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Figure 2.

False color image of raw intensities in the reference channel. Columns represent arrays and rows represent spots. Only human microRNA spots are shown. The intensities have been location- and scale-transformed within each row (spot) to lie between 0 and 1; this enables comparison across arrays. Other transformations are possible, and give similar results. There are two interesting features in this plot. First, there is a banding pattern of high and low intensity on alternate arrays. This is presumably due to the fact that two arrays are hybridized on each slide. Second, the last six arrays, run on a different day, have consistently higher intensity, suggesting a batch effect. This effect is also seen in Figure 3 .

We use this graphic to demonstrate the presence of a batch effect in our experiment. There are two well-defined batches: Arrays 159–184 were labeled on 4/13/07 and hybridized on 4/16/07 (159–182) and 4/17/07 (184). Arrays 207–213 were labeled on 5/5/07 and hybridized on 5/14/07. The arrays from the second batch (207–213) have larger intensity in the green channel. The banding pattern visible in this figure is presumably due to the fact that two arrays were printed on each slide.

Other plots designed to highlight this batch effect can also serve as diagnostics for assessing different normalization methods. Dr Martens 101 Smooth Archive 6Eyelet Boot Huge Surprise Cheap Price f5vLp
, which encodes a pairwise distance between all arrays, is an example of such a plot. Another example is Figure 3 , which plots the estimated densities for the green channel log 2 intensities. The two batches are indicated by different colors in Figure 3 , and a visual separation of the two batches is readily apparent in the densities for the unnormalized intensities. The separation is removed by all three normalization methods considered in this article (see the next section), but with some differences in behavior for low intensities. Figure 3 also serves as a diagnostic of array quality; had there been any bad arrays, one or more of the corresponding density estimates are likely to have been aberrant.

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Figure 3.

Histograms (kernel density estimates) of log intensity in the reference channel. The rows correspond to different types of probes, and the columns represent the different normalization methods used. Colors distinguish the two batches, and show a systematic upward shift in the second batch. All normalization methods appear to rectify the batch effect for high intensity spots, but have different effects on the low intensity spots.

Normalization is an essential preprocessing step in the analysis of any microarray experiment. Its primary purpose is to try to ensure that the observed between-array differences are due to biological phenomena, and not due to artifacts that arise due to differences in handling or processing of the samples. Normalization of microRNA microarrays is problematic primarily for two reasons. First, the number of microRNAs measured by the arrays is fairly small, numbering only in the hundreds ( Prices For Sale Up To Date Trigo LaceUp Leather Sneakers Sale Real aYJPHyw
). Second, even among the measured microRNAs, only a small number are expressed at all in a given tissue, and consequently, most of the spots on the arrays cannot be used for normalization. In other words, the usual normalization assumptions do not apply. A careful analysis requires the development of a reasonable normalization strategy, as well as diagnostics that can be used to assess the performance of potential normalization strategies.

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Favoritenstraße is one buzzing street, and a boisterous one by Vienna standards. Here you’ll find almost all big brand chain stores squeezed in amongst the eclectic mix of small, international, cheap and questionable quality shops serving the multicultural community living in the district. The street is loud, and it seems most people are just hanging around for the sake of it with not much to do. It smells like Kebab and Turkish bakeries up and down it. Just sitting in a café, or on a bench, and becoming one with the spectacle of this street will have you experiencing a different side to Vienna.

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Amongst the multicultural vibe that dominates Vienna’s 10th district, Austrian gems are still very present. We asked around a lot to find this one. We wanted a good old Viennese restaurant and literally found it – Zum Alten Beisl means “to the old pub”. The inside is modest, but cosy and has that homey feel of a typical Beisl. A quiet garden is hiding out the back between buildings. These guys know what they’re doing when it comes to great, hearty Viennese dishes. The lunch menu costs 7,90€ and includes soup and a main dish, which is typically a variation of Schnitzel or steak. However, heroes of this place can be found in the section of the menu entitled Wiener G’schichten (Viennese stories), where Tafelspitz, Wiener Gulasch and the adventurous roast kidney can be found. Yep, we said kidney, and it also comes deep-fried. Bon Appetit!

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These guys not only invented the famous Eis-Marillen-Knödel (an ice cream version of the Austrian apricot dumpling dish), but it also seems they invented the time machine. Their legendary ice cream creations (like Spaghetti Eis), or the simple ice cream in a cone or cup, is served by motherly waitresses in white and pink striped dresses, the types that will smile gently when you’re nice but let you know when you’re in the wrong. There always seems to be a queue on sunny days so you better know your order before you’re next in line. If you can’t make up your minds just go with classics like chocolate or hazelnut. The atmosphere at Tichy transports you to a world in which a scoop of ice cream makes everything better.

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There is a unique swimming pool in the 10th district that goes by the name Amalienbad. It’s housed in the classy looking building – complete with clock tower – overlooking Reumannplatz. Inside, a true 20th century design masterpiece can be found, where wood meets ceramics, and beautiful mosaics. There is an odd symmetry playing out here everywhere you look that reminds us of a Wes Anderson movie set. It gets pretty crowded in the evening, but during the daytime, you can go for a relatively peaceful swim in the beauty that is the Amalienbad.

Tim Haslam Writes

Books, blog, and other writings

As I transition into retirement, I’m learning how to reprioritize my time (my wife Diana is helping with this). I’m also learning how to redirect my mental and intellectual focus. When I was a working person, and I’d like to think a “professional,” I had to reserve a certain number of my cerebral neural connections to deal with work things. This meant that these structures within my brain really didn’t belong to me but were rented out to my employers. The boss and the big bosses could trigger these reserved synaptic connections with business related stimuli. Think of it as kind of like a big railroad switchyard with trains coming and going as the B BBs dictated. My job was to ensure that nothing got derailed in the yard and that the trains that were loaded with profit generating ideas got through the obstacles, restrictions, constraints, hesitations and redirections that the same B BBs had thrown out on the tracks. Every once in awhile one of those trains would actually reach it’s desired destination in which case the B BBs would congratulate themselves for their brilliance.

My purpose today is not to cast cynical assertions as to the wherewithal or motives of my prior life B BBs however. This is about what happens to my particular switchyard now that I’m retired. With the exception of a few abandoned business related iron horse concepts, my tracks are pretty much cleared for a new set of trains. What I’m learning though is that this is not a process that I can control. Just as water seeks it’s own level and fills in the intervening voids, intellectually challenging freight just flows into the yard whether I want it there or not. I really wish I could keep the trains with stuff like ISIS, global warming, politics, drought, crime, drugs, vaccine resistant influenza, bachelorettes, narcissistic celebrities, or the racial affiliations of Academy Award nominees from entering my yard but I don’t know how to close off those tracks.

When I was still working and contemplated (using the few neurons I had available at the time) about what I might do in retirement, I considered stuff like travel, house and yard projects, writing more best selling novels writing more vital and acclaimed blogs , volunteering in some save-the-world capacity and generally developing more of my creative self. Note: one doesn’t actually have to do any of those things in retirement. It’s the continued contemplation of them that gets you through each day.

1 “More” in this context assumes that the accumulated sales (sixteen) of my first novel are just a temporary indicator.

2 “Acclaimed” in this context refers to the number of bloglet recipients who have unfriended me on Facebook.

The world just won’t let me manage my switchyard the way I want to though. Just when I start to get my cerebral neurons aligned to my parochial purposes, new things sneak into my head that require cogitation. New things like ETNOs. I’m usually behind the curve when it comes to knowledge of stuff like this, so, I’m sure you all have been aware of ETNOs for some time and are probably well prepared for the impact of them. For any of you who may be further back on this curve then I am, let me explain that ETNOs are, Extreme Trans-Neptunian Objects. As if there weren’t enough to worry about already!

Those darn scientists with their nit-discovering, femto-measuring, tera-counting, subatomic particle detecting devices keep finding more things that I have to worry about. Researchers at the Royal Astronomical Society now believe there are at least two planet-sized objects mixed in with zillions of other smaller rocks that are floating around out there at about 23 billion miles from my house in Walnut Creek, California. With global warming and a Republican dominated United States Congress, it is only a matter of time before some of these ETNOs start heading my way. (This conclusion did not actually come from the RAS study but I remember enough from Mr. Wizard to put two and two together.)

In other disquieting science news, astronomers (amateur) monitoring the activities of the Curiosity Rover as it tracks around Mars have spotted an object they believe to be a pistol. Note, ‘pistol’ is not some esoteric sciency term for some kind of mineral formation, it means the same thing to them as it does to you and I…a gun. There can be only two possible explanations for this. One, the Curiosity Rover instead of being on Mars, accidentally landed somewhere in west Texas or some other desert-like portion of one of our red states where a lot of old guns litter the countryside. Or, the NRA has launched their own secret mission to Mars and perhaps other planets in an effort to stockpile weapons just in case a more liberal Supreme Court determines someday that more guns really aren’t the solution to reducing violence in our country.

All of this stimulation got me to dig a little deeper into the Curiosity Rover and what it’s actually finding up there. According to knowledgeable sources at that knowledgeable source periodical, UFO Sightings Daily, the Rover is sending back photos of all kinds of things that absolutely prove the existence of life on Mars. There are things that if you hold the photo just right and the light is just right and you’ve had just the right amount of Budweiser and you’re imagination generally works overtime, you can see what very clearly sort of looks a little like; two coffins, an Egyptian Ankh cross, the aforementioned gun, the shadow of Big Foot, the shadow of Elvis, the shadow of Jimmy Hoffa, the shadow of the Curiosity Rover, all indicating, beyond a shadow of a doubt that the surface of Mars is littered with things that cast shadows. It is only a matter of time before some of these shadow-casting beings find there way to Walnut Creek. Perhaps hitching a ride on one of the ETNOs that stops by Mars. Those of you who are more familiar with astro-jargon know that when an ETNO is heading for Walnut Creek it becomes a PHA or Potentially Hazardous Asteroid. I think it was Mr. Wizard who said; “Where there’s an acronym, there’s a scientist who knows something that we don’t.”

You can see clearly, beyond a shadow of a doubt that my switchyard is rapidly being overloaded with new types of intellectually stimulating freight. You can also be thankful that I now have the time to perform this kind of thoughtful analysis and am willing and able to advise you of the dangers that surround us. Just to be on the safe side I’ll be wearing my bicycle helmet and body armor whenever I go outside and will also be on the alert for the kind of frightening shadows and acronyms that correspond with election year politics.

P.s. “femto” is a scientific term for teeny-tiny to the Nth power, where Nth is a really ginormous number.

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