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Two trips in the last month. First to New Orleans to attend the specialty chemical trade show called Informex. We didn’t have a booth in the expo this year. It hadn’t served a useful purpose for many years, truth be told. I stood in for a sales guy who couldn’t attend. Nice to be back in the field.
Informex is an odd menagerie of buying, selling, drinking, feasting and spy craft. For the first time I was invited to a gathering with a balcony above Bourbon Street. The hosts supplied ample liquor and Mardi Gras beads so we tossed them from the Royal Sonesta balcony with careless abandon to disinterested stragglers on the street below. No flashing or outrageous behavior to be seen, regrettably. The Sonesta is a 4 star hotel they say. What 4 stars mean on a zero star place like Bourbon Street is beyond me.
The Informex experience varies depending on whether you are a buyer or a seller and if you make a good buy or sale. If you are a buyer, there are lots of free dinners at Antoine’s and the like. If you are a seller, you buy lots of expensive dinners.
There was a lot less trade show junk as in years past. Vendors would give away logo festooned trinkets to ingratiate themselves to passersby (or more realistically, their children). A waste of money usually.
I will say that it is possible to consummate deals, agreements, or understanding in a solid face-to-face sit-down with another party. Far faster information exchange and superior to email or video conferencing. Often you can talk to a decision maker in the form of a CEO or sales manager and shake loose a logjam that has been holding up progress.
The other trip was to Long Island for a campus visit. We stayed in a 3.5 star hotel in a 1 star location. The Long Island Railroad (LIRR) was indispensable for getting into Manhattan. The taxi’s in Nassau county apparently don’t have meters- ask about the fare first. The high point was taking in a Broadway show, “If/Then” starring Idina Menzel at the Rodgers Theatre on West 46th Street. Great show. Menzel has some pipes, that’s for sure.
A less than great show was the Empire State Building experience. The view was nice, once you get to the 86th floor. The in between was an expensive and kitschy meandering from a B-grade SkyRide to a walk through the self congratulatory “museum” on the 80th floor. I won’t discuss my raspy encounter with security while trying to sit on the floor.
During the last year I have been away from the chemistry blogosphere and immersed in reading classic literature and acting in a few plays. I won’t take up bandwidth with a lot of details, but suffice it to say that I would urge young technocrats to spend a bit of time reading some classic literature or doing some artistic activity. In my case, I have a special fondness for 19th century literature. Not a minute I’ve spent immersed in Balzac, Pushkin, Gogol, or the earlier writings of Cicero, brings even the slightest regret for time not spent with chemistry.
Of course, my threadbare-epiphany is in no way novel and barely worth mentioning. Many people spread their wings and glide over the wonderment of new lands. For me, I have simply chosen to spend the time doing so. Scientific greatness is not in the hand I was dealt. There will be no reactions or campus buildings named in my honor. This is the fate for most of us, really. Only it takes some time to come to that realization. Loosening one’s grip on ambition is not gladly done. Those of us who have gotten advanced degrees are, in a very real sense, freaks who have a fiendishly tight grasp and a capacity for extended abuse (you know it’s true!).
The reality of aging is that in the footrace of one’s career, faster, younger and hungrier runners begin to catch up and surpass you. This is actually essential for the continuation of scientific progress and the extension of this age of enlightenment. The trick lies in not allowing one’s vanity to accentuate this natural progression in some humiliating way. The merits of silence become increasingly apparent with age to those who can manage it.
This cancer business has the effect of telescoping one’s life in the sense that the end-game once obscured by the haze of time begins to take shape as would an approaching stranger in the fog. It is the fear of this approaching stranger that causes the afflicted to grasp for any and all treatments, clinical or mystical. At some point it should become clear that spending down your retirement and impoverishing your survivors is destructive and selfish. But you cannot rely on your physician to help with this. Your final act as a mature adult is to decide when to call off treatment. This is not accepting defeat. It is acknowledging biological reality.
Cancer has a large head-game aspect and one’s internal monolog must constantly chant the importance of living in the moment and keeping a cheerful attitude. Those around you will be grateful, even if they do not outright say so.
Th’ Gaussling has been dabbling in the strange land of cheminformatics lately. I’m trying to develop some productivity tools in on various platforms to make chemical information more accessible to fellow staff members.
One particularly useful tool is the InChI, or International Chemical Identifier. The InChI is a character string that is derived from a chemical structure. This string can be hashed (irreversibly) into a shorter string of alphabetic characters called the InChIKey. Using ChemSketch, one can draw a structure and generate an InChI string and an InChIKey string. What you’ve done here is to jump the gap from chemical structure to a searchable character string. These InChIKeys can be planted into documents such as Excel spreadsheets, Word files, and Access databases. A search for the InChI character string can find all of the documents in a folder containing the string or to a record in a database containing it.
Granted, this can be done in other ways. A chemical name can be searched as can a CASRN. Names are subject to syntactical variation and could complicate the search. If you have generated a new structure that is not listed in CAS and the nomenclature is complex, then an InChIKey identifier can serve as an unambiguous term for subsequent searches.
If you hate using the Java based drawing module in SciFinder, an InChI string or SMILES string can be used instead. Just open the structure drawing module and look in the upper left hand corner of the window. There will be a screwy looking button to select for pasting in an InChI or SMILES string. This will cause the Java module to draw the structure for you. It’s pretty handy.
I sit in solitude in the lower dressing room, below the stage, at the Rialto Theatre in Loveland, CO, waiting for my cue to go on. The rest of the cast are upstairs in the new green room dressing and applying makeup. My preference is to get some self time before I go on. I have a bit part in our production of Father of the Bride.
The stage is set and the popcorn machines in the lobby are popping away, blowing a magical waft of diacetyl and hot corn into the dimmed auditorium. The curtain is closed and the blue low-wattage lights backstage are shining on the floor and black curtains in the wings. The stage crew are making last minute adjustments to the set dressings. Background music is playing and a few patrons are shuffling to their seats.
In a minute I’ll apply some makeup so my pasty white face topped with whitish hair will display a bit of facial expression in the bright stage lights. A bit of mascara to darken the eyebrows and some eyeliner to make the whites of the eyes pop out a bit: All to accentuate the emotional spin I will apply to the lines. This will emphasize vocal nuances contrived to convey the emotional intent of the playwright.
One of the key ideas in acting is listening. An actor must listen to the lines being said not only for the cues they may contain, but for pacing and to convey a realistic sense of the interplay. For many of us in life, conversation consists of waiting for others to be silent so we can talk. The best actors sound natural in part because they are also listening.
Opening night of our 2 week run went well. We need to fill the seats with backsides to fund the next production. Snow is predicted for tomorrow, Mother’s day. Hard to tell what effect that will have on attendance.
7:30! It’s show time!
The news feeds are piping articles across the internets about Americans and their views on matters of science. Of particular interest is the finding that 51 % of respondents expressed a lack of confidence in matters of the big bang and cosmic origins and age. Predictably, scientific models of human origins and evolutionary science also elicited a considerable lack of confidence.
As the linked article in The Atlantic suggests, there is nothing new in America about ignorance of science and its panoply of theories, models, images and data. I’ve come to believe that wide spread ignorance of science may be contracting a bit. Some folks might be a little less refractory to science if gently brought into the discussion. It is especially evident when you engage someone in conversation about the concepts with which they might anonymously criticize in a survey. Often if you can get a person past a key mechanistic concept, their dogmatic view of things may soften.
Scientists tend to look at new things analytically and with skepticism. Others may have a devotional world view. The devotional approach is the programming language of faith in and preservation of doctrines. For the scientist, the goal is to strip doctrines to their bare mathematical essence- a single equation that describes the relationships between variables and fundamental constants. If something is observed, measurements can be taken.
Molecular medicine and microbiology unavoidably force one to come face to face with the plasticity of DNA and the short term variability of genetic change. Resistance to drugs or the spread of BT or glyphosate resistant traits into insect and weed populations are a great entry point for talking about molecular evolution. It also allows one to get away from the troublesome paradigm of Darwin, whose work carries religious baggage for many. Irrespective of what Darwin wrote, modern molecular biologists would have eventually postulated and substantiated evolution from the molecule up, as opposed to the Finch down. The Darwin model of evolution has become tired and a little worn. We really should be giving more credit to molecular biology for advances in the understanding of genetic change.
I think those who have devoted their lives to understanding science tend to forget the tremendous expenditure of time and effort that goes into a deep and quantitative understanding of nature. My experience in teaching and in public outreach in science has been that a great many people are willing to be entertained by presentations on extrema, that is, the biggest, the most powerful, the most dangerous, the most poisonous, etc. Folks like to hear about extreme phenomena and scientists are only too happy to talk about the dangers of black holes or volcanoes or ferocious animals. One can spend an evening talking about such things to a general audience and go home with the impression that the public eats this stuff up.
However, if you closely converse with your audience, you may find in many that their interest is genuine but superficial. They are entertained by the gosh-wow aspects of astronomy, but are unwilling to commit the time and effort to enough study to be competent in a topic. They often only want to see the moon through a large telescope and then go home. This is just human nature and science folk cannot be offended by the slender attention span of the public. Learning science requires a good deal of work and focus. That a large slice of the population is suspicious of the big bang theory suggests that said population has not made the time and energy commitment to learning the science.
Last week I finished 38 x-ray treatments on the Varian Linear Accelerator with IMRT for my prostate cancer. This device uses a variable leaf collimator for continuous dose adjustment as the beam rotates around the patient. Each treatment is preceded by a CT scan with a built in CT scanner mechanism on the accelerator. This is performed for purposes of alignment of the target area to the beam which rotates about a fixed axis, coincident with the center of the target.
Along with the 76 Gy of x-ray therapy is hormone ablation with Lupron. The standard treatment for advanced prostate cancer, Gleason 8 in my case, is hormone ablation and radiation therapy to the prostate.
Initially, the trick to impeding the growth of the cancer is to suppress testosterone which is needed for reproduction of the cancer cells. The pituitary controls the signaling for testosterone secretion from the testes. The adrenal glands secrete a small amount of testosterone as well. Lupron suppresses the signaling by the pituitary gland. This is effective for a period of time, perhaps as long as 24 to 36 months.
Eventually the cancer becomes resistant to this approach and enters the so-called refractory or castration resistant stage. In response to the lower testosterone titer in circulation the cancer cells produce more testosterone receptors, called AR for Androgen Receptor. The number of AR’s multiply by 3x to 5x, increasing the sensitivity of the cells to what little testosterone (or dihydrotestosterone) there may be in circulation.
Blocking the androgen receptors is an approach to treating castration resistant cancer, but it does have limitations. This will be explored in a later post.
An observation from a patient’s perspective. Insurance will generally not pay for off-label or experimental therapy. So unless the patient is self-insured, the treatment profile will follow the board approved protocols for a given diagnosis. This isn’t a bad thing, but often a medication or other treatment will show effectiveness in other applications. While the doc has some discretion here, the insurance company may not approve payment. And, they may decline to pay months down the timeline when their internal review staff have had a look at it. They make their profits by declining services, not offering to pay for it.
Initially I had hoped for the possibility of participation in a treatment study if this disease went south, as it is likely to do. What I was told is that because I have had 2 cancers, throat and prostate, I am almost certainly disqualified from participation. This was disappointing but I understand the reason for it. Even so, I am barred from a Hail Mary pass down the road.
So, what now? Well, it is watchful waiting. While PSA numbers are given less importance in checkups for ordinary patients owing to the history of overtreatment, for a post-treatment Gleason 8 patient like myself, the PSA number is a direct indicator of disease progression. Once the disease becomes castration resistant, I suppose that some kind of AR therapy is next. The docs have been evasive when asked. Apparently there are several paths available. But I suspect they would rather the patient focus on the present and not the damaged bridge miles ahead of the train. We’re all headed for that bridge, it’s just that some are further up the tracks.
Never one to allow reason to interfere with sentimentality, my blackened heart is softened somewhat by the recent shipment of Lipton Tea bags delivered to Th’ Gaussling from an online admirer via the US Postal Service.
The tea in this gift shall be symbolically applied to the local waterway, but not before being used to formulate some refreshing iced beverage via aqueous extraction. A vessel filled with aqueous goodness (OPE-Our Pure Essence) will be charged with the anthocyanin and alkaloid laden forest litter for extended exposure to solar radiation. Brownian motion will be relied upon to disperse the colloidal value away from the biomass.
Once so processed, the fortifying beverage will be passed through a pair of kidneys as a symbol of my dark contempt for the IRS. This nephro-raffinate will be discharged into the municipal fluid collection system for a kind of Nicene rectification that will provide further philosophical processing of the…
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