Welcome back to another session of Dentistry and More. Today we have anemia, so we are focusing on classification and oral manifestations. So we are now touching the treatment parts or the general symptoms, but we are mainly focusing on the clinical variants of anemia and that's oral manifestations. So anemia is a condition where the RBC, the number of RBC is less than normal, okay. So that is known as anemic condition. So we have classification based on its morphology and etiology and clinical variants. The morphological classifications are the normalcytic, normalchromic, normalcytic hypochromic, normalcytic hypochromic and microcytic hypochromic. It is based on the size of RBC and the color of RBC. So the size is nothing but the MCV that is mean copiscular volume. So MCV is mean copiscular volume and the color is represented in MCHC that is mean copiscular hemoglobin concentration, MCHC. So in the first classification that is normalcytic, normalchromic, the size is normal and the color is normal, whereas a normalcytic hypochromic, so here the hypochromic that is size is normal but the color is less or defective. Next one is a macrocytic hypochromic and macrocytic the size is large and the color is less. Microcytic hypochromic, the size is small and the color is less. So that is based on the morphology, okay. Next we have etiological classification. So it is based on the etiology or the based on the study of course or origin. So we have hemorrhagic anemia that is due to the loss of plate, it could be acute loss in accident or also could be due to a chronic loss and hemolytic anemia, hemolytic anemia there can be extrinsic hemolytic anemia and intrinsic hemolytic anemia. The intrinsic one are thalassemia and sickle cell anemia, these two are intrinsic type whereas extrinsic type we have many reasons like liver failure, renal problems, liver failure, renal issues, then burns, hypersplenism, hepatitis malaria, a pencil in sulphur drugs problem, poisoning by late call, presence of rich factors or autoimmune diseases like rheumatoid arthritis and ulcerative colitis and all these cases there are extrinsic reasons of hemolytic anemia, there will be hemolysis. So the blood loss for the RBC will be less. Next is a nutritional deficiency anemia where the anemia is caused due to the nutrition problem. So mostly it could be due to iron or protein or B12 or folic acid, all these are required for normal production of hemoglobin. So when this iron or protein or B12 or folic acid is not there, the hemoglobin production will be impaired. Okay, so that is nutritional deficiency anemia, after that we have aplastic anemia. Aplastic anemia is bone marrow disorder and lastly we have anemia of chronic disease, the disease due to rheumatoid arthritis, tuberculosis, chronic renal failure or Portuguese disease. So that is etiological classification. Now we have the most important one that is a clinically significant variant. So anyway it comes under the etiological classification but we are focusing mainly on the iron deficiency anemia, it comes under nutritional deficiency and pernicious anemia or adesence not disease, adesence anemia. It is also a nutritional deficiency anemia, regular plastic also nutritional deficiency anemia, sickle cell anemia is hemolytic anemia, talacemia is also hemolytic anemia. They are due to the intrinsic factors and aplastic anemia is due to the bone marrow disorder. So the first one is iron deficiency anemia is the most common type of anemia. So it develops due to inadequate availability of iron for the hemoglobin synthesis because for hemoglobin synthesis it requires iron. So when iron is not there the hemoglobin synthesis will be impaired and it results in iron deficiency anemia. And here the RBC will be microcytic size will be less and hypochromic the color will be impaired. So it will be impaired or less MCV and less MCHC. So the causes of iron deficiency anemia it is due to the loss of blood or the decreased intake of iron or the poor absorption of iron or over consumption or our requirement of iron. The normal iron is present but body needs more iron for conditions like pregnancy and growth. In these cases body needs more iron. So in those case the hemoglobin synthesis will be impaired when there is poor absorption it will be impaired when there is less intake or loss of blood. It will results in iron deficiency anemia. So what are the features of iron deficiency anemia one is brittle nails and brittle hair then the spoon shaped nails which is known as scolonegias then there will be atrophy of papilla in the tongue. Sorry papilla in the tongue will be atrophied and there will be dysphagia that is difficulty in swallowing. This is dysphagia. Next is a pernicious anemia or Addison's anemia. This anemia due to deficiency of vitamin B12 it is due to the atrophy of the gastric mucosa because of autoimmune destruction of parietal cells. Parietal cells destruction is happening. So the gastric atrophy so destruction of parietal cells results in decreased production of intrinsic factor. Okay so there will be decreased production of intrinsic factor intrinsic factor production will be decreased thereby there will be poor absorption of vitamin B12. There will be poor absorption of vitamin B12 which is actually the maturation factor for RBC. Okay this B12 is a maturation factor for RBC. So this is connected parietal cells are destroyed intrinsic factor is less produced so there will be poor absorption of B12 which is a maturation factor for RBC so there will be less RBC production. So these RBCs are larger but immature with almost normal or slightly low hemoglobin level. Okay so this pernicious anemia is common in old age and it is more common in females. Okay female predilection is there and it is associated with other autoimmune diseases like disorders of thyroid gland and Addison's disease. Characteristic feature of this type of anemia are lemon yellow skin.  Ataxia is nothing but muscular incoordination. So that was about pernicious anemia. Now let's move to the megaloblastic anemia. Megaloblastic anemia is due to the deficiency of another maturation factor known as folic acid. Here the RBCs are not matured. Okay so the DNA synthesis is also defective so the nucleus remains immature. The RBC will be megaloblastic and hypochromic. So features of pernicious anemia also appear in this case but there will not be any neurological symptoms because neurological symptoms are present only with the pernicious anemia. Okay that was about megaloblastic anemia. Now let's move to the sickle cell anemia. Sickle cell anemia is an inherited blood disorder characterized by sickle shaped RBC. So it is also called hemoglobin SS disease or sickle cell disease. It is commonly seen in people in African region and it is sickle cell anemia is due to abnormal hemoglobin called hemoglobin S. So in this alpha chains are normal but the beta chains are abnormal. Okay so hemoglobin has alpha and beta chains but the beta chains are abnormal. So RBCs are like more fragile and which leads to hemolysis because it is attaining a sickle or crescent shaped. So in children this hemolyzed sickle cell aggregate and block the blood vessels leading to infarction that is a stoppage of blood supply and this infarction is common in small bones. Okay so this infacted small bones in hand and four crystals in varying length in the digits. This condition is known as hand and foot syndrome and jaundice is also common in this children because the infarction is seen in small bones mainly the hand and foot. There is a digits only seen the digits so it is known as hand and foot syndrome. Next we have thalassemia. Thalassemia is also known as churlis anemia or mediterranean anemia is an inherited disorder characterized by abnormal hemoglobin. It is more common in Thailand and to some extent in mediterranean countries Thailand and mediterranean countries. So this thalassemia is of two types one is alpha thalassemia and next one is a beta thalassemia. So in normal hemoglobin the number of alpha and beta chains are equal. In thalassemia the production of these chains become imbalanced because of the defective synthesis of the globin genes. Okay so defective synthesis of globin genes. Okay globin genes. So this causes the precipitation of these polyprotein chains in the immature RBCs leading to disturbance in the erythropoiesis. So we have alpha thalassemia which is commonly seen in fetal life or infancy. In this alpha chains are less absent or abnormal or defective. This leads to defective erythropoiesis and hemolysis. The infants may be stillborn or may die immediately after birth whereas a beta thalassemia is more common type which is seen in the adult people where the beta chains are less defective or absent. That also leads to defective hemolysis and erythropoiesis. The next one is aplastic anemia. Aplastic anemia is due to the disorder of bone marrow that is red bone marrow. This bone marrow is reduced and replaced by fatty tissue. This bone marrow disorder occur due to the repeated exposure of x-ray exposure or the toxins like benzene radium or due to the tuberculosis or due to the viral infections such as HIV infection or hepatitis. So that was all about the classification of anemia. We have the first classification was about our morphology then the etiological classification. Then we changed the etiological classification into clinical significant variant. The iron deficiency, phonetious anemia or reticence anemia. Third one is migroglastic sickle cell anemia and thalassemia. Lastly the aplastic anemia. Now what are we going to study is about the oral manifestations. In oral manifestations there are some common symptoms. It includes paler, common oral symptoms. It is common for most of the anemic condition that is paler of oral mucosa. Then glossitis or glossodynia where we taste disturbance. These are common symptoms. Then regarding the aplastic anemia it may increase susceptibility to oral infections. There will be oral infections which may require antibiotic prophylaxis or mouthwash because there are chances of spontaneous or uncontrolled gin-chival bleeding. Gin-chival bleeding. That also we have to deal with anti-fibrinolytic medications or avoidance of intramuscular injections and block anesthesia. So we need to be very careful with the aplastic anemic patients because there are chances of infection and bleeding. Whereas a pernicious anemia patient. Pernicious anemia. There will be ankylalkylitis, then mucocytus and thresh oral ulcer. All these will be for pernicious anemia. Ankylalkylitis mucositis, thresh and oral ulcer. Then regarding the sickle cell anemia. The main contraindication for dental treatment with sickle cell anemia patient is routine care during a crisis. We need to schedule dental appointments during the morning with minimum treatment for a patient with a brief visit. We need to prescribe the brief visit in morning. Then we need to we need to prescribe CNS depressants very cautiously. Use of acetaminophen for treatment of pain because salicylates may induce acidosis and avoid elective surgery such as removal of asymptomatic impact at tooth. And then district monitor prevented dental care at routine follow of visit. A three month recall may be necessary in some cases. So that was about we use oral manifestations. It was basically common oral symptoms. Then we have symptoms of pernicious anemia and the precautions we should take while dealing with a plastic anemia and sickle cell anemia. So that's all for today. We covered the classification and oral manifestations of anemia. So it was a lengthy session but the questions are mostly asked sometimes the clinical variants that is end efficiency anemia pernicious mycoblastics sickle cell palacine or plastic anemia along with the oral manifestations. Sometimes description will be asked in general medicine. So anyway understanding anemia is very much essential not just for that's all for today. I'll come up with a new topic in the industry and more. Thank you.


Hello people of the internet, my name is Johnny, welcome back to yet another FNAF news video and we got a whole bunch of very exciting stuff to talk about today. A brand new plushie wave from YouTube's just got announced with a whole bunch of amazing characters. The FNAF movie has gotten some pretty big updates, Scott responding to the leaked trailer, a poster coming soon. And finally, after so, so much time of waiting, an official ruined DLC teaser has just been released. Well, let's not waste any more time if you are excited for all the news, don't forget to scroll down, tickle that subscribe button if you haven't already. And of course, before we move on to the main heavy hitters, we had a few smaller topics to talk about first. First up, we got a brand new security breach shirt coming from Hot Topic. It's got a tie-dye wash design with a large graphic of a trading card showing Glamrock Freddy. With the text, are you ready? Printed on the back for some reason, I guess. I honestly really enjoy the art of Glamrock Freddy on the front, though the rest of it is a little weird. I don't know why it's a trading card, I don't know why the text, are you ready, is just randomly on the back in a pretty basic font. Yeah, brand new shirt from Hot Topic, let's move on. Next up, we got the Five Nights at Freddy's Ticket to Fun Ephemera Kit. I still don't know if I'm pronouncing that right, I don't know what that means, but unfortunately this kit has been delayed by almost a full year, actually. Originally, it was supposed to come out October 17th, but it's since been delayed to August 6th of 2024. And if you don't know what this kit is, it's basically, it appears to be an activity guide with a whole bunch of in-universe items and merchandise from Freddy Fazbear's Pizza for fans to solve.  Going from October 2023 to August 2024 is a massive delay, so hopefully they're cooking up something extra special with this kit. Moving on now to U2s, we technically have a brand new Foxy U2s releasing pretty soon, and that is Foxy Fusion Z Gamer Edition. The official second figure for fellow FNAF Tuber Fusion Z Gamer, this one looks a lot more like his official profile picture he uses across YouTube and Twitter and all his social medias. And because it resembles Foxy so much, he actually got this officially licensed from Scott himself, it has copyright Scott Cawthon on the bottom. So I mean, technically once again, an official Foxy U2 is coming out pretty soon, I think it looks absolutely amazing, it comes out May 16th for only two weeks. And speaking of U2s, also on May 16th for two weeks only, they're releasing a brand new wave of plushies. Doesn't seem like this has a certain theme with this wave, but it has Ennard, The Mangle, Helpy, Glitchtrap, and Circus Baby. All of these plushies I'd say look absolutely fantastic, I'm especially a fan of that Mangle and Glitchtrap plushie. They both just look so accurate to what the characters look like, especially Mangle, they knocked it out of the park with that one. It was actually designed by community members Spooky the Kitty, so huge shout out to them for making such an amazing design. Next up, we of course got to talk about the brand new update that Security Breach TV just received today. You may remember not too long ago, an update for the site was actually leaked. Seems like Steel Will was trying to update it privately, but accidentally it got showed off to the public, so we knew something was coming. And lo and behold, this is what the site looks like today. As you can see, it is the camera display monitor, and there's a whole bunch of creepy text we're going to go over. If you want more information and speculation on what this device exactly is for The Ruin DLC, I made a whole video about it, again, it'll be linked down below. But just going through, there's a few secret texts we've got to look at, such as something is coming, something is near. Of course, we're referring to the FNAF DLC Ruin. For Security Breach coming out this year, it's going to be very exciting. We got two links to Steel Will's Twitter and YouTube pages. Now interestingly enough, these links are mirrored, very similar to a feature we see in one of the Princess Quest minigames. I saw a lot of people speculating about that. As of right now, it doesn't seem like any video or GIF or some form of media is playing in the monitor right now. But just like Security Breach TV was originally, I'd assume this is going to be updated bi-weekly or maybe even weekly in this case. Probably with a few more teaser videos to show off for new characters and settings and stuff like that for the DLC. Exactly what Freddy and Friends on Tor did for the main game for Security Breach. It's going to be very exciting, so definitely subscribe to the channel just in case this does update. You definitely don't want to miss out on that. And now let's finish this video off by talking about, of course, the upcoming FNAF movie being made by Blumhouse and Universal. Now, you may remember, unfortunately, pretty recently, one of the trailers for the upcoming film got leaked online. And later on in the day, Scott Cawthon actually responded to the leaked trailer, so let's go over that quickly. I wanted to comment on this before the end of the day. I got emails about this early in the day but was at an amusement park with my kids and was unable to see what had happened. I tried to ignore it and enjoy my day, but I was really, really disheartened. I know that Blumhouse and Universal and me, too, have all worked very hard to make something really exciting to share. So the thought of a first look being spoiled was frustrating. And I was really dreading coming home to see what all had happened while I was away. To my surprise, though, I got home and I found a lot of YouTube channels refusing to do videos on it. Twitter channels refusing to repost it, countless members refusing to watch it, and moderators taking a stand against allowing discussions on it. It's really difficult, if not impossible, to prevent people from trying to spoil things for everyone else, but it was really encouraging to see the fanbase pull together and push back against it. For those of you who resisted watching it, I think you'll be much happier when you see a finished product that is edited and polished with VFX and proper sounds. So, to the fanbase and to all of the Twitter accounts, YouTube channels, moderators, and other people who push back against this, thank you. I started my day at humanity, negative one, but ended the day at humanity, plus 100. Speaking like a true redditor at the end of that comment, Scott, but yeah, basically the comment was pretty uplifting, more so just thanking the fans for not watching the leaked trailer, which is totally understandable. Something I do want to point out is that apparently, according to Scott, they're still actively working on the trailer, working on VFX, working on proper sounds. So even what was shown in that leaked trailer isn't even the final product, which is insane. Moving on now, because we do have other forms of marketing we got to talk about with the upcoming films, specifically a poster coming soon, because recently the FNAF movie was added to Blumhouse's official site for their upcoming films. Not much new information, just the title, release date, the actors and actresses starring in the film, of course Emma Tammy the director, the people who wrote the scripts, though off to the left side you can of course see a poster coming soon template. Now, honestly, it's a little unclear whether or not we should take this as official confirmation. Again, it might just be a placeholder until an official poster actually does release. But I still think it's a pretty interesting thing to note because, I mean, frankly, what kind of do for a poster at this point, you know? So hopefully we can get that pretty soon, but it also might release a bit sooner than we might expect, because it might be releasing with the first teaser trailer set to release literally any day now, because the first teaser trailer, set to be only 53 seconds long, just got rated 14A in Canada, meaning it's suitable for viewers 14 and over. It just got rated today, as you can see May 15th from the screenshot. So quite frankly, it could release at any point, I'd say within this week or next week. It's definitely coming very soon. Earlier today we did just get the final trailer for Universal's upcoming film, Fast X. So hopefully pretty soon they're going to be releasing this teaser trailer, which like I said, I know it's not a full length trailer like the one we got leaked, but at least it'll give us something to chew on, you know? But that is going to do it for all the FNAF news today. Tell me what are your thoughts on all the FNAF movie news, the brand new Ruin DLC update. Are you going to be copying some of the new plushies from YouTube? Everything I'd love to know your thoughts on in the comments down below. Thank you so much for watching this video, and I'll see you all on the flip side. Goodbye.


Last session of today. The first speaker is going to be Francesco Giasopto from Colón Normales Superiores de Pisa. Francesco, what do you want? Thanks, Alfredo. Good afternoon, everyone, and I wish, first of all, to thank you for having invited me here to present some brand new results on thermal transport in superconducting systems. So today I will talk about a very basic structure in proximity systems that we named the thermal superconducting quantum interference transducer, so the T-squint. Let's see the outline. So I will start the talk introducing some motivations and the mission of this research. Then we'll introduce some background about proximity effect in hybrid systems and the impact on the density of states. Then we'll show what is the concept of the electrical superconducting quantity of proximity transistors and what is its predicted thermal behavior, okay? So I will show the realization of the thermal script, so how it is realized, what are the expected performances, the results and comparison to theory. In the last part of the talk, I will show how it is possible to use one of such kind of thermal transistor. In order to implement thermal memory cell with topological protection. So the argument that I am treating now deals with what is known as coherent power electronics, so the complementary of coherent electronics. So the idea is to phase manipulate and master, let's say heat transfer in a fully solid state environment and to provide the original novel approach to realize another thermal device like heat transistors, splitters, diodes, refrigerator and exotic quantum circuits that take advantage of these above mentioned building blocks in order to enhance the functionalities. Last but not least, to address and understand some fundamental problem in physics related to energy and heat phenomena. For instance, query dynamics, heat interference, time-dependent effect, noise, the problem of the coherence, quantum thermodynamics, and so forth so on. So in a nutshell, so the main goal of this caloritronics at the nanoscale, so mesoscopic caloritronics, is to develop quantum technology for managing heat in nanoscale circuits. So the physical basis of phase current caloritronics can be easily explained with the aid of this very simple cartoon on the top. So since we are dealing with solid state systems, we will be interested in quasi-particles and electrons and phonons, and so the phase current caloritronics deals with envisioning novel physical mechanisms which are able to control tend to the mesoscopic quantum phase, typical of superconducting circuits, the manipulation of the heat current flowing from hot, let's say, electron reservoirs to colder electron reservoirs. Toward the sense, we have identified basically three more relevant routes in order to manipulate heat in nanoscale systems. So the first one is, the first toolbox is basically the exploitation of the Joyceon effect, so superconducting tunnel junction, a particular temperature bias, the Joyceon tunnel junction, where we have an important component of the heat current which becomes phase dependent, and thanks to this we can realize quite efficient thermal modulators. Then there is another interesting route that is that one based on the proximity effect. So the idea is to use the proximitized layer, so let's say, novel metal of superconductors that have acquired the superconducting correlation thanks to the intimate contact with the nearby superconductors, and so this, let's say, S-prime artificial superconductors, they are characterized by interesting properties in the sense that they are key properties like the denser states, the electron phonon coupling, the entropy, the specific heat, they become all phase dependent, okay? So they can be, in principle, manipulated thanks to the phase. Then there is the third route that is the middle, that is basically the study of how is it possible to control the heat flow between body residing at different temperatures that possibly are not even in galvanic compass, so maybe they are just coupled to quantum circuits, so quantum resonators in the form of squid or whatever, and then so to use basically the electron-photon interaction. So by tuning the electron-photon interaction, in principle, it's possible to control the amount of heat flowing from, for instance, the left reservoirs to the right reservoirs. So now in the following, I will show the first effective implementation of a proximity-based thermal quantum transistors that allows sizable temperature modulation implementation of this first memory cell. So as I was saying, we are dealing with metallic contact between a normal metal and superconductor, so where this is, I mean, this end part can be a short, let's say, metallic piece or even a short metallic superconductor. And we know that in this system, I mean, the charge transport occurs thanks to under-reflection, it's the process for which, I mean, an electrical incident from the normal metal for energy smaller than the superconducting gap is retro-reflected along the incoming electron time-reversed path while at the same time it could prepare condensate the superconductor. So this mechanism allows the propagation of charge, let's say, from one part to the other, but not the propagation of energy, okay? So below the gap, basically, under-reflection prevents the flow of heat current from one side to the other. So now, I mean, if we connect such two of these blocks on the left to realize an SNS junction, for instance, so the electronic correlation due to under-reflection will extend from one side from the other side from the left and right inside the normal metal, and so this will, if they overlap sufficiently, they will realize a novel kind of state inside the normal metal, say, the normal resonator, okay? In particular, I mean, they create the so-called undrived bound state which are responsible for allowing the flow of dissipation and superconduct across the system. So typically, I mean, the system that we are using, at least what I'm going to show are metallic systems, so diffusive systems, disorder, maybe disorder metallic-themed films, and they operate in diffusive regions. So in quasi-one-dimensional geometry, diffusive means, indeed, that mean-free path is much smaller than the characteristic length of the system, much smaller than the phase in length. Relevant parameter in this system are the diffusion coefficient, the superconducting gap of the superconductors, phi is the microscopic phase of the other parameter, and then there is one important scale, energy scale, that is a tau less energy, that is basically the typical, let's say, energy of a disorder coherent conductor. So a system like this can be very successfully, I mean, treated from the theoretical point of view with, let's say, quasi-classical equation. In particular, one class of this is called the Housel de l'équation. This is a sort of, let's say, diffusion equation that allows to calculate some key properties, like, for instance, the denser states in this normal metal. Not only, I mean, the super current spectral density and so forth, so on. We are, in this moment, particularly interested to describe the denser states of the metal because this one will be absolutely relevant for the calculation of the heat current flowing in the proximity metal. So the key properties of the denser states are that is a symmetric function of the energy and possess a gap, so a forbidden region for quasi-particles that can be controlled thanks to the macroscopic phase of the two superconductors, okay? So by changing the phase difference across, let's say, the junction, the SNS junction, we can control the amplitude of the net gap from the maximum value that depends on the length of the junction to the meme that is almost zero when we are at pi. So it's interesting, first of all, to understand what is the impact of the proximity effect on the denser states of the proximity metal of the superconductor. So here on the left, there is a calculation from Kuevas and coworkers showing the denser states versus energy as a function of the length here on the upper panel and the position dependence in the lower panel. So in the upper panel, we see that by changing the length of the junction, so when the junction is very short, with respect to the coherent slender superconductor, then the system behaves almost like a BCS superconductor. So it means that the interlayer acquires the same, at least theoretically, I mean, in this limit, the same properties as the parent superconductor which is giving rise to proximity effect. Then by making the junction longer and longer, what happens is that this artificial superconductor becomes weaker, so the mini-gap becomes smaller and smaller, and eventually when the junction is very long, I mean, this tends to the denser states in the normal state. Is it possible to see what does it happen as a function of the position? So, I mean, if we move along the wire, basically with the denser states as a strong position dependence, okay? Although the gap is position independent. So even more relevant is how we can control at will the amplitude of these denser states, okay? This can occur thanks to the phase dependence. So for instance, if we suppose to change the phase difference across the superconductor from zero to pi, we can see clearly that we can continuously change the amplitude of any gap from the largest values up to zero when, I mean, we close completely and the system resemble a normal metal. Now, I mean, till now I have shown what is expected. So let's see what was shown. So this is a very nice experiment that dates back to 2008 from the Sackley group where they realized aluminum, silver, SNS proximity squid, several different devices with different length of the junction, and they probed with the STM the denser states in this proximity metal, let's say, as a functional position and for different length. And so for instance, if we look at the upper, sorry, the upper left ring that possesses the shorter junction, we see that there is indeed a very nice mini gap developed within the wire. And we see the amplitude of the mini gap is almost constant moving along the wire as we were showing before. Then increasing the length of the wire in another screen, we see that there is less and less pronounced up to the very end where, I mean, for this ring here, we have a much reduced effect by some induced coloration inside the SNS rings. So this is not the full story. The full story is that then it was possible they have shown for the first time that it's possible to manipulate this denser state with the phase. So since this proximity metal is embraced in the ring by changing the magnetic flux, piercing the interferometer, it's possible continuously from zero to pi to go from a situation where the mini gap is fully developed to a situation where at pi it's fully closed and then if you want, you go back in a fully reversible shape. So here on the right, there is a comparison. For instance, just to recall the effectiveness of the quasi-classical theory for treating this system, comparing the experiment, okay, a differential conductance that they obtain as a function of different fluxes piercing interferometer and the comparison with the theory. So the agreement is indeed very nice. So starting from this idea, we almost 10 years ago, maybe even more, we started to work on the possibility of implementing, let's say, a fully solid state, a device-like version of this experiment with the STM. So the idea was indeed to obtain artificial superconductor times the proximity effect and the phase control to the magnetic flux and then the detection through tunnel junction implemented directly in the proximitized weak link. And this, in principle, can give rise to very high sensitivity for flux detection. So this is the idea of the superconducting quantum theory as proximity transistor. So we have this sort of AC squid with the proximity metal in the middle and then there is the tunnel junction connected to this green part that allows to make the tunnel spectroscopy. And so this has been proven in different sources, let's say, to be a very nice interferometer with very nice and very low, let's say, flux noise. So these script setups have been realized in several shapes and materials. Typical aluminum is used as a material for the ring because it possesses pretty low kinetic inductance. And for instance, in this case, the probe can be even normal metal of superconducting. And as we are saying, the weak link can be normal metal or even superconducting. So each of them has its own advantages and drawbacks. So if we look, for instance, at a script with an end probe, I mean, when they say the nanowire is fully proximitized, it will make the spectroscopy to the junction and the standard junction is normal. So the system will evolve from a superconducting like SIN junction to NIN junction when we close the mini-gap, so a fully straight resistive line. And so, and this is the corresponding threshold conductors on the bottom. Whereas for a superconducting probe, this will evolve from an SISS prime junction where we have, in addition, the presence of the supercurrent around zero to a NINIS junction when we close the mini-gap of the superconductor. So this is just to make some history of the properties of this interferometer, okay? So then the question was, okay, now that we are more or less understand how we should behave an electrical interferometer based on proximity effect, the question is, it is possible to use this for very effective heat current manipulation nanoscale circuits, okay? And the answer is yes. So the idea is indeed to create the heat counterpart, the thermal counterpart of the circuit, okay? So a thermal superconducting quantum interferometer proximity transistor, and this is something I would say very, very, very simple to conceive. So as here in this sketch, we have just the superconducting loop with the link in the middle. On the right, we have a normal metal of superconducting probe. They reside at different electronic temperatures. The idea is to study the heat current flowing through the system. So a very simple, let's say, basic understanding of the devices can be gained if we sit and if we suppose to be in the linear response regime in temperatures. That means that the temperature in the two system is the difference between the two temperatures is pretty small with respect to the average temperature of the system. And so in the linear response regime, we can define the thermal conductor of the system. Basically is the convolution of the density of states of the proximity nanowire, the probe injunction, and the squared of the energy, okay? So, I mean, if we study the thermal current, the thermal conduction to this system, here on the left, on the right, top panels for end probe and an S probe, we see that, I mean, the thermal conductor here is shown as a function of temperature for different values of the flux. So we go from the blue, deep blue, where the gap is fully developed, and we see that for low temperature, there is a dramatic retaction of the thermal conductor with respect to the normal state. This is expected because for very low temperature, I mean, it's very gaped. And so, I mean, this is calculated for in the regime of short junctions. So the density of state is almost that one of a BCS superconductor. And then by changing the flux, we just reduce the mini gap inside the proximity wire. So the system will tend to conduct more heat current in the system. But you already see that in a system like this, there is a suppression in principle of several orders of magnitude between close gap over gap. Something similar happens also for a superconducting probe that is here on the right that, of course, may provide an even more isolation, but the drawback is that since one of the two electrodes still is always superconducting, so this means that at the end, the full heat transport in the system will be limited by the remaining superconductivity in the superconducting probe. It's also important to analyze what does it happen as a function of the length. So as we are saying, the longer the junction, the less proximitizes the junction, so the less modulation in term of heat we can provide in the system, okay? So in principle, if we want to operate one of such interferometers, the idea is to realize a system with a very short junction, the shortest possible, so a tau less energy that is large with respect to the gap or comparable to the gap, so that we can achieve this efficient suppression like in the dashed line that corresponds to the very short junction limit. So the idea was indeed to realize a sweep very short with a short junction of the order of a few coherence length at most and then to prove it is possible to achieve this effective manipulation of the heat current. So on the left top, we have the thermal squeeze structure scheme, okay? So let's say this ring embracing in this case a superconducting weak links, so it is an aluminum-aluminum contact. So it's a very short and narrow wire. The wire is typically 400 nanometers. The idea, I mean, if we look at this structure here, if we suppose to heat the normal metal electrode that the red one that is connected to the script, that is a normal electrode, as we are saying, because it provides advantages. If we suppose to give a fixed power to this electrode here, then we study how it does evolve the heat transport across the tunnel junction versus the mini-gap existing in the proximity wire, we see that indeed by reducing the mini-gap dramatically increases the power transfer, and the heat power transferred from the red electrode to the rest of the structure, okay? So here, when we go to 80% reduction in the mini-gap, it basically corresponds to almost four orders of magnitude of variation. Basically, this is given by the amount of residual states, let's say the Dynes gamma inside the system, okay? So a very nice junction or tuning of the environment, of course, to reduce the residual state will be beneficial in order to have this on-off state for heat. So here on the bottom is just a pseudo-color image of one of such structure that we realize with conventional electron billetography, three-angle shadow-mask evaporation, and basically, you see, I mean, the face of the loop, the interferometer, in the middle, we have the small superconducting aluminum and wire, then there is connected aluminum manganese probing electrode, and then we connect additional aluminum probes here on the right, operating as heaters and thermometers in the structure. So what we do basically is that we heat the system, we impose some stationary, let's say, power in the system, and then in real time, we measure the electronic temperature established at the state in this normal metal electrode as a function of the flux appears in the interferometer. So for a given power, of course, what we expect that change in the mini-gap will change the amount of heat flowing out outside, and we can make a modulation of the temperature thanks to the, let's say, control of the spectral properties of the metal, because, I mean, what I didn't tell before is that till now, I mean, we were pretty effective in controlling heat current, but thanks to the interference of Johnson-Cutting, okay? So here, I mean, in some sense, is not really the first time, but maybe the first time is pretty effective in the way of controlling the spectral properties of a metal in order to control the several key parameters, thermal and electric parameters. So in the case, what to expect in the electric behavior of the thermal script? So here is shown. So here, so we have just to resemble a few concepts. I mean, when still we are dealing with the superconducting weak link, in the case that superconducting weak link is short, I mean, it possesses a sinusoidal, sorry, I'm making a mess, a distorted sinusoidal current phase relation, okay?  And so this means that we apply a voltage bias across the script as we see here. We can basically, I mean, for fixed voltage, the current will be a continuous function of the phase. So you see that when the mini-gap is closed, there is low current and then we will maximize that for half integral values of the flux. Here we are in a different regime where our nanowire is longer than the superconducting current slank is of the order of six, size zero. So the current phase relation is already intermediate regime long is becomes completely hysteretic, sorry, becomes hysteretic. And this means that because basically there is the nucleation of a slip in the structure. So I mean, and these two branches that we see this, you see it is completely straight, so the path depends on if we are moving forward backward in the system. And these two branches correspond to different, let's say topological phases or let's say different branches characterized by the different part of the logical index that represent the phase of, let's say, the winding number of the phase, okay? And so, I mean, in this case, what is interesting is that what is expected that basically the current for fixed voltage will reflect this exactly this hystericity, okay? So first of all, I mean, we can characterize the IV characteristic of the script and showing that it can possess basically 50% modulation and indeed also the current behaves as a sketch here. So there is this jump in one side of the other side going backward and forward in the system. So now let's see what is the expected behavior. So as we are saying, I mean, the experiment is performed by heating, giving some power to the central part and then simply by reading the electronic temperature and equilibrium. So what is expected that when there is, there are integral values of the flux, we can close, sorry, completely open the mini-gap so there will be stopping of the heat current flowing from the normal metal to the weak link and for some integral values, there will be a larger flow. So this is shown here in this temperature versus flux. You see it reflects in the same way what we are saying before. So for zero, there is integral values of flux. There is a stopping of heat. So the island is more heated. There is a maximum temperature. And then when we go around half integral values, there is this hystericity thanks to the presence of this, let's say, multi-valued current phase relation in the system. I mean, we have characterized the valve or let's say the transistor for different injected power. So from low to high, so you see that increase in the power increase at the average level because we are increasing the temperature in the system. And then this sort of butterfly that presents the hysteresis is almost or less constant. So what does it happen? Indeed, if we collect just the delta T, that is the maximum duration temperature, is that we can achieve a maximum of 16 millikay of swing in temperature that corresponds to 1.7% at depth of temperatures. And that the average temperature, indeed, increases with the power as expected. Here on the right, there are just a comparison with a simplified thermal model that takes into account the main relaxation mechanism, escape heat escape mechanism present in the structure. And it is able to provide, I would say, your reasonably good behavior that is in a reasonable agreement with the system. So let's see what is the impact of the bus temperature. By increasing the bus temperature, it's interesting to see how does it relax. So we see a low temperature by increasing up to 800 millikelvin. I mean, the effect is present. And basically, the hysteresis reduced. And also, the swing is reduced. The swing is reduced thanks to the increase of the electron phonon coupling in the normal metal electrode. And the width of the butterfly is reduced because by increasing the temperature, we reduce the proximity gap. So this increases the coherence length. And so the junction goes towards the limit where it's less hysteretic. And so we can see here that already the delta T, so the swing in temperature for temperatures of the bus approaching 1K, is still around 20% of the maximum. So we can say that up to 1K is possible to observe the behavior of the reduced of our system. So now it's just the very last slide. I want to show the first implementation of a thermal memory. So as we are seeing, the temperature, since it shows this nice hysteretic behavior, it can, in principle, be used as a memory. So these two different branches are completely, in some sense, separate. So if we think to fix for some fixed reference bias, let's say flux bias, at some point, we can define two positions in this temperature to flux phase diagram. So we have 0 and 1 that correspond to different states. So they can low temperature and high temperature. And then they can encode information. So 0, 1 are categorized by different topological index. And that is discriminated by the parity of the winding number of the phase. So this means that by giving a pulse on the positive direction, for instance, we can make the writing process. And giving a negative pulse, we can go on the other state, erasing. So if, for instance, here, the readout is given for some fixed power, you see a positive bias, we achieve the state 1. Negative bias of the pulse, we achieve the 0 state. This can be repeated continuously with very repeatability. We have then analyzed the stability against flux fluctuation, adding some oscillations on top of this system here, modulation of the flux, in order to show that the system is very stable indeed. And then what's interesting is that this memory shows a fully non-volatile behavior. So this means that we can put the memory in one state. And then we can depower the electrode. And then we can repower the electrode, obtain the same state. And this is because there is this protection. For we, the memory is just given by the circulating current in one sense or the other. And these two states are protected by the very large barrier that prevents stochastic phase leap from one side to the other side. So here, this non-volatile behavior is shown here, as you can see. So when we give power to the system, heat in power, we read, in this case, 0.  So photo on, I mean, in time, this is very stable. And I mean, the different temperature of this memory is apparently pretty low. It's 4 millikelving, but I mean, it's very repeatable in time. So in some sense, it's an interesting concept. OK, so these are just the conclusions. So we have demonstrated phase tuning of thermal properties of nano-size superconductor. And we have shown a sizable temperature variation in the high flux to temperature transfer function with the operation up to 1 Kelvin. We have shown probably the very crystallization of the first tunable thermal memory where the logic state can be encoded by the temperature that has shown robustness against fluctuations and non-volatility. So at the end, I believe that this object can be relevant, or at least is the first step in order to realize some technological application, like energy harvesting, general heat logic architecture, thermal amplifiers, or non-volatile data storage units, and the end, maybe also heat engine. So with this, I have concluded. And I thank you very much for your attention. Thank you, Francesco, for this very interesting talk. And there is a question there in the back. Yeah, thank you, very interesting results. So I have a question about the last data that you showed about the memory encoded in the persistent currents. And I was looking at the X scale and its seconds. And I can tell you that we see something on the time scale of hours, which I'm wondering if you also see. So on the time scale of hours, we see that ionizing impacts in the substrate actually reset these currents. I agree with you, if you do the phase-slip calculation, these persistent currents, they should live forever. Yes. But they don't. And I think what we have concluded by going to Gran Sasso under the mountain, where they do live forever, where forever means three days. Cosmic rays. Yes, there. Well, ionizing radiation. But mostly, you want. So do you see that? Because here, the time scales are still under long, but they're just tens of seconds. Do you see something on the hour? Yes, this is tens of seconds. We have another experiment where we measure the electrical part where it is several hours also. And you don't see anything unexpected? No, we don't see anything. No. You don't see anything? No, no, no. Well, maybe there is a reason. Because the energy barrier for this phase-slip barrier is so huge here. And if you calculate this, the rate for escaping from, let's say, the topological index one to the other is of the order. I mean, the rate e to the minus 280. So it's 70 seconds. So it's absolutely suppressed. Unless you are very near to the switching, OK? Yeah, yeah. Because it's a pretty short junction on this. So I mean, let's say that the corresponding tau is energy is pretty large. Good. Well, that means we might learn something from this geometry. If you don't see this, in our community, we might learn how to suppress. Well, maybe we can make one of these rings put under the mountain. Well, if you don't see escape now, you will not see it under the mountain. Well, maybe there is more interesting. Because if you want to make the qubits, maybe it's more interesting. And this is just a modest, let's say, thermal device. All right, great. Thanks. Another question? Just about the process for the cooling of your device. So I understand that when the gap is smaller in the normal region, it's easier for a quasi-particle to tunnel in. But then, how do they escape from the normal region to the superconducting electrodes, which have still the big gap? I'm not sure that I have understood exactly what you are asking me. Sorry. So I'm trying to understand how the heat is transported through the superconducting part. OK, OK. So you are saying, basically, that I'm injecting, you are injecting a quasi-particle above the mini-gap. Yes. But the mini-gap is a local property, and within the ring, which is here in blue. So you are asking me, how is thermalizing, let's say, when goes, let's say, inside the S-prime part in the rest of the ring? Yes. I would say, I mean, basically, first of all, because the heat that is injected is small. So maybe there is sufficient time in order to evacuate sufficiently. Because I mean, the ring is big. There is a very nice contact to the same material. It is true that there is a slightly reduced mini-gap, but it's an S-prime junction. So some heat, for sure, will go. So basically, it's this, I would say. So there is possibility. So I mean, the experiment is showing that, in principle, it's possible to do this. I agree with you that it's not the perfect evacuation in general, because I mean, the. When you do the calculation, how do you model this? OK. Yes, the calculation is pretty simple. We have a few slides here. One slide to show you this. Yeah. So basically, I mean, is what we use typically for analyzing this kind of system. So we have basically three different boxes. So electrons in the proximity wire, its phonons and the phonon in, sorry, this is in the island. So it's not in proximity wire. In the proximity wire, we have considered everything resides at the same temperature. And by using simply the fact that there is a dramatic impact of the capyta coupling in the system, because it is a very narrow and long wire. So here, apparently, I mean, is we are working at sufficiently high temperature. It is 800, 8,000 Kelvin, 900,000 Kelvin of electron temperature in this long island, where everything is capyta limited. So indeed, the regime where there is capyta limitation or electron phonon limitation is around 700,000 for this kind of structure here. And so I mean, there is nothing complicated. So basically, we solve a system of thermal balance equation, so no linear, let's say, integral equation that states that all the current heat current going inside and outside is equal to 0 at the end. But here, we assume that the weak link has the same temperature as the rest. So it's at the above temperature. So I mean, if we look at the, if you remember, if you want, I can go back to show you the agreement. So I mean, it's a very simple theorem, but it allows to grasp what is going on in some sense. So in this sense, I would say that I agree that in S prime, it's difficult to evacuate. But if, I mean, the time adjunction is 60 kilo, it's pretty opaque, I would say. So at the end, the amount of heat that is going through is not so much. Maybe if we want to make a very effective heat modulator with tens and tens of millikai like we did with the squids, maybe it's more difficult there. So there, maybe we have to think a little bit better what is going on. But for instance, for a memory, it's nice this.  So these two states, four millikelvin of difference, can be exceptionally well resolved and maintain time. So, but the question is, who is going to make a thermal computer? Nobody. So. Sorry, I think we are running out of time, so let's... So as far as I understand correctly, that the hysteresis is like the squid, typical squid hysteresis where you, you know, change the number of flux corner in the loop. No, this is not new to the screening parameter of the squid. So there is a substantial difference. So what you are talking about is when you have a loop, when you have a loop and the screening parameter due to the kinetic inductance or dramatic and that sort of the loop is sufficiently large. This is very small. So here, I mean the screening parameter that is basically the ratio between the screen, the total inductance of the loop and that one of the weak link, here is much smaller than 0.1. So it's very small. Here, the hysteresis stems from the fact that S prime is a long junction. So the current phase relation of a superconducting quasi one-dimensional Joyce-on-junction is, becomes strongly skewed and non-hysteretic. When the length is larger than 3.5, say not. But it's still the squid, the flux in the squid and the current phase relation that does it. It's not the temperature per se. Exactly, yes. Yes, for sure. So one might say that instead of, that you actually encode your memory into the flux degree of freedom and not to the temperature, but you use temperature to read it out. Exactly, exactly, absolutely. Indeed, the first step of this was done on a... We need to move on. I have to escape. Yes. So thank you, Francesco, again. Thank you again. Next speaker.


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Hello and welcome you all for today's class. We will briefly go through the last lecture's main points. Like we discussed the few aspects of the dihydroxylation of olefins and towards the end we saw that it is important that that we need to have the cooxidants which allow the dihydroxylation to take place without over oxidation. So, there should be no over oxidation that for that purpose we saw that the use of tertiary butyl hydroxide or enomo was utilized and it has become very popular as far as the dihydroxylation of osmium tetroxide is concerned. And then it was found that we can also make use of the chiral ligands, chiral ligands such as pyridine based molecules can allow the dihydroxylation to take place and the enantiomeric purity was found to be reasonably good but not very high. So, then it was found that the complex between the ligand which is chiral ligand and the osmium tetroxide OSO4 should not be too tight, it should not be too tightly bound, neither it should be too loose. In either case they should not be any advantage because if it is too tightly bound then we have to use a large excess of the ligand and if it is too loosely bound then of course the enantiomeric purity will be low. In that respect it was found that synchronous alkaloids were a good compromise between the two and it was used for the purpose of dihydroxylation by Sharpless. And initially although the enomo was used it was found that the enomo leads to the optical purity of the dihydroxylated molecule being low in some cases as low as 6 to 8% and therefore it was not the best choice. So, the Sharpless introduced K3 FeCN6 and potassium carbonate in tertiary butanol water as a good source for the reoxidant of the reoxidation of the osmium tetroxide based by product which is osmium 6 and therefore it is water soluble and therefore the hydrolysis of the osmium 6 which is ligand bound occurs faster and then regeneration of osmium 6 to osmium 8 also occurs with this. Then of course we saw the spacers were used and which led to high enantiomeric purity of the product and also it was found that in the case of trisubstituted olefins the use of methyl sulfonamide also gave high enantiomeric purity and the rate of the reaction was also high. So these are the various things that were seen and now we look at the reduction of the different types of organic molecules in an asymmetric fashion. If you recall we had discussed the noble price to be given for oxidation and reduction. So the oxidation based work was awarded a noble price to Sharpless and the reduction based noble price was given to two people William Knowles and Ryoji Noyori. So if you look at it once again so the 2001 noble price was given one half jointly to as you can see here one half was given to Kb Sharpless like about whose work we have already discussed for both cathodic asymmetric epoxidation and diadoxylation and the work of William Knowles and Ryoji Noyori for carrierly catalyzed hydrogenation reactions and of course many other reductions by Noyori especially were given the noble price for 2001. So we will not get into the details of these now and these are the two people who did the reduction part of it. So now we will look at their work. The first industrial cathodic asymmetric synthesis was actually done by William Knowles. William Knowles was working in a company like Monsanto company in United States and his aim was to get the synthesis of L-dopa which is useful in the treatment of Parkinson's disease in as high enantiomeric purity as possible. If you recall we had discussed that whatever optically active molecule that we need to use as a medicine should be in that particular optically pure form because the other enantiomer could be not useful at all. So the first industrial synthesis of this rare amino acid L-dopa was actually done by the contribution of William Knowles and basically he spent a lot of time to find a proper match between ligand and substrate to achieve synthetically useful efficiencies and it was found that the best substrate was an enamide precursor that led to amino acids. So that hydrogenation of such molecules was the main purpose for William Knowles work. This is what is the enamide which was hydrogenated in the presence of this particular rhodium complex and where the chirality comes from this diampamp which is in this case is RR configurated and that gave the hydrogenated product as 95% enantiomerically pure and which led eventually for demethylation and deacetylation and then you get the corresponding L-dopa which was optically pure and that is how the first synthesis which is named as Monsanto synthesis was basically done by William Knowles and that is the reason why he was given the Nobel prize for this work. Now how did Noyori come into picture? So the Nobel Foundation sites the kinetic data suggests that at room temperature the oxidative addition of hydrogen is rate limiting for the overall reaction. So this was just of the various kinds of work that Noyori has done it, it suggests that this is what is the rate limiting step. When appropriate chiral phosphine ligand and proper reaction conditions are chosen high enantioselectivity is achieved. This is what the Noyori has really addressed it. If a diphosphine ligand of C2 symmetry is used the two diastereomers of the enamide coordination complex can be produced because the olefin interacts with either the re-phase or the C-phase. So if we have this enamide which is what we are seeing it in the case of William Knowles work and obviously when the attachment of the hydrogen occurs from either side we are basically trying to induce a diastereometric transition state. And then the two of them should be differentiated two of them should have a large gap and then we can get the corresponding enantiomeric purity through diastereomeric transition state. So this interaction leads to enantiomerically pure phenyl and the lean products and of course various kinds of diastereomeric rhodium complexes have been utilized for a large number of asymmetric reduction work. That is where the Noyori came into the picture. So in order to develop improved asymmetric catalyst the energy difference between the diastereomeric activated complexes has to be increased to larger enantiomeric purity or enantiomeric axis. So as I said that if a double bond say for example the same double bond as we saw in the case of Knowles work if this comes in contact with optically pure ligand where say you have an R star and which has say R configuration. If that comes in contact with this then there are two possibilities one is that you have a possibility of having this particular asymmetric center being generated as R or you have a possibility of this asymmetric center being generated as S. And in the transition state when the double bond is still there and the asymmetry is being induced here the ligand which is present having an R configuration should give us R R as a diastereomer and this one should give S R as diastereomeric transition state. So these are the two different diastereomeric transition states that will form when the ligand modified hydrogen comes in contact with the double bond which is pro chiral and there are two possibilities one R configuration to come and the other S configuration to come and if the ligand has say for example only one asymmetric center and has R configuration which is 100 percent. So we are basically looking at this R R versus S R as two diastereomeric transition states and the larger the gap energy difference between these two diastereomeric transition state will be the larger would be the enantiomeric purity of the molecule that we get at the end of the reduction. So this is what is important for industrial application and such a large gap was basically addressed by the work of Ryoji Noyori who introduced several different kinds of ligands and several different kinds of catalysts for making the high enantiomerically pure produced products. So Nobel Foundation further cites Noyori's discovery of the BINAP ruthenium complex catalyst was a major advance in stereoselective organic synthesis. The scope of the application of these catalysts is far reaching these chiral ruthenium complexes serve as catalyst precursors for the high enantiome selective hydrogenation of a range of alpha beta and beta gamma unsaturated carboxylic acids. So this is how the Noyori's work was basically cited by Nobel Foundation. Now what does Noyori have to say? Noyori says that recent efforts have been mainly directed to the refinement of the original process using standard dehydro amino acids as substrates basically enamides and highly enantioselective hydrogenation of olefin substrates lacking acyl amino functionality remain difficult. So the kind of substrate that was used by William Knowles was found to be good for the preparation of L-Dopa but then Noyori also looked at the hydrogenation of other double bonds which were lacking the acyl amino functionality. That is where and of course during the process he developed introduced the S-BINAP and R-BINAP as two atrop isomer based chiral diphosphine ligands and of course they are as a C2 symmetry based ligands and these are the two which were basically introduced by Noyori in 1980 and for which he really did a lot of work to get to the highly energetically pure different types of molecules. Now besides alpha acyl amino acrylic acids or esters leading to L-Dopa the same enamides which we have talked many times the variety of other substrates were also hydrogenated in excellent chemical yield and high enantioselectivity but then the rhodium catalyst is limited to acyl amino functionality. Basically rhodium based the catalysts having different ligands particularly the kind of ligands that NOLS used or the BINAP were used and therefore the molecules were hydrogenated where this enamide type which were very useful for the synthesis of L-Dopa. But there were these rhodium catalysts were not particularly useful in some other context and therefore Noyori developed many other catalysts and ligands to overcome this and apply new methods for the reduction of different types of molecules. Now rhodium based catalysts using different BINAPs have been utilized in the isomerization of certain olefins and they have been used in the industrial application for the synthesis of a variety of important optically pure molecules. For example, if we start with a pro-chiral allylamine of this type where the double bond geometry is Z and react it with this rhodium catalyst where the BINAP has R configuration then the enamine that is observed after the isomerization of this particular double bond is of this kind where the absolute configuration is as shown. Now the same pro-chiral allylamine when it is reacted with the same rhodium based catalyst but with different BINAP that is now S BINAP then what we get is this kind of parallel enamine in which the absolute configuration of this asymmetric center is opposite to that of what we observed with R BINAP. Now if we change the geometry of the pro-chiral allylamine from Z to E and react with the same rhodium catalyst but with R BINAP then what we get is the chiral enamine of this kind with the absolute configuration of the asymmetric center being as shown here which is opposite to what was observed here. Now the same allylamine when it is reacted with the same rhodium catalyst but now with S BINAP as a chiral ligand then what we get is this type of chiral enamine. What it means that when we start with a pro chiral allylamine of a specific geometry of the double bond and react it with a particular rhodium catalyst with a R BINAP we get a parallel enamine of certain absolute configuration and with the same allylamine when it is reacted with the rhodium catalyst of having a BINAP of opposite configuration then we get the chiral enamine of opposite configuration. So these type of chiral enamines have been utilized in the synthesis of the variety of important compounds which are optically pure and optical purity has been found to be in the range of 90 to 99 percent as one can see that the R group here has a lot of scope for example of this kind of alkyls or phenyls and various kinds of substitutions can be utilized. So it is an easy method for converting a pro chiral allylamine to chiral enamine using rhodium based catalyst and BINAP based chiral ligands. Now this has been utilized in the synthesis of menthol by a company called Takasago who basically have used the process developed by Noyori. So in that process we start with beta pinene which of course can be written up in this way also. And if we do the thermal cracking this the way I have shown here the arrow it breaks and it forms myrcine this is what the myrcine is. So you start with beta pinene and heat it and get the myrcine and then betalithium is used along with diethylamine it stops at this particular stage it does not undergo further polymerization or oligomerization it stops at this particular phase as you can imagine here that if suppose lithium plus comes in here then of course you have chelation like this or the coordination of the lithium plus with this. And the betalithium that NBU minus takes the proton from the diethylamine and this diethylamine then attacks on to this and one can stop it at this stage because of the chelation between now nitrogen and the lithium plus. And then that undergoes the formation of this diethyl gerinyl amine which then in the presence of the catalyst which is what is the different catalyst and undergoes isomerization in a catalytic asymmetric fashion and then we get anionsiomeric purity which is almost like 100% anionsiomeric leak the pure molecule and we get the enamine corresponding enamine which is what is known as citronellol RE diethylene amine or this is the correct hyupac name of this particular molecule. So basically starting from beta pineene one has come all the way to here where this particular asymmetric center is generated and then enamine is formed. Now this particular enamine can be hydrolyzed and we can go to the corresponding optically pure which is more than 98% anionsiomeric pure are citronellol is formed this is the aldehyde and when zinc bromide is used this undergoes what is known as carbonyl ene reaction the ene reaction we will discuss later on more in detail but if suppose you have an ene and an olefin here like this then of course that undergoes upon heating or under some metal catalyzed reactions to form basically a molecule like this. So this is in equilibrium this is called as ene reaction and that also can be done using an aldehyde which is what is known as carbonyl ene reaction and therefore in the carbonyl ene reaction when a Lewis acid like zinc bromide is used zinc bromide coordinates with the oxygen of the aldehyde and then we have this type of proton transfer and that leads to the formation of the corresponding alcohol and this alcohol which has now a double bond because of this ene reaction can be hydrogenated and of course now during the process we have basically formed menthol. So this is how the menthol synthesis has been deported by Takasago company in Japan where the reaction or the process has been borrowed from the work of Noyori. Now another non enamide or non acylaminobase chemistry is the synthesis of esnoproxine which is an anti-inflammatory agent which is formed in 97 percent enantiomeric purity and 92 percent yield where this particular kind of ruthenium complex was used by Noyori where only 0.5 mole percent of this was used and that lead to the hydrogenation of this by using this S binab based ruthenium complex and that lead to esnoproxine in a high enantiomeric purity. Likewise these binab based catalysts this or this have been used for the conversion of this enantiomeric alcohol to this particular saturated alcohol or this saturated alcohol they are enantiomers of each other. So any one of them can be made depending on which one uses either S binab or I binab and likewise this type of double bond also can be hydrogenated and the yields and the enantiomeric purity are as high as 96 to 100 percent and 98 to 100 percent with different types of substituents that have been found. So these alkaloids of isoquinolyne type of alkaloids which are very useful can also be synthesized and then this carbapenam antibiotic type of molecules can also be prepared in optically pure form. As one can see that different tetrahedra this isoquinolyne type alkaloid like tetrahydropapavarin, tautonacinocene, tetroquinol or salsolidine, Nordic glean or morphine type of molecules intermediates they all have been synthesized by the work of New Yorkies hydrogenation reactions using the catalyst based on binab. Now this ruthenium binab catalyst also has been used for the synthesis of different types of ketones. So although asymmetric hydrogenation of ketones is another difficult problem in chemical synthesis a wide variety of functionalized ketones are now convertible to the respective secondary alcohols through homogeneous hydrogenation with halogen containing ruthenium binab catalyst in alcohol media. The reaction proceeds in high anion selective and predictable fashion. This is what is important and as I have shown here different types of molecules which as you can see depending on R enantiomeric purity between 83 to 96% such as this 92% here and if this kind of molecule is to be obtained the enantiomeric ratios range from 98 to 100% for example 96%, 96%, 93% and of course different types of other molecules in which one can get the enantiomeric purity as high as 90 to 100% or 98% and the reactions can be used for the preparation of this kind of lactones also. Now this particular hydroxy ketone which is again a prokaryl ketone and this particular ruthenium complex has been utilized in the synthesis of this 1, 2 propane diol having R configuration here. Now this particular molecule is very useful to prepare using this protocol and economically it is easy to operate and its preparation has been shown to be useful for producing 10 tons of such a molecule per year by using this catalyst and therefore it is very commendable that such a reaction can be done on a catalytic fashion and this is basically an intermediate for the synthesis of antibacterial levofloxacine and therefore it is of high commercial utility. Now this particular molecule has also been used as a catalyst in the hydrogenation of this enone to the corresponding allylic alcohol and as you can see that it is not a hydrogenation of a double bond but it is a reduction of the ketone and it gives the corresponding allylic alcohol in 90% enantiomeric purity which is a building block for the synthesis of vitamin E. Likewise, Neral and Geronial can be converted into the corresponding alcohol where there is a hydrogenation of the allylic alcohol part and using these types of ruthenium catalysts. As we can see that only 0.2 mole percent of the catalyst has to be used with the hydrogen 100 atmosphere pressure at room temperature and if we start with this and use R-binab we get this molecule and the same molecule can be obtained by inverting the geometry of the double bond from Neral to Geronial and use S-binab and we get the same molecule with the same enantiomeric purity and same configuration and therefore both Neral and Geronials can be converted to this using different R-binabs or S-binab type of thing and this particular molecule has also been utilized in the synthesis of vitamin E via this oxidation of the CH2OH to the corresponding aldehyde followed by Wittig reaction and a few more steps to go to vitamin E. So these are the various applications and utility of the hydrogenation reactions and reductions of ketones that have been developed by using rhodium and ruthenium based catalysts and binab ligands, Skyray ligands and also some other ligands developed by NOLS and therefore the work was given the Nobel Prize. So we will stop it at this stage today and take up some other aspects of asymmetric reduction next time. Till then you can study these things which I have told today and look at it and generate questions which you can ask me later on when there is a live interaction or post me whenever it is needed. Till then bye and thank you.