league fixture at Highbury.[7] It was the last league game that United played before the Munich air disaster five days later, which claimed the lives of eight of their players and saw two other players injured to such an extent that they never played again.[7] United won the game 5–4, with goals from Tommy Taylor (twice), Duncan Edwards, Bobby Charlton and Dennis Viollet.[7] Five of the United players who would lose their lives as a result of crash took to the field in the game – captain and full-back Roger Byrne, right-half Eddie Colman, centre-half Mark Jones, left-half Edwards and centre-forward Taylor.[7]

tag: p

text: Another high-profile clash came more than 20 years later, in the final of the FA Cup on 12 May 1979.[8] A capacity crowd saw Arsenal take a 2–0 lead in the first half thanks to goals from Brian Talbot and Frank Stapleton, and with just five minutes left on the clock their lead was still intact.[8] Then, in the 86th minute, Gordon McQueen pulled a goal back for United, and two minutes later they equalised with a goal from Sammy McIlroy.[8] However, barely a minute after United equalised, Arsenal's Alan Sunderland scored an 89th-minute goal to win the cup 3–2 for Arsenal.[9]

text: Although Arsenal and Manchester United had previously contested many significant matches, Sir Alex Ferguson believed the rivalry started in January 1987 when David Rocastle was sent off for retaliating against a foul on Norman Whiteside.[10] It is, however, generally perceived to have begun in October 1990, when a brawl between both sides at Old Trafford resulted in both clubs being docked points in the 1990–91 First Division.[11] The two clubs fined several of their players, and in Arsenal's case, their manager too. Arsenal and United next faced each other at Highbury a little over a month later in the Football League Cup fourth round.[12] United won the tie 6–2, with 19-year-old winger Lee Sharpe scoring a hat-trick.[12]

text: The rivalry intensified following the arrival of Arsène Wenger in October 1996.[14] A league match between the two sides in February 1997 was marred by an incident between Arsenal's Ian Wright and United's Peter Schmeichel; the striker challenged for the ball with both feet and caught the goalkeeper with his studs.[15] A confrontation ensued and police stepped in to keep the players apart after the final whistle.[16] Wright's behaviour was scrutinised at a hearing, where he complained he was subject to racial abuse by Schmeichel, at which point the FA intervened and met with representatives of both clubs.[15] In April 1997, Wright and Schmeichel settled their differences, but the managers' animosity towards each other started to become apparent.[17] Wenger had advised against the Premier League extending the season to ease Manchester United's fixture congestion, to which Ferguson publicly retorted: "Maybe he should concentrate on Ian Wright's tackles rather than Manchester United. He's at a big club, well Arsenal used to be a big club, and maybe next year he could be in the same situation. I wonder what [h]is story will be then."[18]

text: United had won four of the first five editions of the newly-branded league, and were on course to continue their domination after opening up a sizeable lead in February 1998.[19] Injuries and poor results however destabilised the team, and by the time Arsenal visited Old Trafford in March, a title race was looking probable.[20] Wenger was bullish of his team's chances: "I told you last week that the race was not over when the bookmakers stopped betting. Surprise, surprise, they have started taking money again."[21] A goal from Marc Overmars set Arsenal on the way to victory, which put them six points behind with three games in hand.[22] They eventually won the league, and secured the double by beating Newcastle United in the Cup final.[23]

text:
"It was a trauma for us. I can still hear the shouts of their team having won, they couldn’t believe it because they were down to 10 men. And I think that put them on a wave of euphoria and then they won the title – just."

—Arsène Wenger reflecting on the FA Cup semi-final replay[24]

tag: div

text: Arsenal began the 1998–99 season with a 3–0 win over United in the Charity Shield; Ferguson was unconcerned by the result given its pre-season status, but losing to the champions a month later by the same scoreline was, in his words, "a lot less tolerable."[25] Both clubs again vied for domestic honours; United this time pipped Arsenal by a point to regain the title.[26] They also met in the FA Cup semi-final, which was replayed after the original game ended goalless.[27] David Beckham and Dennis Bergkamp scored for their respective clubs either side of half time, Roy Keane was dismissed, and the holders late on were awarded a penalty.[27] Schmeichel saved Bergkamp's attempt and the tie went into extra time. Ryan Giggs memorably scored the winner, picking up possession on the halfway line and dribbling past the entire Arsenal back line before shooting past David Seaman.[27] "A match that had everything finished with a pitch invasion, sporadic fighting and David Beckham carried shoulder-high from the field" wrote Matt Dickinson in The Times.[28] United went on to complete the treble, winning the UEFA Champions League.[26]

text: The rivalry continued into the new millennium, though Manchester United's domestic grip tightened. They finished 18 points clear of Arsenal in 1999–2000 and completed a hat-trick of titles the following season. Any indication United could be caught faded once Ferguson's team trounced Arsenal 6–1 at Old Trafford in February 2001.[29] Dwight Yorke scored a hat-trick, on a day Wenger fielded a relatively inexperienced centre-back pairing of Gilles Grimandi and Igors Stepanovs.[29] At the end of the campaign, Ferguson announced his decision to retire.[30] He reportedly sanctioned a bid to sign midfielder Patrick Vieira, who was upset at Arsenal's transfer inactivity. The transfer never came through; Wenger blamed his rivals for "...approach[ing] to Patrick without contacting us, and that does not really respect the rules."[31] United made an indifferent start to the league campaign, and by February 2002, Ferguson went back on his retirement plan on the advice of his family.[32][33] Arsenal hit their stride as the 2001–02 season came to a close, winning the double for the second time in four years.[34] The championship was decided at Old Trafford in the penultimate game of the season; Wenger described his team's 1–0 win as a "shift of power."[35]

text:
"It's getting tickly now – squeaky-bum time, I call it."

—Sir Alex Ferguson on the title race, 2003[36]

text: United again won the title back in 2002–03, when it looked as though Arsenal would retain it. A late-season encounter between the teams ended in controversial circumstances after the match officials allowed Thierry Henry's second goal to stand despite the player being offside and Sol Campbell was sent off for an elbow on Ole Gunnar Solskjær in a 2–2 draw.[37] Arsenal had beaten United on the way to FA Cup success and both teams contested the 2003 FA Community Shield at the start of the 2003–04 season. In a hotly-contested match, Phil Neville was booked in the first minute for a challenge on Vieira and a minute later, Ashley Cole received a booking for fouling Solskjær.[38] Yellow cards were also given to Quinton Fortune and Paul Scholes for United and Vieira for Arsenal.[38] Substitute Francis Jeffers was shown a straight red for a kick on Phil Neville and, despite originally going unpunished, Campbell was later given a three-match ban by the FA for kicking out at Eric Djemba-Djemba.[39] The game finished 1–1 after 90 minutes and United eventually won the Shield 4–3 on penalties.[38]

text: 2003–04: Brawl and Cup semi-final meeting[edit]

text: The rivalry escalated in September 2003, when Arsenal travelled to Old Trafford. In the match Vieira was shown a second yellow card for his part in an altercation with striker Ruud van Nistelrooy, and during stoppage time, defender Martin Keown brought down Diego Forlán in the Arsenal penalty area. United were awarded a penalty and Van Nistelrooy stepped up to take it, but his shot rebounded off the crossbar.[40] This was followed by scenes of jubilation from the Arsenal players, who confronted Van Nistelrooy after his miss.[40] The resulting scuffle led to another fracas after the final whistle, which ended up with four players from both sides being given yellow cards.[40] The FA took action, later charging six of Arsenal's players (Jens Lehmann, Ray Parlour, Lauren, Cole, Keown and Vieira) with improper conduct.[41] The club was fined £175,000, the largest ever given to a club by the FA at the time.[41] Lauren received a four-game ban, whereas Vieira and Parlour were given one-match suspensions.[42]

text: The next game between these two clubs was held at Highbury in March 2004, again ending in a draw.[43] Ferguson's side then knocked Arsenal out of the FA Cup semi-final at Villa Park the following weekend; United supporters at the ground led a chorus of "Where's your Treble gone?" to their rivals.[44] United went on to win the FA Cup, while Arsenal regained the title without losing a league game. They faced each other in the 2004 FA Community Shield and Arsenal won the match 3–1.[45]

text: 2004–05: Unbeaten run ends, tunnel fracas[edit]

text: By the time Arsenal next played Manchester United, the club had extended its unbeaten league run to 49 games.[47] United stood in sixth place in the table, 11 points behind Arsenal and were intent on ending their rivals' undefeated streak.[48] Ferguson in his press conference described Arsenal's conduct in the equivalent fixture a year ago as "...the worst thing I've seen in this sport. No wonder they were so delighted at the verdicts."[48]

text: The October 2004 league match, staged at Old Trafford, was blighted by a number of fouls, overlooked by referee Mike Riley, including striker Van Nistelrooy's studs-up challenge on Cole.[49] Arsenal dictated much of the play, but as the game headed towards the finish, United threatened. The home side were awarded a penalty when Wayne Rooney was adjudged to have been fouled in the area by Campbell. Van Nistelrooy scored and late in the game Rooney scored to give United a 2–0 win.[50] Tempers flared in the tunnel afterwards; Wenger confronted Van Nistelrooy for his tackle on Cole, but Ferguson intervened and told him to leave his players alone.[51] Pizza was thrown at Ferguson by an Arsenal player, which forced him to change into the club tracksuit in order to carry out his television duties. An investigation into "Pizzagate" never came around as both clubs kept silent.[52]

text: The clubs met again five weeks later in the League Cup quarter-finals at Old Trafford and despite both sides fielding weakened teams, the match was not short of drama.[53] David Bellion gave United the lead in just 19 seconds, but tempers boiled over in the second half; a late tackle by Robin van Persie on Kieran Richardson resulted in a fracas between both sets of players, which concluded with both protagonists getting booked by referee Mark Halsey.[53] The game finished 1–0.[53] In the reverse league fixture, club captains Keane and Vieira had to be separated in the tunnel before the match by referee Graham Poll. Keane accused the Arsenal midfielder of intimidating his teammate Gary Neville, telling the press afterwards: "I said, 'Come and have a go at me'. Simple as that. If he wants to intimidate some of my team-mates then let's have a go at some of the other players. I think Gary Neville's an easy target. I wasn't having it."[54] Vieira gave Arsenal the lead in the eighth minute of the match but United ran out 4–2 winners.[55]

text: In May 2005, Arsenal and United contested the 124th FA Cup Final. It was the first time in the competition's history that the final was decided on a penalty shoot-out. Arsenal beat United 5–4, following a goalless draw after extra time.[56] Arsenal forward José Antonio Reyes became the second player in Cup Final history to be sent off, following his second yellow card near the end of extra time.[57]

text: Chelsea's emergence as title challengers put an end to Arsenal and Manchester United's domestic duopoly.[58] The London club won back-to-back league titles in 2004–05 and 2005–06 under José Mourinho, at a time when Arsenal and United underwent a period of transition.[59] Vieira and Keane had left their respective clubs by the end of 2005, while Ferguson came under intense scrutiny over his management.[60] Nevertheless, he guided his team to Premier League success in 2006–07, and won a further four league titles.[61] At Arsenal, Wenger oversaw the club's relocation to the Emirates Stadium and made the decision to prioritise it over strengthening the squad.[62] The club sold several experienced players, replenishing them with younger talent.[62] Though Wenger solidified Arsenal's Champions League status, the 2005 Cup win was their last piece of silverware until 2014.[63]

text: Though the rivalry cooled, the two clubs were still involved in engrossing battles; The Guardian's Jamie Jackson wrote after a November 2007 fixture: "For once here was enough spectacle to meet the pre-match hype and convince the millions watching around the world that the Premier League may just have the best footballers who can play the very best stuff."[64] In 2009, the teams met in the semi-finals of the 2008–09 UEFA Champions League, which United won 4–1 on aggregate. United defender Patrice Evra was blunt in his post-match assessment: "It was 11 men against 11 children. We never doubted ourselves. We have much more experience and that's what made the difference."[65]

text: In December 2010, Ferguson made a personal plea to the United fans to no longer sing a "sick" chant at Arsenal manager Arsène Wenger, as those kind of chants from fans were considered an embarrassment to the club.[66] With both teams going for the Premier League title in May 2011, Arsenal won their first game against Manchester United since November 2008, to leave United just three points ahead of Chelsea and six ahead of Arsenal going into the final three games of the season.[67] Nevertheless, United won the league, nine points ahead of Chelsea and 12 points ahead of Arsenal.[68]

text: In August 2011, Arsenal suffered their heaviest league defeat in 84 years as they lost 8–2 to Manchester United at Old Trafford. Arsenal had not lost a league game by such a margin since 1927 when they lost 7–0 to West Ham United in the old Football League First Division.[69] This was also the first time they had conceded eight goals in a game since 1896, when they lost 8–0 to the now defunct Loughborough in the old Football League Second Division.[70] A year later, striker Robin van Persie joined United, having stated that he would not renew his contract with Arsenal. It was speculated that he would move to a club overseas, but signed for the Manchester club, the first Arsenal player to do so since Viv Anderson in 1987.[71] Ferguson called Wenger to push through a deal when he learnt of the contract situation.[72] Van Persie was instrumental in United's league win of 2012–13 – Ferguson's last, and coincidentally received a guard of honour by his former teammates before United faced Arsenal at the Emirates in April 2013.[73]

text: The appointment of Mourinho as United manager in 2016 added a new twist to the rivalry, given the previous animosity between him and Wenger.[74] Sports writer Daniel Taylor however argued that Wenger's stagnation hindered any confrontations between the two managers, writing: "Ferguson stopped aiming his barbs at Wenger once it became clear his old enemy was no longer capable of producing title-winning teams and it doesn’t feel like a coincidence that Mourinho also seems indifferent now that Arsenal have dropped even further back."[75] Former midfielder Phil Neville criticised the players for hugging in the tunnel before a league fixture in May 2017, calling the pleasantries a "total nonsense".[76]

text: Ferguson and Wenger[edit]

text: It was not until Wenger's arrival in October 1996 that Arsenal reemerged as a serious league competitor. By the end of the 1996–97 season, Manchester United amassed their fourth title in five seasons,[77] whereas Arsenal finished the campaign in third – their highest position since the formation of the Premier League in 1992.[78] During the season, Wenger commented on rule changes which permitted an extension to the league calendar: "It's wrong the programme is extended so Manchester United can rest and win everything."[79] His observation irked Ferguson, who replied: "He has no experience of English football. He has come here from Japan, and now he is telling everyone how to organise our football. Unless you have been in the situation and had the experience then he should keep his mouth shut, firmly shut."[80]

text: The relationship between both managers was evidently hostile to begin with. Ferguson noted that Wenger was the only manager he came across in the league not to share a drink with after matches – an English football "tradition".[81] In a joint interview with The Times and Daily Mail in 2009, Wenger said his discourtesy was mistaken for mistrust and managers "cannot be completely friendly and open up."[82] When asked if this was the reason he avoided the post-match drink, he replied: "Most of the time, yes. What can you say if you have won? And if you have lost all you want to do is get home and prepare for the next game."[82]

text: In January 2005, Ferguson and Wenger were embroiled in a new row over what had happened in the tunnel after Pizzagate.[83] Ferguson alleged that Wenger called his players "cheats" and never apologised for his team's behaviour: "It's a disgrace, but I don't expect Wenger to ever apologise, he's that type of person."[83] Wenger then claimed Ferguson was guilty of bringing the game into disrepute; he told reporters that he "will never answer any questions any more about this man," but went further to question the motive of the press: "What I don't understand is that he does what he wants and you are all at his feet."[84] Both managers came under pressure from the Metropolitan Police Service, then Sports Minister Richard Caborn and Premier League chairman Richard Scudamore to put an end to the bickering.[85] Ferguson and Wenger agreed to tone down their words, in an attempt to defuse the rivalry. In later years, Ferguson said Arsenal's defeat "scrambled Arsène’s brain" and caused their relationship to breakdown for almost five years.[86]

text: The two managers have "exchanged some of football's best and bitterest verbal swipes."[87] In 1997, Ferguson called Wenger a "novice" for complaining about the fixture programme and later said of his linguistic skills: "They say he’s an intelligent man, right? Speaks five languages! I’ve got a 15-year-old boy from the Ivory Coast who speaks five languages!"[88] After Arsenal's defeat to Manchester United in February 1997 – a match marred by a bust up between Wright and Schmeichel, Wenger referred to Ferguson’s interference: "I was surprised to see Ferguson on the pitch because you can only play eleven."[79] When Ferguson asserted that his team played the best football in England during the 2001–02 season, Wenger quipped: "Everyone thinks they have the prettiest wife at home," a subtle remark that Ferguson initially suspected was a taunt at his own wife Cathy.[89]

text: Such was the media's fascination of both managers' insults towards one another, psychologists were brought in to read and contrast their personalities.[79] John Kramer, a sports psychologist suggested in 2004 that Ferguson and Wenger used their rivalry in order to relax before an important match. To him, Ferguson was "...the past master in terms of creating an environment of keeping his players hungry" by using a persecution complex; Wenger on the other hand diffuses the psychology and would rather "...tell his players they are all superb and will attempt to create an environment where they are able to show off their skills without the rest of it."[90] Kramer concluded that both managers' comments "add[s] to the drama", but was insignificant in the games between the two clubs.[90]

text: Ferguson in his autobiography said a major turning point in his relationship with Wenger was after the Champions League semi-final of 2009; the Arsenal manager invited his competitor into the dressing room and congratulated him on United's win.[86] Wenger admitted their relationship had become genial since his team stopped competing with Manchester United for trophies.[82] The move to the Emirates Stadium in 2006 is often cited as the reason why, given it coincided with a transitional phase for the club. Several experienced first teamers were displaced in favour of youth and the style of football became shifted more towards ball retention.[91] Ferguson assessed the change in philosophy proved that Wenger did not "like to blend them too much with older players;" he also felt the team lacked a much needed balance between attack and defence.[92]

text: Television and radio broadcasts[edit]

text: The growth of the rivalry during the 1990s attracted the attention of broadcasters and has led to fixtures being rescheduled from the 3pm blackout period to primetime viewing in the United Kingdom. League matches are often broadcast on Sky Sports – once as early as 11:15am,[93] while cup games have aired on mainstream channels, BBC One and ITV.[94][95] At the height of the rivalry, the games on Sky had been billed as title deciders, and play was summarised by Martin Tyler and Andy Gray.[96] The April 2003 match at Highbury, advertised as "Face Off",[97] was watched by a British audience of 3.4 million,[98] while the 2005 Cup final was watched by more than 480 million viewers worldwide.[99]

text: In August 1999, the two sides participated in the world's first interactive football match,[100] and 11 years later featured in the world's first 3D TV sports broadcast – both events trialled by Sky.[101] To commemorate the 80th anniversary of the first radio football commentary, the BBC reintroduced its "grid system" to help listeners visualise the action between Arsenal and Manchester United in January 2007.[102] Musician David Gray was enlisted as guest summariser, with John Murray describing the action and James Alexander Gordon calling out the grid numbers to explain where the ball was.[102]

text: The rivalry was explored in an ITV4 special, Keane & Vieira: Best of Enemies, first broadcast in December 2013. The documentary saw the former captains discussing about their relationship, views on their respective managers and what they thought of each other.[103]

text: Crossing the divide[edit]

text: Arsenal, then Manchester United

text:
Name
Pos.
Arsenal
Manchester United

 David Herd
FW
1954–1961
1961–1968

 Ian Ure
MF
1963–1969
1969–1971

 George Graham
FW
1966–1972
1972–1974

 Frank Stapleton
FW
1971–1981
1981–1987

 Viv Anderson
DF
1984–1987
1987–1991

 Andy Cole
FW
1989–1992
1995–2001

 Matt Wicks
DF
1994–1995
1995–1996

 Robin van Persie
FW
2004–2012
2012–2015

tag: table

text: Note: Matthew Wicks never played a senior game for either team

text: Manchester United, then Arsenal

text:
Name
Pos.
Manchester United
Arsenal

 Paddy Sloan
FW
1937–1939
1946–1948

 Jimmy Rimmer
GK
1965–1974
1974–1977

 Brian Kidd
FW
1967–1974
1974–1976

 Jim Leighton
GK
1988–1991
1991

 David Platt
MF
1982–1985
1995–1998

 Matt Wicks
DF
1995–1996
1996–1998

 Mikaël Silvestre
DF
1999–2008
2008–2010

 Danny Welbeck
FW
2008–2014
2014–

text: Note: David Platt never played a senior game for United.

text: Statistics[edit]

text: All figures are correct as of the match played on 6 August 2017.[104][105][106][107]

text: Honours[edit]

text: Numbers with this background and symbol are italicised to denote club holds record in the competition.

tag: ul

text:
Team
League
FA Cup
League Cup
League Centenary Trophy
European Cup/
UEFA Champions League
UEFA Cup/
Europa League
Inter-Cities Fairs Cup
Cup Winners' Cup
Community Shield
UEFA Super Cup
Intercontinental Cup
Club World Cup
Club total

Arsenal
13
13
2
1
0
0
1
1
15
0
0
0
46

Manchester United
20
12
5
0
3
1
0
1
21
1
1
1
66

Total
33
25
7
1
3
1
1
2
35
1
1
1
112

text: Head-to-head results[edit]

text:
Competition
Played
Arsenal wins
Drawn
Manchester United wins
Arsenal goals
Manchester United goals

Football League/Premier League
196
69
46
81
272
297

FA Cup
15
6
2
7
19
19

Football League Cup
6
2
0
4
8
15

Football League Centenary Trophy
1
1
0
0
2
1

FA Community Shield
6
4
2
0
14
7

UEFA Champions League
2
0
0
2
1
4

Total
226
82
50
94
316
343

text: Records[edit]

text:
First competitive meeting: Newton Heath 3–3 Woolwich Arsenal, Second Division, 13 October 1894[104]
First FA Cup meeting: Manchester United 2–3 Arsenal, fourth round, 10 March 1936[104]
First League Cup meeting: Arsenal 3–2 Manchester United, second round, 30 August 1977[104]
First European meeting: Manchester United 1–0 Arsenal, UEFA Champions League semi-final, 6 April 2009[108]
First away victory for Arsenal: 1–0 vs Manchester United, Second Division, 15 March 1902[104]
First away victory for Manchester United: 2–0 vs Arsenal, Second Division, 3 April 1897[104]
Highest scoring game: Manchester United 8–2 Arsenal, Premier League, 28 August 2011[104]
Largest winning margin (Manchester United): 6 goals – 8–2 vs Arsenal, Premier League, 28 August 2011[104]
Largest winning margin (Arsenal): 5 goals – 5–0 vs Manchester United, FA Cup fourth round, 30 January 1937[104]
Most consecutive wins (Manchester United): 5, 6 September 1983–24 August 1985[104]
Most consecutive wins (Arsenal): 4, 9 November 1997–20 September 1998[104]
Longest undefeated run (Manchester United): 9 – 6 wins and 3 draws over 20 November 1954 to 11 October 1958[104]
Longest undefeated run (Arsenal): 5 – 4 wins and 1 draw over 5 April 1922 to 28 December 1926[104]
Most consecutive draws: 3, 26 September 1981–25 September 1982[104]
Most games played against each other in a season: 5, in the 1998–99 and 2004–05 seasons[104]
Record goalscorer: Wayne Rooney (12), Manchester United.[109] He scored on his League debut for the club against Arsenal on 24 October 2004.[110]
Most appearances: Ryan Giggs (50), Manchester United. He made his final appearance in the fixture as a substitute on 9 November 2013.[111]
Highest league attendance: 83,260 at Maine Road, First Division, 17 January 1948[112]


document_title: Vincristine

question_text: vincristine acts on which phase of cell cycle

text: Vincristine

text: Medical uses[edit]

text: Vincristine is delivered via intravenous infusion for use in various types of chemotherapy regimens.[3] Its main uses are in non-Hodgkin's lymphoma as part of the chemotherapy regimen CHOP, Hodgkin's lymphoma as part of MOPP, COPP, BEACOPP, or the less popular Stanford V chemotherapy regimen in acute lymphoblastic leukemia (ALL), and in treatment for nephroblastoma.[3] It is also used to induce remission in ALL with dexamethasone and L-Asparaginase, and in combination with prednisone to treat childhood leukemia.[3] Vincristine is occasionally used as an immunosuppressant, for example, in treating thrombotic thrombocytopenic purpura (TTP) or chronic idiopathic thrombocytopenic purpura (ITP).[3]

text: Side effects[edit]

text: The main side effects of vincristine are chemotherapy-induced peripheral neuropathy, hyponatremia, constipation, and hair loss.

text: Chemotherapy-induced peripheral neuropathy can be severe, and may be a reason to reduce or avoid using vincristine. The symptoms of this are progressive and enduring tingling numbness, pain and hypersensitivity to cold, beginning in the hands and feet and sometimes affecting the arms and legs.[9] One of the first symptoms of peripheral neuropathy is foot drop: A person with a family history of foot drop and/or Charcot-Marie-Tooth disease (CMT) should avoid the taking of vincristine.[10]

text: Accidental injection of vinca alkaloids into the spinal canal (intrathecal administration) is highly dangerous, with a mortality rate approaching 100 percent. The medical literature documents cases of ascending paralysis due to massive encephalopathy and spinal nerve demyelination, accompanied by intractable pain, almost uniformly leading to death. Several patients have survived after aggressive and immediate intervention. Rescue treatments consist of washout of the cerebrospinal fluid and administration of protective medications.[11] Children may do better following this injury. One child, who was aggressively treated at the time of the injection, recovered almost completely with only mild neurological deficits.[12] A significant series of inadvertent intrathecal vincristine administration occurred in China in 2007 when batches of cytarabine and methotrexate (both often used intrathecally) manufactured by the company Shanghai Hualian were found to be contaminated with vincristine.[13]

text: The overuse of vincristine may also lead to drug resistance by overexpression of the p-glycoprotein pump (Pgp). There is an attempt to overcome resistance by the addition of derivatives and substituents to the vincristine molecule.[14]

text: Mechanism of action[edit]

text: Vincristine works partly by binding to the tubulin protein, stopping the cell from separating its chromosomes during the metaphase; the cell then undergoes apoptosis.[15] The vincristine molecule inhibits leukocyte production and maturation.[16]

text: Pharmacology[edit]

text: Vincristine is created through the semi-synthesis coupling of indole alkaloids vindoline and catharanthine in the vinca plant.[17] It can also now be synthesized through a stereocontrolled total synthesis technique which retains the correct stereochemistry at C18' and C2'. The absolute stereochemistry at these carbons is responsible for vincristine's anticancer activity.[18]

text: The liposome encapsulation of vincristine enhances the efficacy of the vincristine drug while simultaneously decreasing the neurotoxicity associated with it. Liposome encapsulation increases vincristine's plasma concentration and circulation lifetime in the body, and allows the drug to enter cells more easily.[19]

text: History[edit]

text: Having been used as a folk remedy for centuries, studies in the 1950s revealed that the rosy periwinkle Catharanthus roseus contained 70 alkaloids, many of which are biologically active. While initial studies for its use in diabetes mellitus were disappointing, the discovery that it caused myelosuppression (decreased activity of the bone marrow) led to its study in mice with leukemia, whose lifespan was prolonged by the use of a vinca preparation. Treatment of the ground plant with Skelly-B defatting agent and an acid benzene extract led to a fraction termed "fraction A". This fraction was further treated with aluminium oxide, chromatography, trichloromethane, benz-dichloromethane, and separation by pH to yield vincristine.[20]

text: Vincristine was approved by the United States Food and Drug Administration (FDA) in July 1963 as Oncovin. The drug was initially discovered by a team led by Dr. J.G. Armstrong, then marketed by Eli Lilly and Company. Eli Lilly required lots of leaves of the periwinkle plant. They needed one ton of dried leaves to produce one ounce of vincristine. Periwinkle was grown on a ranch in Texas to produce vincristine for some time. [21]

text: Suppliers[edit]

text: Three generic drug makers supply vincristine in the United States – APP, Mayne, and Sicor (Teva).

text: Research[edit]

text: In 2012 the FDA approved a liposomal formulation of vincristine branded as Marqibo.[22][23] A nano-particle bound version of vincristine was under development as of 2014.[24]


document_title: Pasteurization

question_text: who invented the process that destroys harmful bacteria in milk

text: Pasteurization

text: History[edit]

text: The process of heating wine for preservation purposes has been known in China since 1117,[5] and was documented in Japan in the diary Tamonin-nikki, written by a series of monks between 1478 and 1618. Much later, in 1768, an Italian priest and scientist Lazzaro Spallanzani's research  proved  a product could be "sterile" after thermal processing.

text: He boiled meat broth for one hour, and the container was sealed immediately after boiling, and noticed that the broth did not spoil and was free from microorganisms.[2][6] In 1795, a Parisian chef and confectioner named Nicolas Appert began experimenting with ways to preserve foodstuffs, succeeding with soups, vegetables, juices, dairy products, jellies, jams, and syrups. He placed the food in glass jars, sealed them with cork and sealing wax and placed them in boiling water.[7] In that same year, the French military offered a cash prize of 12,000 francs for a new method to preserve food.  After some 14 or 15 years of experimenting, Appert submitted his invention and won the prize in January 1810.[8]  Later that year, Appert published "L'Art de conserver les substances animales et végétales" (or The Art of Preserving Animal and Vegetable Substances). This was the first cookbook of its kind on modern food preservation methods.[9][10]

text: La Maison Appert (English: The House of Appert), in the town of Massy, near Paris, became the first food-bottling factory in the world,[7] preserving a variety of food in sealed bottles. Appert's method was to fill thick, large-mouthed glass bottles with produce of every description, ranging from beef and fowl to eggs, milk and prepared dishes. He left air space at the top of the bottle, and the cork would then be sealed firmly in the jar by using a vise. The bottle was then wrapped in canvas to protect  it, while it was dunked into boiling water and then boiled for as much time as Appert deemed appropriate for cooking the contents thoroughly. Appert patented his method, sometimes called appertisation in his honor.[11]

text: Appert's method was so simple and workable that it quickly became widespread. In 1810, British inventor and merchant Peter Durand, also of French origin, patented his own method, but this time in a tin can, so creating the modern-day process of canning foods. In 1812, Englishmen Bryan Donkin and John Hall purchased both patents and began producing preserves. Just a decade later, Appert's method of canning had made its way to America.[12] Tin can production was not common until the beginning of the 20th century, partly because a hammer and chisel were needed to open cans until the invention of a can opener by Robert Yeates in 1855.[7]

text: A less aggressive method was developed by the French chemist Louis Pasteur during an 1864[13] summer holiday in Arbois. To remedy the frequent acidity of the local aged wines, he found out experimentally that it is sufficient to heat a young wine to only about 50–60 °C (122–140 °F) for a short time to kill the microbes, and that the wine could subsequently be aged without sacrificing the final quality.[13] In honour of Pasteur, the process became known as "pasteurization".[2][14] Pasteurization was originally used as a way of preventing wine and beer from souring,[15] and it would be many years before milk was pasteurized. In the United States in the 1870s, it was common for milk to contain substances intended to mask spoilage before milk was regulated.[16]

text: Milk[edit]

text: Milk is an excellent medium for microbial growth,[17] and when it is stored at ambient temperature bacteria and other pathogens soon proliferate.[18] The  US Centers for Disease Control (CDC) says improperly handled raw milk is responsible for nearly three times more hospitalizations than any other food-borne disease source, making it one of the world's most dangerous food products.[19][20] Diseases prevented by pasteurization can include tuberculosis, brucellosis, diphtheria, scarlet fever, and Q-fever; it also kills the harmful bacteria Salmonella, Listeria, Yersinia, Campylobacter, Staphylococcus aureus, and Escherichia coli O157:H7,[21][22] among others.

text: Prior to industrialization, dairy cows were kept in urban areas to limit the time between milk production and consumption hence the risk of disease transmission via raw milk was reduced.[23] As urban densities increased and supply chains lengthened to the distance from country to city, raw milk (often days old) became recognized as a source of disease. For example, between 1912 and 1937 some 65,000 people died of tuberculosis contracted from consuming milk in England and Wales alone.[24] Because tuberculosis has a long incubation period in humans, it was difficult to link unpasteurized milk consumption as the cause to the effect of disease.[25]  In 1892, chemist Earnest Lederle experimentally inoculated milk from tuberculosis-diseased cows into Guinea pigs, which caused them to develop the disease.[26]  In 1910, Lederle, then in the role of Commissioner of Health, introduced mandatory pasteurization of milk in New York city.[26]

text: Developed countries adopted milk pasteurization to prevent such disease and loss of life, and as a result milk is now widely considered one of the safest foods.[27]  A traditional form of pasteurization by scalding and straining of cream to increase the keeping qualities of butter was practiced in Great Britain before 1773 and was introduced to Boston in the British Colonies by 1773,[28] although it was not widely practiced in the United States for the next 20 years. Pasteurization of milk was suggested by Franz von Soxhlet in 1886.[29] In the early 20th century, Milton Joseph Rosenau established the standards (i.e. low temperature, slow heating at 60 °C (140 °F)  for 20 minutes) for the pasteurization of milk[30][31] while at the United States Marine Hospital Service, notably in his publication of The Milk Question (1912).[32]  States in the U.S.A. began enacting mandatory dairy pasteurization laws with the first in 1947, and in 1973 the U.S. Federal Government required pasteurization of milk used in any interstate commerce.[33]

text: The shelf life of  refrigerated pasteurized milk is greater than that of raw milk. For example high-temperature, short-time (HTST) pasteurized milk typically has a refrigerated shelf life of two to three weeks, whereas ultra-pasteurized milk can last much longer, sometimes two to three months. When ultra-heat treatment (UHT) is combined with sterile handling and container technology (such as aseptic packaging), it can even be stored non-refrigerated for up to 9 months.[34]

text: According to the United States Centers for Disease Control between 1998 and 2011, 79% of the dairy-related outbreaks were due to raw milk or cheese products.[35] They report 148 outbreaks and 2,384 illnesses (284 requiring hospitalizations), as well as two deaths due to raw milk or cheese products during the same time period.[35]

text: Pasteurization process[edit]

text: Pasteurization is a mild heat treatment of liquid foods (both packaged and unpackaged) where products are typically heated to below 100 °C. The heat treatment and cooling process are designed to inhibit a phase change of the product. The acidity of the food determines the parameters (time and temperature) of the heat treatment as well as the duration of shelf-life. Parameters also take into account nutritional and sensory qualities that are sensitive to heat.

text: In acidic foods (pH<4.6), such as fruit juice and beer, the heat treatments are designed to inactivate enzymes (pectin methylesterase and polygalacturonase in fruit juices) and destroy spoilage microbes (yeast, lactobacillus). Due to the low pH of acidic foods, pathogens are unable to grow. The shelf-life is extended several weeks. In low-acid foods (pH>4.6), such as milk and liquid eggs, the heat treatments are designed to destroy pathogens and spoilage organisms (yeast and molds). Not all spoilage organisms are destroyed under pasteurization parameters, thus requiring refrigeration.[1]

text: Equipment[edit]

text: Food can be pasteurized in two ways: either after being packaged into containers or before being packaged into containers.

text: When food is packaged in glass, hot water is used to lower risk of thermal shock. Plastics and metals are also used to package foods, and these are packaged using steam or hot water since the risk of thermal shock is low.[1]

text: Most liquid foods are pasteurized using continuous systems that have a heating zone, hold tube, and cooling zone, after which the product is filled into the package. Plate heat exchangers are used for low viscosity products such as milk, nut milks and juices.  A plate heat exchanger is composed of many thin vertical stainless steel plates, which separate the liquid from the heating or cooling medium. Scraped surface heat exchangers contain an inner rotating shaft in the tube, and serves to scrape high viscous material which might accumulate on the wall of the tube.[36]

text: Shell or tube heat exchangers are designed for the pasteurization of Non-Newtonian foods such as dairy products, tomato ketchup and baby foods. A tube heat exchanger is made up of concentric stainless steel tubes. Food passes through the inner tube while the heating/cooling medium is circulated through the outer or inner tube.

text: The benefits of a using heat exchanger to pasteurize non packaged foods versus pasteurizing foods in containers are:

text:
Heat exchangers provide uniform treatment;There is greater flexibility with regards to the products which can be pasteurized on these plate
The process is more energy efficient compared to pasteurizing foods in packaged containers.[1]
Greater throughput

text: After being heated in a heat exchanger, the product flows through a hold tube for a set period of time to achieve the required treatment.  If pasteurization temperature or time is not achieved, a flow diversion valve is utilized to divert under-processed product back to the raw product tank.[37] If the product is adequately processed, it is cooled in a heat exchanger, then filled.

text: High temperature short time (HTST) pasteurization, such as that used for milk (71.5 °C for 15 seconds) ensures safety of milk and provides a refrigerated shelf life of approximately two weeks. In UHT pasteurization, milk is pasteurized at 135 °C for 1–2 seconds which provides the same level of safety, but along with the packaging, extends shelf life to 3 months under refrigeration.[38]

text: Verification[edit]

text: Direct microbiological techniques are the ultimate measurement of pathogen contamination, but these are costly and time-consuming, which means that products have a reduced shelf-life by the time pasteurization is verified.

text: As a result of the unsuitability of microbiological techniques, milk pasteurization efficacy is typically monitored by checking for the presence of alkaline phosphatase, which is denatured by pasteurization. Destruction of alkaline phosphatase ensures the destruction of common milk pathogens. Therefore, the presence of alkaline phosphatase is an ideal indicator of pasteurization efficacy.[39][40] For liquid eggs, the effectiveness of the heat treatment is measured by the residual activity of α-amylase.[1]

text: Efficacy against pathogenic bacteria[edit]

text: During the early 20th century there was no robust knowledge of what time and temperatures combinations would inactivate pathogenic bacteria in milk, and so a number of different pasteurization standards were in use.  By 1943, both HTST pasteurization conditions of 72 °C for 15 seconds, as well as batch pasteurization conditions of 63 °C for 30 minutes, were confirmed by studies of the complete thermal death (as best as could be measured at that time) for a range of pathogenic bacteria in milk.[41] Complete inactivation of Coxiella burnetii (which was thought at the time to cause Q fever by oral ingestion of infected milk)[42][43] as well as of Mycobacterium tuberculosis (which causes tuberculosis)[44] were later demonstrated. For all practical purposes, these conditions were adequate for destroying almost all yeasts, molds, and common spoilage bacteria and also to ensure adequate destruction of common pathogenic, heat-resistant organisms. However, the microbiological techniques used until the 1960s did not allow for the actual reduction of bacteria to be enumerated.  Demonstration of the extent of inactivation of pathogenic bacteria by milk pasteurization came from a study of surviving bacteria in milk that was heat treated after being deliberately spiked with high levels of the most heat-resistant strains of the most significant milk-borne pathogens.[45]

text: The mean log10 reductions and temperatures of inactivation of the major milk-borne pathogens during a 15-s treatment are:

text:
Staphylococcus aureus >6.7 at 66.5 °C
Yersinia enterocolitica >6.8 at 62.5 °C,
pathogenic Escherichia coli >6.8 at 65 °C
Cronobacter sakazakii >6.7 at 67.5 °C
Listeria monocytogenes >6.9 at 65.5 °C, and
Salmonella ser. Typhimurium >6.9 at 61.5 °C.[45]

text: The Codex Alimentarius Code of Hygienic Practice for Milk notes that milk pasteurization is designed to achieve at least a 5 log10 reduction of Coxiella burnetii.[46]  The Code also notes that: “The minimum pasteurization conditions are those having bactericidal effects equivalent to heating every particle of the milk to 72°C for 15 seconds (continuous flow pasteurization) or 63°C for 30 minutes (batch pasteurization)” and that “To ensure that each particle is sufficiently heated, the milk flow in heat exchangers should be turbulent, i.e. the Reynolds number should be sufficiently high.”  The point about turbulent flow is important because simplistic laboratory studies of heat inactivation that use test tubes, without flow, will have less bacterial inactivation than larger scale experiments that seek to replicate conditions of commercial pasteurization.[47]

text: As a precaution, modern HTST pasteurization processes must be designed with flow-rate restriction as well as divert valves which ensure that the milk is heated evenly, and no part of the milk is subject to a shorter time or a lower temperature.  It is common for the temperatures to exceed 72 °C by 1.5 °C or 2 °C.[47]

text: Effects on nutritional and sensory characteristics of foods[edit]

text: Pasteurization, because of its mild heat treatment, increases the shelf-life by a few days or weeks.[1] However, this mild heat also means there are only minor changes to heat labile vitamins in the foods.[4]

text: Milk[edit]

text: According to a systematic review and meta-analysis,[48] it was found that pasteurization appeared to qualitatively reduce concentrations of vitamins B12 and E, but it did increase concentrations of vitamin A. Apart from meta-analysis, it's not possible to conclude the effect of pasteurization on vitamins A, B12, and E based merely on consultation of the vast literature available.[48]

text: Milk is not an important source of vitamins B12 or E in the North American diet, so the effects of pasteurization on the adult daily intake of these vitamins is negligible.[49][50] However, milk is considered an important source of vitamin A,[51] and because pasteurization appears to increase vitamin A concentrations in milk, the effect of milk heat treatment on this vitamin is a not a major public health concern.[48] Results of meta-analyses revealed that pasteurization of milk leads to a significant decrease in vitamin C and folate, but milk also is not an important source of these vitamins.[51][50] However, a significant decrease in vitamin B2 concentrations was found after pasteurization. Vitamin B2 is typically found in bovine milk at concentrations of 1.83 mg/liter. Because the recommended daily intake for adults is 1.1 mg/day,[52] milk consumption greatly contributes to the recommended daily intake of this vitamin. With the exception of B2, pasteurization does not appear to be a concern in diminishing the nutritive value of milk because milk is often not a primary source of these studied vitamins in the North American diet.

text: Sensory effects on food[edit]

text: Pasteurization, because it is a mild heat treatment, also has little effect on the sensory attributes of the foods that are processed.[1] In fruit juices, pasteurization may result in loss of volatile aroma compounds .[4] Fruit juice products undergo a deaeration process prior to pasteurization that may be responsible for this loss. Deaeration also minimizes the loss of nutrients like vitamin C and carotene.[1] To prevent the quality loss resulting from the loss in volatile compounds, volatile recovery, though costly, can be used utilized to produce higher quality juice products.[4]

text: In regards to color, the pasteurization process doesn't have much effect on pigments such as chlorophyll, anthocyanin and carotenoid in plants and animal tissues. In fruit juices, polyphenol oxidase (PPO) is the main enzyme responsible for causing browning and color changes. However, this enzyme is deactivated in the deaeration step prior to pasteurization with the removal oxygen.[4]

text: In milk, the color difference between pasteurized and raw milk is related to the homogenization step that takes prior to pasteurization. Before pasteurization, milk is homogenized to separate the solids (fat) from the liquid, which results in the pasteurized milk having a whiter appearance compared to raw milk.[1]

text: For vegetable products, color degradation is dependent on the temperature conditions and the duration of heating.[53] Pasteurization may result in some textural loss as a result of enzymatic and non enzymatic transformations in the structure of pectin if the processing temperatures are too high as a result . However, with mild heat treatment pasteurization, tissue softening in the vegetables that cause textural loss is not of concern as long as the temperature does not get above 80 °C.[53]

text: Novel pasteurization[edit]

text: Other thermal and non thermal processes have been developed to pasteurize foods as a way of reducing the effects on nutritional and sensory characteristics of foods and preventing degradation of heat labile nutrients. Pascalization or high pressure processing (HPP) and Pulsed Electric Field (PEF) are examples of these non-thermal pasteurization methods that are currently commercially utilized.[1]

text: Microwave volumetric heating (MVH) is the newest available pasteurization technology. It uses microwaves to heat liquids, suspensions, or semi-solids in a continuous flow. Because MVH delivers energy evenly and deeply into the whole body of a flowing product, it allows for gentler and shorter heating, so that almost all heat-sensitive substances in the milk are preserved.[54]

text: Products that are commonly pasteurized[edit]

text:
Beer
Canned food
Dairy products
Eggs
Milk
Juices
Low alcoholic beverages
Syrups
Vinegar
Water
Wines
Nuts


document_title: Salazar (surname)

question_text: what is the meaning of the last name salazar

text: Salazar (surname)

text: Salazar is a Basque surname meaning old hall (from Castilian Sala (hall) and Basque zahar (old)).[1] The name originates from the town of the same name: Salazar, in northern Burgos, Castile. Although nowadays northern Burgos is not a Basque-speaking region, it was during the early Middle Ages when the surname appeared.

text: Its origins are also related to a certain noble family, the Salazars, that held a fief in the area.[2] During the 10th century, the surname appears as mentioned in Navarre, where it spread and there even exists a Salazar Valley. It later also spread to the rest of the Basque Country, being specially common in Biscay during the 15th century. During that time, Lope García de Salazar, a famous writer, took part in the Reconquista of Cuenca, where he was granted a fief and founded a notable family. Some of his descendants took part in the Conquest of America, thus spreading the surname all through the Spanish Americas; others intermarried many noble families, and the surname spread all through the Iberian peninsula.

text: Salazar is also a common surname among Roma people.[2] Due to several censuses made in the Kingdom of Castile during the 14th and 15th centuries, every Castilian subject was forced to take a name and two surnames. The Roma, who used to call themselves only by a first name, decided to take established surnames to add prestige to their families.[3] They chose from among the oldest noble families, usually of Basque origin, thus it is extremely common to find Roma with surnames such as Heredia, Salazar, Mendoza, or Montoya.[4]

text: People[edit]

text: The following is a list of notable people with the surname Salazar:

text:
Abel Salazar (1917–1995), Mexican actor, producer, and director
Abel de Lima Salazar (1889–1946), Portuguese physician, lecturer, researcher, writer, and painter
Alberto Salazar (born 1958), U.S. distance runner
Alejandro Salazar, (born 1984) U.S. soccer player
Alexander Salazar (born 1949), Costa Rican-American prelate of the Roman Catholic Church
Alonso de Salazar (died 1526), Spanish explorer and discoverer of Marshal Islands
Alonso Salazar Frias (c. 1564–1636), Spanish opponent of witch trials
Anaís (Ana Isabel Salazar, born 1974), Mexican actress
Ángel Salazar (born 1956), Cuban-American comedian and actor
Antonio de Salazar (c.1650–1715), composer and choirmaster
António de Oliveira Salazar (1889 – 1970), Prime Minister and Dictator of Portugal from 1932 to 1968
Antonio Sebastián de Toledo Molina y Salazar (c. 1608 –1715), Viceroy of New Spain
Ángel Salazar (born 1961), former Major League Baseball shortstop
Braulio Salazar (1917–2008), Venezuelan painter
Carlos Salazar Castro (1800 –1867), chief of state of El Salvador and Guatemala
Carlos Salazar (born 1933), Filipino actor
Carlos Gabriel Salazar (born 1964), Argentine boxer
Carlos Eduardo Salazar Paz (born 1981), Colombian football player
Carlos Salazar, Argentine politician
Carlos Salazar Herrera (1906–1982), Costa Rican writer and artist
Cristina Díaz Salazar (born 1958), Mexican politician affiliated with the Institutional Revolutionary Party
Diego Salazar (born 1980), Colombian weightlifter
Domingo de Salazar (1512–1594), first bishop of Manila
Eliseo Salazar Valenzuela (born 1954), Chilean racing driver
Elsa Salazar Cade (born 1952), US entomologist
Emiliano Zapata Salazar (1879–1919), a leading figure in the Mexican Revolution
Evangelina Salazar (born 1946), Argentine actress
Fanny Zampini Salazar (1853 - ?), Belgian-born Italian writer, editor, and lecturer
Francisco Cervantes de Salazar (1514? – 1575), Spanish theologian, writer, chronicler and rector of the University of Mexico
Francisco Javier Salazar Sáenz, Mexican Secretary of Labor
Gabriel Salazar Vergara (born 1936), Chilean historian
Jeff Salazar (born 1980), a Major League Baseball outfielder for the Arizona Diamondbacks.
John Salazar (born 1953), member of the U.S. House of Representatives from Colorado
Jorge Ibarra Salazar, Mexican economist
José Salazar (born 1957), Venezuelan triple jumper
José Gregorio Salazar (1773–1838), general, politician, president of the Federal Republic of Central America
Juan de Oñate y Salazar (1550–1626), Spanish explorer, conquistador & governor of New Mexico
Juan García de Salazar (1639–1710), Spanish composer
Kenneth Salazar (born 1955), U.S. Secretary of the Interior and former U.S. Senator from the state of Colorado
Luciana Salazar (born 1980), Argentine model and actress
Luis Salazar (born 1956), former Major League Baseball infielder/outfielder
Manuel Salazar y Baquíjano (1777–1850), President of Peru in 1827
Martha Salazar (born 1970), American boxer
Max Salazar (1932 – 2010), US journalist and writer on Latin music
Noel B. Salazar (born 1973), European sociocultural anthropologist
Oscar Salazar (baseball) (born 1978), Major League Baseball second baseman
Oscar Salazar (taekwondo) (born 1977), Olympic taekwondo athlete from Mexico
Philippe-Joseph Salazar (born 1955), French philosopher and rhetorician
Rex Salazar, fictional protagonist of Generator Rex
Ricardo Salazar (born 1972), MLS and FIFA soccer referee
Richard Jesus (da Silva) Salazar (born 1981), Venezuelan baseball pitcher
Rubén Salazar (1928 –1970), reporter for the Los Angeles Times and KMEX-TV, Los Angeles
Tim Salazar, Member of the Wyoming House of Representatives
Vicente Lucio Salazar (1832 –1896), President of Ecuador in 1895
Kirk Maverick D. Salazar (1832 –1896), has the "will of the D", Model, Trade-Industry Development Specialist, MBA