Round the hill

It seems like just last week [because it was just last week] that we were yomping off up the mountain to find sheep at the tail end of the Upland Grazing Season. I had intended to do this on Saturday but it was a drizzly mizzly ould day from first light to last and you have to be motivated to be looking for sheep while soaking wet. Accordingly I spent Saturday focussed on indoors jobs like sitting my capacious arse on the sofa and carefully watching the ceiling while the laundry was processed by the washing-machine. Later on I woke up and decided to de-clutter the fridge into something edible. A couple of weeks ago I picked about 3kg of crab-apples off one of our trees and a lot more (scabby, half eaten, some bruising) off the ground. The latter filled half a 25kg feed-sack and I lurried them into the sheep-troughs with a handful of sheep muesli [mmmm good]. They were stand-offish, but when I checked back later, all the apples had been eaten, I presume by the sheep. The fresh-off-tree apples were mostly the colour and size of large plums. I had boiled them up and pushed them through a sieve, filled 6 jam-jars and popped them in the oven to kill surface microbes. The pulp, with its dark and pale pink looks uncannily like a settling pint of Guinness. Now, I'm not naive enough to believe that my treatment will have 'canned' the apples for a couple of years of storage - a couple of months is more like it. A bit of pastry, a jar of crab-apple, the heel of a chunk of marzipan >!et voilà!< Apple & almond pies.

Sunday was a different kettle of fish - kippers, I guess, as it was dry all day. You can't afford to miss chances to get out and doing in the back end of the year. In the forenoon, The Beloved announced that she was off up the mountain to bo-peep her sheep - again. It seems a little futile to go and look the sheep if, dogless and a bit crumbly, we lack the resources to fetch them in. But it was a day inviting a walk in the great outdoors and knowing where the sheep are and that they are still walking is surely reassuring. I volunteered to cut across the South Face of The Eiger An Cnoc Rua and meet TB on the other side of the hill where we had encountered Neighbour Martin a week ago. That way we would, hopefully, catch t'buggers in a pincer-movement.

Things were looking good-omen when I upstarted a fox Vulpes vulpes and it bounded away across the heather. 15 minutes later I found 3 of our ewes [see Map L above - here be treasure, Jim Lad]. The neat but intense blue-green spot splotted on the back of the head after shearing had weathered into a smear the size of a soup plate - unmistakable on our hills. 15 minutes after that I found two ewes more looking sheepish as they hung out with a couple of louche black-faced strangers. And a few minutes later, I saw TB against the skyline [R: a bit later when she'd come down from on high]. We met up and headed round the hill and home for tea and medals. It's the first time I've ever formally walked the bounds of the hill which we own in common. It is, as near as dammit, 200 hectares = 2 sq.km. in extent, which is rather a lot of back-garden. If we walked it more often, we'd know it better. As we cut across the hill, a pair of golden plover feadóg bhuí Pluvialis apricaria launched out from under our feet and winged away across the heather scrub. These are red-listed for Ireland but seem to be making a come-back in the Blackstairs: we saw four last week. The grouse cearc fhraoigh Lagopus lagopus has long gone from our part of the world. I remember, the August (1997) after we moved into our present home, meeting two chaps, two guns and two dogs walking up our lane. It was really just for old times sake, they said, it being several years since they'd seen a grouse on the moors, let alone killed one. Plover and grouse inhabit a not dissimilar ecological niche; maybe the plovers can move in because the previous incumbents have died out or moved on. Our friend Roy, an keen amateur naturalist back home in Northumberland, remarked on how few birds he found on our Irish hills compared to home.

Who said mountains? Nietzsche said: "In the mountains of truth you will never climb in vain: either you will get up higher today or you will exercise your strength so as to be able to get up higher tomorrow" actually he said "Im Gebirge der Wahrheit kletterst du nie umsonst: Entweder du kommst schon heute weiter hinauf oder übst deine Kräfte, um morgen höher steigen zu können." because he was born in preußischen Provinz Sachsen [Saxony].

Miscelladay 141018

Does it matter that anyone is reading this stuff? Not really. I do it 'for the record' so that I'll have something to read when I retire. But I wish the freakin' parasites of the interweb would leave me alone. Over the last tuthree months I've noticed a blip of interest from a variety of peculiar 'referrer' sites which turn out to host advertisements for monetizing your blog. There is now another pattern (see above) where, ever other day, 60+ readers tune in all at once and then drift away to the next bright inconsequential thing. I though this might be in response to a tweet about my stuff and a loyal and immediate response from followers. But I think it's just robots. Subtracting that, it looks like, to the nearest whole number, you are the only person reading The Blob today.

Cute of the Day:
We read a book that suggested you ask your kid what an appropriate punishment for misbehaving would be and then carry it out. 6 yo son pinched his brother or something, so we asked what an appropriate punishment would be. He said “pluck out my eyeballs and throw me over a cliff?”. We didn't follow through. And stopped reading parenting books.

Go on what's bin happenin':

• Music:
• Mumford and Sons are back in the saddle Guiding Light. or Vevo version.
• An Ròn [The seal] Julie Fowlis 
• Lonesome Friends of Science John Prine 
• Dvorak Humoresque.
• Eric Satie Once upon a time in Paris
• Philip Glass Metamorphosis
• Pushing Bright Phoebus by the Watersons tribute in words
• Watersons more trad: Hal and Tow.
• Jonathan Pie on [Offensive] Free Speech
• Age quod agis [= do what you do] making a longbow  
• Housework? Woman makes beds  nothing to do with sheets! mostly bamboo.
• Bois de chauffage en Bretagne? Rault Philippe c'est le pied!
• Haute Savoie cyclisme vertical
• Playing Magnus Carlson at chess.
• Genius? My Son the Engineer Dilbert.
• Irish people try Krispy Kreme Donuts for the first time "This is like my first lesbian kiss: I'm confused but I love it" - "This might be the best donut I've had in my whole fuckin' life" - "I might actually drive the whole way to Blanchardstown for that"
• Food? Did someone mention Le Jambon Beurre Sondwich? KISS my sandwich! Keep It Simple Stupid.
• We survived Storm Callum. Hurricane Michael in Florida not so much. Bloke fixed his running GoPro to an immovable object and left town. Starts off with a bit of roof lifting off across the street and after a few hours of horizontal water shows where the street has lifted off it's foundations; no house where the roof was.

Backdrop books

I was watching (several times) a report from U Glasgow's Centre for Virus Research CVR about interferon and its central role in fighting infection. It wasn't obvious-to-all-thinking-people what Dr Watson was talking about, especially if the word interferon was unfamiliar and you didn't know the difference between virus and bacteria. That piece-to-camera was one of a series of 13 similar very short films about the work at the CVR. I thought I'd check a few of the others to see if they were models of clarity. First up was Arvind Patel talking about Hepatitis C Virus:

It was a welcome change to see a scientist talking science without a laboratory in the background. The books are all PhD theses, so the implication is that Dr Patel is standing on the shoulders of giants. and/or he's had a helluva lot of successful PhD students. And I'm sure that the writers of those weighty tomes will have a mini-frisson of self-recognition as a nett contributor.  Next up was Ruth Jarrett talking about Hodgkins Lymphoma and Epstein-Barr Virus EBV [whc prev], which is a likely cause of that cancer. WTF? She's using the same damned string of books as Dr Patel by Dr Steinhauer and Dr Steinthorsdottir and so on:

The camera must be really heavy and hard to move, because the 2 videos were uploaded 4 days apart in 2015, or the producer is showing a want of imagination in ringing the changes. After that I checked out John McLauchlan another worker on HCV at the CVR; he has the World's biggest optical microscope behind him. Now could he be the author of the thesis by J MacLaughlan, outlined in pink just to the right of Prof Jarrett's chin? €5 says they're the same. All good fun an a wholly inconsequential way.  

Two days later, the Numberphile channel released a longish video about artificial intelligence, logic and probability by Rob Miles. He's chosen to sit in front of a string of books as well:

. . .  and a much more engaging shelf of books than a Lutheran bunch of 95 theses. I can see 

• Consider Phlebas by [the late great] Iain M Banks, most excellent
• Sapiens. bestseller by Yuval Noah Harari. recommended to me by a woman from Leeuwarden when I was in the RDS last month
• Watching the English by Kate Fox
• Soonish by Weinersmith & Weinersmith
• Run Program by Scott Meyer
• Data and Goliath by Bruce Schneier
• A book by Richard Dawkins - probably The Ancestor's Tale.

There you go, train a researcher to find things out and t'bugger will spend an hour identifying pixellated book covers after dinner rather than knuckling down and washing the dishes. But I bet some of you will pause youtube sometime soon and go full-screen to see what somebody else likes to read. And I guess I'd be happy to get any of the above list [except for the Dawkins, I have no time for Dawkins] out of the library to see how its reads.

Did someone mention book-shelves? It turns out that one of my [mature] students at The Institute has just started on the Home Education journey when half of his children had adverse experiences in school. I went looking for some heart-warming propaganda to assure him that Home Ed can turn out well. Or at least turn out a couple of independent, tax-paying, community minded adults. There is one short film on youtube which had long ago slipped over my two-week event horizon.  Check out the young now tax-payer [R]. But in the current context, rather check out the books:

1. Nisa by Marjorie Shostak
2. Mother Nature by Sarah Blaffer-Hrdy
3. Seeds of Change by Henry Hobhouse
4. Thee Tangled Wing by Mel Konner, husband of Shostak, and a person in his own right.

all of which are worth reading.

We taught them but they didn't learn

Sorry but I have more [prev] to say about hot, pressurized steel cookers called autoclaves which have to the potential to be a buehm, special delivery were you expecting one?. At The Institute, if we are worth anything at all, we are sending technically competent people out into the world of work. A Certificate, Diploma or Degree from us should carry a belief that The Bearer is a Good Pair of Hands. Knowing how to spell [deoxyribonucleic-acid is a very long word, how do you transcribe it]; knowing the molecular weight of ammonia [17]; knowing the Latin for mouse [Mus musculus]; are all at nothing without being reliable, careful and accurate with equipment.

For all my tough talk, I never did make my third year students write an SOP [standard operating procedure] for the autoclaves which we used every week in F&F - Food and Fermentation Microbiology. This was partly because my services were not required last year for that course because we could only muster 30 Yr3 students. We are back to 3 lab-groups again this year and the course starts today. But I'll be sure to implement my cunning plan of appointing a rotating Autoclave Liaison Officer each week who will, under my eagle eye, load and fire up the autoclaves; so that they have something to pour into their Petri dishes.

Earlier in the week I had my first session supervising wet-lab research projects. I have set my own nine [computer] project students going in their several directions along the edge of the frontiers of science. They have a longer, less intense schedule, so that both lots have a nominal 180 contact hours to make their mark on the world of understanding. If you want, you can treat supervising wet-lab research projects as a dosser's hour between more intense classes: some of my colleagues catch up on marking, some read the newspaper, some prep classes. The only requirement is that there is an adult in the room as the students trick about with potentially dangerous materials. If something goes wrong, we-the-adults should be there and should know what to do, who to call, if something goes wrong. I hadn't been in the job a wet month when one of my people sustained an acid burn. Two years later we had two hot-glop accidents involving students who had been trained <ahem>in the correct use of the autoclave.

My inherently nosy and curious nature would rather find out what the students were doing in their projects than read the newspaper and I hate marking lab books. I therefore made the rounds to find out the aspirations, or at least the game plan, for the three students who had rocked up to class on the first week of project work. In the previous hour two of them had made up some agar and set it all going in the autoclave to sterilize the stuff. Several things were amiss:

• One autoclave was all battened down and heating up but the lid was cold to the touch. That cannot be right because the interior of the pressure cooker has to be full of live steam not mere hot air. But that was okay: just open the steam valve and allow the boiling water to expel the air.
• The other autoclave was never going to come up to pressure because it was shrieking steam from between the lid and the base. I thought the rubber seal-ring might be kinky [it was the last time this happened] so we had to switch off the heat, wait for the pressure and temperature to drop and then check the seal and start again.
• That hypothesis turned out to wrong because the shrieking symptoms were repeated. Called technician. Technician asserts that there can be nothing wrong with her autoclave as it just came back from its biannual service. Then she noticed that the number on the lid (1) did not match the number on the can (2). Some noodle-head had swapped the lids which can be as idiosyncratic about fit as a rifle and its bolt.
• The third autoclave was too full of water. Bad because it takes longer to heat up; worse because everything floats about. We emptied a couple of litres out and set it going.

At that stage, my hour was up and I had another class to teach. But at the first opportunity I sent a warning e-mail to all the project supervisors: "I’ve just had my first hour i/c the Project Students. Please don’t assume that any of them know how to use an autoclave safely. Bob O’Barophobia"

spineless and blind

"Nobody made a greater mistake 

than he who did nothing 

because he could do only a little." 

Edmund Burke

What do we have to do to get The Man to wake up? Would shouting help? A brisk clatter upside the head with a stick? Setting fire to his ministerial car? The UN Intergovernmental Panel on Climate Change (IPCC) Report was released on Monday 8th October. It announced that the prognosis was worse than we have allowed ourselves to believe. Things are progressing down the global toilet faster, less has been done to deal with our carbon footprint; the evidence for climate change and its symptoms have been presented in yet starker contrast. Storms hot-and-wet and freezing blasts; too much rain and none at all; people drowned, frozen to death, starved, electrocuted, displaced and beset by coliforms. If you haven't read the report [Grauniad exec summary] it must be because you are curled up under the duvet hoping the boogie-monster won't eat you. One of my more articulate students asked me what I thought and I answered "We buggered".

That was a wholly spineless response. More adult commentators reckoned that bleakness, like so many things, is on a sliding scale: there are degrees of horror that we can visit upon our children. Hence the quote from Burke at the head of this piece. Ireland could play a powerful role in these interesting times. A small, non-aligned, articulate, educated nation, with some colonial baggage for Third World empathy, speaking English, having a reputation for hard work . . . such a country could lead by example. We could shame bigger countries into taking a more radical position. With only 5 million people and slightly more cows, even punching above our weight on the conspicuous consumption, we can't be causing more than 1% of the problem. But it's a cop-out to allow ourselves to think that all those Chinese, Indians, Germans, Americans are having a far bigger dump in the toilet of armageddon.

Ireland agreed, through the EU, to reduce our carbon emissions by 20% compared to 2005 levels by 2020. How are we doing? NOT! We have conspicuously failed to achieve any part of that target. We have not made any effective sacrifice of our extraordinarily extravagant lifestyle. Piffling about with a bit of recycling is not the answer if we are driving a car to the recycle centre. Next month, we will take delivery of 1 tonne of heating oil to see us through the winter, we won't choose to wear gloves indoors or wear a woolly hat while cooking. I'm still driving to work every day because I choose to live hundreds of metres from our neighbours in the remotest part of Leinster and an 80km round trip away from the nearest place for sensiblework.

My need to embrace shame is as nothing to compared to what Paschal Donohue the Minister of Finance should have taken on when he released his Budget for 2019. His plans rearranged the deckchairs so that nobody was offended or disturbed or compelled by taxation to make the smallest change to their life-style. Except that €0.50 was added to a packet of cigarettes. That will raise a bit of revenue but it will also serve to stop a few people smoking who would otherwise die early and take one for Team Earth instead of the coral reefs, Sumatran tigers, Guatamalan frogs and the corncrake Crex crex which are all being driven to the brink by the mass of humanity and its vanities.

Years ago Jane Gitschier started publishing in PLOS Genetics a string of fascinating interviews with Effective scientists. They are almost as interesting as The Blob. I've written about David Botstein's inspiring insight into post-graduate education. 

Another piece about Pat Brown, who invented microarrays [and PLOS!], is interesting enough but stopped me dead right at the end:
Gitschier: OK, Pat, with that, I think I'm ready to hear about the NEXT big project. 
Brown: OK—I'm serious, and I'm going to do my sabbatical on this: I am going to devote myself, for a year, to trying to the maximum extent possible to eliminate animal farming on the planet Earth. 
Gitschier: [Pause. Sensation of jaw dropping.] 
Brown: And you are thinking I'm out of my mind. 
Gitschier: [Continued silence.] 
Brown: I feel like I can go a long way toward doing it, and I love the project because it is purely strategy. And it involves learning about economics, agriculture, world trade, behavioral psychology, and even an interesting component of it is creative food science. Animal farming is by far the most environmentally destructive identified practice on the planet. Do you believe that? More greenhouse production than all transportation combined.

Well what about it Paschal Donohue? If, with a stroke of the ministerial pen and a bit of support from the Dáil, we could ban smoking in public places [2004] and put a tax on plastic bags [2002], both of which immeasurably improved the quality of Irish life, then surely we could make it illegal to eat meat except on Sunday and then only if you have a chit to say you've been to Mass.

Okay, okay, that is, like Pat Brown's, an impossible aspiration. So why not do something easier: put a carbon tax of €1/litre on gasoline and thus
a) raise a lot of cash for the common good and
b) perhaps discourage me from driving to work, mummies driving their kids to school, Deliveroo [prev] from sending food to the suburbs and all the spoiled brat indulgences that we heedless load on to the unhappy shoulders of this our blue planet.

Good enough

I'm an evolutionary biologist: I've spent a life-time tracking how living things are different and speculating how they got that way. Charles Darwin is credited with the idea of evolution by natural selection. The two most familiar phrases associated with the idea are "nature red in tooth and claw" and "survival of the fittest" neither of which were coined by Darwin! The first is from In Memoriam by Tennyson and the other was first used by Herbert Spencer in his Principles of Biology (1859). My beef is that you don't need to be the fittest to survive (and leave a parcel of offspring) you just need to be fitter than the chap next door. As the old saw has it, you don't need to out-run a hungry lion, you just need to out-run the other fellow on the road. So for me, evolution is the history of good enough. And that has sort of informed my life: I didn't need to be the smartest, fastest, honestest kid on the block.

On Friday afternoon, I was looking for one of the technicians which is quite aspirational because The Institute has many of the attributes of the Mary Celeste after lunch on Fridays. I noticed a lonely white-coated body in the lab and went over to commiserate about the loneliness of the long-distance scientist. Turned out he was an outside contractor at the end of his day 'calibrating the autoclaves'. I've written quite a bit about autoclaves on The Blob, partly because I am terrified of the things and partly because I want to make sure none of my students have a damaging hot, wet, pressurised accident while using one. Accordingly, I pointed to the beige splodge on the lab ceiling where a student had launched boiling agar skywards as well as catching some on her face. Then I told him about appointing students Autoclave Liaison Officer so they'd learn how to use that equipment safely. Having unloaded on the poor visitor, I then asked what he was doing and how he was doing it.

Seems he was popping a WiFi thermocouple into each instrument, firing it up and capturing to his laptop the actual temperature on the 40 minute heat - hold - cool cycle. tsk, tsk, he shared, that autoclave is not actually holding its temperature for the full 15 minutes. But he wasn't about to fix it, he was only the calibrator. The SOP standard operating procedure says to heat the thing up until it achieves a pressure of 15 p.s.i. and a temperature of 121^oC. In any closed system these two statistics are locked together by Gay-Lussac's Law: P/T = constant. On our autoclaves, because the pressure P is measured on a gauge [L: Top L] we don't really need the temperature gauge [L: Mid R] because we believe St Joseph of Gay-Lussac. When the needle reaches the red zone on the dial, we say, then start timing 15 minutes. But one of our autoclaves never quite reaches the red zone because the gauge is set low, and a certain type of student sits around waiting for godot red while everyone else goes to get a cup of tea and a bun. Go on with you, I say, it's good enough at that temperature or if you want to compensate then leave the stuff in for 20 minutes instead of 15 . . . have two buns while you're about it.

Because 15 p.s.i. and 121^oC are only rough rules-of-thumb that have worked in most cases, most of the time since 1884 and therefore they must have a good whack of tolerance built in. It's a racing certainty that your Petri dishes won't be contaminated if only 118^oC is achieved. You sort of know this is a makey-uppy seat-of-pants measure because 15 p.s.i. is as near as dammit 1 atmosphere (or 100 kiloPascals in new money).  The value, originally chosen for convenience, has now become an article of faith. Part of the training that scientists should get is that they learn when to cut corners safely rather than slavishly following holy writ the SOP.

Best outcome biggest price

Biologics is a technical term in MegaPharmSpeak: it is a large molecule often made by microbes in a vat. Monoclonal antibodies are one class of biologics. Most of the other drugs available are termed small molecules. Tofacitinib, the latest trendy treatment for psoriatic arthritis, is bigger than adrenalin or cyanide but a lot smaller than an antibody which is a protein (made up of numerous amino acids: each AA about the same size as adrenalin). Tofa is about the same size as estrogen or a steroid. It seems to act by plugging a receptor site on one of the players in the JAK-STAT pathway, so that in-cell signalling is banjaxed. JAK-STAT is the way in which interferons [recently] send a precisely tailored [you hope] signal from the outside of the cell to the nucleus; where it can switch on a rake of genes to deal with the problem which triggered an interferon response. The woowah cascade [L] is a metaphor: the information (water) starts at the top and bounces from one place to the other until it reaches the information reservoir (nucleus) at the bottom. Each anti-JAK-STAT drug is designed to plug just one of the outlets in the process. Stopping he cascade anywhere will work, so there are plenty of druggable targets . . . one for every multinational in the audience. The problem is that for each block stuff then cascades over the edge of the blocked bowl causing random puddles to form in unexpected places (those are the side effects).

JAK-STAT controls the response of a cell to inflammatory signals and so drugs against the JAK-STAT players damp the symptoms which folks complain about to their consultant rheumatologists. But inflammation is a Good Thing, keeping pathogens and tumors at bay and dealing appropriately with tissue damage. Hence the litany of side effects outlined on the huge paper folded into the pill packet. This is why the rescue dog living with Pat the Salt is always sick: prednisolone, the corticosteroid used to treat her epilepsy, also prevents her inflammatory system from reacting to invasioners. Signalling pathways (all?) get a signal from a receptor at the cell membrane and send a message like a chinese whisper to the nucleus where all the genes (DNA) are bouncing up and down on the chromosome "pick me, pick me". The last step in the pathway is a transcription factor TF which makes that choice: TF-X will switch on gene-Y; it will transcribe its message as RNA (transcription); the RNA will leak out of the nucleus and make a protein which will have some usually useful effect. Plug the JAK-STAT pathway and you don't have that effect. That's good for your symptoms but also good for rogue viruses looking for a toe-hold. In deciding the optimal therapeutic regime, your pharmacist and your doctor are trying to balance the benefits against the damaging, debilitating side-effects. They are not trying to balance the budget, because neither of them are paying for the drugs they so easily prescribe and dispense.
It will help me if I here tabulate some of the suffixes which indicate what sort of drug you're taking or doling out to you aged parent (I had a previous essay on the naming conventions):

-tinib	tyr-kinase inhibitor	Tofacitinib (above)
-mab	monoclonal antibody	Infliximab I
-iximab	chimeric antibody	Infliximab II
-izumab	humanised monoclonal antibody	natalizumab
-imumab	human monoclonal antibody	adalimumab
-vir	anti-viral	oseltamivir
-afil	vasodilators	Sildenafil
-icillin	penicillin-based antibiotics	amoxicillin

Why am I talking to facitinib? Because one of my correspondents has been switched to it from same-old same-old so-yesterday Infliximab. Autoimmune diseases like psoriatic and rheumatoid arthritis are a penance you wouldn't wish on the parish's worst sinner. But the treatment is typically a) uncertain as to efficacy b) beset with unfortunate side effects and c) way beyond the pockets of a normal family who can't afford health insurance. Note that about half Ireland's population qualifies for a medical card, whereby The State is the insurance company. The bill for Tofacitinib is North of €2K/mo - up about 50% from infliximab which was the previous treatment of choice. Rumour has it that the Department of Health has over-spent its budget again this year. When it comes to fantastically expensive therapies [Orkambi or Factor VIII] or sexy-surgery like transplants and coronary by-passes or pretty much any treatment for people who have weeks to live then The Man just cannot say no. Sexual health education? depression? post-trauma physical rehab? drink awareness? prophylaxis? exercise? diet? incontinence and the pelvic floor? None of which shovel money at MegaPharma: They can all go sing for it.

No, you're welcome,
Bob the Tax-payer