The Beth Project

Bookbinding, woo!

I, like many other people, have a passionate and deeply loving relationship with notebooks. All that notebooks and I ask is that you respect our love for the sacred union it represents. There have been a spate of birthdays amongst my friends recently, so I put together some hand-bound notebooks for them.

This one is bound using coptic stitch in gold thread. The cover is made from a repurposed purple pinstriped suit jacket.

I bought the corner protectors from this eBay shop.

The covers are a couple of centimetres wider and longer than the pages.

The signatures are encased in purple, blue, and grey cover papers.

I used this super happy kawaii wrapping paper (from Primark) to line the insides of the covers.

I made it for my awesome friend Sacha, who is a composer. The pages are a mixture of manuscript paper, squared paper, plain, and coloured paper.

I made a PDF of the manuscript paper in LibreOffice Draw. You can download it from here.

The next three notebooks were for my chums Emma, Benji, and Laura. The red fabric used to be a dress, and the blue was a pillowcase.

Manuscript paper for Laura, because she's a classical guitarist, folk musician and composer.

Lined paper for Emma because she's a writer (PDF).

And storyboards for Benji because he's a filmmaker (PDF).

SUPER COOL COVER PAPERS (also from Primark).

I used a mixture of coptic stitch and french tape binding on these books. I learnt the exposed tape technique from this amazing tutorial.

The covers on these books are the same size as the inner papers. I think I prefer making them this way since it's a more economical use of my A4 pieces of cardboard (cannibalised from notebooks and A4 refill pads).

I really like the look of the exposed tape bindings, but I think I prefer to attach covers using coptic stitch as it's a lot less fiddly.

Drug induced pro-arrhythmic risk via afterdepolarisations

If you mess around with the ion currents in and out of a heart cell enough, you can perturb things so badly that you cause the cell membrane to depolarise again prematurely. These "afterdepolarisations" happen all the time in vivo, and aren't usually a big deal; unless a lot of cells do it all together, the effect is too diluted to cause an arrhythmia. However, if enough cells do it together, or if you combine afterdepolarisations with other heart problems, they can cause someone to drop down dead instantly.

There are two ways that these afterdepolarisations can present in a single cell. The cell can depolarise before it's finished repolarising, in which case it's termed an "early afterdepolarisation" and it looks like this:

Early afterdepolarisation The EAD begins at around 0.3 seconds.

Or it can happen after the cell has repolarised - a "delayed afterdepolarisation". This is always accompanied by calcium release from the sarcoplasmic reticulum.

Delayed afterdepolarisation The DAD begins at around 2 seconds. The sarcoplasmic reticulum calcium release current is labelled as .

Drugs that make either type of afterdepolarisation more likely could make arrhythmias more likely. For my project this summer I'm writing some code to combine information from drug tests on single ion channels with heart models to predict EADs and DADs. The hope is that this software could better predict cardiac side-effects from new drugs, and maybe even replace some tests that are currently done on animal tissue.

This week, I wrote a review of the literature around this topic, as well as a MATLAB program to take data from single cell models and detect afterdepolarisations. If you like, you can download the AD detection program, as well as my report and the LaTeX file that made it.

Hodgkin and Huxley's gating mechanisms

Further to my last post, in which I attempt to form a vague understanding of Hodgkin and Huxley's giant squid axon model, I'm now looking at the gating mechanisms they used.

Action potential in nerve

The opening, closing and inactivation of ion channels is vital for the characteristic shape of the action potential.

A) The sodium channels open and sodium floods into the cell: increases.
B) The potassium channels open, allowing potassium out of the cell: increases.
C) The sodium channels are inactivated when the membrane voltage is at its highest: .
D) The potassium channels close and the sodium channels are activated when the membrane voltage reaches its lowest: and increases.

This means that the sodium and potassium conductances vary in a complicated way with changes in the membrane voltage. The 'leak' current is simply directly proportional to the membrane voltage.

The changes in conductivity are modelled as "gates" for the sodium and potassium channels. The gates are represented by a dimensionless variable, which can be between 1 (fully active) and 0 (fully inactive). The rate of change of a gate with time is defined as:

where is the rate of movement of ions from outside to inside, and is the reverse.

Unlike for the rest of the model's features, the gating of the ion channels is not worked out from first principles. Instead, equations were fitted to match empirical data from experiments. Hodgkin & Huxley took measurements of each ionic current while keeping the membrane voltage constant, over a variety of different voltages, and used the data to find and expressions for each gate as functions of voltage.

For the potassium channel, there is only one type of gate, called the "n" gate. The permeability of the membrane to potassium varies with the 4th power of n (for equation fitting-ey reasons).

For the sodium channels, there are two types of gate. The gate being active encourages flow of sodium ions through the membrane, but the gate being active inactivates the sodium channels.