So I'm going to bring this patient conference to an end by hopefully talking about both opportunities and challenges in what all of you care about and what I and others care about and that is, can we cure kidney cancer? So a bunch of us got together by invitation, there's a group in Washington called the Angiogenesis Foundation. This is a foundation that is a 501c3 corporation that was founded entirely on understanding and supporting research that targets blood vessels. And we got together, there were about a dozen of us from around the world and we went through an exercise that I thought was helpful, productive and enlightening and really to look at the critical pathways forward in the treatment of kidney cancer. And I know you have some of this in a handout, the handouts were not blown up large enough for you to see as you'll see in a moment, but you'll be able to get these online. So what are the key points? Well we've approved seven agents, most of them targeting angiogenesis or pathway associated with angiogenesis since December 2005, almost coming up on a decade that has produced a true paradigm shift over the last number of years. And I think you've seen that today, both those of you in the audience that have participated in these trials, participated in the successes and are also relying on these drugs to continue your lives. But there's really some very large challenges. One of the challenges in kidney cancer is the leadership. If you asked yourself who are the spokespersons for leading the effort in the fight against kidney cancer, there are no national leaders that have been given the gavel to really drive this conversation for all of us. So more independent leadership that critically advocates for better data and better drugs. Why is that? Because realistically the support is insufficient for kidney cancer research. And when you ask the question how many dollars, federal dollars, or philanthropic dollars are spent on an annual basis to support some of the diseases called cancer, lung cancer, breast cancer, colorectal cancer, prostate cancer, there are several orders of magnitude greater than the number of dollars available for kidney cancer research. There is a critical need for both basic and translational research to address some unanswered questions. We cannot fall into the habit of saying, well, if something was discovered in another disease, maybe it will work in kidney cancer. And what's taught us over the last decade when we've approved seven drugs over less than a decade is that a better understanding of the biology of kidney cancer drives the research and successes for kidney cancer patients. So we need to understand the biology of kidney cancer. What's a biomarker? A biomarker is is there something in the blood or on a scan or measurable by a test that can identify kidney cancer early.   If you're a person who's had a history of smoking, you go to your doctor and we now have evidence that's profound after a $50 million trial that says that high resolution CT scans are beneficial for the early diagnosis of lung cancer that can lead to a 20% increase in cures of patients at risk. There is no such biomarker for kidney cancer. There are also no biomarkers for therapeutic efficacy. You've heard across the day that there's a lot of toxicity associated with the things that many of you have received. There's a lot of toxicity that's continuing to affect you. It would be nice if we could actually pick out who are the people that are more likely to benefit or suffer from the side effects associated with the drug so that we could tailor the treatments to those patients. I was just at a meeting and gave a conference in somewhere, I think it was San Francisco, where I spoke to Japanese urologists and that was going to go back to Japan where the Japanese urologist community, which are the ones that actually give therapy for kidney cancer, spoke to the nature of the side effects in Japanese patients that are really quite different than the side effects associated with what we talk about in the United States. That's called pharmacogenomics. Pharmacogenomics is really the study of the difference between different genetic people and how they tolerate drugs and how best to deliver it for both benefit and safety. And lastly, head-to-head comparisons. It's okay to develop seven drugs, but as you saw when Dr. Paul pointed to the two buckets, the bucket A, which is the VEGF bucket, and the bucket B, which is the mTOR bucket. The reality is that there's really only two sets of drugs. Some of them have different names. Some of them have many different types, but they're really only two sets of drugs. And one of the things that you would want us to ask and I wanted to answer is what makes drug A different than drug B? Is it better? Do it first? What's right for me? How should I use it? And oftentimes there's inadequate data in the literature for us to be able to make those recommendations because those questions have not been asked and answered. So what we did is we used actually a management tool that is often used in big business. And this management tool is you look at a situation analysis, you define the state of kidney cancer therapy or anything that you're looking at. You look at emerging kidney cancer therapies. You look at the future state in mapping the challenges. What is the future state? What are the obstacles and challenges for achieving the future state? And how does one prioritize? And for any of you that are in the business world, you're familiar with these management strategies about almost any problem or project or product that you would ever consider. How do you develop solutions? How are their leadership issues? Are there strategies? In our case, clinical strategies, biomarkers for therapeutic efficacy and defining patient centered values, i.e. don't just think about it from the perspective of developing drugs, but think about it from the perspective of developing things that people will want to enhance their life. Very nice talk by my colleague at City of Hope, Matt Lascalza, which really solidified in a very short period of time, we can't forget that we have to define the patient-centered values. And lastly, you generate that into action, develop a research agenda, an action agenda and commitments, and then you identify the resources to put behind that to succeed. So this is what we spent the day kind of in our regular clothes. And it seems like a complex, and there will be many slides like this, it seems like a complex way of approaching problems, but actually it's very solution oriented. So for example, if one wants to look at the desired future state and discuss it, you look at the desired future state, for us it was in five years. And you identify the priorities, research, prevention, treatment, effective drugs, priorities. I think the one thing that was dramatic, and I think we would all agree in this room as at the end of the day, we want to make sure that the questions that are being asked and the dollars that are being expended are leading to the things that you would want. Well, what you would want is you would want something called complete responses or no evidence of disease and long term survival. Because industry loses track of what you want. Because there's a lot in between, and pardon my English, there's a lot in between where you can make a ton of money and not get to the end point. And what we need to be sure is that we as advocates for this disease advocate for the end points that are of value, which is cure. So what are some of the barriers in prioritization? Well, there is inadequate funding for basic research, clinical trials and advocacy. Sitting in the audience is one of my patients, Barry Hoven, who started a foundation called Cureit, the purpose of which is to raise money for laboratory and translational research in kidney cancer and is giving out awards to the American Association of Cancer Research. It's going to be through funding of basic research, clinical trials and advocacy that get us to the next step. Undefined mechanisms of tumor biology. I am struck by over 30 years of dealing with this disease that the home runs are not always easy, but they're there. And it's kind of like in the baseball analogy, you have to wait for the right pitch to hit the home run and not every pitch that comes in is going to be a home run ball. Well you have to identify what's the matter or the manner of the right pitch and how you go after the science associated with the right ball that you want to try and hit out of the park. You can't wait for, no one hits a home run if the ball doesn't get to the plate. You have to get that information to try and hit that ball and search for that cure. There's been a significant disincentive to develop better agents. So the market is a problem. We have seven drugs that are making a lot of money for some companies. What's the incentive to develop the eighth drug? And it's not like new cars where there's another car coming out or another model coming out every year. So what we need to do is we need to make sure that we're on the path of making sure the kidney cancer is advocated for so that a decade from now we don't look back at the last decade and said, yeah but the decade before you developed seven drugs and in the last decade we developed, we developed nothing. Because remember between 1992 and 2005, how many years is that, 13 years, there were no drugs developed in kidney cancer. Not because we didn't try, but there were no drugs developed. Want to make clinical trials available to more and more people? We want to align incentives, sometimes incentives are misaligned or the incentives for the patient, the same as the incentives for the physician, the same as the incentives for government, the same as the incentives for the pharmaceutical industry. Many of us are worried about incremental change. I think that most of you in the audience would say, if I have an opportunity to participate in a trial that has a modest benefit for me, is that as important as participating in a trial that is a paradigm shift where I have the opportunity to reach one of those barriers that's associated with long-term control of my disease? And in oncology, especially in 2014 where the federal dollar available for research is decreasing, it is absolutely critical that we use every one of those dollars in a valuable way. We struggle for fragmentation of delivery of care and quality of care. I mean, you're here today, all of you are seeing your doctors and I'm hopeful that all your doctors are as familiar with the data as you are now, but most cancer doctors in the community see four or five kidney cancer patients a year. I see 20 a week. Do you think the level of care is the same for a doctor who sees four or five a year and one who sees 20 a week? So my view of kidney cancer care, it should be focused and centered around centers of excellence. You should see the people, like the people that we talked about today, because they're the experts who are able to give you not only today's therapy, but tomorrow's options. Scientific researchers can't allow industry to drive the clinical agenda and I think you can imagine that the industry agenda and the questions that they ask and answer are driven by things that are important to industry. And if they help you, God bless, but they're not always aligned. And we have to make sure that all of our voices are heard so that industry knows exactly what are the end points that we want for ourselves and our patients. We need to develop guidelines for therapy to make sure that they're followed, especially when a physician who may not be an expert in this disease sees a patient who has kidney cancer. And this is what the barriers look like and there are many of them and you'll be able to see these online and they're very granular. This is the leadership challenge and there are substantial amounts of leadership challenge. I'm not getting any younger, many of the people that are associated with my generation of kidney cancer scientists are not any younger. We hope that the Dr. Paul's of the world will continue to thrive over the next decade and generations because we need leadership in this area to lead to future cures. We have to remember who we serve. We serve you. We don't serve our institution. We don't serve industry. We don't serve the federal government. We serve as the person who we sit in a room and talk to them about a life-threatening disease and we have to make sure that the patient-centered value associated with the delivery of care for kidney cancer patients is not lost in the process of development. Lastly, we have to make sure that centers of excellence in community oncology practice are aligned. I talk all over the world and the questions that I get now as compared to a decade ago are more sophisticated, but many of the questions that I get are still pretty naive, which means that we haven't penetrated with information across all of the domains across the country so that people actually know how to take care of the individual kidney cancer patient. And lastly, where do we want to get to? We want to get to a paradigm shift, a paradigm shift meaning that instead of me walking into a room talking about current therapy, it's a paradigm shift where we walk into a room and talk about emerging technology that might lead to an endpoint that is very different than what we deal with in 2014. Will vaccines be that opportunity? Maybe. Will checkpoint inhibitors be that opportunity? Possibly, but we can't just stop with those targets. We have to continue to discover, put resources behind it, and be creative. I wanted to leave you not so much from the perspective of CEDARS, but from the perspective of how to deliver care. These are the clinical trials that we have at CEDARS for patients with kidney cancer. I don't need to go through that, but in every one of your visits, in every one of your conversations with your doctors, you should ask the following question. I know what I'm receiving now and I'm happy to be receiving it and benefiting. What else is going to be available for me should this stop working? And if that person has that available or access to know what is available, you're in the right place. If the person says to you, I have no clue, you might want to revisit exactly where you're receiving your care. So with that in mind, I thank you all for coming. We have a few moments before we all go to other things. I thank Nancy for establishing and setting this up, as always. Let's all give Nancy a hand. I thank the Kidney Cancer Association for its advocacy across the country and the world in support of kidney cancer patients. And it's nice to see you all again. Take care.


Multiple studies published over the last two decades suggest that exercise can mitigate the deleterious effects of age on immune function, thus increasing anti-cancer immunity, in part by stimulating natural killer cell activity. Natural killer cells, part of our immune system, were to eliminate both tumor cells and virus-infected cells, and we can boost their activity with physical activity. Here's the difference in natural killer cell activity between women involved in athletic competitions compared to their sedentary counterparts. There is a growing consensus that natural killers appear to be the immune system component that is most responsive to the effects of both acute and chronic exercise across the board, from older women to younger men. Significantly higher NK activity in racing cyclists in their 20s. Even just moderate exercise, though, like daily walking, appears to significantly improve NK activity within six weeks. This may be why exercise helps protect against cancer. But sustained vigorous exercise may actually impair natural killer cell immunity, which may be one reason endurance athletes like marathon runners may appear to be more likely to get upper respiratory tract infections. In an upcoming video on preserving athletic immunity with chlorella, I feature a study that showed consuming chlorella appear to prevent the loss in immune function as measured by antibody production. But what effect might the green algae have on natural killer cell activity? Petri dish and animal studies suggest that the algae chlorella could affect natural killer cell activity, but there was no direct evidence for the effect of chlorella supplementation on such a response in humans until this randomized double-blind placebo-controlled trial gave people about two teaspoons of chlorella a day for six weeks, and compared to placebo, they got a significant increase in natural killer cell activities. Does this actually translate, though, into clinical benefits? We didn't know until now. The efficacy of chlorella supplementation in adults with chronic hepatitis C infection. It's estimated that up to 4 million people in the US have chronic hepatitis C virus infection, the leading cause of liver transplants, and estimated to kill a quarter million Americans this decade. The current treatment is costly and brutal, costing up to about $85,000, and nearly half can't even complete the course of drugs, some part of the many complications associated with the treatment. So that's why there's such a need for novel treatment options. After three months of chlorella, there were reported improvements in quality of life, but that could have just been a placebo effect since the control group wasn't given green sugar pills. This however is harder to explain, a significant improvement in ALT, which is a marker of liver inflammation, which could be explained by beneficial immunostimulatory effect of chlorella supplementation. No serious adverse effects were reported, so why not give it a try? Well, the brand they used was tied to a disturbing case report recently, chlorella-induced psychosis. A 48-year-old woman in Omaha suffers a psychotic break out of the blue two months after starting chlorella. They stopped it and started her on an anti-psychotic drug, and a week later, she was fine. Now, chlorella has never been linked to psychosis before, so presumably it was just a coincidence that the psychosis started after she started taking chlorella, and the reason she felt better after stopping it was because the drug was kicking in. But seven weeks later, still on the drug, she became psychotic again after starting back on the chlorella. They stopped the chlorella again, this time that's all they did, and the psychosis resolved. Now, maybe it wasn't the chlorella itself, but some toxic impurity or adulteration. We don't know. While chlorella is marketed to promote mental health, this case underscores the importance of educating the public about the potential adverse effects and the need for more research in herbal products being marketed here in the United States.


We have been discussing about the geomaterial characterization and in particular thermal characterization. So, as discussed last time, one of the real life application of thermal characterization would be the formation of heat induced cracking of the soils. And this is a big challenge for geotechnical engineers to overcome and design the foundations and the structures so that they do not get exposed to the environment even after the thermal cracking occurs. So, in today's discussion I will be elaborating about the mechanisms, what thermal cracking is all about, what are the mechanisms of cracking of soils and how to quantify the cracking characteristics and how to use this information in the practice of geotechnical engineering. Of course, this will be followed by electrical and magnetic characterization. Mostly the cracking is associated with the fine-grained materials, such as clays or the expansive soils where the mineralogy is very active or the clay minerals which are active in nature. When we say active minerals, the tendency of the minerals is to react with water or the environment and in the process they shrink and swell. So, shrinkage is because of the expulsion of the moisture and when the drying takes place and swelling is the reverse process when the minerals come in contact with water they have a tendency to adhere the water onto their surface. In short, the swelling and shrinking causes the cracking to occur that means there would be a limit of swelling and shrinking process before the cracking occurs. So, cracking is something which is ultimate effect of the swelling and shrinking process. These type of situations become very critical when we talk about the clays which are used as a core of the dam, earthen dams, sometimes landfill liners also and the landfill covers. These could be the liners and covers for the radioactive waste repositories also as we have discussed embankment, slopes. In the sporting world normally this concept is used quite a lot where they apply the concepts of cracking of soils and how to mitigate it, how to remediate it particularly in case of cricket pitches and tennis courts. In fact, my research in the cracking of fine grained soils started with my association with the BCCI when we were doing this pitches for World Cup 2011 and then I found that this idea became so intricate that I guided almost two PhDs on this and we devised lot of philosophies and the facilities which can be utilized for characterization of fine grained materials. It is a very interesting topic to study by geotechnical engineers as well as the people who are associated with these type of projects. Now another thing is that when you construct something on the soiled mass which is prone to cracking, the safety of the structure becomes a very, very important issue. Most of the time in the realm of environmental geotechnology where we talk about the permittivity of the compacted soil mass, the big question would be after the soils crack particularly the fine grained soils they become more porous, more conducting. Sometimes we also call this as the secondary porosity of the material. So after cracking the material becomes highly conducting and this could be alarming situation when you deal with the liners at the covers for the landfills. So imagine a situation where the thermal gradients are coming from the landfill and they are getting exposed or the clay liners are getting exposed to the thermal gradients which are coming from the landfill where lot of chemical reactions are occurring and if these liners crack the chances are that the environmental water will migrate through the covers which have been designed as well as the liners through which the leachates will go into the geoenvironment. As far as the conventional geomechanics is concerned the cracking is going to cause you know loss of bearing of this data and sometimes if the cracking tendency is too much then differential settlements also might prevail in the system. It so happens that the cracking of the soils is linked with the tensile strength of soils and I am sure you will realize that in conventional geomechanics we have not given much weightage to the tensile strength of geomaterials. All the tests which are performed are related to the compression of the soils and we really talk about the tensile strength of the soils. But it has been realized in the recent past that the tensile strength of the soils is the one which controls their stability rather than the compressive strength and hence it becomes very important to study the mechanism of crack formation in the fine grained soils and which is attributed to the tensile strength mobilization. This also necessitates development of instrumentation and the hypothesis which can be utilized for determination of tensile strength of soils. I had another interesting encounter with the geomaterials which used to crack and this is an example of a large structural fill which was created somewhere close to Bombay in Gujarat. Soils in Gujarat are quite you know active because of the mineralogy and this case happened where the structural fill was created and unfortunately there was a flash flood and because of the flash flood several hectares of the area which was structurally filled up with the soils cracked and then this became a very interesting case to study. So here what I have shown is the if you look at the pattern of the cracks which get developed on the entire structural fill the basic idea of compacting the soil to create a structural pad gets defeated, number one. You can always say that this was a poor choice as far as the material is concerned to create a structural fill and yes that is true. So the contractor need not to be paid for this type of a filling because he was supposed to be extra cautious while selecting a material as a structural fill material. Now in short once these type of cracks develop we do the third dimension mapping also of the cracks and we try to realize that how much portion of this compacted fill has become default. If you have done structural analysis of the retention schemes particularly retaining walls and the retaining walls which are exposed to desiccation cracking the simple question which is asked is what is the earth pressure before and after development of the tension crack and I am sure you have done this analysis to show once the structural crack develops soil is not in touch with the retaining wall at all and hence the earth pressures are going to be different than the earth pressures which are going to be under full contact of the backfill with the wall. So this is where it becomes very important apart from you know knowing what is the amount of seepage which is getting induced into the subsurface of the back fills because of the crack formation and if the depth of the cracks is quite high the situation might become quite alarming as well. In simple words if this type of a situation occurs somewhere the structural fill has lost its integrity and hence you cannot accept this type of a situation. Now if you think about the conceptual model that why soils crack the tensile stresses which develop in the system are to be blamed for cracking of the soils and tensile stresses develop due to the desiccation of the soil mass or the drying of the soil mass. So I am sure you must be realizing that this is a situation which does not occur because of the mechanical loading of the soils. This situation occurs because of the thermal loading of the soils. And thermal loading causes expulsion of water from the soils or the drying we call this as a desiccation also and then the tensile stresses mobilize. If the tensile stresses are higher than the tensile stresses which are at the limiting stage of cracking the soils will crack otherwise they remain within the permissible limit. So this type of models are normally used you have a thin layer of the soil which is fine grain material clay and this is where the tensile stresses develop because of the heating. Because of the stretching of the clay layer there will be primary cracks which get developed air enters into the system and this system does not remain at equilibrium because of the development of the primary cracks. These cracks multiply in the form of the secondary and tertiary crack and you know the holes system which was compacted as the backfill material becomes quite pervious and loses its structural stability. So this is a simple model which is used to define the cracking characteristics of the soils. Now the question is how would you determine the tensile stresses in the material and how would you link it with the thermal effects and the desiccation effects which might be happening because of the environmental conditions. And that is the reason this subject is now becoming quite important to be studied by all those who are in the practice of geotechnical engineering as well as geoenvironmental engineering. Now if I change the context and if I say rather than heat drying the soil mass there is some chemical activity which is occurring in the system and because of that there could be internal heating process which is going on. So this is equivalent to the situation when the soil mass was getting heated up from the outside or externally heated. So truly speaking the source of heat generation is not very important this could be within the system this could be outside the system. What is important is that how the moisture gets released from the pores and that process causes the cracks to develop. So if you talk about the mechanism of mobilization of the tensile strength this is a complicated process we have to again start with the three phase system and if you remember we have talked about the soil water air interface or the interaction all the three phases interacting with each other which is the main reason for mobilization of the tensile strength of the fine-grained materials. And this is where we assume that in case of the dry soils we have apparent cohesion. If you remember the shear stress versus normal stress relationship or the failure envelopes of the soils I hope you will realize that the initial portion is a OC material OC response where the C remains constant and then there comes a point of sigma P prime pre-consolidation pressure and beyond which the material becomes NC alright. So if you plot tau versus sigma relationship so you will get a OC response followed by NC response on the shear strength profile and the point of intersection of these two responses is the pre-consolidation pressure. So for less moisture soil we consider them as the dry soils and we consider this as the apparent cohesion. Apparent cohesion could be the over-consolidation value of the shear strength which is associated with the soils. However when we talk about the partially saturated soils this is where the capillary phenomena takes the important role and we talk about the surface tension and surface tension is nothing but suction in the soil mass. So the best way to model the mechanism of mobilization of the tensile strength would be to bring in the suction parameter. I think now you can realize that why conventional geomechanics does not talk about the tensile strength of geomaterials because they are forcefully we have saturated the soil samples. We have made sure that the soil does not remain under unsaturated state. However the tensile strength is going to get mobilized when the soils become partially saturated or they tend to become unsaturated. This is an interesting fact that the soils that swell exhibit higher tensile strength alright. So that is the arrangement of the water retention system on the minerals of the fine-grained materials. So more the holding capacity of the moisture, more the swelling pressure and once the swelling pressure is very high the tensile strength of the material is going to be high. Now what we do is we try to relate the tensile strength by width you know so many parameters. So tensile strength is a function of the moisture content of the soil it is gamma t. Now gamma t basically indicates the total unit weight of the material which is a function of specific gravity and soil type corresponds to mainly texture and Cl is the clay content. So higher the clay content, higher the sigma t value, cation exchange capacity then plastic index, specific surface area and the suction, metric suction alright. So all these terms put together would create the sigma t value, yes please. That high swelling pressure, swelling soils have more tensile strength means when we study that suppose compaction curve so the dry side are supposed to have more swelling tendency. So they should have more tensile strength should develop. I think you are not correct if you plot gamma d versus w and the suction pressure which develops as a function of moisture content you will realize the maximum amount of suction is at the OMC alright. So what you are thinking is a totally reverse process. So if you plot gamma d versus w and if you plot the pore water pressure versus w so if this is the OMC what you will realize the suction pressure is going to be maximum at the OMC. So what this indicates is that degree of compaction also plays a very important role and I hope you can easily follow this concept by the fact that the more the compacted a material would be you have expelled out most of the air which was present in the soil mass and hence the suction is going to be much more. So as you compact the soil alright the suction builds in okay a reverse process is like this the more compacted the soil the more the suction present in it but suppose if I fill or if I saturate the entire system then the suction gets lost and hence the shear strength decreases. So this is the complete cycle which you have to consider. The simple logic is the more I compact the soils the more suction gets building because I have expelled air from the pores. Now this is the tensile strength which also influences the sensitivity of the soils. In conventional geomechanics we have talked a lot about the sensitivity and we have ascribed sensitivity to the ratio of the shear strength alright we say sensitivity the shear strength of the soil in its undisturbed state to the remolded state. So one of the ways of looking at the tensile strength could be if I use the concept of sensitivity and if I talk about the shear strength parameters associated with the soil mass in its undisturbed as well as the disturbed state remolded state. Now this is where the type of loading becomes very very important. So when we are talking about the tensile strength you know we have to understand what type of loading the soil mass is undergoing through. So there are 3 types of loading which normally we talk about tensile stress, tensile stresses, compressive stresses and shear stresses. Under no shear condition if I consider what tensile and compressive stresses do to the sample this becomes a critical situation and then we have to try to understand you know what tensile and compressive loading does to the arrangement of the grains in the soil system. And this is where I would like to introduce the concept of the maximum exposed surface area which is responsible for you know tensile and compressive loading and ultimately it gets linked to the tensile strength. Now if you really want to understand how exposed surface area influences the tensile strength of the material we have to go into the micro mechanics of the system and the micro mechanics looks like this. So if you start with let us say tensile loading or the compressive loading and these are the grains which are in the soil mass and if I stretch it you know what is going to happen when I stretch it all the particles get repelled from each other that means in other words each particle is now free to exhibit the 100% surface area to the environment. So this is a case when tensile loading causes you know exposure of the grains to the environment I hope this part is clear to you. So the more you and more you stretch the material the particles get stretched out and they are free to now interact with the environment. Environment could be water contaminants which are present in the liquid phase gaseous phase sometimes solid phase also bacteria. So all these are the attributes of the environment. What happens in case of the compression loading I think you can realize when the compression loading occurs the particles come closer to each other certain amount of their surface is getting hidden because of the compressive forces that means when we talk about the compression loading we are not doing justice with the material modeling because when you bring particles together to each other there is a sort of a shadow effect. So each particle is shadowing certain fraction of the surface of the another particle alright. So what it indicates is the fundamental difference between tensile loading and the compressive loading is that exposure of the surface gets changed and hence we are not really modeling the grains the way we should have modeled them for finding out what should be the response of the loading on the geomaterials particularly the fine grain materials. So this is a very convincing model which has been used by people to put forth this analogy or the philosophy that why tensile loading should be considered for characterization of the soils. So truly speaking the tensile strength is a parameter which can be utilized to characterize the geomaterials. So the question is how would I go ahead how would I obtain the tensile strength of the soils having done all these things with all convincing statements that tensile strength is the most important governing parameter as far as the geomaterial characteristics are concerned. You know there are two techniques which can be utilized one is the direct measurement either in the laboratory condition or in the field condition alright. So the type of photographs which I showed you where the entire backfill has cracked I can do the image analysis and I can find out how the tensile strength is getting mobilized. Sometimes we use softwares or the image analysis packages and we get the information however this is a very complicated process and one of my PhD scholars who is a faculty member now at IIT Mandi Dr. Uday Kala he was the person who started imaging of the cracks which develop in the fine-grained materials and this was his PhD thesis where we have taken soil samples which after desiccation crack or we have accelerated the cracking process by creating the environmental conditions in the laboratory so we did the simulation. So when you do these type of software based image analysis thing we get accurate and direct measurement of the crack patterns and their geometry area included in each segment I will show it to you intersection of the cracks and its initiation in a particular soil mass. I hope you realize that the whole system is very dynamic because the cracking pattern is a function of time and the moment soil gets exposed to the environment desiccation starts evaporation starts and there could be a situation where all of a sudden the entire soil mass may crack. So if you want to capture the whole process of cracking of the geomaterials you have to utilize the modern gadgets where the entire sequence of desiccation can be videograpped and then you can discretize the events and then you can stitch them to see how this whole situation has got developed and created. Another interesting or the big challenge would be having all these parameters known that is what type of cracking pattern is what type of geometry the cracks follow what is the area included in each segment of the crack you know what is the line of intersection of the cracks can I link all these parameters to the basic soil properties because our hypothesis is that soils are very intelligent materials. So they do not just crack for the fun sake and another thing is the crack pattern is a unique fundamental behavior of a given soil mass provided the environmental conditions are maintained. So using these hypothesis what we have done is we have linked or we have tried to link the parameters which we have listed over here with the physical, chemical and mineralogical characteristics of the soils and the way the suction profile gets developed in the soil mass. So suction profile gets developed in the soil mass when the soil gets dried up expulsion of moisture alright and this expulsion of moisture is because of the heating which is a coupled phenomena. So now I am sure you are dealing with a situation which is a dynamic situation everything is a function of time here until now you have not talked about the material properties as a function of time here the moisture content in the soil mass is a function of time the suction in the soil mass is a function of time the crack width and the depth and the geometry of the crack pattern itself is a function of time. What we did is we have selected soils of known properties expose them to the known environmental conditions we call this facility as a environmental chamber where we can create different types of temperatures and humidities over a period of time. So I am sure you are getting a feel of how environmental loading can be simulated on the soil mass clear the way you used to do consolidation test where you started with one sigma value and then you keep kept on doubling it after a certain time when the dial gauge reading becomes constant when we talk about the environmental loading you know we have to have a specialized setups where we expose the soils to different temperatures humidity wind velocity solar cycle and so on and then we simulate the loading conditions on this and these loading conditions are the thermal loading and of course the size of the sample because you will realize that the analogy is from the consolidation test if you take the odometer sample after the consolidation is over you know the pore water pressure is not going to be uniform within the sample is going to be less at the two edges where the porous stone was kept and the pore water pressures are going to be maximum the center of the sample isochrome concept. So sample size plays a very very important role alright.


Hello and welcome to the Grand Line Review, your source for everything One Piece and more specifically, sagas in minutes. The series that aims to equip you with the basic knowledge to leap into the wilderness of One Piece. And today, we'll be going on a dark journey of internal and external strife with the gut-punching saga that is Water Seven. Water Seven is the fourth saga of the series consisting of four arcs which are told over a whopping 139 chapters and 110 anime episodes. So it's a sizable piece of story. And we commence with following the straw hat landing back onto the blue sea as they quickly find themselves on the island of Long Ring Long Land. Here they made a bunch of bizarre creatures including Tonjit as well as a pirate named Foxy who challenges the straw hats to a Davy backfight, which is essentially a pirate contest that allows the winners of certain events to poach crew members or even take the opposing crew's flag. And so a nice comical contest starts up consisting of three events culminating in Luffy donning an afro and defeating Captain Foxy in one of the most hilarious battles of One Piece history. And I very much hope you enjoyed this brief moment of comedy because this is where things are going to start getting pretty real. First up, the crew encounter Marine Admiral Al Kiji, a man of unfathomable power at this point in the story, who manages to easily dismiss Luffy, Zora, and Sanji as well as warn the crew that Robin is a threat to the world due to her ability to read the ancient language as well as a threat to them as every organization that she has ever been a part of has ceased to exist with her going on to be the only survivor. However, for Mr. Al Kiji, this is a private visit and he allows the straw hat to leave Long Ring Long Land because of Luffy's helpful actions in bringing down the corrupt warlord Sir Crocodile on Alabaster. However, being completely outclassed by a Marine Admiral is but one problem as the crew also discover that their ship, the Going Merry, is in desperate need of repair and so they travel to the shipbuilding island of Water Seven to find a ship right to help. Having landed in Anime Venice, the crew splits up into four different groups. With Zora staying with the ship, while Luffy, Nami, and Usopp took the gold attained from Skypeia in order to exchange it for 300 million berries. Meanwhile, Sanji goes off and does his own thing as does Chopper and Robin. However, Robin soon encounters a mysterious figure in a mask claiming to be a member of CP9, a term that Robin is apparently familiar with and thus he abducts her. Luffy and Nami find their way to dock one of the Galila Company to contract a ship right to take a look at the Going Merry. However, after an inspection, it is deemed that the ship is unfixable due to having a broken keel. In the meantime, Usopp is attacked by Thugs belonging to a group known as the Frankie family who stole most of the money the straw hats traded for their gold.  At this point, Luffy makes the tough decision to part with the Going Merry and to buy a new ship. A cause of action that does not sit right with Usopp who claims that Merry is as much their crewmate as anyone else and starts an altercation with Luffy that culminates in Usopp leaving the crew and challenging Luffy to fight for the rights for the Going Merry. During this fight, Usopp displays a stunning evolution, able to hold his own against Luffy using the various technologies and tricks that he has acquired throughout his journey. However, ultimately, Luffy still wins the battle but tearfully leaves the Going Merry to Usopp as Luffy and the rest of the crew move onward. The next morning, the crew receives news that Iceberg, the mayor of Water Seven, was shot by Robin. And just to make things even worse, it is announced that Aqua Laguna, a tidal wave that engulfs the lower part of Water Seven, will be hitting the city that very night. As Luffy and the straw hats work to figure out what is happening with Robin, it becomes apparent that several members of Galila are in fact agents of CP9, a world government organization that specializes in espionage and assassination. Their mission on Water Seven was to acquire the blueprints for the ancient weapon Pluton, which were thought to be held by Iceberg, as well as capture Niko Robin and present her for execution on the judicial island of any lobby. The group succeeded in the latter, blackmailing Robin, by threatening to kill the other straw hat pirates and securing her cooperation in their plans. However, they failed to acquire the blueprints to Pluton, which were actually being held by Frankie. And as it happens, both Frankie and Iceberg were apprentices of a fishman shipwright named Tom, who is best known for having built the Oro Jackson, a ship used by the former pirate king, Goldie Roger. Knowing this, CP9 also moves to capture Frankie and take him along with Robin aboard the sea train bound for any sobby. Shortly before the train departed, both Sanji and Usopp independently boarded it, managing to free Frankie and attempt to rescue Robin. However, Usopp, having left the crew, took it upon himself to craft an alternate identity, becoming the superhero Saga King, because he was too ashamed to face the crew. Ultimately, their efforts would be unsuccessful though, as Frankie was recaptured, while Sanji and Saga King were forced to regroup on another train with the rest of the crew. This train consisted of the remaining straw hats, the Frankie family, and Galila, who had formed an alliance to pursue Robin, Frankie, and deliver vengeance upon the agents who infiltrated Galila. And thus, the small army went on to invade the island of any slobby. Luffy, being impatient and such, went marching on ahead and found his way to the Tower of Justice rather quickly, where he was pit against Blueno. And in order to swiftly defeat him, Luffy revealed Gears 2nd, a technique that he had developed after encountering Al Kiji to ensure that he would be able to protect his crewmates. After taking down the cow look-alike, Luffy yelled for Robin at the top of his lungs, prompting the rest of CP9 to step out, and they would eventually be greeted with the six members of the straw hats who had come to declare war on the world government, but more importantly, reclaim Robin. After breaking into the Tower of Justice, the straw hats each faced off against various members of CP9, with many of them displaying power ups of sorts, such as Nami's new and improved climate-attack techniques, Saaji's Diablo Jamba, and Zora's Ashura. During these fights, the idiotic leader of CP9, Spandam, also accidentally summoned a teeny tiny buster call on the island, which is a fleet of ten marine battleships filmed by five vice admirals who are charged with destroying an entire island with no questions asked. This was also an event that Robin had witnessed once before, as she grew up on the island of Ohara, which was populated by scholars seeking the true history of the world. Upon discovering this, the world government had the island eradicated using a buster call, however Robin survived due to the sympathetic actions of Vice Admiral Kuzan, who would go on to become Admiral Alkegi. However, due to Robin's knowledge, a bounty of 79 million berries was placed on her head at the age of eight years old, and so she began a life consistently on the run, being betrayed by everyone she came into contact with until she met Crocodile and joined Baroque Works. And you know what, even then she was eventually betrayed by him, so yeah. Which was why it was all the more impactful when Robin found the straw hats and became part of their crew, because for the first time in her life, she had found a place where she belonged, with people that she felt she could trust. And so Robin eventually overcame her fear of the world government, as well as her resignation to death, and exclaimed to Luffy that she wanted to live, prompting the current events inside the Tower of Justice. With almost every member of CP9 defeated, Robin was then freed by Frankie, and the straw hats began to face the full force of the buster call, whilst Luffy was still locked in combat with the final CP9 member Rob Lucci. After giving everything he had to give Luffy eventually overcame Lucci, however the straw hats were still faced with an impossible situation, surrounded entirely by marine forces. And at that very moment, they all heard a voice prompting them to jump into the ocean, to which they did and landed on the Going Mary, which had come all the way to any lobby in order to rescue them after begging Iceberg to patch it up. Because by the way, in this world, some ships do have a sense of sentience, and the Going Mary happened to be one of them. After saving the crew, Mary began to completely break down, and it was decided that it was time to lay her to rest. The straw hat stayed with Mary as she burned, and the ship gave a touching goodbye to the crew, grateful for the time she got to spend with them. And with that, an invaluable member of the straw hat pirates was lost, but her legacy would live on with a new ship built by Frankie, known as the Thousand Sunny. As it turns out, Frankie's dream was to build a ship capable of sailing the entire world, and he had spent the money he stole from the straw hats on wood from the treasure tree, Adam. Frankie then gifted the ship to the straw hats and was even recruited to become their official shipwright. A position that the Frankie family begged them to give him, because as a result of his actions on any lobby, Frankie had been assigned a bounty of 44 million berries. In fact, as it would turn out, all of the straw hats were given bounties, with Luffy's in particular being raised to a staggering 300 million berries. Prior to leaving War Two Seven, Luffy also received a visit from his grandfather, Monkey D. Garp, who was a vice admiral of the Marines. Garp then informed Luffy that the latter half of the Grand Lion was known as the New World, and was ruled by the Yonko, or the Four Emperors, one of which was Luffy's idol, Red Head Shanks, the others being quite the strongest man in the world, and two as of yet unmet characters, known only as Big Mom and Kaido. To top everything off, it was also revealed that Dragon was Luffy's father, Dragon being the man who saved Luffy in Locktown, and who was known as the leader of the Revolutionary Army and the most wanted man in the world. Luffy also had a brief reunion with Kobe, who was serving under Garp, and who had undergone quite a growth spurt, and now held the dream of becoming a Marine admiral. As the straw hats were about to leave War Two Seven with Robin safely returned, and a new recruit in Frankie, all that was left was to re-acquire Usopp, who would go on to apologize for his actions, and be warmly welcomed back into the crew as they embarked on their next adventure. But just before we leave this saga, two more events of staggering importance to the greater world would occur, the first of which being a meeting between Shanks and Whitebeard, two of the aforementioned Four Emperors of the Sea.  However, Whitebeard refused to do so, and the two had somewhat of a heated disagreement, which ended in them both drawing their weapons and committing a single strike so powerful that it split the very sky above them clean open. At the same time on Benaro Island it was too late anyway as Ace had finally tracked down Blackbeard. Ace had been hunting him down to secure vengeance as Blackbeard was responsible for the murder of Thatch, the fourth division commander of the Whitebeard Pirates. Blackbeard committed this act in order to obtain a Devil Fruit that Thatch had discovered known as the Yami Yami No Mi, a Logia type fruit that gives its use of the ability to conjure, manipulate, and become darkness, which is also said to be the most evil of all Devil Fruits. And Blackbeard goes on to demonstrate this power first hand by engaging in combat with Firefist Ace, and while the results of this battle were unknown at the time, it would go on to be the catalyst for an entire saga to come. Next time on Saga's In Minutes things are going to be getting spooky as we explore the world's largest pirate ship situated in the mysterious Florian Triangle during the Thriller Bark saga. If you enjoyed this video and the content this channel produced in general, then please do consider donating to the Grand Line Review Patreon because the sport of all of your amazing people is what continues to make this channel possible. And if you'd like to see more videos like this but apply to other anime and manga series, then please do check out my second channel New World Review for all of your wider needs. And if you'd like to join the fun at any time then please do head over to my Discord server where a wide array of shenanigans retakes place on a daily basis. And finally please do comment with your thoughts on the Water 7 saga. This has been the Grand Line Review and I'll see you next time.