By the fall of 1983, we had committed to announcing and shipping the Macintosh at Apple's next annual shareholder's meeting, to be held on January 24th, 1984. The failure of the Twiggy disk drive almost caused us to be late (see Quick, Hide In This Closet!) , but it seemed like the new Sony 3.5 inch drive solved all of our problems, and the rest of the hardware was ready to go. The Macintosh ROM was frozen in early September and sent out for fabrication. All that remained was finishing the System Disk, and our two applications, MacWrite and MacPaint.
The software team worked hard over the Christmas break of 1983. The Finder still wasn't finished, and there were lots of performance problems, especially when copying files between disks, which seemed interminable. There was lots of integration testing to do, like cutting and pasting between applications, or applications interacting with desk accessories. As the New Year rolled around, it was clear that we were running out of time.
By the first week of January, the software team was working around the clock, testing and fixing problems that were found. Every employee in the building was drafted as a tester, and we held a series of dinners where Apple bought catered food for anyone who stayed late to test [story:90 Hours A Week And Loving It].
Finally, the deadline for finishing the software was less than a week away, and it seemed obvious that there were still too many bugs for us to ship it. Late on Friday evening, we convinced ourselves that we needed an extra week or two to fix the remaining problems. Steve Jobs was on the East Coast, along with Bob Belleville and Mike Murray, doing press for the introduction, so we arranged for a conference call early Sunday morning to tell him about the slip.
Jerome Coonen, our software manager, spoke for the team, as we gathered around the speakerphone. We were exhausted, and progress was slow. There were still bugs that we hadn't gotten to the bottom of yet, and it didn't seem possible that we could make it in the time remaining. Jerome proposed that we ship "demo" software to the dealers for the introduction, and update all the customers with final software a few weeks later. We thought Jerome was pretty persuasive as we held our breath waiting for Steve to respond.
"No way, there's no way we're slipping!", Steve responded. The room let out a collective gasp. "You guys have been working on this stuff for months now, another couple weeks isn't going to make that much of a difference. You may as well get it over with. Just make it as good as you can. You better get back to work!"
We did manage to wrangle an extra couple of days, by virtue of working the weekend and moving the deadline to 6am Monday morning, when the factory opened, instead of Friday afternoon. We agreed to go home and rest up, and then come into work on Monday ready for the final push.
The final week was one of the most intense I ever experienced. Steve wanted Bill Atkinson and myself to fly to New York to present a Mac to Mick Jagger, but I decided that I needed to stay in Cupertino to help with the bug fixing. Some of us were pausing work to get photographed for magazines like Newsweek and Rolling Stone, which made others on the team feel terrible that they were being left out. At times, the atmosphere got pretty tense.
Friday finally rolled around and it was clear that there were still too many bugs in both the Finder and MacWrite. Randy Wigginton brought in a gigantic bag of chocolate covered espresso beans, which, along with medicinal quantities of caffeinated beverages, helped us forgo sleep entirely for the last couple of days. We starting doing release cycles that were only a few hours apart, re-releasing every time we fixed a significant problem.
When a new release was ready, we would all grab it and start testing again. At one point, around 2am on Sunday night, I stumbled across a bug in the clipboard code. I thought I knew what it might be, but I was so tired that I didn't want to deal with it. I tried to pretend that I didn't see the problem, but Steve Capps was watching my expression and knew there was something wrong. I also was too tired to sustain a pretense; he grilled me about the problem and then helped me craft a fix, since I was too tired to do it on my own.
Around 4am, we had a release where everything seemed to go wrong - even MacPaint was crashing, which was usually rock solid. But our final release, around 5:30am seemed to be much better; the worst problems seemed to have receded and we thought we might actually have a decent release candidate.
We all focused on testing the final release as much as we could until 6am, when Jerome would have to leave to drive it to the factory. It looked pretty good, but soon someone found a potential show stopper - the system seemed to hang when a blank disc was inserted during MacWrite - the disk didn't start formatting like it should. I realized that it was probably hung up waiting for an event, so I reached out and tapped on the space bar, and formatting commenced. Jerome thought the bug was bad enough to hold up the release, but he left to drive it to the factory anyway, figuring they needed to start duplication even if it was just going to be a demo release.
The sun had already risen and the software team finally began to scatter and go home to collapse. We weren't sure if we were finished or not, and it felt really strange to have nothing to do after working for so hard for so long. Instead of going home, Donn Denman and I sat on a couch in the lobby in a daze and watched the accounting and marketing people trickling into work around 7:30am or so. We must have been quite a sight; everybody could tell that we had been there all night (actually, I hadn't been home or showered for three days).
Finally, around 8:30 Steve Jobs arrived, and as soon as he saw us he immediately asked if we had made it. I explained the formatting bug to him, and he thought that it wasn't a show stopper, which meant that we were actually finished. I finally drove home to Palo Alto around 9am and collapsed on my bed, thinking that I'd sleep for the next day or two.
And as if to rub their noses in it, the Chinese premier confided that he re-read Adam Smith over the summer (note "re-read") to reassure himself that the founder of modern economics wasn't the dogmatic opponent of government intervention that liberal market ideologues contend.
Linux and "MacBook Air killers":
* Sony Vaio Z-series and Linux --- any of the Z series laptops.
* Lenovo ThinkPad X301 and Linux
* Dell Latitude E4200/E4300 and Linux
* Dell Adamo and Linux (soon)
* HP Vodoo Envy 133 and Linux (soon)
* MSI X-Slim Series X320 and Linux (soon)
* Toshiba Portégé R500-11J and Linux (soon)
Rail campaigners are backing a 100mph fast train route across the centre of England linking Oxford and Cambridge.
The fast train route would go via Bicester, Aylesbury, Milton Keynes and Bedford with integrated links to connect Ipswich and Norwich to Swindon.
The plan involves a combination of existing, upgraded and reopened lines.
Peter Lawrence, of Railfuture, said: "We want to link fast growing communities without causing road congestion or crossing London."
The group believes the route would encourage inward investment from industry and tourism as well as providing much-needed additional capacity for passengers and freight.
"At a time when environmental concerns are top of the agenda, it's more important than ever to invest in green transport such as rail," Mr Lawrence said.
"In Wales and Scotland miles of new railway are being built. Why not in England?
"We're calling on the East of England Assembly and development agency to work with their colleagues in the South East and continue to press for this strategic rail link".
It is proposing a review of the rules, that would see revisions being approved before they were added to the site.
The first stable release in the 1.6 series is now available for download.
Dr Goncalo Abecasis, one of the researchers from the University of Michigan, thinks that the discovery may allow further progress than this, with proteins produced at the "hotspots" offering possible targets for future treatments.
"This discovery highlights the role of several genes in mediating the immune responses that result in psoriasis," he said.
"Some of the highlighted genes are already targeted by effective psoriasis therapies - others may become targets for the psoriasis treatments of the future."
Control slideshow media
Before OpenOffice.org would play any movies and audio when the slide opened, but Impress 3.1 can flexibly start, pause, and stop media using custom animation effects.
The minor spliceosome is a ribonucleoprotein complex that catalyses the removal (splicing) of an atypical class of spliceosomal introns (U12-type) from eukaryotic messenger RNAs in plant, insects, vertebrates and some fungi (Rhizopus oryzae). This process is called noncanonical splicing, as opposed to U2-dependent canonical splicing. U12-type introns represent less than 1% of all introns in human cells. However they are found in genes performing essential cellular functions.
* Introduction to Drosophila
* Advanced genetics
* The Drosophila genomes
* Evolutionary genetics
* Genetic analysis of complex characters
* Genetic screens
* Mosaics and P-element systems
* Genetic analysis of sex determination
* Transcriptomics and Proteomics
* Developmental genetics
* Professor Michael Ashburner (University of Cambridge, UK)
* Dr Scott Hawley (Stowers Institute for Medical Research, MO, USA)
* Dr Casey Bergman (University of Manchester)
* Steve Russell (University of Cambridge, UK)
* Ruth Lehmann (New York University School of Medicine, USA)
* Daniel St Johnston (The Gurdon Institute, Cambridge, UK)
* Kent Golic (University of Utah, USA)
* Brian Charlesworth (University of Edinburgh, UK)
* Trudy Mackay (North Carolina State University, USA)
* Leslie Vosshall (The Rockefeller University, NY, USA)
* Bruce Baker (Stanford University, CA, USA).
If you don't have home broadband then fear not, because there are lofty plans afoot to guarantee all UK households access to broadband.
A draft report by Lord Carter on the future of UK telecoms and the media sector proposes a "universal service commitment" to broadband along the lines of what's in place for postal and telephone services.
According to the FT the report, due out in a few weeks, calls for a minimum of 2Mb broadband to be made available to every home in the UK by 2012 - no matter what cloud-scraping mountaintop or out of the way hamlet you're stuck in.
* 5 big leeks, outer leaves trimmed back, washed
* Olive oil
* 3 good knobs butter, divided
* 3 cloves garlic, peeled and finely sliced
* A few sprigs fresh thyme, leaves picked
* A small wineglass white wine
* Sea salt and freshly ground black pepper
* 1 pint good-quality vegetable or chicken stock
* 12 slices ham, preferably Parma
* 2 (8-ounce) packages fresh lasagne sheets
* All-purpose flour, for dusting
* 2 handfuls freshly grated Parmesan, plus extra for serving
For the Pangrattato:
* 1 small handful dried porcini mushrooms
* 1/2 ciabatta bread, preferably stale, cut into chunks
* Sea salt and freshly ground black pepper
* Olive oil
* 2 cloves garlic, crushed
* 1 sprig fresh rosemary
Halve the leeks lengthways and cut at an angle into 1/2-inch slices. Heat a wide saucepan, add a splash of oil and a knob of butter, and when you hear a gentle sizzling add the sliced garlic, thyme leaves and leeks. Move the leeks around so every piece gets coated. Pour in the wine, season with pepper and stir in the stock. Cover the leeks with the slices of Parma ham, place a lid on the pan and cook gently for 25 to 30 minutes. Once the leeks are tender, take the pan off the heat.
To make the pangrattato:
Whiz the mushrooms and bread with a pinch of salt and pepper in a food processor until the mixture looks like bread crumbs. Heat a generous glug of olive oil in a frying pan. Add the garlic cloves and the rosemary and cook for a minute, then fry the bread crumbs in the oil until golden and crisp. Keep shaking the pan - don't let the bread crumbs catch on the bottom. Drain on paper towels, discard the rosemary and garlic and allow the bread crumbs to cool.
Bring a big pan of salted water to the boil. Lay the lasagne sheets on a clean working surface and sprinkle with a little flour. Place the sheets on top of each other and slice into 1/2-inch strips. Toss through your fingers to shake out the pappardelle, then cook in the boiling water 2 minutes or until al dente.
Remove the Parma ham from the saucepan, slice up and stir back into the leeks. Season to taste with salt and pepper, then stir in the Parmesan and the rest of the butter. Drain the pasta, reserving a little of the cooking water, and add the pasta to the leeks. Add a little of the cooking water if need be, to give you a silky, smooth sauce. Serve quickly, sprinkled with some pangrattato, extra Parmesan and any leftover thyme tips. Serve the rest of the pangrattato in a bowl on the side.
"Our agreement with the producers of "Jamie at Home" only permit us to make 2 recipes per episode available online. Food Network regrets the inconvenience to our viewers and foodnetwork.com users"
As I said this morning, this is not a bank rescue plan. But if it had been, it would have failed miserably. Barclays' share price has fallen again today. At the current price of 90p, this bank's entire market value is £7.5bn. And remember, this is a bank that said on Friday night that its profits for 2008 were considerably more than £5.3bn. In other words, investors currently value this giant international bank at a little over one year's profits. Which is little short of extraordinary. And let's not even mention that Royal Bank of Scotland's shares are down by more than 50%, on the supposedly reassuring news that taxpayers will be sharing in its future pain. Confidence has drained from the banking system. And to state the obvious, today's myriad announcements from the Treasury have not succeeded in rebuilding that confidence, which is so vital to a functioning economy.
It was a creed written into the founding documents that declared the destiny of a nation: Yes, we can.
It was whispered by slaves and abolitionists as they blazed a trail towards freedom through the darkest of nights: Yes, we can.
It was sung by immigrants as they struck out from distant shores and pioneers who pushed westward against an unforgiving wilderness: Yes, we can.
It was the call of workers who organized, women who reached for the ballot, a president who chose the moon as our new frontier, and a king who took us to the mountaintop and pointed the way to the promised land: Yes, we can, to justice and equality.
Yes, we can, to opportunity and prosperity. Yes, we can heal this nation. Yes, we can repair this world. Yes, we can.
Spain's economy will contract 1.6 percent this year and unemployment will jump to nearly 16 percent, the government predicted Friday in a desperately gloomy outlook for a country that had been one of Europe's great success stories.
The length of a man's fingers may predict his success in the City, research findings suggest.
Land earmarked for the construction of Heathrow's third runway has been bought by anti-expansion protesters.
Fertile queens and sterile workers are alternative forms of the adult female honeybee that develop from genetically identical larvae following differential feeding with royal jelly. We show that silencing the expression of DNA methyltransferase Dnmt3, a key driver of epigenetic global reprogramming, in newly hatched larvae led to a royal jelly–like effect on the larval developmental trajectory; the majority of Dnmt3 small interfering RNA–treated individuals emerged as queens with fully developed ovaries. Our results suggest that DNA methylation in Apis is used for storing epigenetic information, that the use of that information can be differentially altered by nutritional input, and that the flexibility of epigenetic modifications underpins, profound shifts in developmental fates, with massive implications for reproductive and behavioral status.
Professor Mark Blaxter of Edinburgh University hopes to redress this deficit by sequencing more invertebrate genomes, starting with the earthworm. Blaxter says his lab is taking a leap of faith by applying new sequencing technologies to the challenge of a whole genome, and is spending a mere £25,000 on the project, compared with previous genome projects costing millions. The whole process is surprisingly fast – the donor worm was squashed in October and he estimates the lab will have a completed genome by March 2009.
Multiple Sequence Alignment and Insertion/Deletion Annotations
For the analysis of TFBS evolution, we developed a new multiple alignment program, “ProbconsMorph”, by integrating Probcons , a consistency based multiple sequence alignment program, and Morph , a pair-wise sequence alignment program that is specially designed to align regulatory modules. Morph uses a pair-HMM as a generative model for alignment of two orthologous CRMs, and is parameterized by the given motifs, as well as various evolutionary rate parameters that it fits to the data. It uses maximum likelihood inference to simultaneously perform TFBS annotation and alignment. It reports for every pair of positions in the two sequences, the posterior probability that they are aligned. Morph was run to produce such a probabilistic alignment of every pair of species. Probcons takes such pair-wise alignment probabilities and builds a multiple sequence alignment progressively, while using the “consistency transformation”: the probability of alignment of two nucleotides and is updated based on the alignment probabilities of and and of and , where is a nucleotide from a third species. We have shown previously that Morph provides practical benefits for inference of evolutionary events and rates by computing a better alignment; ProbconsMorph is an effective and efficient extension of this program to more than two species. We made two simple modifications to Probcons to integrate it with Morph: firstly, Probcons was made to work on DNA sequences (the current implementation handles protein sequences only), and secondly, it was made to accept a phylogenetic tree as input, rather than estimate the tree at run-time. The ProbconsMorph software is publicly available at our site http://europa.cs.uiuc.edu/TFBSevolution/.
CEGMA distribution contains several directories and files compressed in a tar.gz file. Source code and documentation files are included in the distribution, as well as several parameters files and other extra information. If you prefer not to install the software you can contact us at genparra(at)ucdavis.edu, and we will run the pipeline in your favorite genome.
A question came up on the ensembl-dev mailing list to the effect “how do I create an Ensembl species core database from scratch”. As this is something that we have to do once in a while, I thought it may be a good topic for a blog post.
I will concentrate on getting a ‘minimal’ database populated, i.e. the sequences, genome assembly and genes (without additional annotation).
In my experience, the exact approach for each species differs, mainly due to the different formats and semantics of the source data. The following description will probably need tweaking for a particular species.
KATHERINE AULL's laboratory in Cambridge, Massachusetts, lacks a few mod cons. "Down here I have a thermocycler I bought on eBay for 59 bucks," she says, pulling out a large, box-shaped device she uses to copy short strands of DNA. "The rest is just home brew," she adds, pointing to a centrifuge made out of a power drill and plastic food container, and a styrofoam incubator warmed with a heating pad normally used in terrariums.
In fact, Aull's lab is a closet less than 1 square metre in size in the shared apartment she lives in. Yet amid the piles of clothes she recently concocted vials of an entirely new genetically modified organism.
Aull, who works as a synthetic biologist for a biotech company by day, created her home lab after hearing about a contest on the science fiction website io9.com for "mad scientists with homebrew closet labs, grassroots geneticists, and garage genome hackers".
After two months of tinkering, she engineered a microbe that she says is capable of performing simple logic operations, which could be the forerunner to basic biological computers. "Biology is wet, squishy and imprecise. It drives engineers insane," Aull says. "This would allow us to take the noise out of biology."
The shadow chancellor, George Osborne, today called for a three-pronged strategy to stimulate the flow of credit: state insurance for £50bn of lending to business; a cut in the cost of the capital that's been provided by the Treasury to banks and also a reduction in the fees levied for guaranteeing interbank lending; and a new Bank of England facility to swap corporate loans for cash.
This would amount to a substantial extension of the nationalisation of the credit-creation process - and Osborne acknowledges that more draconian nationalisation may yet be necessary.
It's quite something when the Tories complain that a Labour-controlled Treasury is being too cautious in rolling back the boundaries of the private sector and too feeble when pumping up the role of the state.
NEW YORK (GenomeWeb News) — George Mason University is starting a center that will focus on the human microbiome and will conduct genomics studies of microbes that could be involved in diseases, the university said this week. Funded in part by the National Institutes of Health and the US Department of Defense, the MicroBiome Analysis Center that will attempt to “map the world” of the bacteria, viruses, fungi, and protozoa that inhabit humans, and to study their effects on human health. The MBAC, which will focus on using multitag pyrosequencing, specifically will study microbial imbalances in the gut, mouth, respiratory tract, urinary, and reproductive systems. Using pyrosequencing will allow researchers at the center to “examine, count, and barcode hundreds of thousands of microorganisms per day” using samples from different parts of the human body. "This center will allow us to sequence and characterize these microorganisms in order to study their relationship to diseases such as obesity, cancer and irritable bowel syndrome," MBAC Director Patrick Gillevet said in a statement. Gillevet developed and patented the multitag pyrosequencing technology which will “serve as the backbone of the center’s research efforts,” GMU said. "Before this technology was developed, we would have been hard-pressed to identify a couple hundred of microbes per sample,” Gillevet said. “Now, we are identifying 50,000 or 60,000 microbes per sample. We can literally do in an afternoon what it took us 10 years to do in the past.” Gillevet’s team is currently working with others at Rush University Medical Center in Chicago to study the presences of microorganisms in patients with breast cancer, Crohn’s Disease, inflammatory bowel disease, cirrhosis of the liver, and HIV. "Finding the microbes responsible for particular diseases may increase the likelihood of developing new diagnostic tests and treatments for them,” he said.
The first baby in the UK tested before conception for a genetic form of breast cancer has been born.
Pre-implantation genetic diagnosis (PGD) involves taking a cell from an embryo at the eight-cell stage of development, when it is around three-days old, and testing it. Using PGD to ensure a baby does not carry an altered gene which would guarantee a baby would inherit a disease such as cystic fibrosis, is well-established. But in 2006, the Human Fertilisation and Embryology Authority said doctors could test for so-called susceptibility genes, such as BRCA1.
R first appeared in 1996, when the statistics professors Robert Gentleman, left, and Ross Ihaka released the code as a free software package.
Gene annotation underpins genome science. Most often protein coding sequence is inferred from the genome based on transcript evidence and computational predictions. While generally correct, gene models suffer from errors in reading frame, exon border definition, and exon identification. To ascertain the error rate of Arabidopsis thaliana gene models, we isolated proteins from a sample of Arabidopsis tissues and determined the amino acid sequences of 144,079 distinct peptides by tandem mass spectrometry. The peptides corresponded to 1 or more of 3 different translations of the genome: a 6-frame translation, an exon splice-graph, and the currently annotated proteome. The majority of the peptides (126,055) resided in existing gene models (12,769 confirmed proteins), comprising 40% of annotated genes. Surprisingly, 18,024 novel peptides were found that do not correspond to annotated genes. Using the gene finding program AUGUSTUS and 5,426 novel peptides that occurred in clusters, we discovered 778 new protein-coding genes and refined the annotation of an additional 695 gene models. The remaining 13,449 novel peptides provide high quality annotation (>99% correct) for thousands of additional genes. Our observation that 18,024 of 144,079 peptides did not match current gene models suggests that 13% of the Arabidopsis proteome was incomplete due to approximately equal numbers of missing and incorrect gene models.
Thomas Thurman, champion that he is, took my request for a theme for Metacity that clones the XFCE Prelude theme and went ahead and did it. What a hero.
Anyway, I’ve tweaked his work a little to make it closer to the XFCE theme (primarily making the border thinner and nudging some of the colours, and hiding the buttons on inactive windows) and you can grab the theme file. Save it as $HOME/.themes/Prelude/metacity-1/metacity-theme-1.xml, then say System > Preferences > Appearance > Customise > Window Border and choose Prelude.
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