 And here's to tell you a little bit more about that, is Professor James You. Woo! Wow, thank you for going to the last year. Thank you so much, everyone. As you said, this is beautiful, but I cannot tell you what it is, but I was very eloquent. Thanks. All right, so my title of my talk is, None of the scenes go down on goal. I want you to, before I start, I want you to thank Rick and Rebecca for organizing these wonderful events and these opportunities for women out there. So, let's see. I am a, so tonight is all about machines. And I started my academic training by building machines, hardware and transportation. So wherever I go, and whenever I see you, I see machines. And I'm going to start with a few obvious cases of machines in cars, especially machines full, so I just go and this really beautiful, large-spin coffee machine. All of them have, even though they have a different degree of complexity as well as purposes, they have some common pieces that is just that the building blocks are more or less the same. And I'm going to say that a very good part of it is that for a three electron laser, there's going to be magnets between the capacitor. This 50-year-old 10th place, he's the capacitor that's used to accelerate the electrons. And the magnets, the blue and the red over here are used to band the electron beams. And you know what is this Eiffel? We can take it apart. It's not shiny on the outside, but when we take it apart, we can see that, okay, there's some batteries and there's some capacitor here as well. There's just something that I have to recognize. Now, I'm going to show you a different type of machine, and I'm going to ask you when you're watching it, do you believe that this machine is beautiful machine and what type of building blocks might you guess that there is an infinite one? How did she do this? And one of the building blocks that makes up this intricate, beautiful bi-machine, when I graduated from Western School, I had no idea what the answer was, but when I was looking for jobs and studying what to do next, I found out one of the answers, which is there are two key building blocks. Just like capacitor and resistors, these are called molecular motors and molecular tubules. Molecular motors is the thing that clearly has been introduced to you that was placed, what do you call this thing, to the space like a chandelier and drinks a glass of wine, of course. And if you walk down this thing that's close to a mole, there's some additional sense of moles and molecular tubules. It's not a molecular highway. So it carries its job, it's to carry around something I'm going to call transcript with carbons and some sort of chemical materials back and forth inside itself. And this consists in all of ourselves. So when the plane is coming, then you have to see, it takes these discrete steps. Each step, it consumes an ATP, which is a denoting triphosphate. Triphosphate is the triphosphate. What it does is it breaks apart the three bonds, three bonds straight into two bonds straight and one free phosphate. It breaks apart one bond. The bond is breaking apart the one bond, it gains energy, it gains energy, and then it can take a step. And when it's full of the next ATP, it breaks apart a lump and takes another step. So, let's see. This is great, and I'm trained as a physicist, so I'm always looking for universal laws. It was very pleasing to find out that these two developing blocks are the universal law, humans, animals, and plants. Not only that, viruses hijack these mutinaries, and we are seeing these green dots that are moving inside of an infected axon through their own processes. And these green dots will hurt these viruses. Some of the viruses understand them, and I feel challenged. So, okay, let's see. Now, you weigh some of the pieces of axon, and here is a cartoon of a type of a special cell inside of us, which is neurons, and these motors are carrying materials back and forth from the cell body, which is from your central nervous system to the tip of the neuron processes, sometimes through fingers, sometimes through toes. Here, a tall person can be a ninja, which is six hundred and ninety-two longer than the individual travel distance of his body. So, it's pretty difficult to test. You might ask me, what are these car walls? They can be neural transmitters, they can be survival signals, neural transmitters from the cell body to the distal area, and survival signal from the distal area back to the cell body. Okay, so, you see, the person who all sounds like humans, because of that, the failure in these fundamental building blocks becomes the issue. The ambulance, the number of diseases, which is including neural degeneration as well as cancer. So, when we were supposed to stop at Earthline, I was fortunate enough to be part of the study where we found out the mechanism for one type of effect, failure in these motors, how you can how wide and how you can lead to logarithmic diseases in life models. So, essentially, the effect of these drone travels as long, so they can effectively shuttle in materials to that destination. So, this is kind of impressive, right? I'm going to use this. The full-time design enables everyday function. So, it includes vision, hearing, cell division, and for if statistics is right, we'll just be half of you. So, experience will have to swim to find an optimized spur X during Jackie's DNA, which is somewhere here, and the ability to swim long range all happens in the pale, and it's these two components that enables this pale and swim. If you're interested, I have a final slide to sort of hand-waving me, like that. So, I want to do the study, but it tells a very, very messy, so all this happens in a cell, and there are different types of carbons, and there are different numbers of motors per carbons. And this is just way too overwhelming, and there's a feedback mechanism that's best left for the biocardist, biogist experts to do. So, what we do is to look at these motors and the mineral system to study them. First, what does the capacitor do? What does a resistor do? What happens to an RC circuit and so on to building it up on the mineral system? So, we have them in test tube, and the two components, more ideologious and more continuous. You know, well, clean and well-controlled environment. And the tools that I use predominantly is called optical trap. It's basically just a manual version of a tractor beam to move really timing objects around. It's a focused laser spot that interacts with the bioelectric field, such as the glass beams or plastic beams, and it takes advantage of the light property which is in bends as it crosses the boundary of two mediums. So, you can go home and listen. Red jello always jello and shine a laser point here through across the boundary. If you're not shiny straight up, you'll see an angle. You'll see that angle changes as the laser light entry or exit the jello as it crosses the boundary of two mediums that has different industrial direction. Now, if you bend the light, so you can put a trace to have different long, capacitive way that has a different angle that imparts certain amount of momentum in certain direction onto that classical of glass beam. And the method is that the beam will want to be globally confined to the center of the laser beam. So, that's called a laser trap or laser tree-zoo. It's developed by Dr. Roshan when the laser of Spain first came into a reality in the late 70s and used by Stephen Chu to trap mutual items and one of our clients in 1997 and pioneered by Stephen Block to do synchromology studies. Now, let's see. So, the ability to... So, why do we use it for synchromology type of studies? It's because these motors, as Rick pointed out, it's really, really tiny. There about 80 nanometers long, 20 or 10 nanometers across, it's just impossible to see optically. I'm asking you for our assembly label, which is a whole other awesome technique that has new state papers. So, if you want to, when you do these homogenous spatially, you'll stick a number of teeth and then use the laser trap to move it around. Here's a trick that's made by one of my summer students, just moving around a flat beam across the beam inside of a field of view that's superimposed with a micro-base. So, the cross-section, so the length of this is about 20 microns. With the size of that, it's about... if you take a piece of my hand and divide the width of it by five times, that's the cross-section. So, here, there's no noise on this. On this piece, then you cannot see the laser trap, because I put a field of light. I have a field of light on the camera, but you can see that the position of the piece is very nice and steerable. Now, you can cut the piece with noise and bring it to microtubules that are prefixed on the glass surface. The advantage of this is that the interaction between the noise and the microtubules are many walls in the glass. What that means is that the further away it is, the less likely they're going to come together and allow me to keep data. So, if I use the trap to bring them together, then I can observe the interactions. So, if you probably already can see here, I have a field that's coated with any number of motifs that's controllable by me in a self-made environment and positioned above the microtubule as a pre-tip on the glass surface. And we have observed it, so if you can slide it, it's not as big an image. We're using some sort of interference interferometry that's built into the microtubules to measure interference in contrast to my glass surface. So, any standard technique, the result is, the result is that you can see reasonably small bits, such as 20 nanometers that I need to, which is the width of the microtubule, but sadly, in fact, a spherical particle will look half wide and half wide. So, we can watch, we can grab a bead, possessing it onto the microtubule and just watch it go. We can measure velocity, travel distance, and force. This conceptually is exactly the same as what we do in physics 1 labs. You pick a ball, you drop it on an incline or a pecan, and watch how fast it's running down the hill. This kind of technique allows us to make these animations. These animations are not just jumped up, but they'll put together based on what we have learned through optical tracking studies as well as fluorescent studies, at least on the hand overhead, hygromotion. And I saw this in 2006 and when I was moving up I started by school and I fell in love with it. I just wanted to know everything about this from my humanities even though I failed the arts in high school. My score was a steady 33%. But at the time I didn't show me this. So I just wanted to know everything about it and it was the same optical sound as every step you take. And so if you watch the video I think yes. And I'm entertained because what's it called? Now, but last year last year for the longest time I started with my computer just this thing that I walk on. What's the big deal? I was just a sunboard and then we put it on the glass slide and that's it. But last year I sat down and realized that hey, there's some reading and say, hey, this is my computer this thing is not trivial. This has a not trivial structure specifically it's an intricate lattice structure it's made of these yellow and blue units again a silk building block that I put together in a very well-controlled periodic manner it's a tube so these these balls tube balls they line up like a string of pearls and the string of pearls is white and white string of pearls and the string of pearls will line up 13 of them form a sheet and the sheet will close up to form a tube so these are very micro-tubes it's very descriptive it's a micro-tubes its cross-section is it's 24 nanometers you're in hiding but its length can be really, really, really long that is to say up to a minute of memory to your life and it's a period which is amazing what's more amazing is that these things have great mechanical structures so if you're going to hold people find a piece of acrylic pipe and try to bend it it's really hard to bend it you can maybe untie it a little bit it has the same stiffness this module has the same stiffness as these acrylic pipes it has the same similarity as modules so when I look at this I'm like oh great if I need more really small and then go inside and build these larger structures I'll probably make some mistakes and if I make mistakes how does that impact the technologies that work on these structures so that's the question but first let's see whether or not there are these nature-making mistakes that will make imperfect micro-tubules the answer is yes he's amazing studies using steering force microscopy so that they're they're missing two walls and also these lines can merge from two into one so this has these two pictures have completely changed my experience when I eat that corn and you can use your young experience to have a job this time so these two modules merge into one it's really hard to see but in this process in this theory of processing this is very very small it's called lighting effects so these micro-tubules are entry structures they're not very necessarily perfect and what should it be so how does it impact the motion of the model and that's something that has been keeping a very stressful head for the last several months once I realized it seemed perfect so what do we do we use the truck to take a beam that's holding with model positioning on the road to you and just watch it go in this video up here you'll see that there's a red arrow so there's a trap here that traps model use and attracts the beam and it's moving and perhaps you'll be with me that sometimes it causes and maybe it's a trick to the eye so that's real cost somewhere here it also costs so the question is isn't just multiple models that are trading inside the over portable the all micromolecular quality or is this some long line structure of the road that I walk in so how do we differentiate between them so we just integrate it's put at one as a prime starting always from the same position and see whether or not the opposite is at the same position and there are some example traces you see that y axis is position and x axis is time these flat lines indicates pauses not changing positioning with time and if I look at how often the pass along certain direction position on the micromolecular you can see that there are third possible occasions and if I make microtubules in a specific way since that there are more defects in some populations and there are less defects in some populations and compare them in parallel I will see that the probability of pausing the pausing frequency probability that I will see pauses along microtubules of each population is more when there is more defect when I know that microtubules is more imperfect versus less likely to pass when microtubules are more perfect so the more means that all the scatter falls to the other point this line indicates one to one so if there is no relations all this dots will be along this line and there is more probability of pausing along a perfect microtubule you will see other dots on the bottom so this consists of the hypothesis that imperfection perhaps interferes without having more work but these are all symbology I can only speculate so that it seems the check is really good and if I don't sign the check my colleagues will say what is how do you know it's not the other interpretation and it's a really good question so what we do is to look at not only the actual position which is how the modus are moving but the beam is moving along the microtubule but also the most important particular truth of microtubule and from the actual position we can find out where the positive are occurring and look at where the corresponding position of the piece in the particular truth of microtubule and the idea is that microtubule only has certain width if the so it's possible that these policies are really just arising from some sort of artifact of bees somehow interacting with the glass surface because the microtubule is sitting on the glass surface maybe the bees are just running into the glass surface and just like you are driving on a highway perhaps stopping because the car is running into the curb side so the curbs are on the edge of the road so I'm looking at whether or not the policies happen predominantly along the edge of the microtubule and here the long data of the position of the bees that are in the direction of the perpendicular to the microtubule and this little blue distribution is where the policies occur we can do some sort of a theory to filter out the noise which is this red lines so that we can overestimate the width of the microtubule landscape that the road was and still find that the location of the policies in the direction of the perpendicular to the road and doing this we can divide up the landscape of the microtubule in the perpendicular direction into three sessions the middle session the sides and the very edge so if you view this as a subcontinent highway the very edge will be where the curves are so we're testing whether or not the policies are occurring when bees are just not specifically running into the cross surface so if that were true I would see all the policies happening on the very edge probably here are the probability of that of seeing the cross in the middle of the road on the side of the road and on the very edge of the road and what we see is that we have an equal likelihood of causing in any word perpendicular to the road so that means that my policies are not due to the bees are interacting with not specifically with the clusters and that would be huge relief I think we have preferences so we can change the change how we put together these assemblies to have more less effect and the policies that we see are again independent of it's not due to the artifact where the bees are running into the cross surface so we can do one thing which is to reduce the travel distance what I have shown you as far as bees go in with many, many motors so they travel very, very long distance so that means if you think back to the neurons it's long each it's a very long distance to travel so how many will possibly achieve that distance one way is to have multiple motors but what we can dial down that multiple motor is because my medical school is only say 20 microns in field of view so I want to measure some business that's magical if everything will come to the view that I can imagine that I would distance so here we have the bees visiting our medical school our medical school and they like it well and then it falls off when it falls off you normally will see this well defined rule of right hand right feature it's because the interference pattern changes changes once you de-case from that local point and look at the travel distances the take home is that so access is how far the bees travel why access is the population how many of the distance that happens the more crossed it looks like the shorter the travel distance will be and the one year the more extended the distribution looks like more bars there the greater the travel distance will be and the difference is how these two are significantly different and these two are significantly more different what's different about them they are starting with I'm using the same population with bees, so you come here with modus but the only difference between them is that there are different magnitudes so when you dial down the number of modus today has a chance of the bee has a chance of dissociating from the eye so how far the travel is also dependent on the material that it travel on so the two most very short what we find is that imperfection in the load condition matters, just like the medical scale matters for how these modus travel if you have imperfections here you can lead to different if you're watching the cargo transport motion it can serve different type of motion if you have a lot of modus here there is only one modus carrying a cargo if you have a lot of modus carrying a cargo you'll see pause events it will mean to go pause and pause if you have just a few modus carrying a cargo you'll have premature dissociation at the imperfection site so this of course I'm not a biologist I'm only speculating here our favorite speculation is that perhaps imperfection is viewed as the irony perhaps we can view it as one more degree of control in regulating how materials are shadowed around in ourselves maybe we can take advantage of it instead of just go for go we can say alright so if we put all modus on us we can have cargoes there just meandering and pausing and go for example I don't want to start too much but if we want to lead to unloading a cargo from the magnitude maybe we'll have three modus but we'll have the perfection site set and unloading sites so to summarize what I think improbable is accurate nature lucky to every day to be able to really hold on to the nano version of being a cargo car or a phone where we use the phone for and the dating that I say to you today is predominantly analyzed and done by Gui Nian and Gui is good in my life and it's in collaboration with a wonderful theorist and the one for the largest to isolate these modus for us and we're supported by L.A. H James McDonald's foundation I'm using this site collectively I want to thank you again and happy to take part in this just playing part momentum on the plastic beams momentum is it's proportional to a force so the net force is towards the center of the laser focus in a very the way I view it is that the optical trap is a three dimensional spring so the beams are small further away from it the greater the force just like physics one the hook here you measure the force from the spring based on its displacement of the spring the hook is in the relaxed position because just like the spring if you are too far away it breaks down and the optical trap oh yeah it's so there are different ways of doing it you can bundle the micotubes together you can then you can ask in parallel ways you can ask one another in the same orientation in the same direction in the same orientation or opposite of other locations you can sometimes say I'm intentional when you make them so the two micotubes is the one code, the other version one code, the other version is actually the team's school or you can make cross sections that's actually very interesting I used to be in the cross sections and the older one was looking on the armchair cross last question there are proteins and bacteria these are all proteins they are the state that has been good both of the nature proteins these are active proteins so let's thank Jing again