Wednesday, November 28, 2012

San Diego conference session ST-5 “DNA Translation: It's All in the Genes”

San Diego conference session ST-5 “DNA Translation: It's All in the Genes” by Leo van Zanten, is reviewed by Karen Tkaczyk

I arrived at “DNA Translation: It's All in the Genes” looking forward to learning. As a chemist with no formal biology training, and a translator who frequently works on biological subject matter in pharmaceutical texts, I always feel my work benefits from a better understanding of biology.

Not all scientists can explain their fields clearly to those without the same background, but this was not the case here. Leo van Zanten, a Dutch translator with a background in plant breeding, is knowledgeable and well able to explain his subject. The topics introduced were clear and structured logically, moving from chromosomes to DNA, then genes, proteins, RNA, PCR and forensics. The visuals were impressive and enhanced the explanations.

We started with an introduction to chromosomes, explained through the seminal fruit fly study. Chromosomes store DNA, so we moved there next, with descriptions of the double helix, nucleotides and base pairs. Since DNA forms the language of life, here the first creative element of the session appeared. 

Leo used a word-related analogy to help wordsmiths in the audience understand scientific concepts:
– The alphabet only has four letters: A, C, T and G
– Every word is only three letters long: AGA GGC
– A word is the name of an amino acid
– A sentence is a gene

Just as the concepts were becoming trickier, Leo snapped us to attention with a clip from ‘Jurassic Park’ to help explain more about these pieces of DNA string. Later, well-timed video clips clarified other concepts.

From genes we moved to proteins. Here, I was at home. At one time I could name and draw the structures of all twenty amino acids that are used to produce proteins. But, oh, shock! Horror! Leo called organic chemistry boring! He insulted my first scientific love!

Next we covered DNA transcription and translation: the process where the DNA code is used to produce polypeptides or proteins. Lastly, we moved into modern methods in the field: polymerase chain reaction (PCR) and gel electrophoresis. Leo explained how these techniques are applied in forensics and paternity testing. As he concluded, he explained how forensic scientists analyze DNA to help solve crimes, referring to popular crime dramas to help anchor the audience. We ended back in Hollywood, with a clip from ‘Gattaca’. Remember the alphabet?

This session delivered a well-planned balance of theoretical and practical, and mixed high scientific register and popular culture effectively. Leo was so engaging that I have forgiven him for calling organic chemistry boring.

Karen M. Tkaczyk, PhD, CT, MITI, is an ATA-certified French>English freelance translator. She is originally from the UK and now lives in Nevada. Her translation work focuses on chemistry, its industrial applications and intellectual property. Karen holds an MChem in chemistry with French (University of Manchester, UK), a diploma in French, and a PhD in organic chemistry (University of Cambridge, UK). She worked in the pharmaceutical industry in Europe, and then in pharmaceuticals and cosmetics in the US. Since 2005 she has been technical translator and editor. Karen is the current administrator of the ATA Science and Technology Division.

Sunday, November 18, 2012

Drugs of Abuse: A Pharmacological Perspective

Drugs of Abuse: A Pharmacological Perspective
R. A. (Bob) Lyon, Section Head R&D Proctor and Gamble
Reviewed by Brian Howells

Outline of drug action in the central nervous system
The talk began by outlining the functioning of the central nervous system, wherein the neuron bodies emit electrical signals along the dendrites to the terminal branches to release neurotransmitters into the synapse to communicate between nerve cells, etc., and the various levels at which drugs can affect this process: before the synapse (presynaptic) by affecting firing, synthesis storage and release of the neurotransmitters, or inhibiting their re-uptake so that their effect persists for longer, or after the synapse (post-synaptic), by interacting with their receptors to potentiate or block their effects on their target.
They can stimulate, or mimic, the action of natural substances (agonists, e.g. serotoninergic drugs such as LSD, which are 5HT-2A agonists) or block this action (antagonists such as Naloxone, an opioid antagonist).

The language of drugs (Reference USA)

Drugs can be used for medical or non-medical (“recreational”) purposes. Medical drugs are classified broadly as over the counter (OTC) or prescription (Rx, ethical); there is also a further category of “behind the counter” for OTC substances which can be used as starting materials for illegal drugs (eg. pseudoephededrine, a nasal decongestant which can be used to make methamphetamine).

Potential drugs of abuse are “scheduled”, ranging from Schedule 1, with no known medical use and high degree of danger from abuse (e.g. heroin and LSD), to Schedule 5, with medical use and low abuse potential (e.g. codeine, an opiate). Benzodiazepine and amphetamines are 3-4, and cocaine is 2, because of medical use in eye surgery.

Designer drugs are synthetic drugs employing chemical modification to avoid scheduling. Until identified and scheduled, they remain legal; however, since they are not subject to any conventional approval process, they are potentially extremely unsafe.

Route of administration - how the drug is administered e.g. orally, nasally, by smoking, intravenously, rectally, vaginally.
Drug delivery device - the device used to administer the drug, e.g. sugar cube, pipe, syringe, cup.

Addiction: psychological craving
Dependence: a physico-chemical need for the drug for well-being
Withdrawal: what happens after cessation in dependents
Tolerance: the need for more in order to get the same effect

Classes of drugs of abuse

Central nervous stimulants: include caffeine, nicotine, amphetamine, cocaine, and “bath salts”. Effects include high energy/focus and decreased need for sleep.

Caffeine: adenosine receptor antagonist, side-effects diuresis, nervousness, rapid tolerance, addictive, leads to dependence (withdrawal effects)

Nicotine: nicotinic receptor agonist; side effects increased blood pressure and heart rate; rapid tolerance, addictive, leads to dependence (one of most addictive)

Amphetamines (illegal synthetics): increase dopamine and norepinephrine release and block reuptake; side effects increased BP and heart rate, psychosis and long term psychological changes (schedule 2)

Cocaine: snorted, smoked or injected in increasing order of effect. Increases dopamine release and reuptake; side effects increased BP and heart rate (potentially lethal) (schedule 2 -use as anaesthetic in eye surgery)

“Bath salts”: designer drugs (mephedrone, methylenedioxypyrovalerone, etc., Ivory Wave, Vanilla Sky, etc.). Cheap high, effects similar to amphetamine; side effects include paranoia, hallucinations and suicidal tendencies (schedule 1)

Central nervous system depressants: include alcohol, opiates/opioids, barbiturates, benzodiazepine; effects, relaxation, analgesia, sedation

Alcohol (ethanol): affects acetylcholine, GABA (γ-aminobutyric acid) and NMDA (N-methyl-D-aspartate). Exact mechanism not fully understood; general depressive effect with dose response from relaxation to death; side effects foetal alcohol syndrome, alcoholism, liver disease; tolerance, addictive, leads to dependence. Warning as to the potentially dangerous effects of combining with a stimulant such as caffeine and guaraná (e.g. Four Loko)

Opiates/opioids: e.g. morphine, codeine, thebane; µ opioid receptor agonists; side effects include constipation; highly addictive/dependency creating (withdrawal)

Barbiturates and benzodiazepines: GABA receptor agonists; anxiolytics and hypnotics (librium, valium, rohypnol)

Psychedelics: principal effects are enhancement or modification of reality

Marijuana: mildly hallucinogenic, contains delta 9-THC and >60 other cannabinoids which act as cannabinoid 1 and 2 receptor agonists; effects include euphoria, laughter and relaxation; side-effects, anxiety, coughing and paranoia
K2; Spice and THC are more potent and more addictive

LSD, psilocybin, mescaline, DMT, dimethoxytryptamine (santo daime); serotonin 5HT2A agonists; effect (8-12 hr) is alteration of experience, vivid colours, the setting determines the trip; side effects include weakness, jaw clenching and increased heart rate; rapid dependence, no dependence or addiction; potential applications to enhance spirituality in terminal patients

Ecstasy, (N-methyl)-3,4-methylenedioxyamphetamine), MDMA; adrenaline uptake inhibitor, serotonin 5HT2A agonist

Dissociative: e.g. PCP (phencyclidine), ketamine and dextromethorphan; NMDA antagonists, altering distribution of glutamate, associated with out of body experience/detachment.

PCP is addictive and associated with psychotic side effects; ketamine is used as an animal tranquilizer, and can lead to amnesia, depression and breathing problems at high doses. Dextromethorphan is an OTC cough suppressant which causes similar effects at high doses

Saliva divinorum, κ-opioid agonist, can induce dissociative effects and “visions”; used in Mexican native religion.

Delirants: alkaloids atropine and scopolamine are (competitive) muscarinic cholinergic antagonists, associated with tachycardia and hyperthermia.

Brian Howells
Brian Howells has a bachelor’s degree in agricultural science and has been a freelance translator from Japanese to English for around 25 years specializing in technical (principally chemical) and patent-related translation. For the last 20 years he has been living on the beach in São Paulo state, Brazil.

Friday, November 16, 2012

Basic Concepts of Pharmacology in Drug Development

Review of Basic Concepts of Pharmacology in Drug Development - S&TD conference session 2012 by R. A. (Bob) Lyon, Section Head R&D Proctor and Gamble - reviewed by Brian Howells
The objective of the talk was to outline the process of drug development, the principles underlying this process and some of the associated terminology and techniques.

Drugs are exogenous substances that bring about a change in biological function through a chemical interaction with the endogenous mechanisms within the body.

The overall flow of drug development is as follows

Identification of a target mechanism in the body which brings about a desired alteration in biological function (e.g. 5HT1A (serotonin) receptor activation, alleviating anxiety)
Screening of numerous compounds in vitro to try to identify compounds having the desired effect and narrow down to a single “lead compound” which has the best and “cleanest" effect (low toxicity and fewest other, possibly undesirable, effects)
Various animal studies, examining the specific and general pharmacology of the lead substance, and its safety (toxicity, mutagenicity, effect on reproduction, etc.)
Phase I (preclinical) studies on humans, typically healthy, investigating safety (adverse effects), tolerance (dosage) and pharmacokinetics (absorption, distribution, metabolism, excretion)
Phase II clinical studies on small numbers of target subjects to investigate efficacy (proof of concept - effect on target, e.g. anti-anxiety) safety, and dose-effect relationships in this population
Phase III large-scale clinical studies on the target population
Submission to the regulatory authorities
After approval (possibly with contingencies)
Phase IV

This process typically takes of the order of 10 years, and costs of the order of $500 million.

Principles of drug action

Drugs largely work by interacting with signalling between cells. In the talk, this was illustrated by signalling at the synapse between neurons.

There are various possible targets for this interaction, which include:

·         a direct effect at the cell level to stimulate or block the release of a chemical substance such as a hormone, neurotransmitter or enzyme (e.g. releasing agents);

·         activation or blocking of the receptors for such chemical substances, provoking the receptor to produce a response by mimicking the natural substance (agonist); or blocking or altering the receptor so that the natural substance cannot produce a response (antagonist)

·         activation or blocking of a transporter substance, to enable a substance, or nerve impulse, etc., to reach its target, or stop it from so doing.

·         activation or inhibition of an enzyme, by altering the molecule to make it more or less active, or by mimicking a natural substrate and blocking active sites

·         stimulation or repression at gene level, to activate or inhibit expression of an enzyme

There are numerous possibilities, and the molecular mechanisms are exceedingly complex.

Expressing drug dose/response (in vitro)

Agonists can be full agonists, giving a 100% response, or partial agonists, giving less than a 100% response. The effect of an agonist is typically expressed as ED50 or EC50 - the dose or concentration giving a 50% effect. The maximum effect is Emax. For measuring dose [D] vs. effect, log[D] vs. (E/Emax) is generally used, which gives a sigmoidal curve.
The dose-response is an expression of the affinity of the agonist for the receptor or receptor occupancy.
Potency expresses dose/effect - i.e. is related to EC50; in general, high potency is preferred since a lower dose is likely to generate fewer side effects.

Antagonists do not have intrinsic activity but shift the effect of an agonist. Antagonism can be competitive, when binding to a receptor is reversible and the antagonist competes with the agonist, or non-competitive, when the antagonist binds irreversibly or alters the receptor. Competitive antagonism increases EC50, and it may be possible to achieve a maximal effect with more agonist. Non-competitive antagonism on the other hand lowers Emax, because fewer receptors are available.

The remarks on competitive and non-competitive antagonism also broadly apply to competitive and non-competitive inhibition of enzymes, except that in this case competition is between an inhibitor which can reversibly bind to an active site on the enzyme, and a natural substrate.

Effectiveness of course needs to be weighed against safety. One index of this is the therapeutic index, which is
ED50 for a therapeutic effect/ED50 for a lethal effect

Measuring drug-receptor interaction

Radioligand binding was introduced as a method for studying receptor interactions, by radiolabelling drugs (ligands) to study affinity for receptors by comparison with the same or different unlabelled ligands.

Reviewed by Brian Howells
Brian Howells has a bachelor’s degree in agricultural science and has been a freelance translator from Japanese to English for around 25 years specializing in technical (principally chemical) and patent-related translation. For the last 20 years he has been living on the beach in São Paulo state, Brazil.

Wednesday, November 14, 2012

A Pink-Ribbon Perspective: The ATA Conference from the Viewpoint of a First-Time Attendee

A Pink-Ribbon Perspective: The ATA Conference from the Viewpoint of a First-Time Attendee - by Amy Lesiewicz
Last month I attended my first ATA Conference at the urgings of my mentor, a German to English translator named Amanda Ennis. She assured me that it would change my life, and she wasn’t wrong.
I opted to come a day early and take advantage of two of the pre-conference seminars. My first stop after picking up my name badge with my pink “first-time attendee” ribbon and color-coded language dot was Corinne McKay’s seminar entitled Beyond the Basics of Freelancing. In just three hours, Corinne taught us about marketing, specialization, pricing, negotiating, working with direct clients and agencies, invoicing, scheduling, and more. At once, I felt that this was the best three-hour investment I’d ever made in my career, and I’ve been kicking myself ever since for not reading her book years ago. During the seminar, I met a Japanese to English translator who shares my specialization (chemistry) and an internet acquaintance who shares my language pair (Russian to English).
My next seminar was all about negotiation. Although I didn’t find everything in that session to be immediately applicable for me, I did have two “light bulb moments,” one intentional and one quite by accident. The first was the concept that negotiation is not an event, but a process. Although I love translating and hate business, I realize now that I am a businessperson, like it or not, and negotiation is part of the process. Resenting the time “wasted” on negotiation will get me nowhere; instead, I should learn to think of that time as an investment in each project and a learning opportunity for future negotiations.
The second light bulb moment came when the presenter stated that a technical translation could be split between multiple translators without any real impact on the outcome, but a marketing translation cannot. I have read this type of attitude expressed in various online forums, but I didn’t expect to hear it from a presenter at the ATA Conference. Various similar comments throughout the conference made me realize that perhaps I need to become more active in the ATA and other groups to promote scientific and technical translation. I am just as passionate about the art and science of translation as my literary counterparts!
Once the main conference got underway, I found myself drawn to many of the medical and technical sessions, in addition to sessions aimed at helping independent contractors with some non-linguistic aspects of our careers. I was pleased that many of the subject-matter expert presenters, as fellow translators, placed an emphasis in their sessions on terminology as well as the science or medicine they were discussing. For example, I never knew before that the word vaccine comes from the Latin word for cow – because the first vaccine was developed based on the observation that milkmaids were immune to smallpox after exposure to cowpox (thanks to presenter Tapani Ronni). Two of my favorite presentations were in the Science & Technology Division track: DNA Translation: It’s All in the Genes by Leo van Zanten (whose creative use of humor and multimedia kept his presentation interesting and entertaining, as well as very informative) and Basic Concepts of Pharmacology in Drug Development by Bob Lyon (though not a translator, Bob fielded several linguistic questions with great answers and provided very clear and thorough explanations of terminology).
One important point I picked up from Chris Durban’s presentation on The Care and Feeding of Direct Clients was her axiom that as a specialist, I should be able to mingle with professionals in their element and blend in with them for at least two minutes. Could I pass for a research chemist in a room full of PhD scientists and R&D experts? I also enjoyed Judy Jenner’s 10 Habits of Highly Successful Translators and Interpreters and a great presentation on making my own website from Tess M. Whitty.
Unfortunately, the Slavic Languages Division annual meeting fell into the same time slot as Carola Berger’s session on some very cool physics stuff. Since I would never presume to translate anything in the field of theoretical physics and my interest was pure curiosity rather than professional education, I felt I should attend my language division meeting, but I still wish I could have been in two places at once. The Slavic Languages Division Banquet also conflicted with the S&TD dinner, and I opted for the Russian and Georgian food, which brought back memories of my favorite restaurants in Moscow.
My flight out of San Diego was delayed, so I missed my connection in Dallas. This turned out to be a blessing in disguise, because I was quickly rebooked and ended up sitting next to a fascinating medical doctor and researcher who is also bilingual. He received his medical education in Spanish and his scientific education in English, and I found it interesting that this affected the way he understands and approaches medicine and research. We had a wonderful conversation about the intersection of science and language, and the advantages it has brought us both professionally and personally. He told me that people who are monolingual as children and study a foreign language as an adult have one language center in the brain, which they use for both languages. People who are raised bilingual from birth or early childhood develop two language centers, one for each language, in opposite hemispheres of the brain, so when they translate or transition between languages, impulses have to travel across the narrow bridge between the hemispheres called the corpus callosum. (I immediately wondered if that is why the translation field is dominated by women: there are gender differences in the structure and activity of the corpus callosum, though these differences are still a matter of dispute.) This chance meeting was the perfect capstone for the conference; I got to meet someone outside the translation profession and practice some of my new skills, and we exchanged ideas and business cards. We’ve already connected via e-mail and I hope we’ll stay in touch.
Amy Lesiewicz is a Russian to English translator who specializes in scientific translation. As a chemistry student, her academic advisor suggested that she take French, German, or Russian so that she could read important chemistry journals in a second language. The Russian class fit into her course schedule the best, so she enrolled, expecting to take no more than a few semesters. She earned her BS in chemistry and went on to earn an MA in Russian and a Certificate of Advanced Study in translation. After three years at an engineering company translating for Russian oil and gas projects, Amy is now a freelance translator.

Sunday, November 11, 2012

How to Translate Engineering Material and Live to Tell the Tale

A review of Don Jacobson’s presentation at the ATA 53rd Annual Conference about Translating for the Design and Construction Professions in Israel, reviewed by Ami Argaman, a Hebrew-English translator.

Ten minutes before this session began, I found Don Jacobson standing alone in the lecture room. By the time he started, two others had joined me, and later a third sneaked in. However, Don did not appear fazed by the poor turnout: he was there to share his experiences and knowledge, and so he did, regardless of the size of the audience.

Jacobson, who was born, raised and educated in the United States, but has been living for many years in Israel, explained to us that large construction and design projects in Israel often require the cooperation and partnership of companies, builders, investors and designers from various countries. Hence, the materials involved – proposals, RFBs, bids, plans, etc., – need to be rendered in several languages. He is mainly involved in translating from Hebrew into English.

The presentation began with a historical background of Israel and its language, followed by descriptions of its topography, demography, politics and economy. The types of construction were delineated, and the needs for each one of them analyzed.  

Several projects were described, analyzed and discussed:

-          The newly completed light-rail system in Jerusalem
-          The ongoing construction of a rapid railway between Tel Aviv and Jerusalem
-          The ongoing construction of the Cross-Israel Highway 6 expressway
-          The Carmel Mountain tunnels that bypass the City of Haifa
-          The still-planned light-rail system in Tel Aviv.

There was extensive discussion of the difficulties and challenges involved in rendering the complex concepts, the engineering papers and proposals, some of which are language-specific and culturally based, and some also poorly written to begin with, so have to be interpreted as well. As three of us were also Hebrew linguists, albeit not experts in this particular field, the session turned quite interactive, with the audience actively participating in deliberating about the translational issues and evaluating Jacobson’s solutions.

One fascinating example featured the original Hebrew design idea, which read [my literal translation – aa]: “The gallery that is deployed on the ground floor constitutes a cultural front in the direction of the city and a grass theater in the direction of the plaza that the structure creates.” This, of course, makes no sense whatsoever in English. Following a lively discussion, Jacobson presented his interpretive solution: “The art gallery, which covers the entire ground floor, together with the grassy amphitheater facing the plaza created by the structure, will act as a cultural magnet oriented toward the city.” Impressive!

As the small audience was fully engaged, the session ended with an extensive segment of questions, which Jacobson answered and explained, thus expanding the boundaries of presentation. We left the room feeling that it was educational, informative, language-challenging and at times even entertaining.

Ami Argaman, who was born and raised in Israel but has lived most of his adult life in the U.S., has been a professional Hebrew-English translator for the last 20 years. For the last 10 years, he has been serving as a language specialist and a Hebrew speaking-proficiency master tester for the U.S. Federal Government.

Thursday, November 8, 2012

Review of the presentation by Nicholas Hartmann, ST-4 “An Introduction to Aviation and Air Travel”

Nicholas Hartmann’s presentation on aviation and air travel was the very first SciTech session I attended at my very first ATA conference. As a pink-ribboned newbie, I did not quite know what to expect. Actually, I was afraid to be overloaded with dry terminology and vocabulary. I could not have been more wrong!

Nick explained the physical principles of flight, something I personally could relate to, and then went on to explain the inner workings of an aircraft. He answered one of the issues I had worried about every time I boarded a plane, namely, how the wings could be attached well enough to the main body of the aircraft to withstand all the forces they are subjected to in flight. The answer, as Nick explained, is of course that there is only one big wing, which is intertwined with the fuselage such that it doesn’t break off. I also learned that the seemingly sagging wing (singular!) of a plane that is just about to take off is nothing to worry about, because the sagging is due to the fuel that is partly stored in the wing.

Just as the flight-phobic part of the audience (me) was feeling reassured about the safety of air travel, he showed some terrifying landing strips next to mile-high walls of rock. After I made a mental note of never booking a flight to anywhere near these locations, the pictures of too short landing strips next to sunbathing beach-bodies and downhill skiers became funny. He then proceeded to “translate” the various cryptic symbols one encounters on the runway into plain English, before getting into the nitty-gritty of the inner workings of airplane engines, especially modern jet engines. I can’t do the humor Nick injected here justice: he illustrated this with a toy pinwheel and a toy fan. It was a hilarious and at the same time an instructive and illuminating explanation of an engineering principle.

In summary, while I’m still not a fan of flying after Nick’s very clear talk with just the right amount of geeky humor, I now understand the underlying structures and principles much better and won’t be quite so apprehensive the next time I board a plane. Unless I see the numbers in the square signs next to the runway go from 3 to 2 to 1… (These numbers denote the distance to go till the end of the runway in thousands of feet.)

Written by: 

Carola F. Berger
spacerCarola F. Berger was a researcher in theoretical particle physics for over a decade before becoming a freelance English>German translator and consultant. She has a Diplom-Ingenieur der Technischen Physik in engineering physics from the TU Graz, Austria, and a PhD in theoretical physics from Stony Brook University (Fulbright Scholar). She was a researcher at the INFN Torino, Stanford University, and the Massachusetts Institute of Technology. She also conducted research visits in North America, Europe, and Russia before settling down in California as a translator specializing in technical and scientific texts.