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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 anaphase-promoting 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 anaphase-promoting 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 CSF-arrested Xenopus eggs and is destroyed by the SCF TrCP ubiquitin ligase, suggesting that endog- enous Emi1, an apparent 44-kDa protein, requires a stabilizing factor. However, anti-Emi1 antibodies crossreact with native Emi2 Erp1 FBXO43, a homolog of Emi1 and conserved APC inhibitor. Emi2 is stable in CSF-arrested eggs, is sufficient to prevent CSF release, and is rapidly degraded in a Polo-like kinase 1-dependent manner in response to calcium-mediated egg activation. These results identify Emi2 as a candidate CSF maintenance protein.
cyclin B meiosis maturation-promoting factor oocyte maturation
Upon fertilization of Xenopus eggs, calcium signaling inactivates CSF arrest, which requires the Xenopus Polo-like kinase 1 (Plx1). The target of Plx1 in this pathway remains unknown (13). In human somatic cells, MPF and human Polo-like kinase 1 (Plk1) target Emi1 for degradation by the Skpl Cullin F-box protein (SCF) TrCP ubiquitin ligase (14 –17). Specifically, Plk1 phosphorylates Emi1 on its DSGxxS sequence, creating a consensus degron recognized by TrCP (17). Thus, Xenopus Emi1 (xEmi1) could be a Plx1 target downstream of calcium signaling. An apparent paradox is how Emi1 levels are sustained in the CSF-arrested egg amid high MPF and Plx1 activities. In line with 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 clarify our understanding of Emi1 regulation in Xenopus eggs and find that Emi2, an Emi1 homolog, may contribute to CSF arrest. Methods
Reagents. Sera from four rabbits immunized with maltose binding
o prevent parthenogenesis, unfertilized eggs from many animals arrest in metaphase of meiosis II (MII). Sperm penetration triggers the release from metaphase arrest and the commencement of alternating cycles of DNA replication and cell division in the embr yo. The regulator y basis for metaphase II arrest was first characterized in frog eggs 30 years ago and termed cytostatic factor (CSF) (1). CSF is operationally defined as an activity, rather than a single molecule, present in unfer- tilized eggs that blocks cleavage of dividing blastomeres upon injection (reviewed in ref. 2). Mos, an activator of the mitogen- activated protein kinase Rsk pathway, is a key component of CSF that appears at the onset of meiosis I (MI) and activates CSF to block cleavage of blastomeres (3). The anaphase-promoting complex (A PC) is an E3 ubiquitin ligase that triggers M-phase exit by directing proteasome- dependent cyclin B destruction (4), resulting in the swift inac- tivation of the cyclin B Cdc2 kinase, or maturation- promoting factor (MPF) (5, 6). A rise in intracellular calcium after fertil- ization induces metaphase II release by relieving the A PC from repression. Early mitotic inhibitor 1 (Emi1), originally cloned from a Xenopus oocyte cDNA librar y, blocks the cleavage of injected blastomeres similar to CSF (7) and efficiently inhibits the A PC in vitro (8). Recently, Emi1 was shown to be required for maintenance of CSF arrest in frog and mouse eggs. Immunodepletion of Emi1 from Xenopus CSF egg extract causes rapid cyclin B proteolysis and exit from metaphase arrest independent of calcium mobilization, and ablation of Emi1 by small interfering RNA in mouse oocytes induces parthenogenesis (9, 10). Recent work has shown that the Mos mitogen-activated protein kinase Rsk pathway establishes, but is not required to maintain, CSF arrest (11, 12). Therefore, CSF arrest is a complex process established by the mitogen-activated protein kinase pathway and maintained through inhibition of the A PC.
protein (MBP)-Emi1 fusion protein were affinity-purified by f low- ing over a column of GST-Emi1 immobilized on CNBrSepharose resin with acid elution. Other antibodies used were against -cate- nin, cyclin B2, Plx1, Plk1 (Zymed), myc epitope, and actin (Santa Cruz Biotechnology). xEmi2 was PCR-cloned from an oocyte cDNA library, and a human Emi2 (hEmi2) clone was purchased from Invitrogen. pCS2-cDNA constructs were linearized and in vitro-transcribed to generate mRNA by using a mMessage Machine kit (Ambion, Austin, TX). pCS2cDNA constructs were in vitro- translated (IVT) in rabbit reticulocyte lysate (TNT, Promega) and labeled with 35Smethionine. All Emi1 and Emi2 experiments used Xenopus sequences unless otherwise noted as hEmi1 and hEmi2 for human sequences. MBP-fusion proteins and GST-Plk1 were expressed in Escherichia coli and purified by batch binding bacterial protein lysate to affinity resin and elution with maltose or gluta- thione, then dialyzed into XB buffer (20 mM Hepes, pH 7.7 100 mM KCl). Point mutations were engineered with a QuikChange kit (Stratagene).
Handling of Xenopus Oocytes. Oocytes were obtained and
processed for H1 kinase activity and immunoblot as described (19). Oocytes were injected with 30 ng of MBP-Emi1 fusion protein or 10 ng of various mRNA in total volumes not exceeding 50 nl. Maturation
Freely available online through the PNAS open access option. Abbreviations: APC, anaphase-promoting complex; CHX, cycloheximide; CSF, cytostatic factor; Emi, early mitotic inhibitor; hEmi, human Emi; xEmi, Xenopus Emi; GVBD, germinal vesicle breakdown; IVT, in vitro-translated; MI, meiosis I; MII, meiosis II; MBP, Maltose binding protein; MPF, mitosis-promoting factor; Plk1, human Pololike kinase 1; Plx1, Xenopus Polo-like kinase 1; SCF, Skpl Cullin F-box protein. Data deposition: The sequence reported in this paper has been deposited in the GenBank database (accession no. AY928267).
whom correspondence should be addressed. E-mail: firstname.lastname@example.org.
© 2005 by The National Academy of Sciences of the USA
4318 – 4323
March 22, 2005
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 add-on 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 come-back 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 well-established 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 anti-trust 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
DOMUS 1928–1999, VOL. I–XII Eds. Charlotte & Peter Fiell / Hardcover, 12 vols. + index CD, format: 21.8 x 31.4 cm (8.6 x 12.4 in.), 6,960 pp. (580 pp. each volume)
Seven decades of domus: the best of the best in 12 volumes, 7,000 pages and 20,000 images
ONLY € 500 / $ 600 £ 350 / ¥ 75.000
For over seventy-five years, domus has been hailed as the world’s most influential architecture and design journal. Founded in 1928 by the great Milanese architect Gio Ponti, the magazine’s central agenda has always remained that of creating a privileged insight toward identifying the style of a particular age, from Art Deco, Modern Movement, Functionalism and Postwar to Pop, PostModernism and Late Modern. Beautifully designed and comprehensively documented, page after page domus presents some of the most exciting design and architecture projects from around the world TASCHEN’s twelve-volume reprint features selected high- lights from the years 1928 to 1999. Reproducing
the pages as they originally appeared, each volume is packed with articles that bring to light the incredible history of modern design and architecture. This set of 12 volumes reflects one-to-one the actual size of the original domus agazine. A truly comprehensive lexicon of styles and movements, the volumes are accompanied by specially commissioned introductory texts hat not only outline the history of the magazine but also describe what was happening in design and architecture during each era covered. These texts have been written by many of the magazine’s renowned past editors: Mario Bellini, François Burkhardt, Cesare Maria Casati, Stefano Casciani, Germano Celant, Manolo De Giorgi, Fulvio Irace, Vittorio Magnago Lampugnani,
Alessandro Mendini, Lisa Licitra Ponti, Ettore hat not only outline the history of the magazine but also describe what was happening in design and architecture during each era covered. These texts have been written by many of the magazine’s renowned past editors: Mario Bellini, François Burkhardt, Cesare Mariahat not only outline the history of the magazine but also describe what was happening in design and architecture during each era covered. These texts have been written by many of the magazine’s renowned past editors: Mario Bellini, François Burkhardt, Cesare Maria Casati, Stefano Casciani, Germano Celant, Manolo De Giorgi, Fulvio Irace, Vittorio Magnago Lampugnani, Alessandro Mendini, Lisa Licitra Ponti, Ettore
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.