On FlashPaper A Format for Sharing Documents on the Web
An image embedded in FlashPaper. (Coffee with a drop of milk)
One of our goals at Scribd is to create "the best way to publish a document online." For short and simple documents, it is generally best to display the text in HTML format. However, for any document that is more than a few pages long or has complex formatting, HTML doesn't work very well. We could allow people to just attach their document as a PDF or Microsoft Word file, but then the site wouldn't be any fun to browse, because users would have to download each document they want to view. We saw the difficulty with sharing formatted documents as a real problem, and we looked for a way to solve it. What we found was a product called Macromedia FlashPaper, which we had actually never heard of. The document you’re reading now, by the way, is in FlashPaper format. FlashPaper documents are Flash SWF files that look and function a lot like PDF files.
FlashPaper works great for technical articles, faithfully preserving formatting.
A role for the anaphasepromoting complex inhibitor Emi2 XErp1, a homolog of early mitotic inhibitor 1, in cytostatic factor arrest of Xenopus eggs Jeffrey J. Tung* † , David V. Hansen* † , Kenneth H. Ban* † , Alexander V. Loktev*, Matthew K. Summers*, John R. Adler III*, and Peter K. Jackson* †‡ *Department of Pathology and † Program in Cancer Biology, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305
Communicated by Marc W. Kirschner, Harvard Medical School, Boston, MA, February 9, 2005 (received for review November 30, 2004)
Unfertilized vertebrate eggs are arrested in metaphase of meiosis II with high cyclin B Cdc2 activity to prevent parthenogenesis. Until fertilization, exit from metaphase is blocked by an activity called cytostatic factor (CSF), which stabilizes cyclin B by inhibiting the anaphasepromoting complex (APC) ubiquitin ligase. The APC in hibitor early mitotic inhibitor 1 (Emi1) was recently found to be required for maintenance of CSF arrest. We show here that exog enous Emi1 is unstable in CSFarrested Xenopus eggs and is destroyed by the SCF TrCP ubiquitin ligase, suggesting that endog enous Emi1, an apparent 44kDa protein, requires a stabilizing factor. However, antiEmi1 antibodies crossreact with native Emi2 Erp1 FBXO43, a homolog of Emi1 and conserved APC inhibitor. Emi2 is stable in CSFarrested eggs, is sufficient to prevent CSF release, and is rapidly degraded in a Pololike kinase 1dependent manner in response to calciummediated egg activation. These results identify Emi2 as a candidate CSF maintenance protein.
Upon fertilization of Xenopus eggs, calcium signaling inactivates CSF arrest, which requires the Xenopus Pololike kinase 1 (Plx1). The t arget of Plx1 in this pathway remains unk nown (13). In human somatic cells, MPF and human Pololike kinase 1 (Plk1) t arget Emi1 for degradation by the Skpl Cullin Fbox protein (SCF) TrCP ubiquitin ligase (14 –17). Specifically, Plk1 phosphor ylates Emi1 on its DSGxxS sequence, creating a c onsensus degron rec ognized by TrCP (17). Thus, Xenopus Emi1 (xEmi1) c ould be a Plx1 t arget downstream of calcium signaling. A n apparent paradox is how Emi1 levels are sust ained in the CSFarrested egg amid high MPF and Plx1 activities. In line w ith this paradox, a recent report suggests that Emi1 is unstable and undetectable in Xenopus eggs (18). On the other hand, Emi1 appears to be present in mouse eggs (10). In this study, we want to clarif y our underst anding of Emi1 regulation in Xenopus eggs and find that Emi2, an Emi1 homolog, may c ontribute to CSF arrest.
cyclin B meiosis maturationpromoting factor oocyte maturation
Methods Reagents. Sera f rom four rabbits immunized w ith maltose binding
T
o prevent parthenogenesis, unfertilized eggs f rom many an imals arrest in metaphase of meiosis II (MII). Sper m penetration triggers the release f rom metaphase arrest and the c ommencement of alternating cycles of DNA replication and cell div ision in the embr yo. The regulator y basis for metaphase II 30 years ago and arrest was first characterized in f rog eggs termed c ytost atic factor (CSF) (1). CSF is operationally defined as an activ it y, rather than a single molecule, present in unfer tilized eggs that blocks cleavage of div iding blastomeres upon injection (reviewed in ref. 2). Mos, an activator of the mitogen activated protein kinase Rsk pathway, is a key c omponent of CSF that appears at the onset of meiosis I (MI) and activates CSF to block cleavage of blastomeres (3). The anaphasepromoting c omplex (A PC) is an E3 ubiquitin ligase that triggers Mphase ex it by directing proteasome dependent cyclin B destruction (4), resulting in the swif t inac tivation of the cyclin B Cdc2 kinase, or maturation promoting factor (MPF) (5, 6). A rise in intracellular calcium af ter fertil ization induces metaphase II release by relieving the A P C f rom repression. Early mitotic inhibitor 1 (Emi1), originally cloned f rom a Xenopus ooc y t e cDNA librar y, blocks the cleavage of injected blastomeres similar to CSF (7) and efficiently inhibits the A P C in vitro (8). Recently, Emi1 was shown to be required for maintenance of CSF arrest in f rog and mouse eggs. Immu nodepletion of Emi1 f rom Xenopus CSF egg extract causes rapid cyclin B proteolysis and ex it f rom metaphase arrest independent of calcium mobilization, and ablation of Emi1 by small inter fer ing RNA in mouse ooc y t es induces parthenogenesis (9, 10). Recent work has shown that the Mos mitogenactivated protein kinase Rsk pathway es t ablishes, but is not required to maint ain, CSF arrest (11, 12). Therefore, CSF arrest is a c omplex process es t ablished by the mitogenactivated protein kinase pathway and maintained through inhibition of the APC. 4318 – 4323
PNAS
March 22, 2005
vol. 102
no. 12
protein (MBP)Emi1 fusion protein were affin it ypurified by f low ing over a c olumn of GSTEmi1 immobilized on CNBrSepharose resin w ith acid elution. Other antibodies used were against cate n in, cyclin B2, Plx1, Plk1 (Zymed), myc epitope, and actin (Santa Cr uz Biotechnolog y). xEmi2 was PCRcloned f rom an ooc y te cDNA librar y, and a human Emi2 (hEmi2) clone was purchased f rom Inv itrogen. pCS2cDNA c onstr ucts were linearized and in vitrotranscribed to generate mRNA by using a mMessage Machine k it (Ambion, Austin, TX). pCS2cDNA c onstr ucts were in vitro translated (I VT) in rabbit reticuloc y te l ysate (TNT, Promega) and labeled w ith 35 Smethionine. A ll Emi1 and Emi2 ex periments used Xenopus sequences unless other w ise noted as hEmi1 and hEmi2 for human sequences. MBPfusion proteins and GSTPlk1 were ex pressed in Escherichia coli and purified by batch binding bacterial protein l ysate to affin it y resin and elution w ith maltose or gluta thione, then dialyzed into XB buffer (20 mM Hepes, pH 7.7 100 mM KCl). Point mutations were engineered w ith a QuikChange k it (Stratagene). Handling of Xenopus Oocytes. Ooc y tes were obtained and processed
for H1 k inase activ it y and immunoblot as described (19). Ooc ytes were injected w ith 30 ng of MBPEmi1 fusion protein or 10 ng of various mRNA in tot al volumes not exceeding 50 nl. Maturation Freely available online through the PNAS open access option. Abbre viations: APC, anaphaseprom oting complex; CHX, cycloheximide; CSF, cytostatic factor; Emi, early mitotic inhibitor; hEmi, hum an Emi; xEmi, Xenopus Emi; GVBD, germinal vesicle breakdow n; IVT, in vitrotranslated; MI, m eiosis I; MII, meiosis II; MBP, Maltose binding protein; MPF, mitosisprom oting factor; Plk1, hum an Pololike kinase 1; Plx1, Xenopus Pololike kinase 1; SCF, Skpl Cullin Fbox protein. Data deposition: The sequence reported in this paper has been deposited in the GenBank database (accession no. AY928267). ‡ To whom correspondence should be addressed. Email: pjackson@stanford.edu.
© 2005 by The National Academy o f Sciences of the USA
www.pnas.org cgi doi 10.1073 pnas.0501108102
Like Acrobat, FlashPaper is great for documents that are long and have complex formatting. But because they’re Flash, FlashPaper docs can be viewed in a webpage, so you don't even have to open a new window, and they don’t require installing any new plugins. They can even be embedded in an external webpage, similar to YouTube's video player.
When we started showing FlashPaper to people, we heard a lot of complaints about Adobe Acrobat. It seems that a lot of people dislike Acrobat, and the biggest complaints are the incredibly slow load times and the fact that it still seems to suffer from bugs that lock the user’s browser. Acrobat 7 improved the load times over Acrobat 6, but the plethora of rarely used Acrobat plugins and features still slows things down. FlashPaper has only a few features, which makes it poor for use in big corporations, but a lot faster to load. Doc. Our mascot.
Given these advantages, we naturally wondered why FlashPaper isn’t used more. We can’t say for sure, but we like to think the reason isn’t the technology behind FlashPaper, but rather FlashPaper’s long and convoluted history. The FlashPaper product line has actually been owned by no fewer than 4 corporations, each one in turn having been bought by the next.
Figure: FlashPaper even works for sheet music!
A Brief History of FlashPaper It was originally called Flash Printer when first developed at Blue Pacific Software but at this point, it didn't have an interface and was Windows only. Later eHelp Corporation acquired the product and bundled it into the RoboFlash Toolkit, which was an ungainly combination of 6 Flash addon tools. In October 2003, eHelp was acquired by Macromedia for about $65 million, and the RoboFlash Toolkit was basically split up. Macromedia created the name FlashPaper, and added a nice navigational interface to the product. However, they didn’t release it as a separate product, instead bundling it with Contribute 2, a web publishing suite. Eventually, Macromedia unbundled FlashPaper from Contribute and added some significant features like the ActionScript API that makes Scribd possible. When Macromedia first released FlashPaper in 2003, it generated a lot of commotion in the technical press. At the time, Macromedia and Adobe were the archenemies of the desktop publishing world. Adobe had created the highly successful PDF standard, and FlashPaper was seen as Macromedia’s comeback format. Despite mostly rave reviews in the technology press (“the best software graphics innovation for 2003”, according to one), FlashPaper bundled with Contribute was slow to catch on as a competing format to the already wellestablished PDF. Perhaps it would have eventually, but soon afterwards, Adobe acquired Macromedia in a $3.4 billion transaction. That transaction got a lot of attention, with plenty of talk of its impact on developers and possible antitrust issues. But Adobe can hardly compete with itself, and after the acquisition, FlashPaper dropped off the map.
Figure: FlashPaper is great for magazine and newspaper articles
The quintessential works of Modernism Seven decades of domus: the best of the best in 12 volumes, 7,000 pages and 20,000 images D OMUS 1928–1999, VOL. I–XII
Eds. Charlotte & Peter Fiell / Har dcover, 12 vols. + index CD, f ormat: 21.8 x 31.4 cm (8.6 x 12.4 in.), 6,960 pp. (580 pp. each v olume)
ONLY € 500 / $ 600 £ 350 / ¥ 75.000
For ov er sev enty f ive years, domus has b een hailed as the world’s most inf luential architectur e and design journal. Founded in 1928 by the great Milanese architect Gio Ponti, the magazine’s central ag enda has always r emained that of creating a privileged insight toward identifying the style of a particular age, fr om Art Deco, Mo dern Mov ement, F unctionalism and Postwar to Pop, Post Modernism and Late Modern. Beautifully designed and comprehensively documented, pag e after pag e domus pr esents some of the most e x citing design and architec tur e projects fr om ar ound the world TASCHEN’s twelve v olume r eprint f eatur es selected high lights fr om the years 1928 to 1999. Reproducing the pag es as they originally appeared, each v olume is
packed with articles that bring to light the incredible histor y of modern design and architectur e. This set of 12 v olumes reflects one to one the actual size of the original domus agazine. A truly comprehensiv e lexicon of styles and mov ements, the v olumes ar e accompanied b y specially commissioned intr oductor y te xts hat not only outline the histor y of the magazine but also describ e what wa s happ ening in design and architectur e during each era cove r ed. These te xts have b een written by many of the magazine’s r enowned past editors: Mario Bellini, François Burkhar dt, Cesare Maria Casati, Stefano Casciani, Germano Celant, Manolo De Giorgi, Fu lvio Irace, Vittorio Magnag o La mpugnani, Alessandr o Mendini, L isa L icitra Ponti, Ettor e hat not only outline the histor y of the magazine but also describ e what wa s
happ ening in design and architectur e during each era cove r ed. These te xts have b een written by many of the magazine’s r enowned past editors: Mario Bellini, François Burkhar dt, Cesare Maria hat not only outline the histor y of the magazine but also describ e what wa s happ ening in design and architectur e during each era cove r ed. These te xts have b een written by many of the magazine’s r enowned past editors: Mario Bellini, François Burkhar dt, Cesare Maria Casati, Stefano Casciani, Germano Celant, Manolo De Giorgi, Fu lvio Irace, Vittorio Magnag o La mpugnani, Alessandr o Mendini, L isa L icitra Ponti, Ettor e
ScribdPaper We think that as a straight alternative to PDF, FlashPaper doesn’t do that well. For one thing, you can’t easily email or save FlashPaper files. That’s why we made a special FlashPaper player for Scribd (“ScribdPaper”) that tries to combine the best aspects of the two formats. FlashPaper is used for viewing on the Web, where it allows fast previews and no downloads. But the Scribd player also allows you to save a PDF version to your computer. The even bigger problem with FlashPaper is that to distribute FlashPaper files yourself, you need to buy the FlashPaper software, create your FlashPaper file, and then upload it to a web server embedding it in custom HTML. We’ve tried to make this process simpler by doing most of that for you. Admittedly, FlashPaper has some significant drawbacks as a document viewing format, one of them being the confusing “double scrollbar” effect you get when viewing an embedded FlashPaper document. If these drawbacks turn out to be a real problem, we’re not necessarily wedded to FlashPaper and do have some other ideas for better formats up our sleeves. But for now we’re trying an experiment in this new way of displaying documents, and we’re looking forward to seeing how it turns out.
Docs are cool.