grad school
Watch out grad. students...
I was checking out my feeds this morning and this one caught my eye:
I immediately thought, “There are robot scientists?” I then collapsed into an inner monologue that centered on the fact that there are robot scientists that I didn’t know about and wondering which of the many scientists I have met over the years were indeed robots. Don’t get me wrong, I am not very surprised. I mean, have you met many scientists? It makes sense. I was more intrigued that this fact had made it to the popular media and the cover was about to be blown off the entire thing.
Obviously, I clicked through. The results scared me more than robot scientists did, which for the record, they do not.
Somegeniuses idiots make a robot that does science. There are lots of robots that do science, my lab has two, but the problem is they gave this robot the ability to think. I really hope that they gave it a heart too otherwise we might be living i, Robot soon. This would not be good.
What the hell? Isn’t this what I have been doing for the last 19 years? Learning how to reason, formulate theories, and discovering scientific knowledge on my own? Uhg. I wish I had known this was going to happen because I would have done something else with my life and then bought this robot and become a scientist overnight. It makes this whole PhD thing seem like a waste of time.
So the question is, does it work?
So, what you are telling me is that this robot was able to derive the Newton Laws from first principles all by itself? What a waste of time those two semesters of physics I took were. I also bet the robot has more personality than a lot of biophysicists I know (babump chhhhhh, I will be here all night).
It seems as though grad. students are about to become obsolete and the tool of the past. I don’t blame the PIs, I would spend the money on a robot that probably does what I do and does a better job of it.
Plus, as my boss would say, “It can’t get pregnant.” I hope they didn’t build this feature in!
It does seem like my job is safe for a little while though.
Hopefully by the time I become a PI these things will make everything I do automated and I can sip mixed drinks on the beach somewhere and run my entire lab though my iPhone. Here’s to hoping!
Original article can be found here.
Robot scientists can think for themselves.
I immediately thought, “There are robot scientists?” I then collapsed into an inner monologue that centered on the fact that there are robot scientists that I didn’t know about and wondering which of the many scientists I have met over the years were indeed robots. Don’t get me wrong, I am not very surprised. I mean, have you met many scientists? It makes sense. I was more intrigued that this fact had made it to the popular media and the cover was about to be blown off the entire thing.
Obviously, I clicked through. The results scared me more than robot scientists did, which for the record, they do not.
Some
Two teams of researchers said on Thursday they had created machines that could reason, formulate theories and discover scientific knowledge on their own, marking a major advance in the field of artificial intelligence.
What the hell? Isn’t this what I have been doing for the last 19 years? Learning how to reason, formulate theories, and discovering scientific knowledge on my own? Uhg. I wish I had known this was going to happen because I would have done something else with my life and then bought this robot and become a scientist overnight. It makes this whole PhD thing seem like a waste of time.
So the question is, does it work?
Just by crunching the numbers -- and without any prior instruction in physics -- the Cornell machine was able to decipher Isaac Newton's laws of motion and other properties.
So, what you are telling me is that this robot was able to derive the Newton Laws from first principles all by itself? What a waste of time those two semesters of physics I took were. I also bet the robot has more personality than a lot of biophysicists I know (babump chhhhhh, I will be here all night).
It seems as though grad. students are about to become obsolete and the tool of the past. I don’t blame the PIs, I would spend the money on a robot that probably does what I do and does a better job of it.
Plus, as my boss would say, “It can’t get pregnant.” I hope they didn’t build this feature in!
It does seem like my job is safe for a little while though.
Lipson does not think robots will make scientists obsolete any day soon, but believes they could take over much of the routine work in research laboratories.
Hopefully by the time I become a PI these things will make everything I do automated and I can sip mixed drinks on the beach somewhere and run my entire lab though my iPhone. Here’s to hoping!
Original article can be found here.
0 Comments
Help Me Raise Money for Cancer Research
03/30/09 01:50 PM Filed in: Charity
I am participating in the Relay for Life at Brandeis, which is a 24 hour walk-a-thon to raise money for cancer research. Any donations would be greatly appreciated!
Lesson Learned: Don't give thesis proposal to someone going camping.
I have my last major hoop to jump through on Thursday of this week in order to become an honest to goodness PhD. Candidate and therefore have to write my thesis proposal and orally defend it. I have one of the best science writers I know as a best friend and therefore I use her as my personal editor. This usually works fine. She rips me to pieces, I cry, fix my idiotic use of the English language, and move on, but this time she was going camping and took my proposal with her. The results I have yet to see, but the pictures speak for themselves.
Burning Proposal our new yearly tradition.
Apparently, it is not available.
Needless to say, I am scared to get it back.
Burning Proposal our new yearly tradition.
Apparently, it is not available.Smart teens don’t have sex (or kiss much either), nor do students at MIT
08/01/07 09:06 PM Filed in: Science | Interesting
are you smart? were you smart in high school? do you get any? did you get any in high school?
according to a 2000 study of 2,000 adolescents enrolled in the 7th to 12th grades the smarter (or dumber, but that doesn't apply to us, right?) the kid is, the less their chance of having sex is. in summary:
as you can now see, assuming an IQ of 100 is average, there is a distinct difference between the smart kids and the average kids. there is also an interesting difference between guys and girls.
the authors discuss some interesting conclusions:
and second off, as a biochemist, with a reputation on the line:
I GO TO BRANDEIS, NOT MIT!
as for the rest of the conclusions, i will let you ponder, so let me know what you think in the comments!
according to a 2000 study of 2,000 adolescents enrolled in the 7th to 12th grades the smarter (or dumber, but that doesn't apply to us, right?) the kid is, the less their chance of having sex is. in summary:
Controlling for age, physical maturity, and mother’s education, a significant curvilinear relationship between intelligence and coital status was demonstrated; adolescents at the upper and lower ends of the intelligence distribution were less likely to have sex. Higher intelligence was also associated with postponement of the initiation of the full range of partnered sexual activities. An expanded model incorporating a variety of control and mediator variables was tested to identify mechanisms by which the relationship operates.as i read the article i started thinking back to other people's high school years (did you really think i was going to tell you about my sexual exploits? if so you need to bring me to bison county and steadily feed me beer.), and i realized that the study is probably correct!Conclusions: Higher intelligence operates as a protective factor against early sexual activity during adolescence, and lower intelligence, to a point, is a risk factor. More systematic investigation of the implications of individual differences in cognitive abilities for sexual activities and of the processes that underlie those activities is warranted.
as you can now see, assuming an IQ of 100 is average, there is a distinct difference between the smart kids and the average kids. there is also an interesting difference between guys and girls.
the authors discuss some interesting conclusions:
Even very “early” behaviors, such as holding hands and kissing, are inversely related to PPVT scores, suggesting that higher intelligence is associated with a generalized delay in the onset of all partnered sexual activities.i also found another discussion of the same topic, which had some other interesting points regarding college aged students, since the first study only went through the 12th grade. This study looked at MIT and Wellesley:
The peak crime rate occurs in the IQ range from 75 to 90; this is approximately the same range in which the probability of having sex is highest in the Add Health sample (using AHPVT scores standardized to an IQ metric). Although many factors influence adolescents’ sexual behavior, just as many factors influence delinquency, it is clear that higher intelligence is a protective factor and lower intelligence, to a point, constitutes a risk factor.
The idea that brighter adolescents postpone holding hands and kissing because they believe that such activity will start them down the path to coitus (and toward the negative consequences that coitus may entail) implies an extremely far-sighted concern with a “slippery slope” that is hard to take seriously.
More intelligent adolescents do evidence a stronger attachment to conventional values and institutions, and higher expectations about goal attainment. For example, they make better grades in school, they have higher expectations about attending college, they believe their parents are more disapproving of sexual activity, they report higher religious attendance, and they are more likely to be involved in structured activities such as school clubs. Each of these factors is also associated with sexual postponement and appears to play a role in the protective effect of intelligence.
Previous analyses on measures of sexual interest, sexual motivation (e.g., masturbation), and conservatism of sexual attitudes from the Biosocial Factors data indicate that higher intelligence is not associated with lesser sexual interest, just with a postponement of acting on that interest.
The inclusion of multiple control and mediator variables yielded no change in the relative odds of having sex among adolescents who score very low on the AHPVT. This suggests that the elements and dynamics of the protection process differ for adolescents who fall at opposite ends of the intelligence distribution.
For males with IQs under 70, 63.3% were still virgins, for those with IQs between 70-90 only 50.2% were virgin, 58.6% were virgins with IQs between 90-110, and 70.3% with IQs over 110 were virgins.
Each additional point of IQ increased the odds of virginity by 2.7% for males and 1.7% for females.
By the age of 19, 80% of US males and 75% of women have lost their virginity, and 87% of college students have had sex. But this number appears to be much lower at elite (i.e. more intelligent) colleges. According to the article, only 56% of Princeton undergraduates have had intercourse. At Harvard 59% of the undergraduates are non-virgins, and at MIT, only a slight majority, 51%, have had intercourse. Further, only 65% of MIT graduate students have had sex.so what does this tell us? first off, brandeis grad students are way more sexually active than MIT's.
The student surveys at MIT and Wellesley also compared virginity by academic major. The chart for Wellesley displayed below shows that 0% of studio art majors were virgins, but 72% of biology majors were virgins, and 83% of biochem and math majors were virgins! Similarly, at MIT 20% of 'humanities' majors were virgins, but 73% of biology majors. (Apparently those most likely to read Darwin are also the least Darwinian!)While still consistent with pregnancy fears and competing interests, lower sex drive seems like a better fit. In fact another revealing finding from the Counterpoint survey was that while 95% of US men and 70% of women masturbate, this number is only 68% of men and 20% of women at MIT!
But lower sex drive and anxiety about sex's consequences can't be the whole story either. Half Sigma also showed that the smartest men in the GSS (approx. IQ >120) were also more likely to visit a prostitute. (Hardly indicative of cautiousness) This may suggest intelligent men are less able to find willing sex partners. Are smart men less attractive to women? Perhaps in some ways. For instance HS found that smart men were less likely to be athletic, and this paper shows, unathletic men and women have fewer sex partners. Athletic men, with more willing sexual partners are also less likely to visit a prostitute. Athletic activity gives men more masculine bodies, which are more attractive to women. A more masculine physique correlates with (PDF) an increased number of sex partners.
So intelligent people have lower libidos and less masculine physiques. What hormone is responsible for both sex drive and masculine builds? That's right: testosterone.
And two new papers suggest that testosterone may depress IQ. One team found that salivary testosterone levels were lower for preadolescent boys with IQs above 130 and below 70. (the same two groups most likely to be virgins in adolescence)
and second off, as a biochemist, with a reputation on the line:
I GO TO BRANDEIS, NOT MIT!
as for the rest of the conclusions, i will let you ponder, so let me know what you think in the comments!
Um, I want this kind of Thesis
so i was wandering around the internet and found this on wired...and i thought to myself: wow whatever my thesis project turns out to be it is not going to be as cool as that.
here is the video of her thesis defense:
anyways hears to a cool thesis, to all those geeks out there who are salivating as you read this, and to any women who wants to play video games!
do you realize how much money she could make with this...i mean it brings a whole new meaning to playing video games!Jennifer Chowdhury attended the interactive telecommunications program at New York University, where her prototypes drew on her engineering training, her artistic aspirations and her sense of humor. Her master's thesis project, Intimate Controllers, is not explicitly sexual -- but it's not something you would use with your sibling, either.
Intimate Controllers is a set of sensors embedded in underwear that direct the action on a video game. Rather than sit separately on the couch and jam fingers against small plastic buttons, players touch each other to control the game.
here is the video of her thesis defense:
anyways hears to a cool thesis, to all those geeks out there who are salivating as you read this, and to any women who wants to play video games!
Ion Channel Glossary
05/17/07 08:54 PM Filed in: Science
since officially joining the miller lab four days ago, i have been in ion channel literature hell. all i have been doing for the last four days is reading about the project i am going to be starting and all the necessary background. it really is interesting, but ~every four sentences i have to stop and look up the definition of a word.
it isn't like i am looking up 'dog' or 'pumpkin.' i have to look up words like 'constant field theory,' 'flicker,' or 'microiontopforesis' and i have come to find that these aren't your normal words. so i decided to be nice and put together a glossary for people so hopefully when they search for one of these obscure words they find this!
so anyways, here we go!
Access resistance: the electrical resistance between the inside of the patch pipette and the inside of the cell during a whole-cell recording. Compromises recordings by introducing a voltage-divider error and slowing the response time of the voltage clamp. Access resistance can be reduced by using larger patch pipettes and can be compensated electronically with the patch clamp amplifier.
Action Potential: the electrical signal, which rapidly propagates along the axon of nerve cells as well as over the surface of some muscle and glandular cells. It is the result of a change in membrane electrical potential, the underlying cause of which is a change in flow of ions across the membrane due to voltage-activated ion channels.
Activation: opening of a channel due to the presence of a gating signal.
Anion: a negatively charged particle.
Anomalous Mole-Fraction Dependence: where conductance or reversal potential goes thru a minimum or maximum as a function of the ratio of ionic concentrations. Calcium ion channels and Calcium-activated potassium channels are well-known examples of ion channels where this occurs.
Axon: highly specialized relatively long extension (process) of a neuron used for conduction of electrical messages (i.e. action potentials). Axons are considerably more specialized and therefore easier to understand than other excitable tissues. They contain the "bare minimum" of ion channels necessary for excitability. Larger vertebrate axons are insulated by myelin.
Block: when ion flow thru an ion channel is prohibited due to a physical obstruction within the pore; and can occur due to another ion, a drug or a toxin. Such molecules, which block ion flow, are known as "blocking agents". "Use-dependent block" or "phasic block" occurs when the drug (toxin, anesthetic, etc) blocks only the open form of the channel.
Cation: a positively charged particle.
Charge: the fundamental property of matter that is responsible for electrical phenomena. Charge (Q) is measured in Coulombs (C). Elementary charge, e = 1.602 x 10-19 Coulombs (C)
Conductance: refers to the rate of ion travel thru the channel and is often measured in siemens (S). Ions with high conductances are often said to have binding sites in the channel that are relatively high in free energy compared to an ion with lower conductance (which sticks more tightly to binding sites). Conductance is often designated as current divided by voltage, and since voltage is usually "clamped" in patch clamp experiments, relates directly to current of ions.
Conductivity: the ability of a substance to pass current. For a membrane, the conductivity (Gm) is measured in units of S/cm2 and G=Gm*area. For a cable (e.g. axon or dendrite), the conductivity (G,, for intracellular conductivity) is measured in units of S/cm and G=Gi*length/area (i.e. cross-sectional area).
Constant Field Theory: a theory to describe the permeabilities of membranes to ions. First put forth in the 1940s by Goldman (before ion channels were proven to exist in membranes), it attempts to describe ion movement in terms of simple diffusion thru water-filled "pores" in a membrane. Ions are assumed to move independently of one another and the channel properties. Also called the "independent electrodiffusion model", it has been successful in describing some aspects of ion permeabilities thru certain ion channels. The other major theory used to describe ion channel permeabilities is the "Rate Theory Model".
Current: the rate of charge movement. Current is measured in amperes (A), which is equivalent to coulombs per second (C/s). I = dQ/dt = Coulombs/sec = Amps (A).
Deactivation: closing of a channel due to removal of the gating signal (i.e. the opposite of activation).
Desensitization: closing of a ligand-gated channel despite the presence of a bound activating ligand. For example, glutamate receptors desensitize in the continued presence of glutamate.
Desolvation: where the ion is rehydrated when it moves outward from the ion channel pore into the bulk solution when it exits pore.
Dwell Times: can give information on kinetic processes. The amount of time a channel remains in the closed position. Also used to describe the amount of time an ion spends in an ion channel pore at a particular binding site.
Electro-osmosis: when ions forced to move thru a pore carry with them water molecules. Similar to streaming potential, but just the opposite.
Eyring rate theory: used to help explain what occurs when an ion traverses an ion channel pore. States that relative permeabilities relate to heights of energy barriers (which differ for different ions) and relative conductances relate to depths of the wells (i.e. ion binding sites) in the energy diagram.
Flicker: occurs when molecules other than the ion enter the channel opening and briefly blocks ion conductance. This can be seen on single-channel recordings as squiggly lines during the open time, as well as a lower overall conductance. "Desensitization" is believed to be due to too much ligand, for example acetylcholine and nAChR channels, blocking the channel rather than activating it. For CFTR, NPPB or DPC induces rapid flicker and therefore block pore.
Flux Coupling: a factor, which may reduce the ability of an ion to move thru a pore. It is due to the crowded conditions in the narrow part of the pore. When molecules diffuse within a restricted space, they lose their independence compared to the bulk solvent.
Flux-Ratio Criterion: an important test for whether or not ion channel pores can admit multiple ions at the same time. It was proposed by Ussing in 1949 and can be used to reveal flux coupling. A tracer ion is needed to measure the unidirectional flux across a membrane from both sides.
Gating: process by which ion channels open and close their pores. Some, such as voltage-gated ion channels, open and close depending on the electrical potential of the cell membrane. Others depend on such factors as cell volume, intracellular metabolic state (ATP concentration, etc), intracellular ligand and/or second messenger presence (Calcium, cyclic AMP due to light, etc), and extracellular ligands (neurotransmitters like acetylcholine, GABA). It always involves a change in the shape of the protein (called "allosterism").
Gating current: a current resulting when charged residues within an ion channel protein move through the electric field. In voltage-gated channels, a change in membrane potential causes the protein to move; this movement gives rise to the gating current.
Hodgkin-Huxley Model: developed by work with the squid giant axon, it was the first model to describe the ionic basis of excitation correctly. It had the effect of revolutionizing electrophysiology.
Inactivation: closing of a channel in the continued presence of the gating signal. The term "inactivation" is usually only applied to voltage-gated channels, whereas "desensitization" describes the analogous process for ligand-gated channels.
Kinetics: as applied to ion channels kinetics usually encompasses the study of rate of change ion channels undergo during gating, ion passage, etc. Kinetics is often used in order to uncover specific "mechanisms" channels undergo when changing from one state to another and to explain the phenomena of gating, "jumps", "bursts", "transition times", sub-conductance modes, ligand interactions, etc. Complex mathematical treatments involving the kinetics of ion channels have been undertaken in order to gain insight into how ion channels accomplish this.
Markov model: a probabilistic process over a finite set of states, often used to described channel behavior. Transitions between states are determined by rate constants. A zero-order Markov process has no memory; a first-order Markov process has a memory of one step, i.e., the possible states that a channel can occupy at time t depends on which state it was in at time t-1.
Membrane Potential: the inside potential minus the outside potential. The outside of the cell is often considered to be at ground potential (0 mV).
Microiontophoresis: where, during patch clamping of receptor ion channels such as nAChR, agonist is electrophoresed locally thru the microelectrode where it binds and activates the receptor.
Modulation: anything, which changes or modifies gating can cause "modulation". These can include ligand binding to the channel, post-translational modifications like phosphorylation, or changes in the process itself." Certain neurotransmitters such as GABA, serotonin, nitric oxide, and others can modulate ion channels indirectly by binding to other sites on cell membrane. They do this by influencing GPCRs. By changing the internal ion melieu of the cytoplasm, changes in the cell itself can take place. Fatty acids have been shown to bind directly to ion channels and modulate them.
Multi-Ion Pore: when an ion channel's pore is able to conduct more than one ion at a time. CFTR is believed to by one because of the presence of anomalous mole fraction effects in mixtures of chloride and SCN-.
Ohm's law: describes the relationship between voltage, current, and resistance, V=IR or R = V/I = Ohms (Ω); I = g V or g = I/V = Siemens (S).
Open State Probability (Po): the amount of time an ion channel is in the open configuration.
Permeability: describes how fast ions are able to move thru an ion channel (the rate of movement). The "depth" of the energy well for a particular ion generally determines it's permeability, or conductance. However, if an energy well is too deep, it can slow down the ion's rate of travel. Note: all binding sites for an ion in a channel have energy wells specific to the interaction that takes place.
Pore: part of ion channel, which forms path ions use to move from one side of membrane to other. Often lined with some hydrophilic amino acids. Sometimes filled with water. Pore lengths have been inferred for some ion channels by blocking the pore during conduction experiments using blocking agents with long spacer arms. CFTR's pore is estimated to be around 5.8A at its narrowest point. Narrow pores will necessitate removal of some or all of an ions hydration shell before allowing passage.
Potential Difference: the same as voltage. Another definition is the difference in potential energy experienced by a charged particle in two locations (the work required to move a charge from point A to B). Potential difference (E) is measured in volts (V). E = Joules/Coulomb = Volts (V).
Rate Theory Model: used to describe ion movement thru ion channels by considering ions not in terms of passive diffusion (i.e. electrodiffusion model) but as being able to bind to specific sites within the ion channel. The Rate Theory is an attempt to apply reaction rate theory developed by Eyring for enzymes to ion channels in hopes of gaining insight into particular mechanisms of ion conduction. The ultimate description of ion movement using this theory would involve use of "molecular dynamics simulations" in silico.
Rectification (of channels): characteristic of an ion channel, generally independent of gating, that biases the preferred direction of current flow to either the inward or outward direction. Rectification can be due to an intrinsic property of the channel or be conferred by voltage-dependent block by an extrinsic agent. For example, the relatively high concentration of K+ ions inside a cell can cause outward rectification of some K+ channels, because more K+ ions are available to carry outward current than the number available to carry inward current. This is called GHK rectification. Another type of rectification is caused by polyamines. These charged molecules are only present inside cells and at depolarized potentials they move into the pore of some voltage-gated and ligand-gated channels, thus limiting outward current (i.e. inward rectification). These factors cause the channel conductance to be voltage dependent, thus resulting in rectification.
Relative Conductance: when the conductance for a substitute ion relative to that of a standard ion is determined.
Relative Permeabilities: reflect the ability of an ion channel protein to pull an ion from solution into the "capture volume" within the pore vestibule. It may therefore be highly dependent on hydration energy. Some permeability sequences reflect low-affinity ion-pore interactions (ex: I>Br>Cl>F). The reverse sequence often indicates a high affinity interaction. CFTR has a more complex sequence, which indicates a combination of both low and high field strength interactions (Br>Cl>I>F). For most anions, the relative permeability is determined by the relative hydration energies of the ions.
Resistance: the inverse of conductance. That is, the ability of something to impede current. Resistance (R) is measured in Ohms (Ω).
Resistivity: the inverse of conductivity. Membrane resistivity (Rm) has units of resistivity (Ri) has units of Ωcm.
Reversal Potentials: often abbreviated E(rev). For CFTR (and other anion channels), it is the amount of negative membrane potential needed to be applied to reverse the flow of chloride when the concentration is at standard conditions. For CFTR this value is -30.31 mV. For example, if a particular anion requires a more negative E(rev) than for chloride then it may either permeate or conduct better than chloride depending on which is being determined, permeability (uses Goldman-Hodgkin-Katz equation) or conductance.
Selectivity: used to describe the variability in rate of movement of different ions thru the same ion channel. The "height" of the energy barrier of an ion channel's selectivity filter will help determine ion it let thru. Often, the term selectivity is not properly defined and can refer to either of the two processes of permeability or conduction. The distinction should always be made.
Selectivity Filter: a distinct part of an ion channel involved in selecting the type of ion it lets thru. First described by Hille in 1971, it is thought to be situated in the narrowest part of the pore, because this is the part of the channel where the protein and ion would presumably interact the most.
Siemens: a measurement of current conductance (often abbreviated "G") thru ion channels and is abbreviated "S". Is equal to the ratio of current (measured in amps) divided by voltage (measured in volts; note: this comes from ohm's law). It also equals 1/R. One picosiemen equals 10^-12 siemens and is convenient to use for ion channels. For example, the ion channel gramicidin has a conductance of 30 pS for cations. This is equivalent to 6.28 X 10^6 ions per second per applied volt of conductance of cations thru the pore when the concentration of cations is equal on both sides of the membrane.
Single-channel Conductance: a measure of the current that flows thru an open channel in response to a given electrochemical driving force.
Solvation: occurs at the mouth of the pore. During ion permeation, where ion is partially or fully dehydrated and therefore stabilized by interactions with the pore wall.
Streaming Potential: a measurement of ion channel permeability to water molecules. Osmotic gradients are set up and membrane potential simultaneously measured while changing potential. Used to predict water to ion ratios. When water is forced to flow thru a pore by setting up osmotic or hydrostatic pressure differences, they may drag the ions as well. This creates an electric potential difference called the streaming potential.
Subconductance: when conductance is less than what is usually seen. Probably due to subtleties in kinetics of gating and are yet not fully understood. For example, GABA(A) and glycine receptor ion channels appear to have multiple subconductance levels and it is therefore believed that direct transitions between the states can be reached from the closed state. It is believed by some that all channels have subconductance levels, but most are not as obvious as in GABA(A) and glycine receptors.
Tail current: current that flows during the repolarizing phase of an action potential or voltage command. K+ tail currents can be used to determine the reversal potential of voltage-gated K+ currents. In a physiological context, tail currents are often carried by Ca2+ ions and result from the increased driving force as the action potential repolarizes.
Translocation: describes the process of ion transit thru the channel. It is highly dependent upon the driving force for anion permeation and reflects the strength of interaction between the anion and each binding site. More tightly binding ions have a reduced rate of current flow (conductance) due to longer dwell times at any of several possible binding sites within the pore.
Valence: a term to describe the charge of a particle. Na+ and Ca++ have positive valence, while Cl- has negative valence. Moreover, Na+ is monovalent, and Ca++ is divalent. In the Nernst equation and the GHK voltage equation, valence is represented by the variable z.
Voltage: the force created on a charge caused by the separation of charge. Voltage (F) is measured in volts (V). Voltage is equivalent to potential difference.
Voltage-Clamping: a procedure used during study of ion channels, which has the effect of keeping the voltage, produced on a membrane (due ion movement) unchanged. Allows the experimenter to measure only current produced by the ion movement thru the channel. Requires use of a second electrode to measure cell potential. Allows a direct measurement of ionic current across a membrane. This in turn allowed ion channel "kinetic" studies to begin.
i did use two websites a lot so here are the links to the original sites: CFTR Review Page and the Brown University Wiki.
it isn't like i am looking up 'dog' or 'pumpkin.' i have to look up words like 'constant field theory,' 'flicker,' or 'microiontopforesis' and i have come to find that these aren't your normal words. so i decided to be nice and put together a glossary for people so hopefully when they search for one of these obscure words they find this!
so anyways, here we go!
Access resistance: the electrical resistance between the inside of the patch pipette and the inside of the cell during a whole-cell recording. Compromises recordings by introducing a voltage-divider error and slowing the response time of the voltage clamp. Access resistance can be reduced by using larger patch pipettes and can be compensated electronically with the patch clamp amplifier.
Action Potential: the electrical signal, which rapidly propagates along the axon of nerve cells as well as over the surface of some muscle and glandular cells. It is the result of a change in membrane electrical potential, the underlying cause of which is a change in flow of ions across the membrane due to voltage-activated ion channels.
Activation: opening of a channel due to the presence of a gating signal.
Anion: a negatively charged particle.
Anomalous Mole-Fraction Dependence: where conductance or reversal potential goes thru a minimum or maximum as a function of the ratio of ionic concentrations. Calcium ion channels and Calcium-activated potassium channels are well-known examples of ion channels where this occurs.
Axon: highly specialized relatively long extension (process) of a neuron used for conduction of electrical messages (i.e. action potentials). Axons are considerably more specialized and therefore easier to understand than other excitable tissues. They contain the "bare minimum" of ion channels necessary for excitability. Larger vertebrate axons are insulated by myelin.
Block: when ion flow thru an ion channel is prohibited due to a physical obstruction within the pore; and can occur due to another ion, a drug or a toxin. Such molecules, which block ion flow, are known as "blocking agents". "Use-dependent block" or "phasic block" occurs when the drug (toxin, anesthetic, etc) blocks only the open form of the channel.
Cation: a positively charged particle.
Charge: the fundamental property of matter that is responsible for electrical phenomena. Charge (Q) is measured in Coulombs (C). Elementary charge, e = 1.602 x 10-19 Coulombs (C)
Conductance: refers to the rate of ion travel thru the channel and is often measured in siemens (S). Ions with high conductances are often said to have binding sites in the channel that are relatively high in free energy compared to an ion with lower conductance (which sticks more tightly to binding sites). Conductance is often designated as current divided by voltage, and since voltage is usually "clamped" in patch clamp experiments, relates directly to current of ions.
Conductivity: the ability of a substance to pass current. For a membrane, the conductivity (Gm) is measured in units of S/cm2 and G=Gm*area. For a cable (e.g. axon or dendrite), the conductivity (G,, for intracellular conductivity) is measured in units of S/cm and G=Gi*length/area (i.e. cross-sectional area).
Constant Field Theory: a theory to describe the permeabilities of membranes to ions. First put forth in the 1940s by Goldman (before ion channels were proven to exist in membranes), it attempts to describe ion movement in terms of simple diffusion thru water-filled "pores" in a membrane. Ions are assumed to move independently of one another and the channel properties. Also called the "independent electrodiffusion model", it has been successful in describing some aspects of ion permeabilities thru certain ion channels. The other major theory used to describe ion channel permeabilities is the "Rate Theory Model".
Current: the rate of charge movement. Current is measured in amperes (A), which is equivalent to coulombs per second (C/s). I = dQ/dt = Coulombs/sec = Amps (A).
Deactivation: closing of a channel due to removal of the gating signal (i.e. the opposite of activation).
Desensitization: closing of a ligand-gated channel despite the presence of a bound activating ligand. For example, glutamate receptors desensitize in the continued presence of glutamate.
Desolvation: where the ion is rehydrated when it moves outward from the ion channel pore into the bulk solution when it exits pore.
Dwell Times: can give information on kinetic processes. The amount of time a channel remains in the closed position. Also used to describe the amount of time an ion spends in an ion channel pore at a particular binding site.
Electro-osmosis: when ions forced to move thru a pore carry with them water molecules. Similar to streaming potential, but just the opposite.
Eyring rate theory: used to help explain what occurs when an ion traverses an ion channel pore. States that relative permeabilities relate to heights of energy barriers (which differ for different ions) and relative conductances relate to depths of the wells (i.e. ion binding sites) in the energy diagram.
Flicker: occurs when molecules other than the ion enter the channel opening and briefly blocks ion conductance. This can be seen on single-channel recordings as squiggly lines during the open time, as well as a lower overall conductance. "Desensitization" is believed to be due to too much ligand, for example acetylcholine and nAChR channels, blocking the channel rather than activating it. For CFTR, NPPB or DPC induces rapid flicker and therefore block pore.
Flux Coupling: a factor, which may reduce the ability of an ion to move thru a pore. It is due to the crowded conditions in the narrow part of the pore. When molecules diffuse within a restricted space, they lose their independence compared to the bulk solvent.
Flux-Ratio Criterion: an important test for whether or not ion channel pores can admit multiple ions at the same time. It was proposed by Ussing in 1949 and can be used to reveal flux coupling. A tracer ion is needed to measure the unidirectional flux across a membrane from both sides.
Gating: process by which ion channels open and close their pores. Some, such as voltage-gated ion channels, open and close depending on the electrical potential of the cell membrane. Others depend on such factors as cell volume, intracellular metabolic state (ATP concentration, etc), intracellular ligand and/or second messenger presence (Calcium, cyclic AMP due to light, etc), and extracellular ligands (neurotransmitters like acetylcholine, GABA). It always involves a change in the shape of the protein (called "allosterism").
Gating current: a current resulting when charged residues within an ion channel protein move through the electric field. In voltage-gated channels, a change in membrane potential causes the protein to move; this movement gives rise to the gating current.
Hodgkin-Huxley Model: developed by work with the squid giant axon, it was the first model to describe the ionic basis of excitation correctly. It had the effect of revolutionizing electrophysiology.
Inactivation: closing of a channel in the continued presence of the gating signal. The term "inactivation" is usually only applied to voltage-gated channels, whereas "desensitization" describes the analogous process for ligand-gated channels.
Kinetics: as applied to ion channels kinetics usually encompasses the study of rate of change ion channels undergo during gating, ion passage, etc. Kinetics is often used in order to uncover specific "mechanisms" channels undergo when changing from one state to another and to explain the phenomena of gating, "jumps", "bursts", "transition times", sub-conductance modes, ligand interactions, etc. Complex mathematical treatments involving the kinetics of ion channels have been undertaken in order to gain insight into how ion channels accomplish this.
Markov model: a probabilistic process over a finite set of states, often used to described channel behavior. Transitions between states are determined by rate constants. A zero-order Markov process has no memory; a first-order Markov process has a memory of one step, i.e., the possible states that a channel can occupy at time t depends on which state it was in at time t-1.
Membrane Potential: the inside potential minus the outside potential. The outside of the cell is often considered to be at ground potential (0 mV).
Microiontophoresis: where, during patch clamping of receptor ion channels such as nAChR, agonist is electrophoresed locally thru the microelectrode where it binds and activates the receptor.
Modulation: anything, which changes or modifies gating can cause "modulation". These can include ligand binding to the channel, post-translational modifications like phosphorylation, or changes in the process itself." Certain neurotransmitters such as GABA, serotonin, nitric oxide, and others can modulate ion channels indirectly by binding to other sites on cell membrane. They do this by influencing GPCRs. By changing the internal ion melieu of the cytoplasm, changes in the cell itself can take place. Fatty acids have been shown to bind directly to ion channels and modulate them.
Multi-Ion Pore: when an ion channel's pore is able to conduct more than one ion at a time. CFTR is believed to by one because of the presence of anomalous mole fraction effects in mixtures of chloride and SCN-.
Ohm's law: describes the relationship between voltage, current, and resistance, V=IR or R = V/I = Ohms (Ω); I = g V or g = I/V = Siemens (S).
Open State Probability (Po): the amount of time an ion channel is in the open configuration.
Permeability: describes how fast ions are able to move thru an ion channel (the rate of movement). The "depth" of the energy well for a particular ion generally determines it's permeability, or conductance. However, if an energy well is too deep, it can slow down the ion's rate of travel. Note: all binding sites for an ion in a channel have energy wells specific to the interaction that takes place.
Pore: part of ion channel, which forms path ions use to move from one side of membrane to other. Often lined with some hydrophilic amino acids. Sometimes filled with water. Pore lengths have been inferred for some ion channels by blocking the pore during conduction experiments using blocking agents with long spacer arms. CFTR's pore is estimated to be around 5.8A at its narrowest point. Narrow pores will necessitate removal of some or all of an ions hydration shell before allowing passage.
Potential Difference: the same as voltage. Another definition is the difference in potential energy experienced by a charged particle in two locations (the work required to move a charge from point A to B). Potential difference (E) is measured in volts (V). E = Joules/Coulomb = Volts (V).
Rate Theory Model: used to describe ion movement thru ion channels by considering ions not in terms of passive diffusion (i.e. electrodiffusion model) but as being able to bind to specific sites within the ion channel. The Rate Theory is an attempt to apply reaction rate theory developed by Eyring for enzymes to ion channels in hopes of gaining insight into particular mechanisms of ion conduction. The ultimate description of ion movement using this theory would involve use of "molecular dynamics simulations" in silico.
Rectification (of channels): characteristic of an ion channel, generally independent of gating, that biases the preferred direction of current flow to either the inward or outward direction. Rectification can be due to an intrinsic property of the channel or be conferred by voltage-dependent block by an extrinsic agent. For example, the relatively high concentration of K+ ions inside a cell can cause outward rectification of some K+ channels, because more K+ ions are available to carry outward current than the number available to carry inward current. This is called GHK rectification. Another type of rectification is caused by polyamines. These charged molecules are only present inside cells and at depolarized potentials they move into the pore of some voltage-gated and ligand-gated channels, thus limiting outward current (i.e. inward rectification). These factors cause the channel conductance to be voltage dependent, thus resulting in rectification.
Relative Conductance: when the conductance for a substitute ion relative to that of a standard ion is determined.
Relative Permeabilities: reflect the ability of an ion channel protein to pull an ion from solution into the "capture volume" within the pore vestibule. It may therefore be highly dependent on hydration energy. Some permeability sequences reflect low-affinity ion-pore interactions (ex: I>Br>Cl>F). The reverse sequence often indicates a high affinity interaction. CFTR has a more complex sequence, which indicates a combination of both low and high field strength interactions (Br>Cl>I>F). For most anions, the relative permeability is determined by the relative hydration energies of the ions.
Resistance: the inverse of conductance. That is, the ability of something to impede current. Resistance (R) is measured in Ohms (Ω).
Resistivity: the inverse of conductivity. Membrane resistivity (Rm) has units of resistivity (Ri) has units of Ωcm.
Reversal Potentials: often abbreviated E(rev). For CFTR (and other anion channels), it is the amount of negative membrane potential needed to be applied to reverse the flow of chloride when the concentration is at standard conditions. For CFTR this value is -30.31 mV. For example, if a particular anion requires a more negative E(rev) than for chloride then it may either permeate or conduct better than chloride depending on which is being determined, permeability (uses Goldman-Hodgkin-Katz equation) or conductance.
Selectivity: used to describe the variability in rate of movement of different ions thru the same ion channel. The "height" of the energy barrier of an ion channel's selectivity filter will help determine ion it let thru. Often, the term selectivity is not properly defined and can refer to either of the two processes of permeability or conduction. The distinction should always be made.
Selectivity Filter: a distinct part of an ion channel involved in selecting the type of ion it lets thru. First described by Hille in 1971, it is thought to be situated in the narrowest part of the pore, because this is the part of the channel where the protein and ion would presumably interact the most.
Siemens: a measurement of current conductance (often abbreviated "G") thru ion channels and is abbreviated "S". Is equal to the ratio of current (measured in amps) divided by voltage (measured in volts; note: this comes from ohm's law). It also equals 1/R. One picosiemen equals 10^-12 siemens and is convenient to use for ion channels. For example, the ion channel gramicidin has a conductance of 30 pS for cations. This is equivalent to 6.28 X 10^6 ions per second per applied volt of conductance of cations thru the pore when the concentration of cations is equal on both sides of the membrane.
Single-channel Conductance: a measure of the current that flows thru an open channel in response to a given electrochemical driving force.
Solvation: occurs at the mouth of the pore. During ion permeation, where ion is partially or fully dehydrated and therefore stabilized by interactions with the pore wall.
Streaming Potential: a measurement of ion channel permeability to water molecules. Osmotic gradients are set up and membrane potential simultaneously measured while changing potential. Used to predict water to ion ratios. When water is forced to flow thru a pore by setting up osmotic or hydrostatic pressure differences, they may drag the ions as well. This creates an electric potential difference called the streaming potential.
Subconductance: when conductance is less than what is usually seen. Probably due to subtleties in kinetics of gating and are yet not fully understood. For example, GABA(A) and glycine receptor ion channels appear to have multiple subconductance levels and it is therefore believed that direct transitions between the states can be reached from the closed state. It is believed by some that all channels have subconductance levels, but most are not as obvious as in GABA(A) and glycine receptors.
Tail current: current that flows during the repolarizing phase of an action potential or voltage command. K+ tail currents can be used to determine the reversal potential of voltage-gated K+ currents. In a physiological context, tail currents are often carried by Ca2+ ions and result from the increased driving force as the action potential repolarizes.
Translocation: describes the process of ion transit thru the channel. It is highly dependent upon the driving force for anion permeation and reflects the strength of interaction between the anion and each binding site. More tightly binding ions have a reduced rate of current flow (conductance) due to longer dwell times at any of several possible binding sites within the pore.
Valence: a term to describe the charge of a particle. Na+ and Ca++ have positive valence, while Cl- has negative valence. Moreover, Na+ is monovalent, and Ca++ is divalent. In the Nernst equation and the GHK voltage equation, valence is represented by the variable z.
Voltage: the force created on a charge caused by the separation of charge. Voltage (F) is measured in volts (V). Voltage is equivalent to potential difference.
Voltage-Clamping: a procedure used during study of ion channels, which has the effect of keeping the voltage, produced on a membrane (due ion movement) unchanged. Allows the experimenter to measure only current produced by the ion movement thru the channel. Requires use of a second electrode to measure cell potential. Allows a direct measurement of ionic current across a membrane. This in turn allowed ion channel "kinetic" studies to begin.
i did use two websites a lot so here are the links to the original sites: CFTR Review Page and the Brown University Wiki.
6 freaking months...so sad right now...
so David Ng of The Science Creative Quarterly and The World's Fair fame wrote a piece entitled: "Hypothetical question of the day: How long do you figure your post graduate degree would've actually taken if everything you did, worked?."
needless to say i am extremely depressed with his results.
i love how in science this is completely accepted...can you imagine another career in which a 5% success rate is allowed?
"i am sorry we only deliver 5% of babies successfully."
"i am sorry i only win 5% of my cases."
"i am sorry i only make 5% of my customer's meals."
"i am sorry only 5% of my products work."
"i am sorry only 5% of my buildings stay standing."
"i am sorry only 5% of my students graduate."
oh science, i don't know if this is why i love thee or hate thee...well actually it depends if it is a "magic fingers" day or not!
well here's to 54 months of crap intertwined with 3 months of genius...yay grad school!
needless to say i am extremely depressed with his results.
so this means that in my 5years of graduate school career [i hope?] about 3 months will be the actual work that gets me my PhD, awesome, freaking awesome...
Several years back, myself and some colleagues (all in the molecular biology genre) had a discussion about this over some drinks. Specifically, we tried to calculate how long our doctorates would have actually taken, if we assumed that all the experiments we did in our theses worked right off the bat. Always with the first time success, reproducible results in triplicate no problemo, no troubleshooting required, or literally, a case where we had "magic fingers" for the entire length of our graduate career.
And so, if we assumed that taking courses was not factored in, and that we would have about 3 months to actually write up the damn thing, we all agreed that our Ph.D. would have taken somewhere in the 6 month range to complete. 6 freakin' months!
Anyway, in the end, I took just over 5 years, which means for the 3 months or so of "thesis bound" results, there also existed about 54 months of "non-thesis" bound results. And that is like a 5% success rate - which ultimately means that, really, you just have to work one day every three or so weeks, and as long as you pick the right day, you'll still get your degree in the normal length of time.
i love how in science this is completely accepted...can you imagine another career in which a 5% success rate is allowed?
"i am sorry we only deliver 5% of babies successfully."
"i am sorry i only win 5% of my cases."
"i am sorry i only make 5% of my customer's meals."
"i am sorry only 5% of my products work."
"i am sorry only 5% of my buildings stay standing."
"i am sorry only 5% of my students graduate."
oh science, i don't know if this is why i love thee or hate thee...well actually it depends if it is a "magic fingers" day or not!
well here's to 54 months of crap intertwined with 3 months of genius...yay grad school!
academia and industry; what about the grad students
05/03/07 08:49 PM Filed in: Science
Gershom Edwin Samuel wrote a great article over at The Science Creative Quarterly about the interface between academia and industry [ACADEMIA-INDUSTRY - ALLIANCE AT WHAT COST?]. in it he discusses the implications of the fusion of these two cultures and the benefits and risks for each.
Samuel brings up some interesting points such as the key differences between the two cultures:
for example, if there is a discovery by a graduate student, which greatly benefits the company that is funding the work, the company will most likely not want the data published, for then it becomes part of the public domain and more importantly available to competitors. the PI might have signed a contract before the work was started, stating that the work will not be published for three years if the company feels that it has future implications for monetary gain, but what about the grad student?
this poor student busted their ass trying to get results just to have them withheld from being published because industry funded their work. since in most grad programs publications are what get you out faster and determine where you get a post doc or job after finishing your PhD this student's career may be damaged before it begins since their current and any future work on this project is no longer publishable. never mind the fact that three years is half of the time you are in grad school and about three quarters of the time you are actually working on your thesis project.
in the simplest terms, the grad student is being punished for doing good science.
i do understand the monetary crunch and how funding via industry can be beneficial to both the PI and the company, but i plead with the PIs out there, who do accept funding from industry, to think about your grad students and make sure that if you put someone on an industry based project, that it will be amicable to their career as well as yours.
Samuel brings up some interesting points such as the key differences between the two cultures:
In the academic world, there is a traditional rule; for career advancement (to obtain tenure and receive full professorship), one has to secure research grants and publish papers. Thus, the old saying “publish or perish” is a reality...In contrast, for pharmaceutical industry, the vital thing is the new-drug application to the FDA. A journal article is worth nothing without the FDA approval. However, publication in prestigious journals along with FDA approval is just like icing on the cake that would influence physicians to prescribe the company’s product. (Bodenheimer, 2000)he also talks about disclosure, conflict of interest, and the "JAMA Fiasco:"
The lead author — Lee Cohen, director of Massachusetts General Hospital’s Center for Women’s Mental Health, is a consultant to three antidepressant manufacturers, a paid speaker for seven of them and has his research work funded by four drug makers. None of those ties were reported in the study. Dr Cohen and his colleagues maintained that it was not relevant to disclose their ties with industry in the paper in part because the study was funded by the government, not drug maker (Armstrong, 2006). Such incidents ruin the academia’s reputation as independent truth seeker and reduce public trust in research. Henceforth, more often questions will be raised on integrity of research, researchers and science journals.one key point regarding the fusion of industry and academia that Samuel doesn't talk about is the rock and the hard place that graduate students can be put in.
for example, if there is a discovery by a graduate student, which greatly benefits the company that is funding the work, the company will most likely not want the data published, for then it becomes part of the public domain and more importantly available to competitors. the PI might have signed a contract before the work was started, stating that the work will not be published for three years if the company feels that it has future implications for monetary gain, but what about the grad student?
this poor student busted their ass trying to get results just to have them withheld from being published because industry funded their work. since in most grad programs publications are what get you out faster and determine where you get a post doc or job after finishing your PhD this student's career may be damaged before it begins since their current and any future work on this project is no longer publishable. never mind the fact that three years is half of the time you are in grad school and about three quarters of the time you are actually working on your thesis project.
in the simplest terms, the grad student is being punished for doing good science.
i do understand the monetary crunch and how funding via industry can be beneficial to both the PI and the company, but i plead with the PIs out there, who do accept funding from industry, to think about your grad students and make sure that if you put someone on an industry based project, that it will be amicable to their career as well as yours.
It's Miller Time
05/02/07 08:46 PM Filed in: Science
so my tenure as a roton [rotator] is coming to a close. one more full week of lab work followed by my final chalk talk [i can't even express to you how excited i am to sit in the audience while the new first years give their presentations next year]! this means i have to choose a lab to reside in...which i have done and more importantly the lab has accepted me!
i have joined Chris Miller's Laboratory of Horrors [Chris if you read this i am just kidding don't take it out of me...please?!]. Chris is a HHMI Investigator and was recently [yesterday] elected into the National Academy of Sciences. his work focuses on the basic mechanisms by which ion channels and pumps work along with the workings of other membrane transport proteins. much of Chris' work focuses mostly on CLC type Cl- channels and pumps.
needless to say i am extraordinarily exited about joining Chris' lab because i have a feeling that if he doesn't kill me, i will be a much stronger scientist in the end [and yes there is a distinct possibility of being killed].
for the next week i am mentally preparing myself to be the lowly new graduate student in the lab because i have a feeling that as a roton i was cut some slack, but now as a full fledged member of the lab i am going to have no slack being cut. i am ready to be destroyed.
Chris can rebuild me. he has the technology. he has the capability to build the world's first bionic scientist. kene piasta will be that scientist. better than he was before. better, stronger, faster.
i have joined Chris Miller's Laboratory of Horrors [Chris if you read this i am just kidding don't take it out of me...please?!]. Chris is a HHMI Investigator and was recently [yesterday] elected into the National Academy of Sciences. his work focuses on the basic mechanisms by which ion channels and pumps work along with the workings of other membrane transport proteins. much of Chris' work focuses mostly on CLC type Cl- channels and pumps.
needless to say i am extraordinarily exited about joining Chris' lab because i have a feeling that if he doesn't kill me, i will be a much stronger scientist in the end [and yes there is a distinct possibility of being killed].
for the next week i am mentally preparing myself to be the lowly new graduate student in the lab because i have a feeling that as a roton i was cut some slack, but now as a full fledged member of the lab i am going to have no slack being cut. i am ready to be destroyed.
Chris can rebuild me. he has the technology. he has the capability to build the world's first bionic scientist. kene piasta will be that scientist. better than he was before. better, stronger, faster.
science the next big cult
so i saw this comic and could not stop laughing because as i am working my way through grad school, i am finding that i really am changing the way i think...i really am becoming a scientist.
i am really starting to wonder how everything works and think about how to figure it out. my rotations are really starting to get me to understand good experimental design and how to apply what i have learned in my classes to the lab. the literature is not as scary as it used to be (but it still is another language sometimes).
oh man i think i just came to the realization that i joined a cult...awesome.
i am really starting to wonder how everything works and think about how to figure it out. my rotations are really starting to get me to understand good experimental design and how to apply what i have learned in my classes to the lab. the literature is not as scary as it used to be (but it still is another language sometimes).
oh man i think i just came to the realization that i joined a cult...awesome.