Not even this week's bus

The Poetry Bus comes around too often these days. Already this week’s ride is disappearing around the bend and I’ve had all of about five minutes to consider my poem.
Sometimes that’s enough.
But sometimes there’s the sort of prompt that really deserves a bit of thought, and care, before being allowed out in public. The latest one is one of these: argue with god. I’m not in the mood for some flip little thing, four lines and a sting. The eventual poem may well be four lines long, but they’ll be well-considered ones. A few weeks ago we had The path not taken, another topic that deserves far better treatment than I’ve been able to give it.
Where to start?
Which one to pick?
There have been some radical options. One of the big ones happened in 2002, the September I got my current job. The other road there would have been ... um... I have no idea what it would have been like.
I was coming to the end of the possibilities for temporary contracts at the Center. I had been a post-doc for two years: that’s done. Then an Assistant at the University for a year. Then I was paid through a charitable organization for a while. And that’s about as far as a foreigner could go without winning some kind of permanent contract. Grant after grant was turning down funding my salary.
But I didn’t have anything else lined up. Job searching takes a huge amount of effort, and I had preferred to invest myself in the work I was doing, in hopes of a good publication that would make funding easy. So the end of my contract loomed, and there was no After.
Thinking about After was so stressful I just didn’t.
What would I do? Where would I live? If I moved back to the States, a ticket I could barely afford, what State should I go to? I didn’t have a job in any of them. What would I do with my cat?
Finally, I figured I would sell all my stuff (how? To whom?), give the cat to a friend, and just become one of those after-college people, traveling around and taking pictures and writing about it. I would become a travel writer. I would have adventures and recount them with wit and sell these stories to magazines and newspapers and whoever buys those sorts of stories.
Never mind I had no clue how to go about shopping my writing around. Never mind the little I did know said the creative writing biz was nearly impossible to just break into and make a living at right away. And travel photography! Hah! Looking at my bank account, two unsalaried months of rent would be it before going red.
That was the plan.
I was fresh from reading a memoire of a guy who joined the Peace Corps and spent a year in Africa, showing people how to farm fish to improve their diet and make some cash. Incredible story! Not only did he get to have this fabulous year, which was often difficult and discouraging, but always intense, but he published a book out of it. Perhaps the PC would take me too.
So that was the path.As you know, I didn’t take it. My boss was casting around for a person to run the diagnostic lab, and I had thought he didn’t want me for the post, and he had thought I didn’t want the job, but we eventually cleared all that up and here I am.

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I'll always wonder if I would have survived out there, my home on my back, hoping for something around the bend.

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On the tail incident.

About two weeks ago on my other blog I posted a story in which the stuffed rat Bjorn had his tail damaged in a disagreement with the other rats.
Why this tale of violence?
A couple of things:
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It was really a story of sibling or schoolyard rivalry, and how kids can gang up against one who seems to be too favored by the adults. In their attempt to put the other in his place, they go too far and try to cut his tail off. (Which doesn’t work entirely, but that was a technical problem - I was hoping the pruning shears would do it.)
None of the rats admits or complains to Maurice that there was any problem at all. No ratting, no whining.
It’s like the time when one of my brothers was picking on the other, who then broke one of the large windows at the front of the house. Rather than point the finger and get the other in trouble, the first brother hightailed it to the shop to buy an new windowglass and install it before our parents got home from work. I’m not sure they noticed the window right away, but the hole in the front door was still evidence of an altercation.
But anyway, when you’re little you might go running to Mom or Dad but when you’re a bit older you keep the kid feuds between kids.
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The other thing, it was just plain fun to go over the edge. People don’t expect that.
Toys don’t usually get better after you break them. But why not do it? Now I’m big, and employed and all, I can buy as many Ikea rats as I want. They’ve got them by the bin-full! Why not a tail off here, an explosion there, a bit of disembowelling, why not? There’s an exciting devlishness in going through with the threat. Now you’ll never know if next time the toy will make it to the end of the post. How about my wind-up dinosaurs, Harold and Marguerite - fun little guys, hmm? How would Harold do against a 16-ton weight? Wile E Coyote always got up afterward and staggered away...
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So now Bjorn has a band-aid holding his half-severed tail together. I may have shocked a few readers into not coming back, but I can live with that. I don’t like it when all the endings are happy - you stop allowing for the possibility of not having a happy ending, and the only suspense in how long it takes before the deus ex machina comes.
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Not even December

So I was hoping to turn over some more of the vegetable patch this weekend, and get it mulched for the winter. But when I opened the door there was this.

Natalie's been out.

And the veg patch looks like this. Sad old tomatos. Looks like having done half the area will have to be enough!

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Friday Photo Shoot Out: Favorite Shop

I would have been with the crowd showing chocolates & pastries for the Temptation theme, but I figured I would leave that for this week. This isn't my real favorite chocolate shop, but they had a huge truck parked out front and I just couldn't get a photo!
So many choices!

And of course the ASM.
No, their shop isn't the greatest (too expensive, and the team socks have too much polyester), but the team is.
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For more Shootouts, click here.

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Existing

I never did finish my P-bus poem for today. So typical of my days for weeks now, maybe I should just take some things off my calender altogether. But no, not the fun things! Here's the fragment, which on its own has a certain enigmatic quality - you'd never know the theme is to write about our lives. Perhaps I'll finish the thought for another week.
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Like a rock in a stream
Water going by
Just going on by
Taking bits with it, tiny microscopic bits.
In time, worn smooth
A long time
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Click here for other takes on Enchanted Oak's theme.
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Trials and tribulations of a manuscript

First review:
Who cares? A piddling paper on a piddling family. The authors have this one unusual family, and from there are suggesting the whole world change the way people with mutations in this particular gene are treated. One family is an anecdote. Just because they escaped getting stomach cancer* doesn’t mean that the next family that comes around shouldn’t be recommended to have prophylactic gastrectomy. Get outta here!

Alright, that’s a pretty crude paraphrase, but you get the idea. Our paper was very forcefully struck down. While naturally depressed at the failure, I was secretly satisfied that the complaints were exactly the points I thought my coauthors insisted too heavily on. But such are the squabbles between coauthors. I have something of a reputation with my boss for setting my sights too low in submitting papers. I don’t set them too low: I really try to send a manuscript where it has a decent chance of getting in.

Admittedly, if you don’t shoot for the stars, you’ll never bag one. But I hate the multiple rounds of rejection this entails, plus the precious time lost at it. If my performance review says my goal is to publish 3 papers this year, should I really mess around with fanciful submissions that will never succeed? And I play a certain counterweight role against my boss, who is thinking Nature or Science every time we have the least result.
So we (I) revised, and added a second, smaller family with the same story that we’d found in the meantime, and submitted to a very good, though not quite so lofty journal.

Second review:
Nice paper, but not big enough news for us. Get a dozen such families and we'll consider it.

Finally the senior author was convinced that the top journals weren’t interested in our story. They have bigger fish to fry. So we resubmitted to a good, middle-level journal.

Third review:
Nice paper, very important for the medical community. Will be one of the milestone papers in the changing evaluation of the effects of mutations in this gene. A few minor modifications, and we’ll be happy to publish it.

Certainly, this wasn’t exactly the same manuscript as the first submission; we rewrote in view of the first batch of criticism. But it’s essentially the same message, based on the same family. And it's the level of journal I wanted to target in the first place. I'm just very pleased to get to the end of the story!

*this is usually fatal, and terribly hard to catch early. Prophylactic gastrectomy (removing the stomach from healthy people at risk) in young adults is the only reliable way to avoid it. But just imagine living the rest of your life with the dietary restrictions that involves!

Friday Photo Shoot Out: Temptation

These days I'm very tempted to stay in bed in the morning.

No matter how much laundry & how many cats pile up there.
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The Shootout is here.
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I’ve finally joined the Italian club.

Yes! It’s been a month already, in fact. Two.
I’ve had three lessons, but yesterday was skipped for the holiday and the week before was skipped because our teacher was recovering from a minor medical thing. So it’s been:

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Lesson 1 with a woman who doesn’t usually teach beginners so she didn’t know how the book worked and wasn’t ready to get us started learning a whole different language. (I really admire people who teach entry-level classes in a foreign language. I may know how to speak/read/write English, but I’ve really no idea how I’d go about teaching that to someone who didn’t at all.)
Lesson 2 I had to skip for a meeting out of town.
Lesson 3 I prepared for by reading up and doing all the exercises for “Lesson 2” in the book, thinking that would meerly catch me up to where the others were the week before. But in fact, that evening’s class covered just about the first third of “Lesson 2”. Aha. The book’s lessons correspond to what a college student might do in a 2-hour class. But this is a more or less casual club, a hobby sort of thing. The students are all middle-aged (I’m the youngest! I love being youngest once in a while.), and nobody wants the kind of cadence the book offers. So we’re getting through it as we get through it.

Lesson 4 covered more of “Lesson 2”, but didn’t quite finish it. We’re all still at the frustrated stage where we don’t have enough words yet to say anything.
And now this 2-week break before getting back to it. I don’t know what people will retain from the early lessons by the time we meet again. Might have to start over!
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I think learning a new language is mostly a vocabulary thing. Plus some lessons to show you how to put the words in order, maybe a bit of conjugation. Of course. Essential. But if you have some vocabulary, you can start using it to express thoughts, even if the results are all garbled up in your own usual grammar. We all know the mistakes that non-English speakers make when they talk to us. But switching the verb and noun around isn’t such a huge burden to understanding. Yes, well, there are plenty of examples of how getting it wrong can go very wrong. But overall, you can get something across. And if you listen to films in the language, and read books or magazines in it, or go there and talk to people, you find out pretty quick what the major rules are.
Italian isn’t so different from French. Both romance languages and all that. Half our words in English are pretty much the same ones in French or Italian or Spanish. (The ones that aren’t can be counted on to be German or Greek.) When I came to France, I found that English with a cartoon-french accent worked pretty well. Should be the same with Italian! Right?

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So I bought a book in Italian last weekend. A slim volume by Primo Levi, a book I’d read before in translation. Perhaps I could have found something happier, but the selection barely covered one narrow shelf and at least with this one I have an idea of what’s going on.
Thus far I’ve read about five pages. There’s a balance to strike between making a dictionary pause for every word you really can’t imagine what it might be, and barreling through with these holes in your understanding because otherwise by the time you get to the end of the sentence you don’t remember how it started.
But I’m doing it. I’m reading in Italian.

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Friday Photo Shoot Out: Overhead

Look up these days, and what do I see.

Miss Fluffy on the fence.

"Sun-dried" apricots.

A few apples still.

The occassional flying rabbit.

Accompanied by some jumping rats.
The autofocus doesn't like this sort of moving target!

Oops. Get the ladder out.

Birds in trees are more visible these days.

But mostly the things hanging over my head are on my desk.
Or maybe it's me sinking under them.

I am definitely in over my head these days.
Like this paper.
I hope it will be leaving for a journal in the next few days, along with two others.

Then life will be better.

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Join the Shootout here.
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some science for ya

A quick word about how this sequencing thing works, then. A strand of DNA is made up of four different nucleotides, A, C, T, and G. They're mixed together pretty evenly, with a slight excess of A's and T's. When there's a stretch of one nucleotide repeated, say 8 A's in a row, that can cause problems when you want to replicate the strand. The polymerase (the enzyme that makes new DNA) can lose count, and do only 7 before going on to whatever comes next. Isolated polymerases in the laboratory make lots of that kind of mistake, and although the replication machinery in our cells (which includes the polymerase but also dozens of other proteins in an enormous complex that proofreads and makes sure the replication is faithful to the old strand to be copied) is quite good at making good copies, these 'homopolymer' sequences are often the source of mutations. A mistake is made, a base lost, and everything that comes after is out of phase.

So when I'm looking for mutations in a gene to tell a family where their cancer risk comes from, I pay special attention to these homopolymers.

Our new sequencer reads sequence by a trick that means each base incorporated into the strand being synthesized emits a certain amount of light. One base, one unit of light. Two bases of the same kind, two light units. The counting is pretty good through 5 bases, but once you get up to 7 or 8, it's hard to tell exactly how many units you have. Ten identical bases in a row, and the machine doesn't have time to get through all that in a single cycle, and so you just can't read 10 or more.

Our sequencer also reads each molecule of DNA that you give it one molecule at a time. Each one is called a 'read'. The software lines up the reads against the reference sequence and tells you how many of what kind of bases you have from start to finish.

Let me show you its counting problem.
The software knows that you have to have a whole number of bases. 7 or 8. No such thing as 7.6 bases. So it takes all of the reads with intermediate values for the number of bases in a series, and rounds off to the nearest whole base.

With data like this, no problem. The dark bars is what the furnished software says, and the light bars come from our own analysis of the raw data, admitting fractions of bases. 87% of the data rounds off to 8 bases, and that's great.
But most of the samples come out like this. The furnished software says about 45% of the sample has 7 bases, and another 39% has 8. If all I know is these two numbers, I'm thinking there's a deletion of a base on one of my patient's two copies of this gene. But look, there's clearly (well, okay) a single population of values, centered at 7.4 bases. This sample does not have a mutation, it has a bunch of intermediate data that's been incorrectly interpreted. I analyzed this one using a different method, and there is definitely no mutation.

So what about this?
This is just exactly what I expect from a real sample with a deletion of one base on one of her two copies of the gene. Ironically, the commercial software gives me exactly the same values as the preceding example! The second experiment to confirm or reject the proposed mutation is underway, but it looks pretty good. Two populations of values. The difference between the peaks is not exactly one base (it's 0.8), but it's pretty close. If this sample doesn't have a mutation, we'll be having some serious talks about the technique. I have some other examples of real deletion mutations, and they look just like this.
What really kills me is this sample - and these four graphs come from four samples in the very same experiment, showing the same bit of sequence. This data is ugly. I appear to have two distinct populations, at 7.2 and 8.1 bases. But the trough between the two is not so clear. And it's not so symmetrical. I do have the confirmation experiment done for this one, and guess what:
No mutation.
All the DNA has 8 bases.

Not 7. Not 6.

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sigh.

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No, we did not miss that boat.

Boss just back from the American Genetics meeting, all in a huff we'd been scooped.
Ah, boss, it's true we didn't submit an abstract to this meeting (we didn't have any chance of actually going, and didn't know you planned to), but look! The authors are our Belgian colleagues! We're on that paper. The program they mention for treating homopolymer data is ours.
And yes, the manuscript is millimeters away from resubmission.
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Poetry Bus goes bathing

Jessica set the bus destination this week: bathing. Click here to sign on and take the tour.
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The pleasure of the Bath
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Nothing better
than a candlelit soak
while it snows out.

Damn this drafty old house
with its shower stall.
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Magpie 39

Oh, look, a pile of leaves. I wonder if there's any bugs.

bugs ;;; bugs ;;; bugs

Oh yes, bugs. Very juicy.

buUUgs!

There's Clara. She wants my bugs.

I'll peck her if she tries.

peck.......peck.......peck

thinks she's so fine in her red feathers

I'll peck her. She's not getting mine.

buUUgs!

Oh, there's Rocky. Sooo handsome

Shake my feathers out, yes. Ohhh yes

Bug! got it.

Rocky's scratching in the dirt, looking us over with his bright eye,

Here! Right here!

I'll just walk over to that tree, show him my good side.

Here's Bess, strutting around, thinks she's so fine.

Get out of my way!

Peck you! I will.

Doesn't know a grub from a piece of wood, that Bess.

Ain't no bugs over here

bugs ;;; bugs ;;; bugs

buUUgs!

Oh, here's the Farmer! Where's the bucket of corn?

Where is it!

Gotta get there first Gotta get the corn.

Where is it? Get out of the way, you chickens!

Peck you! I will!

Here's a nice pebble. I like that one.

Here's the Farmer. He's picking me up!

He's got my feet! Help!

He's taking me away!

buUUgs!

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For other Magpie 39 Tales, click here!

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Pass the deck

I love to shuffle cards, just love it.
People think I’m some kind of card shark because of this. They think I have some sort of secret communication with the cards that lets me know how to play.
Well I wish it were true. I wish I were a better bridge player and could keep track of who’s holding what all the time.
My secret communication is limited to the physical shuffling of them. I love the snapping zip of a good frank shuffle down on the table, followed by the softer susurration of the arched halves of the deck flying into place between my crossed thumbs.
I wish there were more cards in a deck. Not too many more, just a dozen or twenty more. Just enough to let the zipping and the shusshing go on a little longer before the next cut.
I’m quick at it, too, which really impresses my new bridge buddies. Cut, zip, shussh, smart rap on the table to even them up, and start over. They don’t know I’ve been shuffling since before I could properly hold a deck in my hands. They don't know this doesn't mean I'm good at anything aside from shuffling.
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ABC Wednesday

P is for ...

Pandemonium!

Click here to know all about Pan.

and here for ABC Wednesday.

November is time for Lexington

I didn’t plan on getting Lexington. I’d had Natalie for a couple of months, and she wasn’t great friends with Pandemonium, but he was occupied enough not to need another companion. But then the aging father of a friend of a friend died, and I was asked if I might have room for his cat.
Er, ah, why not?
So I inherited a large, white, male and apparently nameless cat, whom I called Lexington. Pan seemed content enough to share the apartment with yet another cat. Natalie was less content. Lexington thought it was just fine, because while Pan didn’t bother him one way or another, Natalie was a cat he could dominate.
He was subtle about it. He never chased her or growled or put a paw out that I saw. But Nat took to hiding under furniture whenever he came into a room. She was denied the catfoodbowl. After a few weeks she was hiding under furniture whether Lexington was in the room or not.

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So we had to find another home for Lexington. He was used to being the king of the house, but I already had Pan for king, and wasn’t interested in his kind of serf. My friend’s mother took Lexington in, and that seemed to work out pretty well. She does have to keep her other cat in a separate room, but her apartment is large enough for that. Lexington is Hector now, and he’s a true emperor in his realm.
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