Day4: Scott was determined to try the crux again for a while and then continue regardless of outcome, so we packed up most of our stuff into 1 bag, and jumared up to the boulder problem, hauling via 1:1. After 30 minutes of fairly demoralizing attempts, he was close to calling it quits until I again suggested he check out the Teflon Corner somewhere to the left, and out of view around an arete. This parallel pitch ends at the same anchor/ledge as the boulder problem, and is reached by walking left 2 pitches lower and doing a 5.10 approach pitch instead of the .11cR pitch we'd done the day before. Scott lowered down out of view, clipped something as a directional as he didn't have a single carabiner on his harness, and told me he'd found the Teflon. It was interesting to belay a famous pitch without actually seeing it, but I could tell Scott was quickly looking at redemption. After brushing some holds and chalking some smears, he was able to quickly make progress. In just 2 real tries from the belay ledge he managed to toprope this alternate crux option without falling - and though I was belaying I only ever saw the fingertips of his right hand as he reached the end of difficulties. He said there were a 3 fixed steel draws and about 20' of hard climbing above the belay, so he'd probably have fallen farther on our circuitous blind toprope than if I'd grabbed our bags, swung over, pulled the rope and belayed him from below as per normal. Given how quickly he climbed this, I think more folks should try the teflon corner, especially if you aren't an avid boulderer and it's not wet due to early spring runoff. He never tried the alternate approach pitch (P.20 or so) that leads to the Teflon, but he had already climbed a much harder approach pitch to the boulder problem.
[Soapbox Alert] - El Cap has never been onsighted or flashed, by any route, by anyone, ever. A few climbers have come close. Each is a much more skilled and accomplished climber than myself. But nobody has started up a route they hadn't tried before and climbed to the top (even sharing leads) without falling on at least one pitch. Here are a few close calls - at least one of which had the climber publicly claiming he Flashed the route despite climbing the route in 2 parts between a rest on the ground, and after a fall on his first choice of cruxes. [/Soapbox]
culture harder than the rest rar
Next, the expression levels of terminal differentiation genes and inflammatory disease marker genes were analysed in monolayer N/TERT keratinocytes that were stimulated with pro-inflammatory Th1 or Th2 cytokines. Upon stimulation with Th1 cytokines (TNFα, IFNγ, and IL-1α) the expression levels of FLG and LOR decreased (normalized to unstimulated keratinocytes) and in particular in N/TERT2G keratinocytes this downregulation was significantly stronger as compared to primary keratinocytes (Fig. 3A). The expression of psoriasis-related host defence genes PI3 and DEFB4 33,34,35 (encoding SKALP/elafin and hBD2, respectively) was increased in both primary and N/TERT keratinocytes, but N/TERT keratinocytes showed a significantly stronger upregulation and this was most pronounced in N/TERT2G cultures (Fig. 3B). After stimulation with Th2-cytokines (IL-4 and IL-13), we observed a minor decrease (only statistically significant for FLG) in FLG, LOR and IVL expression in N/TERT keratinocytes (Fig. 3C), while markers for AD, C-C motif chemokine ligand 26 (CCL26) and carbonic anhydrase 2 (CA2)30,36, were found to be upregulated (Fig. 3D). Overall, the N/TERT keratinocytes appear more responsive to Th1 cytokine stimulation than primary keratinocytes. Upon addition of Th2 cytokines, N/TERT1 keratinocytes express less CA2 than primary keratinocytes and N/TERT2G keratinocytes. CCL26 is upregulated by both N/TERT cell lines and the primary keratinocytes upon Th2 cytokine addition, albeit a stronger induction rate of primary keratinocytes. These differences are, however, not statistically significant due to the high interdonor variability of the primary keratinocytes.
Th1 and Th17 cytokines affected the epidermal morphology as haematoxylin eosin stainings showed parakeratosis (retained nuclei in the stratum corneum), thickening of the stratum corneum and the absence of a stratum granulosum in these cultures (Fig. 4C,F), all features of psoriatic skin. Treatment with ATRA improved the epidermal morphology in both cytokine models (Fig. 4C,F). The changes in epidermal morphology were accompanied by lowered protein expression levels of the terminal differentiation protein FLG, while psoriasis markers hBD2 and SKALP were upregulated. ATRA treatment lowered hBD2 and SKALP expression but did not restore FLG protein levels (Fig. 4G and Supplemental Fig. 5). These results indicate that N/TERT cells can be used to generated PS-HEEs and we were able to validate the model by the treatment with a known anti-psoriatic drug.
The initial study first describing the N/TERT1 and N/TERT2G cell lines11 already showed the potential of N/TERT keratinocytes to retain normal growth and differentiation characteristics in vitro. These data together with the herein presented direct comparison to human primary keratinocytes clearly indicate that N/TERT keratinocytes largely behave like primary keratinocytes. N/TERT keratinocytes tend to differentiate quicker than primary keratinocytes as shown by the gene expression peaks at day 4 of differentiation in N/TERT keratinocytes and at day 7 of differentiation in primary human keratinocytes (Fig. 1). Therefore, when using N/TERT keratinocytes in a monolayer culture system, one should be cautious about the time of harvesting when differentiation status is critical for the experimental outcome.
As do many of the readers, I feel thusly:1) Yes Agile/XP isn't all it's cracked up to be, but it's better than most of the alternatives.2) Google's approach sounds brilliant, but how in the world can it work at [my place]? We've got corporate customers, and corporate culture, and lesser quality coders, etc.2b) I'm jealous.
It's all about the people.At Google, I think it is pretty rare to find someone who is not an A-lister and who treats software development as only his job.That way, there is trust amongst the team, and between management, business, and developers. I agree that the initial culture is important, but it can only be sustained if your people are "right".Also, developers have the power at Google.Compare this to the normal, everyday IT world of software, and where the managers and team members don't really have that trust, because there is wide variation of skill within a project, and sometimes the manager does not really understand technology either.A couple of books that describe what a good team mentality should have are the oft-mentioned Pragmatic Programmer and Practices of an Agile Developer from the pragmatic programmers.Don't be fooled by the "Agile" in the name. It reads more like an "extension" to the pragmatic programmer than a tome about xp programming.
And what about if Google doesn't hit another jackpot, say, before it has some bad news and the very generous valuation and one-way ride straight up from IPO, etc. etc. starts to turn a bit? Google is a company that has never known hard times, at all. Thus, it is very young, *totally* unproven at this point. Let's see if it can maintain the same level of pampering when the finances aren't quite so rosy.Relying heavily on advertising is a model that is very likely to fluctuate at some point. And as previous posters have pointed out, Google hasn't successfully found other revenue models. And, as previous posters have pointed out, much of the software that Stevey is so proud of is, yes, used by millions, but no, not used by millions of paying customers. It's a loss leader to promote more eyeballs and brand awareness -- to support and increase ad revenue. So, given all of the above, might it just be possible that what works for Google isn't a universal fit for everyone? And, might it also be possible that it might not actually be how Google does things (can afford to do things) forever either?Google is, obviously, a group of very smart people. But, as this post argues/posits/asserts/protests, if you can take just one tiny step back/out of Google-world, I think you will see these smart people are not living in the "real" world, by which I mean, *the world that their customers live in.* It is a world of "grad students" making cool products that need only be loss leaders. It is a world of very smart people who are all together feeling how smart they are, constantly reinforcing to each other how smart they are -- and thus is precisely blind to whatever such a narrow, particular, specialized culture might not consider important/relevant, might not be interested in, etc. Meanwhile, it's customers are just regular people. And if the Google culture is indeed as impressed with itself as you are Stevey, if it indeed fosters the idea that there is one way to do things that is the right way for all situations for all times, and it's the way Google does it and it's obviously better, which is basically what you are claiming, then this is a company ripe for a fall.Humbleness wins over arrogance, every time. When you think you're the best, you have stopped learning anything about all the things you already think you're the best at.
Great post Steve, read it all & loved it.To all those who are jealous here is some good news. You can make your own google. I have done it. All you need to do is stop caring.I am fortunate enough to work for the software organisation of a large company. Through no fault of my own I was assigned to what is basically a maintenance project. It's not all bad. For example I got to travel to the nerve centre and spiritual home of the company (where honestly 50% of the building occupants are managers) and witness how people actually worship & slave to a bug tracking database. Anyway where was I? Oh yes google. Another benefit of working for a large company is that it's very easy to float around aimlessly in the vast sea of mediocrity and have a great time. We can't bring pets to work and there is no chef but for me the 20% do-your-thing rule is in full effect (company policy 0%). I'm actually developing some better tools for doing what we do, since we are so tools improverished (among other things). And it's fun! At lunch time I like to go out for a 7km run then eat a nice meat pie and drink an iced coffee. Better than a massage! The rest of the time I basically cruise spending it fixing whatever silly mistake some overstressed engineer made 4 years ago.My ambition is to exit the workforce and live off my accumulated savings while developing free software. I intend to achieve this using patience and a positive attitude. Eventually, due to the reality of working as a software engineer for a multinational company in a relatively expensive country, I and my colleagues will be released from the tethers of employment. This is the greatest incentive and I am really looking forward to it. But in the mean time it's leisure as usual.So think about it and you can have your own google. 2ff7e9595c
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