Imagine you leave your phone on a bus. It happens all the time, and there are two possible outcomes:

• A thief picks it up and wants to steal personal details
• A good samaritan picks it up and wants to return it to you

It is important to be prepared for both these outcomes. But by default the Android OS does not allow you to do so. You can add a pattern lock to prevent the thief from accessing all your data, but this prevents the good samaritan from finding out your contact details to return it to you.

Now this problem is solved is solved by a new app. Pattern Lock Pro gives you a beautiful pattern lock which you can customise to add your contact details even before unlocking has taken place.

Pattern Lock Pro displays your name on the lock screen. It also displays an alternative phone number and email address on the lock screen.

It is a pattern lock with contact details including your name, alternative telephone number an email address.

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Agrobacterium tumefaciens is a bacterium which, with the help of the Ti megaplasmid, manipulates plants into providing it with a safe and nutritious environment. The discovery of this interaction has been important not only for understanding the natural history of the bacterium, but for its use as a tool to transform plants. This has both allowed better understanding of plant biology and allowed genetic modification for agriculture.

The bacterium was first isolated by Erwin Smith. He was investigating a daisy with Crown Gall disease and found he could isolate a bacterium which produced a slimy exudate. He inoculated healthy plants with the bacterium and found that they developed tumours. This property gave the bacterium its species name – the tumour causer.

In the 1930s, Braun characterised the bacterium further. He took a tumorous plant and heat killed the bacteria by incubating it at 65° C for three days. The plant cells survived and so cells from the tumour could be grafted onto healthy plants. They continued to divide and formed new tumours. This indicated that the bacteria had passed some determinant to the plants, the Tumour Inducing Principle, rather than constantly producing some chemical to cause the tumours.

Research somewhat stalled here until the growth of molecular biology in the 1970s. Gel electrophoresis allowed the detection of plasmids in bacteria at this time, and scientists attempted to isolate them from Agrobacterium. They found that strains causing Crown Gall disease had a 250 kb megaplasmid. This property gave the plasmid its name the Ti plasmid (tumour inducing).

What is transferred?

Mary Dell Chilton prepared RNA from tumour cells, which she labelled and used to probe restriction fragments from the Ti plasmid. They hybridised, demonstrating that DNA is present in plant cells and transcribed into RNA.

Forward genetic mutant screens helped to shed light on this transferred (T-) DNA. Normally infected plants form tumours, this is due to high expression of two hormones. Cytokinin and auxin. In tms mutants less auxin was produced triggering shoot production. Conversely in tmr mutants less cutokinin was produced causing roots to form. When these loci were cloned it was shown that they coded for proteins involved in the biosynthesis of their respective hormones.

Another fascinating feature of the T-DNA is that is codes for the synthesis of a protein synthesing a particular opine. The exact opine depends on which strain of bacterium is involved. The non-transferred portion of the Ti plasmid codes in part for the metabolism of the respective opine. This means that any bacterium which loses the plasmid will no longer be able to benefit from resources produced by the plant.

What triggers DNA transfer?

In a mutant screen a series of virulence genes were identified. They were named vir A-G. These were probed by transforming the bacterium with a merodiploid reporter vector.

Analysis showed that virA was expressed constitutively, but that the other vir genes required plant washate for their activation. The inducers involved were wound phenolic compounds – acetylsyringone was found to be especially powerful. This allowed the discovery of an elegant regulatory mechanism involving a positive feedback loop. virA and virG are needed to activate the operon but do so only upon activation by a wound phenolic compound. This increases the rate of virG expression from a very small level and so in turn allows faster activation of the operon. This allows the virulence genes to be expressed in an all-or-nothing fashion.

What is the mechanism of transfer

Mary Dell Chilton sequenced the regions on either side of the T-DNA and found a 25bp repeat in direct orientation. Patty Zambryski showed that these borders were crucial for virulence. They attempted a Southern blot with a probe for T-DNA on induced Agrobacterium cells and found that they could identify this DNA even if they did not denature their sample before blotting, indicating the T-DAN was single stranded. They proposed a conjugation like mechanism. virD1D2 forms a nuclease which cuts at the borders. It is coated in the virE2 product and targeted to the plant through a type IV secretion system (the same type used by Heliobacter pylori). Once inside the plant importins target the protein DNA complex to the nucleus where it inserts.

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Each of us has around 10^13 cells in our body, a mutation in just one of these can lead to a cancer. Thus it is crucially important that each cell has an advanced system for the detection of DNA damage and the control of appropriate response measures. These may be repair, via a number of pathways dependent on the type of damage, or senescence or even apoptosis when damage is severe.

Extent of damage

As many as one million lesions may occur per day in a single human cell. Damage can occur from endogenous sources, such as reactive oxygen species produced by metabolism. But it also created exogenously, by ultraviolet light and other ionising radiation, mutagens and viruses.

These can cause

1. Oxidation of bases
2. Alkylation of bases
3. Hydrolysis – e.g. deamination, depurination, depyrimidation
4. Formation of ‘bulky adducts’
5. Mismatched bases

Every time a cell undergoes division its telomeres shorten. When these reach the Hayflick limit, the cell goes into senescence, an irreversible dormant state.

DNA repair

Direct reversal

• Pyrimidine dimers, which are formed by UV irradiation, are repaired by photolyase on its activation by UV (photoreactivation).
• Guanine methylation is reversed by methyl guanine methyl transferase
• Some C and A methylation can also be directly reversed
• The adaptive response in E.coli, upon alkylation of DNA backbone. Ada suicidally transfers alkyl groups onto its cysteine residues (not catalysis, stoichiometric). Methylation of ada -> activation of itself, + other alkylation responsive genes.

Single strand damage

• Base-excision repair (BER) after oxidation, alkylation, hydrolysis or deamination
  Damaged base is removed by DNA glycosylase
  AP endonuclease recognises “missing tooth” and cuts phosphodiester bond, allowing resynthesis by DNA polymerase. Then ligase seals backbone.
• Nucleotide excision repair (NER) recognises bulky lesion s which distort the helix (e.g. thymine dimers). Requires Uvr system in E. coli, = UvrABC + DNA Helicase II. UvrA-UvrB scans DNA, UvrA recognises distortions, leaves complex to be replaced by UvrC. UvrB cleaves bond downstream of DNA damage while UvrC cleaves upstream. Helicase II breaks hydrogen bonds to remove excised segment. The gap is filled by DNA Pol I.
• DNA mismatch repair (MMR) is strand-specific, the daughter strand is recognised as the one to be corrected. Three proteins are involved mutS, mutH and mutL. mutS forms a dimer that recognises the daughter strand’s mismatched base and binds, mutS recruits mutL dimers. MutH binds to hemimethylated sites, and is activated by mutL. It nicks the daughter strand and recruits DNA helicase II. MutSHL then travels behind the helix along the single strand it creates towards the mismatch. An exonuclease digests the tail left behind. The process ends past the mismathed site and PolIII can then repair the daughter strand.

Double strand breaks

• NHEJ – DNA Ligase IV uses microhomology to rejoin two ends (also used in VDJ recombination. Ku?
• Micro-homology mediated end joining (MMEJ) uses the Ku protein too
• Homologous recombination-uses sister chromatid/ homolgous chromosome

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I’ve recently become a fan of the BBC gameshow OpenConnect. I’ve raced through the walls that can be played on the BBC website but now that I have run out I thought I would make some more and launch a version to which other people could submit.
Visit PuzzGrid!

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Our story begins long ago with an ancient jawless fish from whom came every tetrapod, from an axolotl to a zebra-finch, and almost every fish in the seas, lakes and rivers. This fish’s parents were ostracoderms (hard shelled dermis), extinct fishes covered in an armour made from scales of dermal bone. They had cartilaginous endoskeletons to provide some structural support. But this fish was on its way to gaining a feature which would separate it from the ostracoderms, developing a jaw. The first stage was to develop jointed branchial arches rather than the one-piece branchial basket we now see in lampreys, this in itself allowed better ventilation which provided the oxygen needed for a fish that was becoming an active pelagic predator. Over generations these joints would have become more pronounced, until eventually they were such that they allowed the next step in the journey towards jaws.

The two front gill arches developed into the mandibular and hyoid arches. The former the jaw itself, and the latter the support from which it hung. This allowed a buccal pumping mechanism to better ventilate the gills. The gill slit between them became the spiracle or in our case the ear cavity. This jaw was adapted for co-option into the predatory life style as a weapon.

Some of these gnathostome fish (jawed mouth fish) were living in freshwater, they made their bodies more dilute in an attempt to become more isotonic with the water. These fish, still heavy with their dermal bone used their fins as wings to generate lift and wafted a heterocercal tail to force water downwards generating lift. This required a great deal of energy and so posed a problem, it was solved differently in two different groups.

In one which would give rise to the chondrichthyans (cartilaginous fish) the dermal bone was lost and replaced with dermal denticles, a skin of tooth-like projections. This decreased the density of the fish and allowed them a role as important pelagic predators, still beating their tails to generate lift and using an oily liver to increase their buoyancy. Their only structural support came from cartilage, which they made stronger in their vertebrae by using calcium phosphate, creating a form known as prismatic cartilage. The chondrichthyans would go on to form the sharks, skates and rays and the chimaeras.

Another group of gnathostomes would give rise to the osteichthyans (bony fish). They would have lived in anoxic conditions, perhaps caused by vegetation decomposing in warm water. Such fish would have stayed near the surface of the water, where oxygen would be most concentrated and here they evolved the strategy of swallowing air from above the surface, so that it passed through their gut. It could be inefficiently absorbed as it passed through the gut. But there was selective pressure for an invagination of the gut wall to allow a greater surface area for oxygen absorption. Gradually this pocket would have become a specialised lung. This lung provided a store of air in the body, decreasing its density. This allowed the potential for the evolution of endochondral bone, created by the ossification of cartilage by osteoblasts laid down during development, the feature that gives the osteichthyans their name.

The buoyancy these fish now enjoyed freed their fins from generating lift as wings, they could now be adapted as flexible appendages for steering. This was achieved in two different ways by different groups.

The actinopterygians (ray finned) withdrew their endoskeleton and left their fins supported by rays connected by webs of skin. This gave them greater flexibility and manoeuvrability but did not provide very much strength. However when surrounded by water strength is not a very important characteristic and the actinopts have gone on to dominate the sea, comprising 95% of all fish species. Many moved out of anoxic environments and separated their lungs from the gut, so that it was used simply for buoyancy and known as a swim bladder. Only the basal Polypterus has lungs that look very similar to those of other osteichthyans. Many moved into marine environments but they betray their freshwater past with hypotonic bodies. A major group, the Teleosts, use their original lungs as swim bladders but have re-evolved secondary lungs. The electric eel is one which has a secondary lung in its mouth. The actinopts also no longer needed their heterocercal tail for upthrust given their newfound buoyancy and so withdrew the notochord which had run along the top of their ventral tail. This formed a symmetrical, homocercal tail with which to generate simply thrust.

The sarcopterygians are another group of osteichthyans which took a different path when their fins were freed up. Again they achieved greater fin flexibility, but they did so without withdrawing their endoskeleton. Instead they reduced the number of basal elements to allow flexibility while maintaining strength. In the water column this was probably not of great significance. But such strong limbs were ready to be co-opted firstly for strong underwater movement along the bottom of water, as in Acanthostega, and later after further skeletal modifications, to form the terrestrial tetrapods to which we belong. Sarcopts also adopted a different approach to modifying their freed tail to provide forward thrust instead of upthrust. They did not withdraw their notochord but placed it down the middle of a symmetrical, diphycercal tail.

evolution · fish

This site has not been updated since 2007.

From now on it will be used to occasionally publicise scientific things I write which I think others might find useful. Enjoy!

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I found this image on Reddit. It shows the space needed to transport a certain number of people by car, bus or bicycle. If you look closely though, you’ll see that different zoom levels are used in different photos. This is my attempt to rectify that with a bit of cropping. The photos still show the significant problems with cars.

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I got really sick of the comment spam on this site and realised that it was my responsibility as a web master to prevent it and thus ensure that only deserving sites had their sites boosted by links from this site. Akismet was, and remains, installed – but it wasn’t really cutting it. Although it has stopped an extraordinary 105,428 comments and trackbacks since installation. I’ve now implemented reCAPTCHA which means you have to type a couple of blurred words to make a comment. While this requires effort on the part of the user, which is a great shame, the good news is that your efforts do not go to waste. ReCAPTCHA uses one of the words you input to check you are human, the other helps to make electronic copies of scanned in books, a la Project Gutenberg.

Apologies for the inconvenience, blame the spammers!

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Unless you live in a different Internet to me, you can’t have failed to notice the abundance of annoying flash-based ads which make irritating noises.

Perhaps the best example of this is the horrific buzzing mosquito you can only shut up by attempting to win a laptop, it starts buzzing without any activity from you at all. If you haven’t seen a copy yet I’ve hosted it here. But there’s also the talking smilie faces, the voices whispering about you, etc. If you use a tabbed browser and have as many tabs open as I do, you have to search through them all to find the culprit.

And it’s not only the loud flash ads that are problematic, ads on newspapers cover the text you want to read and have confusing, hard to find ‘X’ buttons.

The solution
This whole situation seems very reminiscent of another form of advertising, the popup. Popups used to be everywhere, they were really irritating. Then browsers and toolbars came in that blocked them. Now, even if you use a legacy browser without a popup blocker, you’ll be hard pressed to find many popup ads.

Why? Because there’s no point in them. It’s a waste of bandwidth to send the javascript to make a window popup if 90% of your users won’t see it. So many websites have moved to advertisements which their users appreciate more, like contextual advertising (Google Adwords, etc.) which displays things people might actually be interested in if they’re on your page.

Some however have embraced the almost equally irritating flash ads. But we can make them stop, as we made popups stop. If a significant proportion of the internet installs flash ad blockers it will become economically unviable to fill space on a website with an irritating flash ad, when it could be filled with text-ads visible to all.

Firefox users

There is a firefox extension called AdBlock which will block all advertisements. I’m against this (as a publisher who makes money from text-ads) because it removed the only revenue stream from a lot of websites and would force a lot of sites to close. We should block unreasonable ads rather than all ads. We consider popups unreasonable and I think we should consider most flash ads unreasonable too. Inobstrusive text ads are not, in my opinion.

So instead use FlashBlock, it replaces all Flash animations with a little play button you can click to make them appear. It’s really unobtrusive, using Flash based websites isn’t hard. You can add sites like youtube to a whitelist to avoid too many play buttons.

Internet Explorer users

Well my first advice would be get Firefox, it’s so much better, but I know you’ve heard that a thousand times before.
So if you really must continue using IE I suggest you try FlashSwitch which lets you toggle flash in the system tray.

If as many people as possible take these measures it will soon become pointless to display annoying flash ads.

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… I apologise. I’ve suddenly noticed a vast amount of emails being bounced to my catch-all address. This means that an evil spammer is sending emails which are forged so that they appear to be from VariousRandomAddresses@splasho.com. If you’ve received such a message please be assured that it has nothing to do with this blog. If there was anything I could do to stop it I would, but it’s totally unconnected to me. I can strongly recommend the excellent SpamBayes for spam detection if you’re not on GMail or similar.

I also apologise for the apparent death of this blog, I still hope to post on it occasionally I just apparently haven’t had anything interesting to say for many months.

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For most of this year, this blog has had a post every day. THe vast majority of these were simply links to sites that interested/entertained me a bit. Given that there are so many other sources of these links out there I’ve decided to mostly stop that. I recommend Reddit, Digg, MetaFilter, Waxy and Kottke.

I will now be posting less often but my posts will hopefully of a higher quality, there will be:

• Original articles on things, usually techy
• My opininion, which I find interesting but you may not.
• Links to the wonderful things I’ve created
• Links to random things which REALLY entertained me, but not every day

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I feel guilty for laughing so much at this page because of the poor innocents at whose expense I was laughing, but laugh I did.
[Via boingboing]

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