Bobbie goes to Hollywood

Optional soundtrack - FG2H The Power of Love

We are signed up to Blackstairs Farming Futures BFF, and I have undertaken to log all the evidence of human impact on the environment that will be here in 200 years time. "the environment" here being the 200 hectares which we own in common with 18-20 other neighbours. It's fun because I get to name the artifacts which I find. The more obvious artifacts like the Sitka spruce Picea sitchensis plantation, or the sheep-proof fence that separates it from the commonage; or the sheep themselves? None of them are likely, let alone guaranteed to be there, then. But the stones, split by judicious and musical hammers and wedges? The rocks remain [Horslips] [Maxwell]. I show [L] the most obvious example [it's the parallel lines of wedge-holes, silly] of a project to craft a lintel or doorstep from a granite boulder. For whatever reason the mason stopped his own gallop one minute and cried "Feck it! this is going nowhere" and started work on a more promising rock. It is a snap-shot in heritage time quite as vibrant and informative about human activity as Stonehenge or the pyramids if a trifle more humble.

BFF is a pilot study to help imagine and then create a more productive future for Ireland's upland habitats: there's got to be more to it than burning the heather, running some sheep and planting out more spruce deserts. Can we, with a deft twist of a limiting factor in the environment [Iron; Foxes Vulpes vulpes; Pasteurella haemolytica; blocked drains; impenetrable forests of gorse Ulex europaeus] change the whole landscape like The Man Who Planted Trees? Yesterday, eleven of our commoners rented a minibus and directed it to a Teagasc showcase in Hollywood, County Wicklow. We The Eleven sat in the Hollywood Community Hall for an hour being talked at by ecologists and agrifunctionaries. |Then we were bussed up towards the hills to a commonage called Granamore [view below] to see how ten farmers with mountain rights can get round a table and then round a trough of sheep dip and talk out a sustainable future for their lives and livelihoods . . . and give access to hikers and orienteerers and kite-flyers. They told us a little about the practicalities of road-mending; river-fording; draining; controlled burning and a bit of tree-planting.

One qualified statement got me thinking. They showed a poster of sustainable stocking rates (in ewe-equivalents / hectare) for
upland grassland 1.5-5 ee/ha;
dry heath 1-1.5 ee/ha;
wet heath 0.75-1.0 ee/ha;
blanket-bog <0.75 ee/ha.
Those rates are different for the different habitats but all those habitats are represented on Granamore Common . . . and here are no fences. How to keep most of the sheep out of the blanket bog and more on the few patches of good, palatable, nutritious grassland? One cunning plan that has had some success is to lug a 20kg bucket of mineral lick [essentially candy for cows and sheep] to the areas covered in deergrass Trichophorum cespitosum or matgrass Nardus stricta as a honeypot. While there the sheep will eat some matgrass [though it's a bit bleh to normal sheep], trample some deergrass and give better grass elsewhere a chance to grow after, say, a controlled conflagration. All that is predicated on the fact that farming hill sheep is a really unproductive way to earn cash for children's shoes and cornflakes. Farmers will be better off spending time taking sheep to the mart; working in the mart; shearing, ploughing, mowing and baling for their neighbours; working for Teagasc or as a teacher.

Chris "Drummer" Stewart [Driving Over Lemons is wonderful] retired young to Andalucia to potter and write. He earned an honest crust as a sheep-shearer and got to know his neighbours. Several of them were shepherds who were active on the hills more or less all the time. I always thought that the shepherd and his mastiff's primary task with sheep was to prevent predation; and to stop them wandering into the next village for vino tinto y tapas. Wrong! especially now that we have decimated all the top predators. The shepherd can, by her presence, gently shift the flock wholesale from areas-to-be-protected to areas-where-they-are-a-grazing-asset. Even a chap can serve this purpose: load up his smartphone with credit and let him off up there being useful.

Is the mouse a good model?

A few years ago I was embarrassed to admit that I'd never heard of the 4th biggest city in China. [Ans: Tianjin 天津市 - it is near Beijing in the NE of the People's  Republic]. The 3rd biggest city in PRC, after Shanghai and Beijing is Chongqing 重庆市. Now I had heard of Chungking because it was the Capital in Exile in WWII after the Japanese sacked Nanking and occupied Beijing and much of the N of the country. Note the last character 市 is the same for both cities: it means city! Our ignorance of China is immense: the population of Chongqing alone exceeds that of the island of Ireland: could we take the trouble to find out more?

That opportunity was provided last week at the end of a 3 week Summer Programme at The Institute for students of Southwest University (SWU 西南大学) in Chongqing. I was 'volunteered' for 6 contact hours to play some computational-biology games.  They paid me, but not enough to create a whole new course, so I modified part of a comparative immunology module I developed a few years ago. The question I put to the students was

"Is the mouse a good model organism for developing 

a novel therapeutic against such-a-disease".  

One pharmaceutical research avenue which has been fruitful is the development of monoclonal antibodies specific for key molecules in immunological / inflammatrory response pathways. Monoclonal antibodies MABs are amazingly specific in seeking out rogue actors which get over-excited in  a particular disease. What I know about normal human physiology, after teaching it for 7 years, is that the whole system is a set of checks and balances; disease is when this delicate, multiply redundant, complex of interactions goes AWOL. MABs are given dork-dopey names , mostly ending in -mab so that Google-savvy patients don't be bothering their doctors to try the latest me-too drug they read about in Hello magazine.

The standard protocol for a new drug prospect is to build on our increasing knowldge about the molecular fundamentals of a disease and ask . . . if we could put a damper on MAPK then it wouldn't be able to gee-up STAT3 and the whole over-heated system would cool off. MegaPharm is only interested in drugs that will make them a load of money, but they have to ensure that a) they do indeed work in the way intended and b) they are safe to use: that their side-effects are not too damaging. The usual thing is to try out the prototype drugs on a couple of hundred lab mice Mus musculus, and then do some statistics to see whether the idea might be a runner.  If none of the mice get the screaming abdabs [technical term] and enough of them get better, then it's time for the first human trial.

In 2014, I wrote about the most famous case where that next step went horribly wrong with a test of TGN1412 which seemed in mice to counteract the effects of CD28. It was a salutary reminder that mice and men are similar, yes, but also different. Nobody died in that first human trial but several of the human guinea-pigs were badly roughed over and won't ever properly recover.

That gave me the bones of a hypothesis to test with the boys and girls from Chongqing. Let them compare a list of drug targets to see how similar those molecules were in Mus musculus and Homo sapiens. TGN1412 was to be a treatment for Rheumatoid Arthritis. My correspondent G who is pain-wracked by RA has been taken off Infliximab because her condition is no longer responsive to having her TNFα tricked about; so she would welcome a novel therapy to help her get out of bed in the morning. But TGN1412 and multiple organ failure is a bridge too far even for her.

The kids from Chongqing were invited to choose one molecule from a list that had been used as a target for a named monoclonal antibody. Starting with Infliximab and ending with TGN1412:

They were then requested-and-required to use the Blast server at NCBI to find the homologous [equivalent] gene in mouse and see just how similar they were. I show above the target-list and, in the last column, the answer for the class. The specific hypothesis under test was that CD28, the TGN1412 target, would be noticably more different mouse-vs-human. And the answer is . . . No!  I emphasised that nothing like this analysis had ever been carried out before since science began in the 17thC: the kids from Chongqing were pushing the Frontier of Science.
Here's some more detail on IL13 one of the crappier comparisons. At 59% identical, you might think that IL13 is missing in mouse and P20109 is something else entirely. But a reciprocal best hit analysis shows that the two sequences are indeed orthologous and probably have the same structure and function in both species.
IL13 Mouse P20109 Query vs Human P35225 Sbjct
Expect 2e-40 Identities 76/130(59%) Positives 93/130(71%) Gaps 8/130(6%)
Query  6  TAVLALACLGGLAAPGPVPRSVSLPLTLKELIEELSNITQDQ-TPLCNGSMVWSVDLAAG 64
          T V+AL CLGG A+PGPVP S +L    +ELIEEL NITQ+Q  PLCNGSMVWS++L AG
Sbjct  20 TTVIALTCLGGFASPGPVPPSTAL----RELIEELVNITQNQKAPLCNGSMVWSINLTAG 75

Query  65 GFCVALDSLTNISNCNAIYRTQRILHGLCNRK-APTTVSSL--PDTKIEVAHFITKLLSY 121
           +C AL+SL N+S C+AI +TQR+L G C  K +    SSL   DTKIEVA F+  LL +
Sbjct  76 MYCAALESLINVSGCSAIEKTQRMLSGFCPHKVSAGQFSSLHVRDTKIEVAQFVKDLLLH 135

Query 122 TKQLFRHGPF 131
           K+LFR G F
Sbjct 136 LKKLFREGRF 145
The fundamental problem is more complex than 22 undergraduates from China can solve in 90 minutes; but we probably knew that. I still think it's an empowering exercise.

Might have been

<Guest Blog Alert> [never done this before]
I wrote recently about my exercise-induced arse-ma; which put the kibosh on my prospects with the loneliness of the long-distance runner. It struck a nerve with my correspondent [recent] G who wrote about her own lack of wind so eloquently that I'm posting it here (with her permission):

Exercise-induced asthma - the bane of my life and only recently diagnosed by an occupational therapist of all people. When I was 15 and gasping for air after a couple of minutes on the trampoline double and triple somersaulting, my PE teacher used to make cracks about me giving up the cigarettes (a few years before I took them up). This made a huge impression on me in terms of unfairness and amazingly one of these incidents was memorialised in a poem by a schoolfriend forty years later. 

When playing hockey, if a game was very defensive and as a left back I had to be on the move continuously then I'd see things like the far corner of the hockey pitch lift up and roll itself towards me. Charles Bonnet Syndrome [prev] or purely oxygen deprivation? When I told the PE teacher, she suggested for the first time that I give up smoking - at 12, in a convent - FFS! She had to be on drugs to think that! 100 yards sprint was no bother to me, the fastest in the school, till I'd finished it... but the three rounds of the hockey pitch after dinner every day, that the couchiest potatoes in school found easy, never happened for me. I could never finish one round... a long and short side and I'd hit my wall with no running through it. Courtney Dauwalter is a better woman than me.

Five years ago, before the chance discussion with the OT, I was determined to take a crack at running in the dark instead of standing on sidelines and started running, using a Couch to 5K app. By the time I'd repeated six weeks of Week 1 without any visible difference in my fitness, I muttered curses and let the weather get the better of me and ceased my running endeavours. It has been a constant wonderment to me how one of my friends can get out there and do 5K cold from the couch without wanting to die during or after it. 

How did a woman fresh out of a four year PE teacher training course in Thomond College which presumably contained both sports physiology and psychology modules fail to see that the most active sporty girl in the entire school wasn't a smoker but had a real health problem? She never put together that, while I excelled at all sports, that basketball, netball, tennis: any sport requiring stamina were washouts for me after very promising oxygen-loaded starts. 

What could have been! Such tiny things to mould a character and change a life. The Blob sometimes hits a nerve [ouch].

[coulda beena contenda]

G's nearly on her pension now but, in her youth, people who knew the field talked up her potential as an Olympic gymnast. But that dream would have required getting many ducks in a row, and for network and exteernal support, G hadn't even a feather, let alone one full duck.

“Strange friend,” I said, “here is no cause to mourn.” 

 “None,” said that other, “save the undone years, 

 The hopelessness . . . Strange Meeting Wilfred Owen

Catchup ketchup 18Aug19

As The Blob gradually fills out the last remote corners of my universe, new stuff is likely to recall a bloboprev.

• Remember 4Ocean $20 bangles = 0.5kg trash? Harry Chan has lifted 80,000 kg of trash
• from the sea. Those surfer dudez from 4ocean owe him $3.2million.
• Three years ago it was bottle-flipping. To which I applied a sciency view. Three decades ago in California, it was cup-stacking . . . but it's only come over my horizon in the last three days at Vox via Tywkiwdbi. 
• The Cup Song and Amhrán na gCupán
• Where Dreams Go To Die - documentary on Gary "Newfie" Robbins and The Barkley Marathons [prev]. If you're invested, you can find out how Gary did in 2018 on your own.
• Courtney "Ultra" Dauwalter runs along.
• The Right Stuff. 17th April 2018, SWA 1380 suffered a catastrophic engine failure between New York LGA and Dallas DAL. Debris flew back and smashed a window in the fuselage causing decompression and oxygen masks. Captain Tammie Jo Shults dealt with the emergency as if it was a hang-nail that needed fixing. Radio traffic between 1380 and Philadelphia Tower; 12 minutes on the edge of your seat. Banker Jennifer Riordan was the only fatality.
• We shall overcome with Nimo Patel [prev]
• The Boss
• The Troubles
• Rev King
• The Baez
• Peter Fonda dead. Play Flow River Flow
• Medical error? [prev] Think a bit before pointing fingers, says Dr Rohin Francis: crap detection needed on poor data.
• Me n Rohin agree on the recurrent pharyngeal nerve.
• WHAT ABOUT THE KETCHUP; YOU PROMISED KETCHUP!
• How to make industrial ketchup [sound off for sanity!]

Legless in Gaza

My correspondent / source G ordered me to watch No Limits a documentary by John Zaritsky about Thalidomiders. I've had a peek at Thalidomide before, largely to give tribs to Frances Kelsey who, as the newest hire at the FDA, stalled drug company Richardson-Merrell from marketing the devil's spit-balls in the USA. The few [N = 17] US cases of Thalidomide-induced damage seem to have come from freebies given out in handfuls by Merrell as pre-sale promotion for the new wonder-drug. Merrell was interested in the distribution rights because Thalidomide had been so profitable for Grünenthal, the German parent company that held all the intellectual property.

Although I knew the story, there were numerous details which had escaped my notice (or slipped my memory since, as likely).

The Nazi connexion. Otto Ambros was appointed Chairman of the Grünenthal Board. We've met him before as one of the developers of the nerve gas Sarin, when he worked for IG "slave-labour" Farben in WWII. Dr. Heinrich Mückter was Grünenthal's Head of Research and claimed a tidy royalty for each packet of Thalidomide sold. During the war Herr Dr. Mückter had worked im Osten, doing experiments, without informed consent, to develop a typhus vaccine on Polish civilians and the inhabitants of the Krakow ghetto.

The off-switch statistics. There was a very high rate of perinatal mortality among victims of Thalidomide-induced dysmelia. It is true that there was were a number of still-births associated with the drug; and presumably a, hard to guesstimate, number of spontaneous abortions and miscarriages. But it is alleged that many full-term babies, without the full complement of limbs, were left in the delivery room by their mothers and taken care of by doctors and nurses who couldn't imagine that a limbless child could live longer than a few days or weeks, let alone a full and active life as an emergency physician; a motivational speaker; or a film director.

The film No Limits is about what it says on the tin No Limits and so has a black [those Nazis, callous doctors and unimaginative midwives, corrupt officials, company lawyers] and  white  [Kelsey, survivors-who-have-done-well, Widikund Lenz, William McBride] view of the people involved. Those who have been bullied; who haven't found love; who have a crap self image; whose general health is getting worse with age; whose life has not been a bowl of cherries; they have no parts - not even walk-on parts - in the film. Nevertheless, hats off to the following people, who survived the drug induced insult to normal development and went on to live their best life: with a little help from parents, foster parents, teachers, spouses, their own kids . . . and indomitable spirit, of course:

Jan Schulte-Hillen

Moni Eisenberg

Louise Mason

Lynette Rowe

Niko von Glasow

Paul Murphy

Eileen Cronin

Alvin Law

But don't accept my take on it, watch the film yourself, it's only 80 minutes long.

. . . Promise was that I

Should Israel from Philistian yoke deliver!

Ask for this great Deliverer now, and find him

Eyeless in Gaza, at the mill with slaves,

Himself in bonds under Philistian yoke.

Samson Agonistes, John Milton

Q. How do you address your father?

A. Sir!
I've looked with a jaundiced eye at Douglas Hofstadter and all his Gödels works. But an essay of his, on how language embeds sexism and inequality, triggered some interesting discussion on MeFi. Sometimes you have to move the goalposts to make people actually look at themselves and their certainties. I was sitting in her garden a couple of weeks ago with The Girl Who Invented Herself TGWIH. Of almost everyone I know, she gets the most cross when she encounters discrimination and unfairness. She doesn't live in Ireland at the moment but is VP AsiaPac for a multinational in Singapore. I forget the details but she was getting indignant at how the government (largely representing the people of Ireland) keeps migrants and asylum-seekers in disempowering and punitive conditions for years while their cases dither and shuffle through the legalities. She seemed to be saying that she'd be delighted to have a Syrian gynaecologist or a Yazidi metal-worker living next door, if not exactly renting the spare room in her Irish home. I confessed that, knowing nothing-at-all about the community engagement of the average Yazidi, I'd be suspicious if not quite hostile if the one vacant council house in our townland was given to a family of Travellers. And I invited TGWIH to agree that she's feel the same, if push came to shove.  That grain of doubt didn't develop into a pearl of wisdom but I thought it was valuable to look closely at our true, uncovered reactions to The Other.

What Hofstadter did in his cited essay was transpose our view of oppressed women with oppressed blacks and see how smug the standard liberal-leaning  PC reader was then:
Quote: Most of the clamor, as you certainly know by now, revolves around the age-old usage of the noun "white" and words built from it, such as chairwhite, mailwhite, repairwhite, clergywhite, middlewhite, Frenchwhite, forewhite, whitepower, whiteslaughter, oneupuwhiteship, straw white, whitehandle, and so on.UnQuote  The MeFi commentary went round the houses and down the street as readers teased out some of the threads in the original essay and struck a few sparks off each other: quoting Simone de Beauvoir's Second Sex etc etc.

Reflecting on how language enforces the trappings of power, Sideshow, a youngish patriarch, moaned gently "My 8 year old daughter even threw a "Hey bruh..." at me (her 38 year old father) the other day. I'm a pretty casual dad, but I had to draw the line there. "  Not me, I answer to pretty much anything if I can hear it properly [increasingly doubtful] and intention is clear: Sir, Pops, Bob, Shonks, have all worked in the recent past.

Lollusc reacted to that with far more enthusiasm than anyone else:  OMG that is so exciting (to me, and probably only to me and like five other people in the world who research kinship systems). There's a phenomenon in some languages of the world called "Crow skewing" (named after the Crow language, for which it was first described). It's where people call their cousin by the same term as they call their father or mother, i.e. they would call their cousin "dad" or their dad "cuz". The principle is basically (terminologically) treating people in your own generation and people in the generation above you the same. It's pretty cool and NO ONE REALLY KNOWS HOW IT ORIGINATES. There's quite a bit of speculation. But calling your dad "bruh" is absolutely how this kind of thing could start. "Bruh" being a term of general friendly affection, but ultimately derived from "bro" < "brother". And then it loses its association with one's actual brother, and gradually loses the "same approx age" requirement, and voila! 

Later on ReclusiveNovelistThomasPynchon added 2c worth: the thing i love about sideshow's daughter's use of bruh is the egalitarian, or at least anti-hierarchical, sentiment it seems to embody. sort of like, "yeah sure bruh, you're a generation up from me, don't make such a deal of it." i believe it's the egalitarian aspect of it that sideshow objects to so strongly. i'm so glad that it's apparently a semi-common linguistic phenomenon. parents get hung up on weird things.

I love it: Crow skewing is so random and outré, that Lollusc is going to have very few places where s/he can share this deep knowledge of the human condition. With so many different ways of communicating with each other with truth and respect, it seems a pity that we too often trash talk instead. Here's a test. From the language and expressed sentiments, what sex do you reckon Lollusc is?

Lazy unimaginative

We spent much of the Bank Holiday weekend with Dau.II in The People's Republic of Cork - hangin' out being guinea-pigs for her latest culinary ventures. mmmmm good, but we didn't allow the food to get cold while she tricked about with camera angles. One item on the agenda was to meet one of her workmates who has recently walked from Le Puy en Velay in central France all the way [todo el Camino Francés] to Fisterra / Finisterra / World's End via Santiago de Compostella. I'd brought along a copy of my Analysis of the Process of Pilgrimage which I wrote in 2004 when I'd finished my trek.  But La Pèlerine wwas much more interested in quizzing us about our Analysis of the Process of Home Education. In trying to convey what happens in an unschooling household, Dau.II pointed out that she's spent the last two years of her life as a home educatee sacked out on the sofa binge-watching boxed sets of DVDs.

Watching so many episodes of House back-to-back rather than one eposide a week like normal people, forced her to notice just how often the black doctor diagnoses the episode's problem patient as suffering from Lupus. In each case, it could be Lupus, because that condition manifests as a really variable, flakey set of symptoms. But it could also mean lazy and unimaginative script writers whose medical knowledge is read from the back of a cereal box Wikipedia.

When passing through Tramore on the way to Cork, I got sight of The Irish Times from 20 Jul 2019. We gave up buying newspapers years ago, long before their content became available on-line. But it is sometimes amusing to read a newspaper, for old time's sake and to check on standards. Back in the early 90s of the last century, the TCD Genetics Department used to 'take' the Irish Times by way of affirming how Protestant we all were. We went through a bit of a jag with competitive crossword solving; whereby one of us would make 5 copies of the Simplex crossword and we'd race to see who could finish it first over lunch. You can train yourself for this sort of party trick, the more you do, the more you get inside the mind of the complier(s).  Just as I learned to do with the Times Jumbo X-word books. For auld lang syne, I knocked off the Simplex for 20/Jul/19.

Two days later, we're in Cork, and The Beloved lashed out half a week's wages to buy the Sat 03/Aug/19 copy of the Irish Times. I started in on the Simplex until I was brought up all standing by a sense of deja vu. Surely I'd seen that clue before in Tramore? . . . and this one . . . and that one too. Returning home via Tramore I was able to verify a bit of annoying auto-plagiarism.
Simplex 20 July
11 ac Land of the tsars (6)
07 dn Large imaginary creatures usually wicked (8)
28 dn Unite a strange relative (6)
Simplex 06 August
3 dn Land of the Tsars (6)
10 ac Giant imaginary creatures (8)
15 ac Relatives get an odd US tan (5)
I have 50+ years of experience with solving crosswords, since my mother taught me the rudiments of the conventions: "odd" and "strange" in the selection above, for example, indicate that anagrams are involved. I've also compiled a few, to prove that I can. The hard part is filling in the grid with words that mesh with each other; making up clues for these answers is easy. So it's pure laziness to use exactly the same clue for "Russia".

I only noticed these coincident clues because I was doing serial puzzles, out of chronological order, like Dau.II bingeing on House and getting slapped with Lupus.