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Journal Journal: Gorillaz movie under negotiation

Hollywood producer Harvey Weinstein is reportedly in talks with Gorillaz co-creators Damon Albarn (of Blur fame) and Jamie Hewlett (of Tank Girl fame) to make a movie based on the animated band. Quoth Albarn, "We're going to try and do something which makes the world not just think of Wallace and Gromit when they think of animation." Will the British lead the way in (English-language) animation for mature tastes, just as they did for comic books? Regardless, now would be a good time to generate some buzz if you want to see this happen.


Journal Journal: RIAA takes a Quantum Leap backwards

While perusing the reviews for the Quantum Leap, Season 2 DVDs on Netflix, I discovered every one contained some variation of the following statement: "Most of the period music has been replaced by some horrible generic music! " That's right, the RIAA has been demanding heavy royalties on music featured on or even played in the background of older TV shows that want to be released on DVD, forcing the TV studios to either pay up, edit, or not be released at all. Shows like WKRP in Cincinnati are priced right out of the market. Nice work fellas.


Journal Journal: Vaccine Blues

Up until recently, the only method for dealing with viral illness (aside from just weathering it) has been vaccination. And essentially, a vaccine is just a sort of advance warning to the body's immune system to let it know what to be ready for in the future. Within your immune system is the potential to identify and filter out trillions of different antigens (foreign substances and proteins), given enough time to identify and bring them to readiness. Even without a vaccine most viral illnesses go away on their own as our immune systems catch on the normal way. We have vaccines and/or successful vaccine-development programs for just about every major viral infection known to man - except HIV. After over twenty years of vaccine research, not one has proven itself even partially effective.

Presumably the main obstacle is HIV's pronounced tendency to mutate into new, unrecognized forms. Furthermore, only a handful of viral proteins are actually exposed where the immune system can detect them and the virus replicates at an extremely high rate, essentially giving us a narrow window on a fast moving target. Perhaps most troublingly HIV attacks the very immune systems necessary to defend against it. The full dynamics of neither HIV's attack nor the immune systems defense is well understood. All we know is that no matter what antigen you try to prepare the immune system with, no matter how much time it has to find the proper antibodies on its own, HIV has proven it can outmaneuver our bodies defenses for years and kill us in the end. An increasingly aired view among researchers is that, for the most part, the human immune system is simply incapable of keeping up with HIV's incredible adaptivity.

Nevertheless, there are at least three somewhat unconventional vaccine approaches that may yet bear fruit.

The first are the DNA vaccines. Rather than using live or killed virus, naked viral DNA is blasted into your cells so that they generate viral proteins and thus stimulate the immune system. While this is a novel system that bypasses many of the difficulties of other vaccination techniques and may thus be widely applicable, there is ample reason to think that it will offer no solution to HIV's ability to adapt. Proponents of this novel technique nevertheless remain cautiously optimistic.

The second is not actually a preventative vaccine at all. It is perhaps better described as a therapeutic vaccination technique, which appears to be capable of reducing viral load to a tenth of its normal levels. Essentially it is a way of helping the immune system do its normal job. Dendritic cells are isolated from the patient, then exposed to killed HIV virions purified from the patients own blood. These cells are now primed to specifically target the HIV virions affecting the patient, and a reinjected, where they mount a massive sustained attack on the virus. The treatment is believed to be effective for about a year, has no side effects apart from swollen lymph nodes, and overall costs less than present drug treatments, which it can be combined with thus enhancing the treatment. But what it definitely is not is preventative.

The third treatment may have actual potential as a preventative vaccine. Again, the biggest problem with HIV is its ability to change - but therefore, if you can find a part of the virus which does not change and target that, it would have no room to maneuver. Researchers in france believe they have discovered just that, and developed a vaccination treatment which appears to work in the lab at the cellular level at least. Furthermore, the vaccine is easy to manufacture and quite cheap. Trouble is, if we could make a vaccine that works then why can't your own body stumble onto that response on it's own? Indeed, in the original paper announcing this research is a table indicating at least some AIDS patients already possess this activity. Nevertheless, it is worth at least trials in vivo.


Journal Journal: DAPY rhymes with Happy

The most immediate treatment for HIV happens to belong in what may be regarded as the simplest and so far only partially effective block on HIV: drugs.

Drugs are chemical compounds which inhibit, enhance, or otherwise interfere with the biochemical processes involved in disease and its defense. Most of the time they are rather small and often completely unnatural. Drugs have long been the method of choice when the body's own systems go awry due to injury, poisoning, or genetic disease, allowing us to intelligently if inelegantly regulate our own biochemical processes with natural plant and fungal compounds or more modern and powerful synthetics. More recently the class of drugs known as antibiotics revolutionized medicine by allowing us to specifically interfere with the biochemical processes at work in infectious bacteria, which are rather different from those of our own. Bacterial infections used to be the greatest danger of pre-modern times, but now rarely cause great worry.

What drugs were not very good for were viruses, which make extensive use of our normal cellular machinery to propogate themselves and have few biochemical targets of opportunity, none of them common. But when HIV failed to yield to vaccines, drugs became our second focus. Modern drug cocktails have become quite effective at keeping the virus in check, but HIV has a pronounced tendency to evolve around them.

The latest salvo in the battle is a class of drugs known as DAPYs, the power of which is twofold. Firstly, they are designed to specifically inhibit reverse transcriptase, a viral enzyme which copies the viral blueprint into our own DNA. In other words, DAPYs prevent our cells from actually becoming infected (most of the other drugs interfere with the replication within the already infected cell). Secondly, it is much more difficult for reverse transcriptase to mutate resistance to these compounds because the DAPYs under consideration are flexible, like a key that can shape itself to fit the lock. Putting it all together means you have a single drug that works as well as or better than today's complicated five-drug cocktails, and it is easy to manufacture and apparently has no significant side effects as well.

So far three DAPYs are working their way through FDA testing, with the latest - R278474, also known as ripilvirine - being the most promising. Its creators are highly optimistic, even going so far as to call it a "magic bullet that stops AIDS in its tracks." But is it a cure? The answer is probably no. In order to completely cure someone of HIV, four things would need to happen simultaneously and complementarily:

1) New infections of cells must be prevented
2) Virions must be cleared from the body
3) Virion-producing actively infected cells must be eliminated, or otherwise permanently prevented from producing virions.
4) Latently infected cells must be activated, so that they may be eliminated as in (3), or otherwise permanently prevented from producing virions.

DAPYs only prevent new infections (1). The immune system and time can handle (2) through humoral immunity and (3) through cellular and humoral immunity and cell death. But (4) is the kicker. Studies indicate HIV could stay hidden inside cells for up to 60 years. During that whole period of time, latent infections could be spontaneously activating and attempting to re-establish an acute infection - which would be largely undetectable like HIV infections now. Even if DAPYs work perfectly and no resistance was ever evolved to them, you'd have to consistently take them for the rest of your life in order to prevent you from becoming infectious again.

So although DAPYs might offer a way for people to avoid developing AIDS entirely, it is no cure for the underlying HIV infection. And if people no longer take AIDS seriously because totally effective treatments are available, they will likely stop taking precautions and undiagnosed infections will spread like wildfire through the population. All well and good if your infection is identified and you don't mind taking drugs for the rest of your life... and assuming HIV doesn't evolve resistance to DAPYs. We'd probably be better off putting it in the water before then.

There is some hope. The mechanisms by which HIV becomes latent, and the means to pull infected cells out of their latent state and thus flush out the viral reservoirs are being studied. But that research is far from yeilding any practical applications. And even if we did have them, how can we be sure the virus has been completely eliminated? In the meantime, DAPYs will be proving themselves in the real world within the next few years.


Journal Journal: The Seven Deadly Things

In the interest of this series of HIV entries I feel I should point out a few basic facts. There are essentially seven major ways of harm to living things:

1) Injury
2) Poisoning
3) Genetic illness
4) Prion infections
5) Viral infections
6) Bacterial infections
7) Parasitic infections

Within each category there are infinite ways to damage, but there are also common strategies for dealing with each. What I want to highlight here is the importance of basic research. A deep understanding the physical, chemical, and biological circumstances which surround these afflictions has allowed huge advances in the treatment of all of them. More importantly, it has been progressively chipping away at the roster of untreatable diseases for which the general strategies do not work.

HIV/AIDS is one such case. Virtually every other virus we have kept at bay has been dealt with the same way: vaccines. Drugs may alleviate symptoms, but there was no substitute for the immune system's ability to seek and destroy viral infections. All a vaccine does is let our immune system know what sort of threats it should be prepared for, so that when they do arrive it is ready to defeat them. Up until now our chief worry was viruses that spread too rapidly upon initial evolution to develop and distribute the vaccine (like SARS or the various flu variants). Generating those vaccines has long been a straightforward if tedious procedure for decades. But attempts to develop a vaccine for HIV in the usual way have all failed, due to its ability to mutate rapidly and attack the immune system itself. This has forced medicine to study the biology of HIV to an unprecedented depth, that we may combat it as we have no other deadly virus before it. All the propositions I will mention in the coming days have relied on this unique effort.


Journal Journal: The Future of the MPAA is BitTorrent

Much has been made of the MPAA's legal attack on BitTorrent Trackers. But I doubt they'll ever take action against Bram Cohen per se. Number one, because they know they don't have a legal leg to stand on - they might as well sue the creator of ftp. And of course since BitTorrent is not a network there is no one to sue there. Nevertheless if they wanted to they could send in their most expensive lawyers and trap the BT software and Bram in the courts.

But more importantly, they surely realize that the efficiency of BitTorrent or BitTorrent-like protocols could make Video-On-Demand substantially cheaper to deliver and allow for far more content to be offered at once. Stifling it would just make them look bad and lose access to time-tested existing code and expertise to help develop their own system.

They just need some updated PVR-type hardware to handle the actual movie-finding, file-sharing, billing, and DRM. Since these would be specialized set-top boxes, the distributors could use the full disk space to intelligently cache frequently requested chunks and ensure even less-popular offerings can be had readily. And if they combined torrent protocols with multicasting (which must be implemented at the network/router level) the technology could be made even faster and more efficient, especially for very popular files where multiple people per network branch are requesting the same thing. Of course they could skip that option and use their own websites to bypass DVD distributors and cable networks entirely...


Journal Journal: The Fight Against HIV 1

I've taken an interest in HIV recently, arguably the most formidable infectious disease we've ever seen since the development of modern medicine with germ theory. Our most advanced medical science has so far been completely stumped by this little retrovirus, a failing only exceeded by the cavalier and frequently cynical approach taken by governments and society in dealing with the threat of this illness. Drug therapies have improved greatly over the years but none offer a cure. Vaccine research has been far more depressing, and the hypothesis that the human immune system is entirely incapable of dealing with AIDS has been gaining increasing credence. My hunch is that the hunt for an AIDS remedy is going to push us to develop a completely new way to prevent/treat disease, which will be broadly applicable to other ailments. Specifically, somatic cell genetic engineering.

However, that sort of work is only beginning, and much research needs to be done. The core of the task is the study of the structure and function of the human and HIV genes involved in infection, a process which is not entirely understood. And while genetic engineering may be the final solution, this basic research is what have enabled a number of somewhat-promising conventional approaches.

I'll be covering all the ones I know about in a series of journal entries, in order of how soon they might be employed in treatment. In the meantime check out my post that inspired this line of journal articles.


Journal Journal: Where's the Love?

My Karma is Excellent. I've metamoderated a handful of times recently. I used to get mod points practically on a weekly basis. So why haven't I seen them in months and months? Did /. forget me? In a possibly related topic, I submitted a story about three months ago ("How Not To Get Into Manga") which to this day is still marked as "pending". UPDATE: Apparently the two are not related; stories can stay pending for YEARS if they think they can be used someday. I'm not sure why anyone would do so, as most stories (including that one) tend to get old quickly.

Technology (Apple)

Journal Journal: Anticipation for Tiger's Core Data

I'm really excited about Tiger. Not for the new apps - I'm sure they'll be better. And not so much for Spotlight, which sounds nice but it doesn't sound like it'll replace the indispensible LaunchBar for me just yet. I'm excited about a little technology buried far down the list of improvements - Core Data.

OS X has long pushed the idea of a Model-View-Controller pattern for application design. View is what you see and interact with. Model is the actual data and meaningful code. And Controller is the layer between the View and the Data, helping them work together. Building your View is a task that is handled well by Interface Builder. Building controllers used to be a lot of busywork and boilerplate, until Panther introduced Cocoa Bindings which greatly simplifies the process. That allows you to spend more time on the true guts of the program in the Model.

But Core Data will introduce a new layer of abstraction within the model between data and code. It will allow you to define the structure of your data and then automatically handle much of the infrastructure like reading and saving files, undos and redos, and so forth. All you will really need to program now (in the traditional sense) will be the application logic, the actual processing of data. It's very exciting. I was writing a program recently, and the main problem turned out not to be the logic (which was scientific analysis) but the saving and access of the complex data structures I had created. If I had been using Core Data which is based on SQLite and can save arbitrary classes things would have been much simpler. It even has an XML-based file format (along with binary and database), which would make sharing and using output across platforms a snap.

That, plus some of the new visual-modelling features of Project Builder, will push the barriers for full-fledged programming even lower, and with a little more effort could even put them in reach for laymen. After all, who hasn't found a task or application that available programs couldn't handle?

Hopefully Apple will do the right thing and release free libraries for other platforms allowing them to easily use, make, and modify Core Data files as well. Cross-platform file exchange is too useful a property to ignore, and for multi-platform programs a must. I filed a feature request for it.

Networking (Apple)

Journal Journal: Making .Mac worthwhile

Apple has for some time had a $100/year internet service known as .Mac which I have never found cause to join. Most of the things it offers - home page, email, remote disk - can be had for free via a variety of other services. Now Apple has always been renowned for integrating hardware and software smoothly, so why not add .Mac to the service side of that equation? Unlike a home or work computer, a .Mac account is always on and available. It is the logical touchpoint for your presence on the web. Much more could be done with it.

For starters, a POTS-integrated VOIP service, also known as an internet telephone that talks to regular phones. But this one provides for direct and delayed voice, text, data, and optionally video from a variety of separate services to a common channel. A text message from a mobile shows up via iChat, and you click a button to reply right back with a phone call. An unlistened voice mail is retrieved over the web, and your text message reply becomes a text message on their phone or computer, or even parsed by a .Mac voice synthesizer and delivered to a normal phone (with disclaimer, of course). Plug an ordinary phone into your modem port and use it the normal way - or have your mac interpret your voice to automatically dial your call with Address Book or LDAP. Design an 802.11g handset that you can configure once and then use at any WiFi access point and you're making calls for free all over the place - make a deal with a cellular carrier and you can not only make and recieve calls anywhere for a fee (and make recieving IP calls more reliable), you have a portable wireless hub everywhere you go. Airport Mobile. Of course, you'd want to avoid telemarketing as much as you do spam - which is why .Mac could use caller ID (or other methods) to recognize friends and family and direct their communications directly to you, have others leave messages, and filter out known junk entirely (with help from a collaborative .Mac spam-and-marketer blacklist).

Another use for .Mac? Maybe TV listings? Or rather, a programming guide suitable for an Apple-branded PVR device or Macintosh program. Just make sure they're capable of handling video-on-demand seamlessly (from the internet or cable or radio or wherever) and home network integration (for playing files off other machines). Take it a step further, and integrate with conent-subscription services, automatically downloading fresh new shows and music. Let independent users make their own "must-see" lists to other's content. Let them extend other's content in powerful ways, such as referencing and splicing in clips, providing subtitles, audio comment tracks, and even overlaying video or sprites. Do it in reverse, allowing people and organizations to publish their video, audio, and data content via the web or subscription, using a model based on BitTorrent to take the bite out of popularity - with .Mac providing a reliable tracker and file-hash/small-file repository.

For that matter, how about blogging? Really, really well integrated blogging? Something with ad-hoc topic-based and community-built .Mac metasites and rss feeds. A way to create an extended family site as easily as a community on par with slashdot. Including an ultimate service tapping all blogs, with peer review, moderation, filtering, and random sampling allowing really interesting posts to bubble up from or sink into obscurity. What the internet has always promised but never quite delivered.

How about a secure way to give you a remote desktop for your home computer? And I mean REALLY secure - like with a USB jumpdrive that doubles as a decryption device/fingerprint reader/keycard. OK, maybe that one's a little risky. How about a little URL redirection service to point people to your public folder on your computer(s) when they're online, to bypass the unavoidable .Mac storage limits?

Through it all, .Mac could make everything work together, in whole or as parts. Your presence in and gateway to the network - your personal thoughts, your comments, your iPhoto albums, your iTunes stream, your iMovies, your email, your telephone, your dropbox, your anything, as an integrated whole or dispersed throughout the network. The possibilities are endless.


Journal Journal: Reinventing Computing

If someone were to reinvent computing, what would it look like? If you could abandon all backwards compatibility, and had the resources to remake the whole system, how would you do it? And I mean ALL the way - up to and including standard mathematical notation, and even our number system and written and spoken language. Obviously we've learned quite a bit over the past several thousand years, but we're also constrained by our need to accomodate past inventions that are too entrenched to get rid of.

For me, I think the primary considerations are the interface and the basic principles.

Interface should be fluid, to accomodate a variety of ways of interacting - through complex visual metaphors, simple text, or even through our aural and tactile senses. It should be possible to interact fully (if less efficiently) through a simple keypad and one-line display, as well as through a GUI, or a speaker/microphone combo. That means that the information returned by a program or command, and the commands given, need to be interpretable in a variety of ways. Once you have that, programming becomes and easier task. For instance, you could invoke a program at the command line, which could return data of any type, with arguments of any type, not just text. The shell would format the result correctly and consistently, just as it parsed your consistently-invoked command. And the shell could be text-based or gui or voice-based or touch-based. Formatting of types could be added or changed on the fly to suit your needs. In all cases, the data returned would possess a type and an address, which could be used in commands for further processing.

The programming langauge of choice would be capable of handling high-level to low-level interactions, would prevent bugs, be crash-resistant, compact, and applied throughout the system. It could be interpreted or compiled, and its notation would be used the same in math expressions or written programs. Instead of the arbitrary base 10, we should work from the ultra-simple and maximally efficient base 2, or a suitable power thereof like 2^4=16. Making that basic change means both computers and humans would be working on the same page, and would prevent errors in translation. Of necessity this will require adopting a number of paradigms at different points, from functional and object-oriented paradigms to low-level optimized routines.

Well all this must sound like a daunting task at best, and an unnecessary pipe dream at worst. I am reminded of when Apple had decided to replace the classic MacOS and had a choice between either Be, with their super-modern, super-fast, built-from-scratch approach, or NeXT with their unix base and well-developed API and tools (and Steve Jobs). They picked NeXT. At the time I was disappointed - I wanted the new sleek hot OS. But in retrospect I think they made the right decision. The unix-based OS X they created can run thousands of general and specialized unix programs developed over decades, helping the Mac (partially) overcome it's main shortcoming - the lack of applications, particularly specialized applications, as compared to windows. OS X is no longer just for mac afficionados and the occasional windows switchers - it's become a system of choice for unix geeks as well. The moral is clear. Whatever system you pick, make it something that can be built and rebuilt piece-by-piece.


Journal Journal: Slaughterhouse Five 1

Watched Slaugherhouse Five last night. Yet again, I am struck by how seemingly every every SF author of that generation believes that inner/world peace lies in the arms of a young, scantily-to-un-clad, airheaded, easy girl. Vonnegurt, Niven, Piers Anthony, Heinlein - you name 'em, they wrote about it at some point. Especially Heinlein. I don't know whether it was just a reflection of that era's societal sexism of the Playboy variety, or the burgeoning free love movement, or just plain old self-importance, but it sure was widespread. Just a simpler time, I guess.


Journal Journal: Somewhere in time...

Have you ever had a book that you read ages ago, but can't quite remember what it was? Somewhere in the distant realms of my childhood, I read my first SF book, thus setting me on my path to geekdom. I'm not sure when it was but these vague memories are bugging me. The book was probably written in the '60s, '70s, or very early '80s. It may or may not have been juvenile fiction, as I seem to recall picking it up at some school. I'm pretty sure it wasn't in an anthology of short stories, but I doubt it was very long. At least part of the story takes place on a ship travelling through empty blackness (whether due to relativistic or some other mode of travel I don't know). However people could go outside. There was a foam gun used to repair holes in the spacecraft, which was used at some point. I keep thinking it involved Tau Space, but I have read and remember Frederik Pohl's Heechee Saga and I don't think that was it.

Well, I realize that's not a whole lot to go on. Just thought I'd put it out there.

On a positive note, I was able to determine another book I was barely remembering, thanks to Amazon's nifty book text search feature: The Hero and the Crown.


Journal Journal: Combinatorial Technology

The release of the Airport Express with its built in USB port and audio jack got me thinking again about a potential digital lifestyle product strategy - what I like to call combinatorial technology. As opposed to (but in reality working alongside) convergence devices, combinatorial technology would intelligently combine smaller less functional devices to do jobs neither could do alone simply by connecting them, without having to deal with complex menus.

So for instance, (next gen color screen) iPod + iSight = Video Camera. iPod + Airport Express= networked drive and music server. iSight + Airport Express= wireless web cam. iPod + iPod = in person file sharing. And so forth. Airport Express is already the best example of this, as +speakers or +printer or +airport creates functionality not available to either alone. Imagine if that USB port could be put to other uses besides just printers.

Of course there's the significant problem of there being too many different jacks/cables/interfaces out there. Frankly I don't understand why technology hasn't moved towards a single physical port/plug style (with perhaps a few variations for slightly different applications such as powered/unpowered, pos-lock, mini, etc) which intelligently and automatically adapts to support the appropriate protocol for the two devices. I.e. you can plug in a cheap mouse or internet connection or a hardrive or monitor or speakers into identical ports, and they just work as if you had plugged them into their exclusive ports we have today. I suppose it would ideally be serial optical with power, although even that could be tweaked (such as sending digital or analog signals over either the wire or the fiber). Anyway, if such a port/plug scheme existed combinatorial devices would be trivial. You could make dongles to support conversion to other plug styles/protocols. Heck, if you made the design compatible with the optical mini audio jack as used on Airport Express (with perhaps a second side plug of different style so they wouldn't be confused) you wouldn't even need to worry about the simple unidirectional analog devices.

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