Iq option home
Peak response for albendazole. Peak area of the IS, albendazole, was plotted A across three batches i.three 384-well test plates. The mean and S. for the three batches B. Sensitivity of the HRMS instrument A 0-minute chromatogram and B 60-minute chromatogram for buspirone 98 turnover generated from full-scan data acquired with the Thermo QExactive. Mass accuracy of the QExactive. Mass deviation of the IS, albendazole, across nine test plates was measured by comparing the theoretical m z value to the observed m z value.
The mass deviation was measured twice, once at the beginning of the batch with the first sample and once at the end of the batch with the last sample i.sample 1152. The reproducibility of the liquid handler system was investigated by comparing the t 1 2 values of control compounds, included twice in each 384-well plate across multiple plates. Ln response over time of the control compounds across three experiments were plotted to demonstrate the reproducibility between and within experiments Fig.
The results show iq option home reproducibility within plates and between plates Fig. The percent coefficient of variation for the t values of buspirone, loperamide, and ketoconazole between experiments was between 15 and 25which is significantly below the 2-fold acceptable limits. Since antipyrine and carbamazepine are stable compounds, no SD was reported. Drug concentration-time profiles for control samples Ln response of control samples were plotted against time.
Letters a and b in the legend correspond to duplicate samples within the same 384-well test plate. Automated Assay Workflow and Throughput Speed. The total preparation and incubation time for each 384-well plate experiment was 2 hours. The automated assay workflow for the high-throughput metabolic stability assay is summarized in Fig. The automated liquid handler system increased efficiency, reduced error, and increased walk-away time for the scientist. Each incubation plate produced six 384-well plates, with six time points 0 60 minutes for each of the 384 compounds.
Adjacent wells were combined from each plate, thus converting six plates into three, which reduced the UPLC HRMS acquisition time by half and further increased the efficiency of the method without compromising the quality of the data. A typical extracted ion chromatogram for a sample that contains two test compounds and the IS is shown in Fig.
Under optimal conditions, two 384-well incubation plates can be assayed in a week by using one robot and one UPLC MS instrument. The UPLC HRMS acquisition was allowed to run overnight and the time required for each batch 1152 samples was 2 days. Once the acquisition was complete, TraceFinder detected integrated peaks and provided separate output files for each sample. These 1152 files were then imported into the Validator software which automatically extracted data from all samples, generated plots Fig.
8and calculated t 1 2 and CL int. These software tools completely eliminated data extraction time and drastically reduced data analysis time. Workflow schematic for the high-throughput metabolic stability assay. Extracted ion chromatograms of the parent compounds in a single sample containing ketoconazole, loperamide, and the IS, albendazole, based on accurate mass with mass tolerance of 5 ppm. For each sample, the analyst has the option of selecting the most appropriate regression fit with the help of Ln response or remaining versus time curves as well as fitted and calculated parameters.
Overview of user interface of the Validator software. Once the regression fit is assigned, the data can be saved and exported for further analysis modeling and simulation. Compound Library. About 3000 compounds were tested using the newly optimized high-throughput method. Most of these compounds were a part of NCGC NIH Chemical Genomics Center pharmaceutical collection, which encompasses publically available approved and investigational drugs Huang et al.2011 and contains more than 2400 compounds that have been approved for clinical use by US, Canadian, Japanese and European health regulatory authorities.
The remaining compounds tested were from NCATS annotated collection. Molecular properties of compounds, such as logP, topological polar surface area, molecular weight, and Lipinski rule of 5, were calculated using Chemistry Development Kit descriptors tool The Chemistry Development Kit Chemistry Development Kit download SourceForge.
org analytical platform Warr, 2012. As seen from the plots, a large portion of compounds have t 1 2 values greater than 60 minutes, belong in the 251 500 mol. Figure 9 includes plots of the distribution of molecular properties and the CYP3A4 t 1 2 of our test compounds. range, and most of them do not violate Lipinski rules. We did not find any direct correlation of calculated t 1 2 values with the preceding molecular descriptors.
Whereas much microsomal metabolic stability data are available in literature, this is, to our knowledge, the first time that such an extensive compound data base is being tested with an individual isozyme. A detailed presentation of the data as well as in silico model development will follow once CYP3A4 CL int values for the remaining 2000 compounds have been determined. Distributions of molecular weight, experimental t 1 2logP, topological polar surface area, and rule-of-five RO5 violations of the metabolic stability data set generated using KNIME analytical platform.
Discussion and Conclusion. A joint team comprised of members from the IQ Consortium and the NIH National Center for Advancing Translational Sciences undertook the task to measure and publish a data base of CL int values for compounds by major metabolic enzymes, for the benefit of advancing drug-design efforts with regard to metabolic stability. Advantages include enabling advanced computational human metabolic models for individual metabolic isozymes; improving hit selection by high-throughput and computational screening; improving computational models for predicting human pharmacokinetics and enhancing lead optimization by guiding structure modification.
For such data to be generated, a high-density assay format was required. Therefore, a high-throughput assay using automation, 384-well technology, rapid UPLC separations, high-resolution MS as well as MS MS using MRM quantitation, and an automated data analysis method was developed and successfully applied. The t 1 2 values of control compounds between runs exhibited more than 4-fold variation.
Initial pilot experiments with the automated liquid handler produced highly variable results. Compounds in the peripheral wells of the plate had t 1 2 values slightly different than if the same compounds were plated somewhere in the middle of the plate, a phenomenon known as the edge effect. This problem was rectified by preheating the incubation plate and enclosing the liquid handler system during the experiment to ensure even heat distribution across the entire plate.
Air entrapment in the narrow bottoms of the 384-well plates caused random splashing and mixing in adjacent samples. This issue was completely eliminated by reducing the dispensing speed of the liquid handler. Since DMSO concentration affects enzyme activity Di et al. 1 in the final incubation.2003the final concentration of DMSO was kept below 0. The enzyme was purchased in bulk quantity to completely avoid interbatch variability.
Of the 3000 compounds tested, the UPLC HRMS produced reliable data for 2642 compounds with an 88. 1 success rate. There could iq option home several reasons for not obtaining reliable data for the 358 undetected compounds such as weak signal, inefficient ionization and adduct formation. Some compounds that undergo ionization in the positive mode may form M NaM Kor M NH4 adduct ions Ortelli et al.2000; Li et al.
TraceFinder can be programmed to identify whether any of these adducts are present for the 358 compounds that were not successfully detected. The method described in this article has several advantages over existing published methods integrating automated incubation, automated data acquisition, and automated data analysis. The high-throughput high resolution MS method also has several advantages, including 1 4-fold higher capacity 384-well format than existing 96-well formats, 2 efficient testing of large number of compounds with minimal labor and supervision, 3 avoiding individual compound optimization as the same generic method can be used to acquire data, and 4 significantly reduced time for data analysis.
Additionally, by using HRMS in scanning mode, it is possible to interrogate the data afterward for a preliminary look at metabolite structure information. In conclusion, we have successfully established and validated an automated high-throughput metabolic stability assay. This system can be used as a rapid assessment tool for initial screening of novel compounds.
Future efforts will focus on developing in silico tools and characterizing additional compounds with the system using CYP2C9, CYP2D6, and other major CYP isozymes. The authors thank Paul Shinn Compound Management, NCATS and the IQ Consortium Drug Metabolism Group members for their inputs in experimental design Drs. Authorship Contributions. Participated in research design Shah, Kerns, Obach, Wang. Conducted experiments Shah, Kerns.
Contributed new reagents and analytic tools Nguyen, Xu. Dennis Dean VertexJim Kerns AstellasPrashant Desai Eli Lillyand Christopher Keefer Pfizer. Performed data analysis Shah, Kerns, Obach. Wrote or contributed to the writing of the manuscript Shah, Kerns, Nguyen, Obach, Wang, Zakharov, McKew, Simeonov, Hop, Xu. Received June 8, 2016. Accepted July 13, 2016. This work was supported by the Intramural Research Program of the National Center for Advancing Translational Sciences National Institutes of Health.
Bursi Rde Gooyer MEGrootenhuis AJacobs PLvan der Louw Jand Leysen D 2001 Q SAR study on the metabolic stability of steroidal androgens. J Mol Graph Model 19 552 556. Di LKerns EHHong YKleintop TAMcConnell OJand Huryn DM 2003 Optimization of a higher throughput microsomal stability screening assay for profiling drug discovery candidates. J Biomol Screen 8 453 462. Guengerich FP 1999 Cytochrome P-450 3A4 regulation and role in drug metabolism.
Annu Rev Pharmacol Toxicol 39 1 17. Guengerich FP 2008 Cytochrome p450 and chemical toxicology. Chem Res Toxicol 21 70 83. Houston JB 1994 Utility of in vitro drug metabolism data in predicting in vivo metabolic clearance. Biochem Pharmacol 47 1469 1479. Huang RSouthall NWang YYasgar AShinn PJadhav ANguyen DTand Austin CP 2011 The NCGC pharmaceutical collection a comprehensive resource of clinically approved drugs enabling repurposing and chemical genomics.
Ito K and Houston JB 2004 Comparison of the use of liver models for predicting drug clearance using in vitro kinetic data from hepatic microsomes and isolated hepatocytes. Sci Transl Med 3 80ps16. Pharm Res 21 785 792. Korfmacher WAPalmer CANardo CDunn-Meynell KGrotz DCox KLin CCElicone CLiu Cand Duchoslav E 1999 Development of an automated mass spectrometry system for the quantitative analysis of liver microsomal incubation samples a tool for rapid screening of new compounds for metabolic stability.
Rapid Commun Mass Spectrom 13 901 907. Li XFMa MScherban Kand Tam YK 2002 Liquid chromatography-electrospray mass spectrometric studies of ginkgolides and bilobalide using simultaneous monitoring of proton, ammonium and sodium adducts. Analyst Lond 127 641 646. Linget JM and du Vignaud P 1999 Automation of metabolic stability studies in microsomes, cytosol and plasma using a 215 Gilson liquid handler.
J Pharm Biomed Anal 19 893 901. MacKenzie ARMarchington APMiddleton DSNewman Iq option homeand Jones BC 2002 Structure-activity relationships of 1-alkyl-5- 3,4-dichlorophenyl - 5- 2- 3-substituted -1-azetidinyl ethyl -2-piperidones. Selective antagonists of the neurokinin-2 receptor. J Med Chem 45 5365 5377. Nassar AEKamel AMand Clarimont C 2004 Improving the decision-making process in the structural modification of drug candidates enhancing metabolic stability.
Drug Discov Today 9 1020 1028. Nebert DW and Russell DW 2002 Clinical importance of the cytochromes P450. Lancet 360 1155 1162. Niro RByers JPFournier RLand Bachmann K 2003 Application of a convective-dispersion model to predict in vivo hepatic clearance from in vitro measurements utilizing cryopreserved human hepatocytes. Curr Drug Metab 4 357 369. Obach RSBaxter JGListon TESilber BMJones BCMacIntyre FRance DJand Wastall P 1997 The prediction of human pharmacokinetic parameters from preclinical and in vitro metabolism data.
J Pharmacol Exp Ther 283 46 58. O Connor DMortishire-Smith RMorrison DDavies Aand Dominguez M 2006 Ultra-performance liquid chromatography coupled to time-of-flight mass spectrometry for robust, high-throughput quantitative analysis of an automated metabolic stability assay, with simultaneous determination of metabolic data. Rapid Commun Mass Spectrom 20 851 857.
Ortelli DRudaz SCognard Eand Veuthey JL 2000. Analysis of dihydroartemisinin in plasma by liquid chromatography mass spectrometry. Chromatographia 52 445 450. Sakiyama YYuki HMoriya THattori KSuzuki MShimada Kand Honma T 2008 Predicting human liver microsomal stability with machine learning techniques. J Mol Graph Model 26 907 915. Shen MXiao YGolbraikh AGombar VKand Tropsha A 2003 Development and validation of k-nearest-neighbor QSPR models of metabolic stability of drug candidates.
J Med Chem 46 3013 3020. Shui WLin SZhang AChen YHuang Yand Sanders M 2011 Driving efficiency in a high-throughput metabolic stability assay through a generic high-resolution accurate mass method and automated data mining. Protein Cell 2 680 688. Warr WA 2012 Scientific workflow systems Pipeline Pilot and KNIME. J Comput Aided Mol Des 26 801 804. In this issue. Automated High-Throughput Metabolic Stability Assay Method. Tweet Widget Facebook Like Google Plus One. Abstract Introduction Materials and Methods Results Discussion and Conclusion Acknowledgments Authorship Contributions Footnotes Abbreviations References.
ASPET s Other Journals. Copyright 2020 by the American Society for Pharmacology and Experimental Therapeutics. Table of Contents Table of Contents PDF About the Cover Index by author Editorial Board PDF Front Matter PDF. Government work not protected by U. Publish date July 10, 2017. An Interview with Famed Value Investor Guy Spier.
It was probably due to his book, The Education of a Value Investor. In it he recounts everything from his lunch with Warren Buffett to how he s beat the market for two decades and counting. Guy is an extremely generous person who does not mind sharing his knowledge with others and occasionally enjoys playing chess competitively or to pass the time. Guy runs the Aquamarine Fund, which is closely modeled on the Buffett partnerships of the 50s.
He earned his MBA from Harvard Business School and has been a successful investor for the past 25 years. In his latest annual report, he discusses his decision to pass on investing in Amazon in 2012. I found his analysis fascinating, so reached out to him about an interview. He responded almost immediately, and the result is a 2 hour interview, which I ve included below.
We talk about everything from Warren Buffett, to Amazon, to competitive chess. Topics covered in the Interview. Chess and the area of pattern recognition Warren Buffett and his confidence with the stock market Why the fear pattern is important when it comes to investments and the economy Investing in debt and equities The insiders game who wins and who loses What is indexing and why it matters Value Traps Buying Amazon stock What is the biggest danger value investors have.
Bill Ackman vs. First Union Realty Amazon s purchase of Whole Foods Different types of reading to keep up-to-date Reading physical newspapers vs. obtaining information online from apps, blogs, and social media How to approach the world of investing intelligently Where some of the best investing insights come from Deciding what investors to follow and the reasons why Recommendations of research tools for individual investors Using stock screens to research companies Tony Robbins and the self-help culture The Aquamarine Fund.
Resources Mentioned in the Interview. The Tim Ferriss Show Entrepreneurs on Fire The Internet Chess Club Chess24 The Education of a Value Investor My Transformative Quest for Wealth, Wisdom, and Enlightenment Aquamarine Fund Trello Stratechery The Information Factiva Dataroma Capital IQ Money Master the Game 7 Simple Steps to Financial Freedom Awaken the Giant Within Value X. Guy Spier Interview Transcript.
Guy I ll send you this file once it s done. I know that podcasts are all about the highest quality sound and I know that s a Hiel PR-40 mic and you have a pop-thing on it and it looks so great. Are you using a USB or is that going into a. Rob I use and by the way, I m hearing feedback on my end. Guy What does that mean.
Rob I can hear my own voice. I don t know if that s getting picked up on the recording or not. Guy I have no idea but it s really hot here and we don t have air-conditioning so I don t know. If I put some did that feedback go away now. Rob Yeah, I think it did. Guy It was feeding out of the microphone and into the speakers. Your sound is feeding out of the microphone and into the speakers basically.
Rob When I bought this microphone and I know nothing about this stuff I just assumed it would have a USB plug on the end of it and I could just plug it into my computer and I was wrong. Then I did some research and ended up buying a Steinberg UR-22 which is just a box and you plug the mic into it and then out the end of it there is another cord that converts it to USB and I just plug it into my computer. Anyway, I think what you also have is reflection of the desk so it s not as high-quality audio but I think what I love about the podcast medium is that there s an intimacy to it which is just incredible.
You re right up there close with your audience. Rob That really took me by surprise. I ve been blogging for 10 years. I started the podcast almost four years ago and when I was blogging I d get an email every now and again from someone who had read an article but it wasn t very frequent. I don t recall when I first heard of Guy Spier.
When I started podcasting, I got a flood of email. I ve gotten to the point now where I read every single email. I tell people that and it s true, but I don t give substantive responses because I can t. I would spend all day responding to email. What I do instead is take a lot of the questions people ask me and answer them on the podcast. I ve had meet-ups where we ll meet up at coffee shops here locally in the Washington, DC area.
So yeah, there is definitely a connection you make with your listeners that you just don t with the written word. Guy Yeah, it s quite incredible and I ve thought about podcasting mainly because of the fun of connecting to people and the incredible closeness you get to them. I record a podcast with somebody and two or three hours later somebody is emailing me about it and I m blown away. I was going to ask you, what fills the bank account if you re not selling advertisement which I think is great, by the way.
Rob The blog basically drives the business side of it the website. It s also very it s a medium that s very there s a high longevity. Iq option home times I ve thought about advertising on the podcast and I came really, really close just a couple of months ago to signing a deal to run ads and it just didn t seem right. It s not that I ll never the day could come when I decide to advertise on the podcast. I don t want to say never but part of me just thought, you have to know when you have enough.
I have enough so I just view the podcast as something I enjoy doing and a way to give back that s not motivated by money. I really enjoy listening to Tim Ferriss podcasts. They re great. There s an element to which he s pushing an angle where he s kind of just pushing some particular thing. And, there I am with whatever it is I m doing and I suddenly realize I ve listened to a few minutes worth of him plugging something.
There s something that s not completely pure about that. At the end of the day people have to put bread on the table so I guess it s is okay. I don t know what you think of John Lee Dumas, JLD. He, as well, has just got a wonderful podcast and it s really inspiring. Again, this applies to the podcast because he s making money out of them as well. He s getting affiliate fees. Rob The truth is, Guy, I don t listen to a lot of podcasts which is maybe ironic, I don t know. I ve listened to both of theirs and I joined John Lee Dumas he had a forum for podcasters when I was first getting started.
He publishes his income online and is making six-figures a month. I think he and his girlfriend moved to Puerto Rico not long ago. Maybe for some of the tax advantages there but he s obviously built up a tremendous business. And Tim Ferris, depending on who his guest is, I think his interviews are some of the best out there.
So you re based in DC and I m honored that you wanted me to come onto your show. Rob You re honored. I m honored that you said yes. I wasn t sure I would even get a return email when I reached out to you. You emailed me right away and I m grateful. And look, I ve got a whole card full of questions. One of the things we want to talk about is Amazon and I m sure you saw that they just signed a deal to buy Whole Foods which I may ask you about.
But yeah, if it s okay I ll jump right in. Rob I want to start with what I think has got to be the most important topic we ll discuss today and that is whether you still play chess. He keeps asking me for games so I play him. Guy You know, I play with my son. I have a question mark in my mind though. Every time I play him, I play him as well as I can.
I don t want to shield him from how well I play which is not all that well. I want to go online and play but it s such a time-sink. The last time I went online which is probably more than a year ago I got so depressed at my rating I had people at a chess rating of 900 beating me so I don t know that I can say I regularly play chess anymore.
Rob When you play online, where do you play. Guy The Internet Chess Club is the place I ve enjoyed playing. I could open that up anytime and start playing. They have a great app which is sitting here on my desktop. It s easy with Blitzin. If you like playing we can play each other. I could pull out a game right now. Rob I d love to actually but I don t iq option home if I m set up with the Internet Chess Club.
I play at chess24. Guy And what s your rating. Rob It s funny you should ask. Guy Did you hear that. Guy I just loaded my Blitzin to see what s going on there. Rob Right now my rating is 2,100 on chess24. Guy You re a very good player. I have never gotten that high. My highest rating ever is about 1,600. Rob Well, if you had asked me a couple of days ago my rating on chess24 could very easily been iq option home or 1,800. I tend to go through spurts where I win a lot and then lose a lot so my rating can fluctuate by 400 points or so, on Chess24.
I d go and play a bunch of 900 rated guys and play really badly or intentionally lose or make a sacrifice where I had no chance of winning up against and watch my rating go down to about 1,200. Guy Actually, when I playing with people with a 1,500 or 1,600 ratings, something I used to enjoy doing would be to deliberately take my rating down.
Then I d get all of these guys challenging me to a 1,200 rated game and I d smash them really good laughs. So the most satisfying thing for me and I m talking to you now, I have enormous respect for you. To play to 2,100 if I m not mistaken, 2,500 is Grand Master. You ought to be able to beat me at every game we play just based on 2,100 compared to what my rating is.
I love open games. I love breaking open anything no strategy left and just pure tactics. When I was playing a lot I really used to enjoy pawn storms. To get a kings opening and then just figure out a pawn storm and to watch and feel the impending sense of doom the other player feels as his defenses are totally ripped to pieces I m sorry I m just diving deep into it. There s a player called Bronstein, whose games one can look at. He always played open games and, of course, the open games are always a wild ride because there are always twists and turns of fate that you d never know how the hell they re going to go.
Just talking about it is kind of fun. What really annoys me is when people play this closed, sort of, trench fighting. I always try to rip those things open. My play is very much in the direction of a duffer in that I find it really, really hard to keep my wits about me and keep a cool and level head as the game gets exciting. When I followed it closely, I just never enjoyed the way Karpov played. I never, ever enjoyed it. And even then, the thing is, the way Kasparov would play is he was a much more dynamic player.
Even he realized that in order to win you really have to button it down and that just makes the play less interesting, it seems, to me. But no, I don t play near as much or enough. There is something about playing on a real board in a real open session. I don t know if you have anything like this in Washington, but in New York City there are these amazing places where you can go and just pick up games.
Rob Yeah, in New York City well, now St. Louis has become more of the chess capital of the US because of the great things they ve done there at the Chess Club and the Chess Hall of Fame, but New York is probably still the dominant location for Grand Masters. I think I read you were a member of the Marshall Chess Club at one point. I ve played there. There are great places to play there in the park. In fact, I m playing in a tournament that starts tonight but, no, it s not like New York City.
Guy But good for you that you re playing. I can t honestly claim that I m a regular chess player. I wish I could but I can t. I ve got Blitzin open right now. But, I ll just go and lose a bunch of games if I go and play laughs. Rob I was trying to download Blitzin and get it set up so we could play but I don t think I can do that and talk to you at the same time.
I tried and failed. In your book, The Education of a Value Investoryou talk a little bit about chess and bridge games and their relationship to investing. I wanted to explore that a little bit, if we could. One thing about chess I ve really gotten back into the game a lot in the last year and will listen to Grand Masters. He s ranked 14th in the world. You can watch him on chess24 play speed chess with different players and he ll talk about the game as he s playing.
Of course, he s winning virtually every single game. The thing I ve noticed is you ll see a position and in my mind I m trying to calculate as I m following the game Okay, he can move his knight there and the other side will move their bishop there, and then he can move his rook He just instantly sees a three, four, or five move combination and he talks about it. Peter Svidler is one of them. In a blink of an eye he sees it.
I know he s a Grandmaster but still, how do you calculate that quickly. At first I wondered, how in the world he could calculate that. After watching him for awhile I realized, you don t. He s not calculating at all. He just sees the pattern. He recognizes the pattern, thinking fast and slow for example. I m thinking slow and probably coming out with a bad result. He s thinking fast because he doesn t really have to think at all. It made me wonder, are there patterns you see as you re evaluating companies or industries in selecting investment possibilities.
Are there patterns that you ve recognized over time that can help you identify investing opportunities. Guy I don t think I m particularly good at it but I think there are patterns of human behavior that I can certainly start to recognize even though I m not necessarily good at managing myself in those patterns. I get very concerned with situations where there is an enormous amount of controversy.
What I really love is situations where there is an enormous amount of fear and that fear is not rationally based. I think people are just not looking there. I haven t come across those situations too often but I can see that happen very, very clearly now and I know if I m operating in a place where that s the case. That s why I think Warren Buffett is so confident that no matter what direction the market has turned and how overvalued things get and how competitive the investment gain gets, there are always going to be pockets where people are just fearful and don t want to tread.
And, if you re willing to tread there, then you ll do fine. I just remembered, a way to reinforce that pattern for me, was in the height of the financial crisis Warren Buffett bought shares of Goldman Sachs. And, it s just incredible because all mayhem was breaking loose and he dove straight into the middle of it and bought shares of Goldman Sachs. There was very little certainty about the way things were going to unfold. I think that was an example of him saying, This is a valuable company.
There is a lot of uncertainty around it but these guys are smart and will figure it out. And I m buying into that uncertainty. And I m buying into that fear. Which, by the way, you re probably going to bring it up later, is exactly what is really hard about companies like Amazon and Netflix and which doesn t exist.
The emotional pattern you need to get in to buy Amazon or Netflix right now is to say, Yes, those guys are all exuberant about the future of this company but I m even more exuberant. You re buying on top of other peoples exuberance and that s a very, very different place to say, buying Goldman Sachs in the middle of the financial crisis.
It s not an analytical pattern but it s an emotional pattern. I think that what s hard when you look at analytical patterns. I wrote my annual report about bundling. Economies are bundling or scaled economies, share. And what s really frustrating about that is that often other people see those patterns as well, if not better, than I do. So I m coming late into that game. But the fear pattern is a really, really valuable one.
I think once you do extraordinarily well without such good analytical abilities in general, you ought to buy off a fearful buyer. You want to be a buyer when other people are fearful. And there s no fear. I think there are some people that would never be able to beat you or me at chess because they re not analytical thinkers.
But, they get a sense of that. They get a sense of where they want to be. There is a guy I met not so long ago who lives in Geneva of all places, who is a retailer. At the time, he was putting all of his money into Canadian real estate. And actually, it was really clear that commodity prices had come down. The tar sands oil was no longer profitable so Canada was suffering but he was buying real estate in downtown Toronto.
He had a sense that that would turn out fine over time. He was shifting his whole real estate portfolio into Toronto real estate. And, he didn t know that much about Toronto real estate but he knew he was buying into a situation which wasn t entirely distressed, but there was fear. There was lack of liquidity and people in Canada were very, very unhappy.
But he wasn t buying some speculative he was buying into real estate where he knew, one way or another, this would work out for him. So he wasn t being as greedy as he possibly could. He wasn t buying into tar sands companies that were losing enormous amounts of money and filing for bankruptcy. I think he was buying downtown Toronto real estate.
Coments:20.02.2020 : 17:39 JoJole:
What s different about G HUB compared to LGS.
22.02.2020 : 21:59 Vudogrel:
You might iq option home give instructions on how to get into your building. Startling, isn t it. We ve gone from an age when people left the lights on at home while away on holiday to deter burglars, to a world in which we happily fill out forms that advertise our iq option home.
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Bose Noise Cancelling Headphones 700 feature a cutting-edge four-microphone system that isolates your voice while cancelling the background noise iq option home you.
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