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In this episode we talk with Manita Pote, a PhD student at Indiana University Bloomington, specializing in online trust and safety, with a focus on detecting coordinated manipulation campaigns on social media. Key insights include how coordinated reply attacks target influential figures like journalists and politicians, how machine learning models can detect these inauthentic campaigns using structural and behavioral features, and how deletion patterns reveal efforts to evade moderation or manipulate engagement metrics. Follow our guest X/Twitter Google Scholar Papers in focus Coordinated Reply Attacks in Influence Operations: Characterization and Detection ,2025 Manipulating Twitter through Deletions,2022
Today we're going to talk about review deletions. In other words, you kill yourself to get great reviews for your business or your products and services and they get deleted. Well, let's talk about why that happens today. Screw The Commute Podcast Show Notes Episode 981 How To Automate Your Business - https://screwthecommute.com/automatefree/ Internet Marketing Training Center - https://imtcva.org/ Higher Education Webinar – https://screwthecommute.com/webinars See Tom's Stuff – https://linktr.ee/antionandassociates 00:23 Tom's introduction to Review Deletions 01:23 Google and Amazon are removing 5 star reviews 04:32 Replying to your reviews will help 07:48 Deletions are based on the reviewer's reputation 09:01 What you can do about it Entrepreneurial Resources Mentioned in This Podcast Higher Education Webinar - https://screwthecommute.com/webinars Screw The Commute - https://screwthecommute.com/ Screw The Commute Podcast App - https://screwthecommute.com/app/ College Ripoff Quiz - https://imtcva.org/quiz Know a young person for our Youth Episode Series? Send an email to Tom! - orders@antion.com Have a Roku box? Find Tom's Public Speaking Channel there! - https://channelstore.roku.com/details/267358/the-public-speaking-channel How To Automate Your Business - https://screwthecommute.com/automatefree/ Internet Marketing Retreat and Joint Venture Program - https://greatinternetmarketingtraining.com/ KickStartCart - http://www.kickstartcart.com/ Copywriting901 - https://copywriting901.com/ Become a Great Podcast Guest - https://screwthecommute.com/greatpodcastguest Training - https://screwthecommute.com/training Disabilities Page - https://imtcva.org/disabilities/ Tom's Patreon Page - https://screwthecommute.com/patreon/ Tom on TikTok - https://tiktok.com/@digitalmultimillionaire/ Google deletes 5 star reviews - https://gmbapi.com/news/google-deletes-5-star-reviews/ Email Tom: Tom@ScrewTheCommute.com Internet Marketing Training Center - https://imtcva.org/ Related Episodes Nix SEO - https://screwthecommute.com/980/ More Entrepreneurial Resources for Home Based Business, Lifestyle Business, Passive Income, Professional Speaking and Online Business I discovered a great new headline / subject line / subheading generator that will actually analyze which headlines and subject lines are best for your market. I negotiated a deal with the developer of this revolutionary and inexpensive software. Oh, and it's good on Mac and PC. Go here: http://jvz1.com/c/41743/183906 The Wordpress Ecourse. Learn how to Make World Class Websites for $20 or less. https://screwthecommute.com/wordpressecourse/ Join our Private Facebook Group! One week trial for only a buck and then $37 a month, or save a ton with one payment of $297 for a year. Click the image to see all the details and sign up or go to https://www.greatinternetmarketing.com/screwthecommute/ After you sign up, check your email for instructions on getting in the group.
In this bonus episode of the Blood podcast, we'll hear from Dr. Nicole Thornton, senior author of the article “Deletions in the MAL gene result in loss of Mal protein, defining the rare inherited AnWj-negative blood group phenotype”, speaks with Blood Associate Editor Dr. Erica Wood about the discovery of the genetic basis for the inherited AnWj-negative blood group phenotype. The discovery that Mal protein is expressed on red blood cell membranes of AnWj-positive, but not AnWj-negative individuals, and that homozygous deletion in MAL causes the AnWj-negative blood group phenotype, helps answer a decades-old mystery related to the high prevalence red blood cell antigen AnWj and forms the basis of a new blood group system.
No-one wins every game, every match, every point. Failure is part of the process of winning. It's an important part because we learn from it. We learn what to do better next time. We learn about choosing other options, being flexible in our thinking, trying another approach. It makes us work harder, strive more.Through failing and working through it, we get stronger, more resilient, but it isn't easy, especially when you're young.Many young athletes want to make their parents proud, impress their coach and have their teammates cheer for them and celebrate their triumphs. But doing well to get the approval of others isn't something we can control. It's fragile and it can make us vulnerable when that is our aim.Winning isn't in our control because it depends on others performing less well on the day than you.It can depend on the standard of the competition, the state of the environment – weather, ground, crowd, so many factors beyond our control.Have you heard of the Feedback sandwich?Overall, what went well?What could I have done more of?What could I have done less of?Overall, what was the positive feedback for me?Let's apply this to your last sports event.This is a bit more like a feedback bap isn't it?!What went well?What could I have done more and what could I have done less ofOverall, what is the positive feedback for meLet's learn something about feedback.Who has an ‘inner critic' who says things like this.“Why do you always do that?”“Why do I never score”“Why is everyone better than me”“No-one passes to me”These are Generalisations and they are never true.The interesting thing about generalisations is actually the exceptions.So write down a generalisation using: always/never, everyone/no-one that you say to yourself.I always …………………………………………….I never………………………………………………Everyone …………………………………………..No-one…………………………………………………..Now change these toSometimes I…………………………………………….Some people……………………………………………Think about those times when that thing did not happen and there you have your ‘model of excellence'.What was ‘the difference that made the difference' on that occasion? Do this more often!Let's look at another way we give ourselves feedback. Coaches, teachers, listen up because perhaps you could change the way you give feedback.Deletions are when we delete the detail or the context so for example“That was better”“You didn't play well today”“That was mean”Ask, how, in what way to get the detail that you can learn from.In order to learn from that feedback we need to know what we did that made the difference so we can do it again.Let me tell you something you may not know. You may sometimes talk about your ‘anxiety' or ‘anger issue'. These are deletions too. Why? Because they don't really tell you anything do they? What is missing? The context. You're not anxious all the time or angry all the time. If this may apply to you, have a go at some of these ways to reframe these deletions to include the context and get more mindset control for your sport.I feel anxious when ………………………………..What worries me is if……………………………………………………………….... makes me anxiousI'm worried about……………………………………I feel angry when………….………………………..…………………………………...makes me angryIf …………………………….……I get really angryNow let's link these so you can see the connection.I feel angry when……………………………………..and I'm worried that………………………………….So next time you feel angry about something, ask yourself what you were worried about. Then give it a score of 0-10 as to how likely that thing is to happen. If more than 5 do something about it and if less than 5, take some deep breaths and choose to calm down. Control your controllables!Another form of deletion is saying‘I can't'Again we have deleted the context.When can't you?Who says?'What if you could?When can you?What ‘can't' you do?I can't…………………………………………………….Now answer those questions above.When can't you?......................................................Who says this?.........................................................What if you could?...................................................When can you?.........................................................In NLP terms, it is called a modal operator of possibility in that it makes what is possible, impossible in that moment. It is a blocker.What can't you do in your sport?I can't…………………………………………………Let me tell you a story.I was training two students at my house a few years ago and we were talking about ‘beliefs of excellence'.I asked N what she'd like to be able to do. She wanted to do a Yoga headstand. “I can do that, said J” and proceeded to show her. N had a go but said “It's no good, I can't do it.”She watched again and tried again but still insisted that she couldn't do it. Each time she just did a little bunny hop and didn't manage to get her bottom far enough over her head to be able to raise her legs up the wall.We went through the structure with J. What did she do first, then next and so on but N still couldn't do it.This brings me to the NLP Modelling process whereby you copy someone who can do the thing you want to do OR importantly focus on the time YOU can do that thing, and identify the successful belief. Think about what you were thinking just before you do the thing and it works brilliantly.J said: “Just before I do a Yoga headstand I think ‘this will be fun'”N laughed and said “I'm thinking, ‘I can't do this'”Of course, we can clearly see that if you think you can't do something then you won't be able to do it. We're literally telling ourselves that we can't do it and because the mind and body are connected, we won't be able to do it.N said she could not imagine doing the yoga headstand as ‘fun' so I asked her to imagine something that she thought was fun, before she attempted the headstand. She did that and she achieved an absolutely perfect yoga headstand straight away.The learning here is that ‘If you always do what you've always done (note the generalisation) you'll always get what you've always got.'. Your old way of thinking did not work.Instead, take a different way of thinking that is successful for someone else or for that time when you have successfully done that thing.When you find yourself using a generalisation in your thinking, ask yourself:“Really? Is that really always true. When was it not true? What happened then? What was my thinking? What was my belief about doing that thing?” Now transfer that more effective or resourceful belief to where you need it now.Then lastly we have Distortions. These are mindreads. We are making an assumption about the intentions of another player, team-mate, the coach or teacher or your parent.You cannot read people's minds. Think about it.He deliberately……………………………………..She made me feel…………………………………They don't like me………………………………….Give yourself and others feedback that you and they can learn from.This is my latest book. You can buy it for Kindle as an EBook or a paperback where your sporty teen can ‘engage' with it, underline bits, highlight, make notes and so on. Thanks for reading Understanding children and teens by Judy Bartkowiak! This post is public so feel free to share it. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit judybart.substack.com/subscribe
What is happening to federal diversity, equity and inclusion data? How does the Workers Retention Ordinance impact the Northwestern community? What is R. F. Kuang's experience like as an Asian American author? The Daily answers these questions and recaps other top stories from the last week. Read the full story here: https://dailynorthwestern.com/2025/03/03/audio/the-weekly-federal-data-deletions-workers-retention-ordinance-r-f-kuang/
Research Affiliates' Rob Arnott delves into the strategy of investing in companies recently removed from major market indices and offers perspective on current stock valuations. VettaFi's Cinthia Murphy presents five ETF predictions for 2025.
News includes a new video from José Valim demonstrating Livebook deployments, Chris McCord's "Pawsitively" project integrating content moderation with Livebook, the release of Zigler 0.13.1, a new AI-centric library called Honeycomb by Sean Moriarity and Andrés Alejos, an Elixir job listing at Apple, and more! Show Notes online - http://podcast.thinkingelixir.com/216 (http://podcast.thinkingelixir.com/216) Elixir Community News - https://www.youtube.com/watch?v=lwLx5beXxsg (https://www.youtube.com/watch?v=lwLx5beXxsg?utm_source=thinkingelixir&utm_medium=shownotes) – How to deploy a Livebook app with Livebook Teams. - https://livebook.dev/teams/ (https://livebook.dev/teams/?utm_source=thinkingelixir&utm_medium=shownotes) – Link to Livebook Teams homepage. - https://docs.google.com/forms/d/e/1FAIpQLScDfvUqT4fs95dqNGyoXwVMDVl059jT6r5MPgXB99XVMCuw/viewform (https://docs.google.com/forms/d/e/1FAIpQLScDfvUqT4f_s95dqNGyoXwVMD_Vl059jT6r5MPgXB99XVMCuw/viewform?utm_source=thinkingelixir&utm_medium=shownotes) – Request to join the free Livebook Teams beta. - https://x.com/chris_mccord/status/1821586189364994202 (https://x.com/chris_mccord/status/1821586189364994202?utm_source=thinkingelixir&utm_medium=shownotes) – Chris McCord shared a demo project called "Pawsitively" which implements a content moderation system. - https://gist.github.com/chrismccord/4824237157902ed1c47f825b1f1d9d27 (https://gist.github.com/chrismccord/4824237157902ed1c47f825b1f1d9d27?utm_source=thinkingelixir&utm_medium=shownotes) – Gist of the demo which uses Livebook and Mistral LLM for content moderation. - https://pawsitively.fly.dev/ (https://pawsitively.fly.dev/?utm_source=thinkingelixir&utm_medium=shownotes) – Play with the "Pawsitively" demo online. - The demo defines everything in a Livebook file and covers “Manual Docker Deployment”. - https://x.com/dnautics/status/1822878889275719795 (https://x.com/dnautics/status/1822878889275719795?utm_source=thinkingelixir&utm_medium=shownotes) – Announcement of Zigler 0.13.1. - https://github.com/E-xyza/zigler (https://github.com/E-xyza/zigler?utm_source=thinkingelixir&utm_medium=shownotes) – GitHub page for Zigler. - https://hexdocs.pm/zigler/0.13.1/Zig.html (https://hexdocs.pm/zigler/0.13.1/Zig.html?utm_source=thinkingelixir&utm_medium=shownotes) – Zigler 0.13.1 documentation. - https://ziglang.org/ (https://ziglang.org/?utm_source=thinkingelixir&utm_medium=shownotes) – Official site for the Zig programming language. - https://podcast.thinkingelixir.com/83 (https://podcast.thinkingelixir.com/83?utm_source=thinkingelixir&utm_medium=shownotes) – Podcast episode discussing Zig and Zigler in depth. - https://x.com/germsvel/status/1823304992876618032 (https://x.com/germsvel/status/1823304992876618032?utm_source=thinkingelixir&utm_medium=shownotes) – German Velasco shows how to use Macro.to_string/1 to convert AST to clearer Elixir code. - https://github.com/elixir-error-tracker/error-tracker/releases/tag/v0.2.0 (https://github.com/elixir-error-tracker/error-tracker/releases/tag/v0.2.0?utm_source=thinkingelixir&utm_medium=shownotes) – Release details for ErrorTracker 0.2.0. - https://evilmartians.com/chronicles/soft-deletion-with-postgresql-but-with-logic-on-the-database (https://evilmartians.com/chronicles/soft-deletion-with-postgresql-but-with-logic-on-the-database?utm_source=thinkingelixir&utm_medium=shownotes) – Blog post about hard and soft deletion with PostgreSQL. - https://x.com/josevalim/status/1821143821649948822 (https://x.com/josevalim/status/1821143821649948822?utm_source=thinkingelixir&utm_medium=shownotes) – José Valim shares a tip on soft deletion with PostgreSQL. - https://dashbit.co/blog/soft-deletes-with-ecto (https://dashbit.co/blog/soft-deletes-with-ecto?utm_source=thinkingelixir&utm_medium=shownotes) – Article on implementing soft deletes with Ecto. - https://github.com/seanmor5/honeycomb (https://github.com/seanmor5/honeycomb?utm_source=thinkingelixir&utm_medium=shownotes) – New AI-centric library Honeycomb for fast LLM inference with Elixir and Bumblebee. - https://x.com/sean_moriarity/status/1820887135291085244 (https://x.com/sean_moriarity/status/1820887135291085244?utm_source=thinkingelixir&utm_medium=shownotes) – Sean Moriarity's announcement of Honeycomb library. - https://x.com/wojtekmach/status/1823339271731683743 (https://x.com/wojtekmach/status/1823339271731683743?utm_source=thinkingelixir&utm_medium=shownotes) – Wojtek Mach explains more about Hex.pm's "Bob" and its future directions. - https://github.com/erlef/build-and-packaging-wg/issues/80 (https://github.com/erlef/build-and-packaging-wg/issues/80?utm_source=thinkingelixir&utm_medium=shownotes) – Proposal on managing Erlang builds. - https://x.com/wojtekmach/status/1823374248569626638 (https://x.com/wojtekmach/status/1823374248569626638?utm_source=thinkingelixir&utm_medium=shownotes) – Further updates on Bob and Erlang builds. - https://jobs.apple.com/en-us/details/200562288/senior-software-engineer-elixir-environmental-systems (https://jobs.apple.com/en-us/details/200562288/senior-software-engineer-elixir-environmental-systems?utm_source=thinkingelixir&utm_medium=shownotes) – The Elixir developer position at Apple. - https://2024.elixirconf.com/schedule/#schedules (https://2024.elixirconf.com/schedule/#schedules?utm_source=thinkingelixir&utm_medium=shownotes) – ElixirConf 2024 schedules are posted. - https://x.com/i/lists/1819858270737268846 (https://x.com/i/lists/1819858270737268846?utm_source=thinkingelixir&utm_medium=shownotes) – Twitter list of ElixirConf speakers. - https://2024.elixirconf.com/ (https://2024.elixirconf.com/?utm_source=thinkingelixir&utm_medium=shownotes) – ElixirConf 2024 official website. - ElixirConf weekly hangouts with speakers at 11am CDT on Twitter. Talks span from August 28-30. Do you have some Elixir news to share? Tell us at @ThinkingElixir (https://twitter.com/ThinkingElixir) or email at show@thinkingelixir.com (mailto:show@thinkingelixir.com) Find us online - Message the show - @ThinkingElixir (https://twitter.com/ThinkingElixir) - Message the show on Fediverse - @ThinkingElixir@genserver.social (https://genserver.social/ThinkingElixir) - Email the show - show@thinkingelixir.com (mailto:show@thinkingelixir.com) - Mark Ericksen - @brainlid (https://twitter.com/brainlid) - Mark Ericksen on Fediverse - @brainlid@genserver.social (https://genserver.social/brainlid) - David Bernheisel - @bernheisel (https://twitter.com/bernheisel) - David Bernheisel on Fediverse - @dbern@genserver.social (https://genserver.social/dbern)
Never underestimate the ability of a dedicated leader to effect massive change.
Backing up to auto-syncing cloud services is very convenient. But what happens when it syncs your mistake?
The Ikigai of Stretch: A New Process for Change In this special, longer episode, we're diving into an extract from a Q&A Zoom call with my son, Joseph Clough. Joseph runs a program that helps people let go of their core issues like anxiety and negative beliefs. We each host two live Q&A calls a month, where we answer questions and introduce new concepts to the program. This particular session focuses on what I call the "Ikigai of Stretch." We explore the concept of Ikigai, which means finding your purpose, and how it can be adapted to help you change behaviors and emotions you don't like. This episode includes a detailed explanation of the Ikigai model, a new fourth circle, and a process I've developed to help you move from your present state to your desired state. The episode concludes with an eight-minute hypnosis process designed to facilitate this change. Make sure you're in a safe, distraction-free environment before you start, especially for the hypnosis segment. Enjoy the journey! 00:00:00" This is an extract from a Q and a Zoom call I did for my son 00:02:20" Paul Clough says finding your purpose in life is key to success 00:09:16" I call it the ikigia of stretch because each one is a 00:12:31" How do I want to be? And, uh, you'll notice 00:18:23" Write down what you want in the world. What is that desired state 00:24:28" You could go to any stationery store and buy a plain book 00:24:49" Ask your unconscious mind what you would like to change about yourself 00:28:44" I ask you to describe what you want to change about yourself 00:38:18" Paul Clough says it's time to fly on your own https://personaldevelopmentunplugged.com/396-the-ikigia-of-stretch Shine brightly Paul Please remember you can leave a comment or email me with questions, requests and feedback. If you have enjoyed this or any other episode please share and subscribe. Just email me feedback@personaldevelopmentunplugged.com If you want to subscribe to the podcast (I know you do) click here to learn more Or simply click here to go straight to Apple Music / iTunes to subscribe OR leave a review Remember for my specially designed programs for developing Supreme Inner Confidence, Free Your Life of Anxiety and specialize Hypnosis tracks go to PaulCloughOnline.com If you want to access my FREE HYPNOSIS tracks go to paulcloughonline.com/podcast Follow and inter-react on twitter @pcloughie I'm a therapist but not your therapist The information with this website or online work, techniques and exercises provided within these free and paid products are for educational purposes only. Do not use the techniques or exercises contained within some of these free or paid products whilst driving or operating machinery, or if you suffer from epilepsy, clinical depression or any other nervous or psychiatric conditions. The information provided is not a substitute for proper medical advice. If in doubt, please consult your doctor or licensed medical practitioner. Any decision you make having received any of Paul Clough's free or paid products are your own and you remain wholly responsible for any decisions and actions you take. Why not look for me and the podcast on SPOTIFY AND the app Castbox I'm also in iHeart radio YouTube - copy n paste UC3BlpN4voq8aAN7ePsIMt2Q into search bar The Libsyn podcast page http://personaldevelomentunplugged.libsyn.com tunein, learnoutloud, Google Play Music Music by Wataboi from Pixabay, Music by DreamHeaven from Pixabay, Music by ccjmusic from Pixabay, >, Music by freegroove pixabay seduction-jazz-112149 from Pixabay, Music by prazkhanal Pixaby ventura-117073 from Pixabay, And the transcript WARNING if you're a lover of the written word this may make you frustrated, or angry - you have been warned - is it an 'ism This is an extract from a Q and a Zoom call I did for my son Hey, this is a different, longer podcast because it's an extract. It's an extract from a Q and a Zoom call I did for my son. My son, Joseph. Joseph Clough. He has a program that helps people let go of their core issues, anxiety, those negative beliefs. And he. He and I do a 1 hour long, at least 1 hour long q and a live call twice what? Twice each a month, where we answer questions and also bring in new stuff to the program. And one I did a little while ago was all about. I've called it the ikigaia of stretch. And I explained Nikki guy about that in the, q and a recording. But it's all about how I think with this new. This new. It's not a new process. I don't think so, but a process that I've sort of developed helping you to change from a behavior you don't like to something you do like, or a behavior you're not doing, and you want to do something stopping you and how to get on, to doing it. So this is an extract. The recording is a little bit wavy. I've cleaned up as best I can, so it's not too bad, but I think you'll really enjoy it because it's just another way, another process of being able to change easily and effortlessly. And at the end, I actually do. It's around about an eight minute, eight minute sort of hypnosis process. So if you're up for that carry on right to the end, just make sure you're. You're not driving. You're not needed. Needed anywhere. your attention is needed elsewhere is not a thing. Okay. Didn't make sense. But basically, you can only focus on this. If you need something else, you must go away and do that, because here's sort of hypnosis, so please enjoy. And at the end of it, I'll quickly wrap up. Paul Clough says finding your purpose in life is key to success This is personal development unplugged, with Paul Clough. In simplicity, there is genius. In simplicity, there is genius. If I haven't spoken about it before, and I think I have, but I'm going to explain it again. There's a thing called ikigaya, which is, like, intersecting circles. An ikigaya came from, I believe. I'm sure I'm getting it wrong, but some type of japanese island somewhere where these people live for millions of years. Well, hundreds of years, no, 100 years ago. Linglo live long lives, and they live wonderful lives because they have this thing called ikigaia, which means following your purpose, finding your purpose. And when you find your purpose, you find exactly the thing that gives you the most zing in life, as it were. And the way I learned it, was there's three intersecting circles. So if you can imagine, and I can't do it on these screens, but if you can imagine three circles intersecting. So one, two, and one down there. The first circle is called the things I like to do. So these are just things I like to do. The next circle, beside that, is entitled the things I'm good at. Because sometimes the things we like to do, we can really like it, but we're no bloody good at it, but we just like doing it. But there's other things that we do that come, so sometimes they just come so naturally. We've worked so hard to make them come so naturally. They're really good at it. And we work so hard because you bloody like to do it. So you've got then the join between the two are the things what you like to do and what you're good at. The third circle is. And this is more about finding your purpose in life as maybe a business or, the way of making it in life is what are people prepared to pay you for? So the bit in the middle that puts them all together, the sweet spot is the things you're good at, the things you love doing and people will pay you for that is where your passion comes, or is. And when you find that, you get that. I don't believe it. You know, oh, I haven't worked a day in my life. You know, I just do the things I love. Now, you have worked. You work bloody hard to get there, but that's a sweet spot. But then this is the thing. I made a note yesterday, because I was talking to Joe about this, and we just having a little chat, and I said, this is what I'm thinking about talking about tomorrow. And he didn't know much about it. I said, oh, here we go. This is what it is. Within about a minute of us closing the call, he sent me a little note. Oh, look what I found. I found another step to your ikigaia. And the third step is a fourth circle. Yeah. Fourth circle is your fourth step. And the fourth circle is what the world needs now. Thought, wow. I put in my little book. So I was so pleased that Joe suddenly found something and felt so compelled to tell me about it, which made my life a little better, because I felt I've learned something from my son. He wanted to share it with me, which is my little bit of beauty in the world, but also it made so much more sense to me because I always got hung up with. This is really about finding your passion in business. But when you add what the world needs, you can even let that bit about what the world will pay you for get smaller. Because isn't that like the selfless service? Liking what you do, being really good at what you like and what the world needs. And, by the way, now and again you might even get paid for it. But you could get paid for it. Maybe in that law of reciprocity, reciprocal action, karma, you put out something good, you do something. What the world needs, you do something for no one to return. And Bam. The world will pay you for it. The universe will pay you for it without you wanting it. So that was Igaia. Now, I wanted to change that a little bit because I like thinking of how I can change things that work into something else. Because if they work, how can we adapt it, mould, it model it. So I started to think of, Well, I want to change. Maybe I want to change an emotion. Maybe I want to change it in a behavior. Maybe I want to change the way I think. Because if you something new. There's a thing called the communication model in NLP. Basically an event happens out there and you take it through your eyes and all your sight. I'll do it again. Your sight, your ears, your feelings, all your senses, smell and taste. You take these things in and you filter it. You filter it. Deletions, distortions and generalizations. And then all your values and your beliefs. And you got all these wonderful filters going on so you can understand what's happening in the world. And then they have, or they affect and become an internal representation in your mind. Such as having that little picture in your mind that you don't always know you've got because you're in it. And that internal representation has a little voice. And we've all got a little voice. And sometimes we don't realize we've got a little voice because we're talking to that little voice. Well, that little voice is talking to us. We're so wrapped up into it we don't realise it. But that's connected to your emotions, your state. And That's connected to your physiology. And When you get all those three together, there's your behaviours. So whatever you affect, if you change your behaviour, you will change your physiology, you will change the state you're in and you'll change the pictures and the voice in your head. But if you change the pictures in your mind, you will change the feelings and you'll change your physiology and your behaviours. They're just interlinked. Everything happens. And I thought, how can we use that? How can we use it in maybe just wanting to. I call it the ikigai of stretch, because each one is a I call it the ikigai of stretch, because sometimes, and I know this happens when people come to mind mastery, sometimes they're looking for that magic aha, moment, that big shift, the thing that knocks your socks off and what have you. Generally it isn't because it's like evolving. You're learning and learning and learning and changing and changing and changing until you effectively you're out the other side without knowing that you've having gone through it and you're in your new normal, because each one is a little stretch and a little more stretch and a little more stretch. So it's things that you can. Yes, sometimes it can be a little difficult, but you know that you're going to get through to the next one and the next one and you feel so good. So I started to think if I could put three circles together and use it as a change machine and the first circle would be the thing I want to change, call it our present state, as it were. So it could be maybe being triggered by something and you fire off an emotion, could be a habit you've got, or maybe it's a skill that you want to learn, maybe it's the emotion you want to get better at. It's like confidence, competence. Or maybe it's like fear that you want to get rid of. And it's not the big fear that we attach to all these core, core issues, it's those little fears, the little things that just maybe just put hold on you, hold you back for a bit. And so that was the first circle, where am I? What is the thing I want to change? The next circle, which is interacting with that one, is, well, some people just want to change. I just don't want this fear anymore, I don't want this anxiety anymore. I want to be confident, I want to be competent, all this thing, I just want to be. But we don't really go into any detail. So how do I want to be, in what context and think about, well, if this thing is triggering me to have fear, how would I like to be? Because sometimes you have to think about what would be the most appropriate resource, emotion and behaviour and skills to have instead. and it could well be, instead of being courageous, it could be something like being aware, just being aware, being able to connect, being able to be in the worlds of every person lately is be vulnerable. But how could be just a little bit vulnerable? Share a little bit. because once I've shared a little bit, because sharing a big bit was too much. But sharing a little bit, maybe that's just a way to start getting that more confident in ourselves, understanding ourselves and getting connection with others. How do I want to be? And, uh, you'll notice So we've got another circle now. So we've got to say, and it's more specific, how do I want to be? And, you'll notice in all of this, there's no why. There's no why do I act this way? Why have I got this fear? Why have I got this anxiety? Why am I getting angry about things? Why I've got these thoughts in my head? Because we don't want to know the why. Why just bring up all those excuses and beliefs that are just there to try to support. We don't want to know. We just want to know. Acknowledging. Acknowledging how we are. We're not accepting it, by the way, because if we accept it, to me, we accept it as being the truth. And it's okay. Well, actually it's not okay because we want to change, but we're acknowledging, well, that's how I am at this moment. At this moment because that's how I want to be. And this will be the effect. So it's not just saying I want to be less fearful. I now want to be more comfortable in this environment, this particular context. And this will allow me to be this and this and this. Maybe it'll allow us, in a career. Maybe this allows us to find a connection with people that we wouldn't have done before. So now we've got the two present state desired state and the effect of that desired state. And again, we're not even talking about the too much of the effects of where we are right now. We just know we want to change it. We know exactly what we want to change. The third one, that interlinks is the things I can do to change. And this is why I call it the stretch, because the stretch is how smaller steps can I make this change to be. So what are all the steps I could make? All the different things and resources. I've got all my resources. What are the things that are going to help me make this change and then finding the smallest one? Because again, we can have this wonderful acknowledgement of, yep, this is, an hour of my life I'm going to change. This is not serving me. And I want to change. And I know exactly how I want to be. I give an example of I'm totally unfit, totally unhealthy. Therefore I know the negativity of all of that. How do I want to be? I want to be fit, I want to be lean. I want to be doing this. And what opportunities are going to give me? Will I be out with friends? I'll be able to do this. I'll be able to join other groups. I've got all these wonderful things that are going to happen. What am I going to do then? What I'm going to do is starve myself and go to the gym 6 hours a day, every day. And the first day I'm going to run 6 miles on a treadmill. And I'm also going to row for 5 miles. And the next day you give up because it's too hard, too big, too far. Because we hadn't taken into account the number of steps it would take. We've just jumped to the end resource. But we need that end picture. That's the big picture. The big picture that we keep in mind while we're doing the smaller steps. Because that big picture, when you dive into it, if you could metaphorically dive into that, you in that desired state, that wonderful place, it would feel bloody awesome. And when you were there, looking through your own eyes, having got there, you'll be able to see all the effects it's had on that change, all the wonderful opportunities you're going to get. And so you've got a wonderful feeling. And we all know what we call that feeling. It's called the feeling of the wish fulfilled. And it feels bloody awesome. And that's why we tend to want to make that big jump. We get confused. We either get overwhelmed or we just get injured. And it feels horrible. It's too much. So we give up. And the worst thing about that is we can create a habit of doing that. And then we get a belief about ourselves, which is a totally bonky belief of, well, you know, I was never meant to be, I'm not good enough for that. People found me out and I suck at it, which is totally wrong. The only thing you sucked at is you made too big a jump. And it was just a, you know. And if we look at that, that's not failure. The first thing you look at, there's I got a result. It was the worst result I could think of. It wasn't the one I wanted. But I know what I can learn from that, which is take bloody smaller steps. Think about it. But holding that big picture in mind, the ultimate vision of that. So what I thought was, well, you can put all your resources in there, but now we could, now you could do this. And I do suggest if you want to do this as a process, you do it in handwriting. To start off with. To start off with. Because it's good to describe your present state. Because I like to get present states to be the most horrible present state you can get. Because that means you are going to move heaven and earth to change. Especially. The only thing about this is once you describe the present state as being probably the worst you can think of. Don't make it sillily worse. If that's a word, make it factual, but don't hide it. Let's be truthful about ourselves. For me, those things I've done, and, I've called myself a dick, and I know I was at that time, and that's something I've got to change. So I would write that down. Write down what you want in the world. What is that desired state But also you have to do the second part of this, which is how you want to be. What is that desired state, that desired behavior, that desired way of being in the world. You have to do both together. Because if you only do the negative side, life's worth not living. Oh, that's just it. Ah. Everything. I just carry on. Now we do the other one, you go, ah. Now I know what I want in the world, but I haven't. I've thought about it, but I've never written it down. Because, again, when you write it down, because if you write the negatives down, knowing you're going to change, you can realize how crappy they are, how silly they are, how they are no longer appropriate, that anger or whatever, or that fear is no longer getting what you want. It's not supporting you. And one thing, is it comfortable? Is it safe? Is it helping little old planet Earth? and is it helping other people? All the ecology. And the answer is going to be no, no, no, no. So now you know you got to change, and then you know which direction you're going to change. And it feels bloody good because when you write it down, you have to describe what it'll feel like. And when you describe what things feel like, you have to feel them because you can't describe them m any other way. You can't go, oh, yeah, I'll be happy. No, I will feel this way. I'll have this wonderful sensation in my heart. And I want to be, it's got to be beating. I'm going to be smiling. And it's going to be painful in my bloody cheeks because I'm going to be smiling so often. I'm going to be loving this bit of world. You have to. That means you relive it now you've got the motivation, the value. This is why it's so important to me. You get a top value. This is why it's so important to me. It's going to make me feel so good, so safe. It is going to be good for me. It is going to be good for other people. It's good going to be good for a little old, planet Earth because I'm going to do good stuff in the world. See how all ecology comes back in. Then you'd write down the things that you have available to you to change. So it could be here if we're changing behaviours or emotions, you go, well, I've got Joseph's, hypnosis tracks. I've got some of the modules for people who've gone through all the modules. You've got all the modules as tools now to be able to change. You've got q and a's here that you can keep asking people exactly what you want. So even though it may not be exactly to do with mind mastery, it is, because it's about you and what you want to do and how you can do it. You may have friends to support you, you may have books. You've got there's maybe old courses that you've been on that you can remember that. Ah, now it makes sense. It didn't make sense then. Now it does. Maybe you've got things like, I don't know where this came from in my head just then, but you've got the beautiful moments in life. You go, that's a great resource. If I start with the state of all the beautiful moments in life, and life is beautiful, life is wonderful, I'm going to be able to get to my desired state, a lot quicker than if I think life's a pail of crap or anything like that. So now I've got a direction, I know where I want, I've got the pull. All I have to do then is begin to think. Out of all of those, I now know where I want to go, I know where I'm leaving. I also know if I jump that far, I'm going to end up with a result, which is what I don't want. So Paul has said, pick the smallest, pick the smallest thing and you pick something. And then you ask yourself, is there a smaller step? Because we always, I'll tell you now, you will always pick the step which is two or three too big, even when you try to pick the smallest one, because we have this thing that we. Oh, well, let's. We have this thing. We have to make it tough on ourselves. Let's make it bloody hard. And, why would you want to make things bloody hard? If there's an easy way or a simple way, work it easy. Sometimes even those little steps take willpower, take a little bit of push, take a bit of looking at that desired state, getting that pull from that motivation, that value. But you find the smallest step and you put it in your diary, you put it in your day, I'm going to do it today. You're even going to record some of it, maybe in one of these saying, that was a beautiful moment when I did that one little step to move towards that goal, that change. It was a beautiful moment because I'm congratulating, the beautiful moment is congratulating yourself for carrying it out. And then you work out the next and the next and the next. And what happens is those small steps don't stay that small. This small step gets bigger and bigger. and you start, it's like when you go to the gym, you, can start to lift heavier weights. You can't in the beginning, or you can run further, run faster, you can walk faster, row faster, you can do anything. You can focus for longer because you're now training yourself towards that goal and what you might find. And here's the kicker. You're going towards that desired state and something comes along and goes, here's something better. Because what do we always tend to say, this or something better? Good old shakti Gawain comes, slaps you on the back of the head and goes, no, you can have something better. So as you're going along towards that goal, something comes a little bit better and you go, oh, I'm allowed to turn a little bit off because now I know I want to go over here because it's going to get a better result. Because if you've done a big, big jump, got overwhelmed and let it go, you've missed it completely. And what a shame you'd have to start again, but now we can do that. So that's something I would do, and I do do on, my puzzle book. I call them puzzle books, which is a book that I have that is all just my little problems or my little things I want to work out in my life. So I have this thing called a puzzle book. I actually sell them, by the way, if anybody wants to buy a puzzle book, I will sell them to you. You could go to any stationery store and buy a plain book But the thing is you could go to any stationery store and buy a book, a plain book. That's it. That's your puzzle book. Don't need anything fancy. You need to have a little one like this. So I don't sell them, by the way, you just buy them. But what we can also do, once you've done all of that, you've got all those things. We can actually just think about it before we jump in, just to make sure. Ask your unconscious mind what you would like to change about yourself And that's what I wanted to do today, really, to finish off with a little bit, a little bit of a process. So, and it's more, the process might, it might resolve something for you straight away. It might give you an idea what your smallest step is or it might hone, in on the desired state, your goal that you want to be, how you want to be. But it's more of a process just to get your unconscious mind and your conscious mind to get thinking of the steps along the way. So what is the thing I want to change? How do I want to be? What are the resources I've got and, what are the smaller steps I can take to get there? So I wonder if you have, if it's okay, something you like to change and it could be something really, really big, not the core issue you're on, in mind mastery because we've got that process and you're going to crack that. You're going to knock that out of the park. You're going to feel so good and you're going to keep telling us, but something that you'd like to either improve upon to change something could be big, could be small. And I want you just to, go inside for a moment and just notice and ask your unconscious mind. Now I've thought about this thing I would like to change. Just ask. And it's always good to ask this question before you do anything. Is it okay with you, my unconscious mind, to make these changes today and have an undeniable experience of it consciously and notice what you get and the answers you'll get is either yes, no, or maybe if you get a note, then you want to explore it further. Before you jump in, you're going to say, well, okay, what's the intention? And just work out, make sure it's the best thing you want. If you get a maybe, that's brilliant. I love maybes in all of this because a maybe says, I'm going to do it. But if I don't find it's a better way, then I'm not changing. And, why would you want to change if it's not a better way? But the thing is, we know it's going to be a better way anyway because it's a desired state you don't want and you're uncomfortable with, and the desired state is something you're going to be really good with and comfortable with. So it's a no brainer for me. The unconscious mind is going to, but it's not going to jump to it, which is what I like. I don't like unconscious minds. Goes, yeah, give it to me. Give it to me. Now, I want you to assess it. Just think about it unconsciously and then move forward. So once you ask that question, if you get a yes and a maybe, fine. If you get a no, pick another one for the moment and that will work out. And when you've got that little thing that you want to change or big thing, just get a different impression. What I'd like you to do, if it's okay, is to close your eyes because we're going to do this eyes closed. You don't have to, but it's nice to have your eyes closed because you've got nothing to distract you. And as I like to always do, I want you to take a nice in breath with me for the count of four. Hold it for the count of four. And then breathe out gently for the count of eight, all the way down. And feel yourself being drawn down. And then breathe normally, but in my normal way, making every in breath more gentle than the one before and feeling every out breath, drawing you deep inside, just a little deep inside where you connect with your unconscious mind. And because this is not true. Well, it is hypnosis, but it's not deep hypnosis because it doesn't need to be. You can go as deep as you want, or you can just be aware of everything. You're going to be aware of everything that's going to happen anyway because you are, consciously leading this. Now, this is where we're going to get conscious and unconscious. integration, guiding, setting your goal, the conscious mind being the goal setter. your unconscious mind being the gold getter. Joseph asks you to describe what you want to change about yourself and I want you to think just now of that first circle, the thing you want to change. And, just in your mind, you could maybe describe it, the way you feel, the way it makes you feel after the effect of it. For me, when I work with bits of anger, I get a little bit of grief after it, I feel sad after. So maybe there's the things that you feel after the event, the effects, but also in the moment. And Just describe to yourself how uncomfortable maybe it is or how it's not healthy because the negative emotion and negative belief is. Well it is unhealthy. Maybe you can acknowledge the positive intention, your unconscious mind trying its very best. Trying its very best. But the behaviours, beliefs and emotions are no longer appropriate because it no longer feels comfortable and its not what you want. So maybe just in your mind describe it to yourself, describe it to your best friend, how it makes you feel in the moment, post moment, the physical feelings. And then let it stay in that circle, that metaphorical circle. Leave all that description in that metaphorical circle and head on to the next one. How you want to be. So it's completely different now. The other one's over there. You are completely cut off from that. You've done your bit there. You're now in the desired state. How do you want to be when you've made the changes? So it's not how you're going to make the changes, why you're going to make the changes, but you've made the changes already. You might see yourself first, over there being the way that you desire. Maybe you're seeing yourself walking, talking, maybe in with people, communicating with people, doing that thing with ease as if you've been doing it forever. so natural now. And you may just then flow into that you and describe everything that you want, how you want to be. Maybe you want to be more calmer, maybe you want to be more aware. Maybe you just want to have more energy. Maybe you want to be more creative. Whatever comes to mind of you, choose. And please do not be an adult. Have that childlike quality of imagination and creativity where anything and everything is possible. Have it the way you choose now. And as you do that, notice how it feels. But also notice from this point onwards what will allow you to do that's even more better. Maybe you'll make better acquaintances, connect with more people. Maybe you'll serve the world better. Maybe your contribution will just go up, and up. Because when you do that it just feels even more better. Feels bloody awesome. Maybe m you see the effects on your family, your friends, your loved ones. And then notice how it affects yourself, your reaction to yourself, how much better you feel about yourself, maybe even how much you love yourself. That's maybe a big jump, but it's a big jump to make because you're here, you're in your desired state, how you want to be. So you're going to have that love, yourself and everybody else giving and receiving love, making a difference to you and the world and everyone else and feel that feeling. And now I want you to hold on to that feeling, just the feeling. And as you move away from that circle, we're going to move into that circle, which we call, the circle of stretch because each step will be a stretch because you're starting from that desired, from that present state, the state you want to change from. And you're moving towards, this feeling. Now, maybe just consider for a moment the skills that you have, skills maybe you're not using at the moment, but you've certainly got those skills. And those skills can actually be emotional skills too, because you've been, if it's calmness, you've been calm before. If you've been connected, you've been connect. If it's connection, you've been connected before. You've made a difference before, you've made people laugh before, you made people feel comfortable before. A bit like my qualities, all those wonderful things. You've got mind mastery here, you've got Joseph, you've got myself all as your support and knowing you've got all those skills, all those resources, you've got that wonderful set of positive beliefs about yourself, holding that wonderful feeling, that wonderful feeling of that desired state, the feeling of the wish fulfilled. Ask your unconscious mind what is the smallest step I can take today that will move me towards this wonderful feeling, this or something better? What is a smaller step, something that's so small that might even seem insignificant to me, but knowing as I build upon it, like a domino rally, getting bigger, faster, quicker, where the steps will get bigger. but what is the smallest step that I can take so when I do it, I can even record it so I can remember it forever and build upon it and just sit quietly for a moment and notice what comes to mind and take any judgment from it. Don't edit it, because this is your best friend. They're going to make this wonderful change with you and have an undeniable experience of it changing consciously and knowing that every step you take, this feeling of the wish fulfilled will get stronger and stronger because it's being triggered by the steps that you take and this feeling is triggering the steps that you take. So it's a wonderful loop. And when you have that little thing, that one step, I'd like you to commit to it. Think of a time when you can do it comfortably and commit to making that step. And then think about recording it later. And then when you've got that, you can open your eyes, come back into the room, m as they say, and notice everything around and just notice how you feel now, how you feel about that old state that you want to change that behavior and how you feel about the steps you're going to take. Okay, so I did. I do hope you enjoy that and you use that process. If you want to learn more about the, program that Joseph runs, it's josephcluff.com and it's called mind mastery. And it's a lovely program. And it's a program where you become what we call part of the mind mastery family, where you get supported along the way by both Joseph and I and everybody in the program. It's such a supportive place to be. We celebrate, we support each other, and people make magical m changes. It's not magic, but they make magical changes. So if you're interested, just hook up with josephcluff.com and have a chat with Joseph. But that's not the push for this. The push is for you to be able to make changes easily and effortlessly. And this is a nice little process to begin to do that. I do hope you enjoyed it. Please do. Share. Share everything you've learned here, if you would, and let me know if there's anything else you need, email me feedback@personaldevelopmentunplugged.com and we'll see if we can get some more processes. We can either develop them, find new ones, get some old ones back out, and find ways that we can really change ourselves in wonderful ways. Okay? Paul clough says it's time to fly on your own So until the next time, my friend, it is time to fly. Warning. You are now leaving the unplugged mind of Paul clough. It's time to fly on your own. Be brave, my friend. Personal development unplugged.
Welcome to Money and Me, hosted by Michelle Martin. In this episode, Michelle speaks with Anand Francis, Senior Investment Strategist at Infinity Financial Advisory, about the recent decision to remove five Singapore blue chip stocks from the MSCI global standard indexes beyond the short-term implications. They discuss the possible ripple effects of these deletions and their impact on City Developments Limited, Jardine C&C, Mapletree Logistics Trust, Mapletree Pan Asia Commercial Trust, and Seatrium, and how this might affect other allocations to the Singapore market by index funds. Anand also shares insights on where investors interested in the AI theme are looking. Additionally, they explore insights on global fund manager allocations and Federal Reserve policies.See omnystudio.com/listener for privacy information.
Fiscal and Administrative Services is providing weekly briefings to the Charles County Board of Commissioners on different aspects of the proposed Fiscal Year 2025 budget. Throughout the month of April and into May, Let's Get Fiscal will have weekly "Budget Bite" mini-episodes to give quick overviews of what was presented and what's coming next! Tune in to this episode to hear about the Commissioners' submissions of their Add/Delete Forms and an additional presentation from the Charles County Sheriff's Office. The Commissioners will vote to approve the FY2025 budget on Tuesday, May 14th!
James Williams and Daniel Davies digest another week of difficult headlines for the new First Minister
The Moose on The Loose helps Canadians to invest with more conviction so they can enjoy their retirement. Download The Canadian Rock Stars List, a selection of the safest dividend stocks in Canada: https://moosemarkets.com/rockstars How to Invest in 2024: https://moosemarkets.com/webinar Webinar Replay: Dividend Income For Life : https://www.dividendstocksrock.com/dividend-income Dividend Portfolio Dashboard: https://www.dividendstocksrock.com/my-dsr-pro/
Today's show opens with an admission that I missed a prediction by a couple of days. I told you that Gov. Ron DeSantis (R-FL), based on his distant 2nd place finish in Iowa would likely drop out after the New Hampshire primary coming up on Tuesday. Turns out, DeSantis couldn't wait until tomorrow. In a video he posted this weekend, he has suspended his campaign and has thrown his support behind Donald Trump. While this was taking place, Nikki Haley decided it was time to throw down the race card for votes. Yes, she continues to show us just how on the Left she really is by telling everyone she was teased everyday about being “brown.” I have to be honest, up until a few years ago, I had no idea her family roots stretched back to India. I had to be told that. But, now she wants to let everyone know she is on Team Oppressed, not Team Oppressor. How's this for breaking news? The J6 Select Committee under Rep. Bennie Thompson (D-MS) and former Rep. Liz Cheney (R-WY) deleted over one hundred documents just days before the committee was disbanded after the 2022 midterms. I ask that given this audience has known this for a long time, now, but it's nice to see the mainstream media finally catching up to us. On the flip side, there is real breaking news from just this past Friday. According to an interview between Jim Hoft of The Gateway Pundit and a Georgia reporter by the name of Amber Conner, the Dominion voting machine story just got even worse. In a trial taking place in Georgia, the lead expert witness showed how to put the machine into “safe mode” and did it by borrowing a pen from the defense team, representing Secretary of State Brad Raffensperger. Add this to the growing list of deteriorating narratives from both January 6 and the 2020 election cycle. I then play a recent soundbite from K.T. McFarland, former Deputy National Security Director, who spelled out how it's been the FBI and the CIA who have been interfering in our elections. Over the weekend, CBS Face the Nation interviewed Gov. Sarah Huckabee-Sanders about Donald Trump and she echoed the same message that came in Gov. DeSantis's speech. There is a record here to compare with back-to-back presidents. It's easy to see who really did put America first. Even a local representative from the Michigan General Assembly, Rep. Hilary Scholten (D) said they see the polls (for Biden) and they are not very good. We then get a quick soundbite from Ngaire Woods from this year's WEF gathering in Davos and it's clear, the elites are in trouble and they cannot afford to have Donald Trump elected. They are losing control of the people and they cannot allow the leader of the free world to continue that trend. Maybe that's why Alex Soros, son of George Soros, posted a less than cryptic message about a bullet hole and 47 – intimating his desire for what he'd like to have happen to the 47th president. Finally, we end with an ABC News segment showing polling on the confidence of Joe Biden's mental sharpness. It is now down to only 28% saying he is sharp enough to do the job. Take a moment to rate and review the show and then share the episode on social media. You can find me on Facebook, X, Instagram, GETTR and TRUTH Social by searching for The Alan Sanders Show. You can also support the show by visiting my Patreon page!
Transformation 3 Rom 12:1-2 #RTTBROS #Nightlight Transformation Romans 12:1-2 (KJV) says "I beseech you therefore, brethren, by the mercies of God, that ye present your bodies a living sacrifice, holy, acceptable unto God, which is your reasonable service. And be not conformed to this world: but be ye transformed by the renewing of your mind, that ye may prove what is that good, and acceptable, and perfect, will of God." Paul urges us to embrace positive transformation in these verses. Renewing our mind means bringing every thought captive to Christ. There are some thinking errors that need to be captured. We talked about Deletions where we leave out the good that God has brought into our life and that produces a victim mentality. Another thinking errors is Generalization. Satan uses generalizations to say to you, "You are always failing" "You will never get this right." Understand that generalizations are another of the lies of Satan to attempt to defeat us. Today let's zero in on the thinking error of distortions. Distorted thinking is when you are lieing to yourself and others. You might be telling yourself lies that make you think you are a victim and helpless. You might be lieing to yourself in such a way that you think you are better than others. Any inaccurate, dishonest thoughts process must be evicted from your mind. How you battle lies is truth. The Word of God represents God's truth for your life. Adapt your thinking to God's word and you will be well on the way to dealing with distortions in your thinking. Ask God to make you aware of all the thoughts that are bringing defeat in your walk with God and your Relationship with others. Then ask Him to renew your mind and replace the stinking thinking with God thoughts. Our Podcast, Blog and YouTube Links https://linktr.ee/rttbros Be sure to Like, Share, Follow and subscribe it helps get the word out. https://linktr.ee/rttbros
Transformation 2 Rom 12:1-2 #RTTBROS #Nightlight Transformation Romans 12:1-2 (KJV) says "I beseech you therefore, brethren, by the mercies of God, that ye present your bodies a living sacrifice, holy, acceptable unto God, which is your reasonable service. And be not conformed to this world: but be ye transformed by the renewing of your mind, that ye may prove what is that good, and acceptable, and perfect, will of God." Paul urges us to embrace positive transformation in these verses. There are two roads we can take - degenerative change that will break us down, or generative change that will build us up into who God desires us to be. If we are not intentionally seeking God and renewing our minds according to His Word, then we will automatically be on the path of degeneration. Renewing our mind means bringing every thought captive to Christ. There are some thinking errors that need to be captured. Yesterday we talked about Deletions where we leave out the good that God has brought into our life and that produces a victim mentality. Another thinking errors is Generalization. Have you ever had your child say "Everyone is doing it" that is a generalization to try and excuse their bad behavior. Generalization affects adults as well have you ever told your mate "You always" or "You Never" we tend to use those statements when we are in a fight and want to win at all costs. Satan uses generalizations to say to you, "You are always failing" "You will never get this right." Understand that generalizations are another of the lies of Satan to attempt to defeat us. Ask God to make you aware of all the thoughts that are bringing defeat in your walk with God and your Relationship with others. Then ask Him to renew your mind and replace the stinking thinking with God thoughts. Our Podcast, Blog and YouTube Links https://linktr.ee/rttbros Be sure to Like, Share, Follow and subscribe it helps get the word out. https://linktr.ee/rttbros
Transformation Rom 12:1-2 #RTTBROS #Nightlight Transformation  Romans 12:1-2 (KJV) says "I beseech you therefore, brethren, by the mercies of God, that ye present your bodies a living sacrifice, holy, acceptable unto God, which is your reasonable service. And be not conformed to this world: but be ye transformed by the renewing of your mind, that ye may prove what is that good, and acceptable, and perfect, will of God." Paul urges us to embrace positive transformation in these verses. There are two roads we can take - degenerative change that will break us down, or generative change that will build us up into who God desires us to be. If we are not intentionally seeking God and renewing our minds according to His Word, then we will automatically be on the path of degeneration. Let get clear on disrupting degenerative change. There are Three thinking errors that will wreck you and keep your mind from positive transformation. Generalization, Distortion and Deletions. I want to talk about Deletions this is when you leave key details out of the story you are telling yourself. For example this last year was a hard year for our family and I was telling a friend it was a hellish year and I would.be glad to see 2023 in the rear view mirror. My friend said didn't you go in a Cruse this last year with your wife. It hit me like a ton of bricks I was deleting the good things of 2023 so I could focus on telling myself the year had been hellish. What balance can you bring into your thinking by adding back in the things you have deleted from the story you are telling yourself. Tell yourself the truth not just part of the truth. Knowing the truth and living in light of it will set you free. Our Podcast, Blog and YouTube Links https://linktr.ee/rttbros Be sure to Like, Share, Follow and subscribe it helps get the word out. https://linktr.ee/rttbros
LibTech India analysed MGNREGS data for first 6 months of this fiscal & found net deletion of 80 lakh workers' names. Deletions highest in UP, while poll-bound Telangana saw increase.----more----Read full article here: https://theprint.in/india/governance/high-deletion-of-names-from-mgnregs-rolls-in-poll-bound-mp-rajasthan-chhattisgarh-ngo-report/1825435/
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Communication Miss: Deletions, Distortions, Generalizations. Do you feel overwhelmed? Do you understand how much you filter out? Filters are used to eliminate things that are not of value. Understand how change can happen quickly when we understand the filters, and we change the Belief! We have natural filters that, unchecked, can cause faulty belief systems, living below our potential, and relationships that never reach their intimate peak. Mr. Black is joined by 2 graduates of Team 248, who will share their first hand experiences. These are authentic, transformational conversations that bring hope to any situation. Maya Angelou; Rise Up, Mother Teresa; Anyway, and other motivational quotes and stories. Check out our website www.LikeItMatters.Net. Be sure to Like and Follow us on our facebook page. Get daily inspiration from our blog www.wayofwarrior.blog. Learn about our non profit work at www.likeitmatters.net/nonprofit.See omnystudio.com/listener for privacy information.
Today on Like It Matters Radio Mr. Black will be joined by Hope-filled guests. Last weekend, Mr. Black took a team of Leaders through the Leadership Experience in Las Vegas. What started as a class of 12 people seeking better, became Team 248- a Team of committed Leaders changing their worlds, by changing themselves. The conversations are Hope filled, Vision creating, and Chain-breaking!! Do you want change? The Time is Now! Tune into Like It Matters Radio, for an hour of power as Mr. Black and guests uncover: Deletions, Distortions, and Generalizations. Be sure to Like and Follow us on our facebook page!www.facebook.com/limradio Instagram @likeitmattersradioTwitter @likeitmatters Get daily inspiration from our blog www.wayofwarrior.blog Learn about our non profit work at www.likeitmatters.net/nonprofit Check out our website www.LikeItMatters.NetSee omnystudio.com/listener for privacy information.
Here's the new live ep of the podcast about #JeffreyEpstein, his associates, the latest news about #HunterBiden, the lack of student debt forgiveness and more. SOURCES: Student Loan Forgiveness Fail: LIVE: President Biden speaks after Supreme Court struck down student debt relief plan — 6/30/23 Notice on the Continuation of the National Emergency Concerning the Coronavirus Disease 2019 (COVID-19) Pandemic Supreme Court hears arguments in student loan forgiveness case Afghanistan: State Department report details damning failings around Afghanistan withdrawal Jeffrey Epstein stuff: Jeffrey Epstein shared photos of young women with JPMorgan Chase exec, lawsuit claims JP Morgan board member's death in wake of Epstein settlement sparks rampant speculation JPMorgan Agrees to Pay $290 Million to Settle Epstein Case https://storage.courtlistener.com/recap/gov.uscourts.nysd.591653/gov.uscourts.nysd.591653.47.1.pdf Jeffrey Epstein Acted Like an Adviser to JPMorgan Executive He's in the picture with Epstein and Gates from 2011. Who Are the Newly Revealed Jeffrey Epstein Associates? Jeffrey Epstein keeps haunting Wall Street long after his death https://twitter.com/ap/status/1673769066274881536?s=46&t=AUePkNReGtiZqngVwUlM6A JP Morgan accidentally deletes evidence in multi-million record retention screwup Hunter Biden stuff: https://twitter.com/cbs_herridge/status/1672223113839276033?s=46&t=gxNlMB6nFUV08skNSgvUCg https://waysandmeans.house.gov/wp-content/uploads/2023/06/Whistleblower-1-Transcript_Redacted.pdf Hunter Biden expected to plead guilty to tax-related misdemeanor crimes as part of a plea agreement Hunter Biden attends White House state dinner days after plea deal Ukraine update: Biden Administration Announces Additional Security Assistance for Ukraine COVID Origin Distraction: Report-on-Potential-Links-Between-the-Wuhan-Institute-of-Virology-and-the-Origins-of-COVID-19-20230623.pdf Peter Hotez stuff: https://twitter.com/ellelatham/status/1672020679611539459?s=46&t=gxNlMB6nFUV08skNSgvUCg Narendra Modi WEF Page cisa-staff-report6-26-23.pdf Thank you to all of the listeners of this episode. Please check out the past episodes when you get the chance and go to My YouTube Channel for more super awkward fun times. New live stream soon.
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.06.23.546272v1?rss=1 Authors: de la Fuente, D. C., Tamburini, C., Stonelake, E., Griffiths, W. J., Hall, J., Owen, M. J., Linden, D. E. J., Pocklington, A., Wang, Y., Li, M. Abstract: Dysregulation in neural progenitor proliferation and neuronal differentiation has been increasingly recognised as a common pathology in neural cells harboring genetic risks to neuropsychiatric and neurodevelopmental disorders, yet the underlying molecular mechanisms remains largely unknown. Deletions and duplications of the 15q11.2 region containing the CYFIP1 gene have been associated with autism and schizophrenia. Using patient-derived iPSCs carrying 15q11.2 deletion and genetically manipulated hESCs with CYFIP1 gain- and loss-of-function (GoF and LoF), we show that 15q11.2 deletion and CYFIP1-LoF leads to premature neuronal differentiation while CYFIP1-GoF favours neural progenitor maintenance. We identified cholesterol biosynthesis and metabolism as a biological process disturbed by CYFIP1 dosage change, leading to altered neuro-oxysterol profiles. 24S,25-epoxycholesterol, which was decreased in CYFIP1-GoF and increased in CYFIP1-LoF and 15q11.2del neural cells, can mimic the 15q11.2del and CYFIP1-LoF phenotype by promoting cortical neuronal differentiation and restore the impaired neuronal differentiation of CYFIP1-GoF neural progenitors. Moreover, the neurogenic activity of 24S,25-epoxycholesterol is lost following genetic deletion of the brain expressed isoform of the liver X receptor LXR{beta} while compound deletion of LXR{beta} in CYFIP1-/- background rescued their premature neurogenesis. This work delineates LXR mediated oxysterol regulation of neurogenesis as a novel pathological mechanism in neural cells carrying 15q11.2CNV and provides a potential target for therapeutic strategies for genetic disorders associated with this risk locus. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
Simon Miller catches up with AEW's Matt Hardy to talk about being BROKEN, the Firm Deletion, Twitter toxicity, not taking himself too seriously, goofy wrestling, working with Ethan Page, one final Hardy Boyz run, and giving back to the wrestling business.ENJOY!Follow us on Twitter:@SimonMiller316@WhatCultureWWEFor more awesome content, check out: whatculture.com/wwe Hosted on Acast. See acast.com/privacy for more information.
To see if you qualify for mentorship: https://api.leadconnectorhq.com/widget/booking/Arj8ncGPep4NP3qiJnm9 Register for FREE Credit Class: www.webinar.catactics.com Credit Repair Support Facebook group: https://www.facebook.com/groups/1128458291282021/ 133. CAT Podcast | MINDSET | Do THIS SECRET to get DELETIONS! - Episode 133 You are blessed, amazing and great and I hope I brought you value in this episode! Feel free to share the episode with a friend, tag me on social media and let me know you're listening and even leave a review! It helps! Thanks in advance! Grab our resources! www.catacticsllc.com Subscribe to my YouTube! https://m.youtube.com/channel/UCUZaHxoQA2-DUqC45_rhPqw IG: Instagram.com/catacticsllc Personal IG: @michobenjamin Connect with Michael on social media: Instagram: instagram.com/michobenjamin Twitter: Twitter.com/michobenjamin
Register for my next FREE Credit Class: www.webinar.catactics.com Credit Repair Support Facebook group: https://www.facebook.com/groups/1128458291282021/ Text “freecall” to 914-353-4741 for free DIY credit repair advice! Text 5mentorship to 914-353-4741 to join my $4.99 MENTORSHIP! Text “weeklymentorship” to 914-353-4741 to join my CHEAP monthly mentorship! 125. CAT Podcast | MINDSET | WHY you are NOT getting DELETIONS! - Episode 125 You are blessed, amazing and great and I hope I brought you value in this episode! Feel free to share the episode with a friend, tag me on social media and let me know you're listening and even leave a review! It helps! Thanks in advance! Grab our resources! www.catacticsllc.com Subscribe to my YouTube! https://m.youtube.com/channel/UCUZaHxoQA2-DUqC45_rhPqw IG: Instagram.com/catacticsllc Personal IG: @michobenjamin Connect with Michael on social media: Instagram: instagram.com/michobenjamin Twitter: Twitter.com/michobenjamin
They invite the charge that not only does the government wish to escape unpalatable facts, but it also wants to ensure that the students do not engage with social and political realities with a critical attitude.
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.03.531058v1?rss=1 Authors: Miller, J. M., Prange, S., Ji, H., Rau, A. R., Butova, N. L., Lutter, A., Chung, H., Merigliano, C., Rawal, C. C., McVey, M., Chiolo, I. Abstract: Pericentromeric heterochromatin is highly enriched for repetitive sequences prone to aberrant recombination. Previous studies showed that homologous recombination (HR) repair is uniquely regulated in this domain to enable 'safe' repair while preventing aberrant recombination. In Drosophila cells, DNA double-strand breaks (DSBs) relocalize to the nuclear periphery through nuclear actin-driven directed motions before recruiting the strand invasion protein Rad51 and completing HR. End-joining (EJ) repair also occurs with high frequency in heterochromatin of fly tissues, but how different EJ pathways operate in heterochromatin remains uncharacterized. Here, we induce DSBs in single euchromatic and heterochromatic sites using the DR-white reporter and I-SceI expression in spermatogonia. We detect higher frequency of HR repair in heterochromatic insertions, relative to euchromatin. Sequencing of repair outcomes reveals the use of distinct EJ pathways across different euchromatic and heterochromatic sites. Interestingly, synthesis-dependent michrohomology-mediated end joining (SD-MMEJ) appears differentially regulated in the two domains, with a preferential use of motifs close to the cut site in heterochromatin relative to euchromatin, resulting in smaller deletions. Together, these studies establish a new approach to study repair outcomes in fly tissues, and support the conclusion that heterochromatin uses more HR and less mutagenic EJ repair relative to euchromatin. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
In this episode of Scaling Postgres, we discuss different pagination solutions, how to return modifications, soft deletion alternatives and how to use JSON with PostgreSQL. Subscribe at https://www.scalingpostgres.com to get notified of new episodes. Links for this episode: https://www.cybertec-postgresql.com/en/pagination-problem-total-result-count/ https://sqlfordevs.com/returning-modified-rows https://brandur.org/fragments/deleted-record-insert https://dev.to/ftisiot/how-to-json-in-postgresqlr-1lj7 https://momjian.us/main/writings/pgsql/beyond.pdf http://peter.eisentraut.org/blog/2023/01/11/postgresql-largest-commits https://supabase.com/blog/postgres-foreign-data-wrappers-rust https://medium.com/@walttonm/using-the-window-function-row-number-to-remove-duplicates-in-postgresql-5aef1edfb78c https://pgdash.io/blog/horizontally-scaling-postgresql.html https://www.percona.com/blog/upgrading-postgresql-extensions/ https://www.timescale.com/blog/a-postgresql-developers-perspective-six-interesting-patches-from-novembers-commitfest/ https://pganalyze.com/blog/5mins-postgres-16-pgbench-random-normal https://www.depesz.com/2023/01/11/waiting-for-postgresql-16-invent-random_normal-to-provide-normally-distributed-random-numbers/ https://www.orioledata.com/blog/buffer-management/ https://github.com/orioledb/orioledb https://www.crunchydata.com/blog/solving-advent-of-code-2022-using-postgres-day-11 https://www.crunchydata.com/blog/solving-advent-of-code-2022-using-postgres-day-12 https://www.crunchydata.com/blog/timezone-transformation-using-location-data-and-postgis https://www.migops.com/blog/avoiding-constraint-violations-while-migrating-oracle-to-postgresql-date-data-type/ https://databaserookies.wordpress.com/2023/01/09/substr-functionality-differences-between-oracle-and-postgresql-what-you-need-to-know/ https://databaserookies.wordpress.com/2023/01/08/unleasing-boolean-data-type-casting-in-postgresql/ https://postgres.fm/episodes/copying-a-database https://postgresql.life/post/francesco_tisiot/ https://www.rubberduckdevshow.com/episodes/69-adventures-in-note-taking/
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.12.10.519926v1?rss=1 Authors: Zhang, X., Xiao, G., Johnson, C. A., Cai, Y., Horowitz, Z., Mennicke, C., Coffey, R., Haider, M., Threadgill, D. W., Eliscu, R., Oldham, M. C., Greenbaum, A. C., Ghashghaei, H. T. Abstract: The Epidermal growth factor receptor (EGFR) plays a role in cell proliferation and differentiation in healthy development and in tumors, however its requirement for brain development remains unclear. Here we used a conditional mouse allele for Egfr to examine its contributions to perinatal forebrain development at the tissue level. Subtractive bulk ventral and dorsal deletions of Egfr revealed that ventral but not dorsal telencephalic EGFR expression is critical for forebrain homeostasis and the presence of transiently EGFR-dependent glial lineages including robust depletion of oligodendrocytes that last the mouse lifetime. Sparse deletion using Mosaic Analysis with Double Markers (MADM) surprisingly reveals a regional requirement for EGFR in dorsal, but not ventral glial lineages including both astrocytes and oligodendrocytes. These findings lead to a model in which EGFR-independent ventral glial progenitors compensate for the absence of EGFR-dependent dorsal glia in the forebrain, thus masking its precise role in the bulk model. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.09.23.509267v1?rss=1 Authors: Longley, C. M., Xu, X., Messier, J. E., Cai, Z.-L., Park, J. W., Chen, H., Reznik, D. L., Jadi, M. P., Xue, M. Abstract: Synaptic excitation (E) and inhibition (I) stay relatively proportional to each other over different spatiotemporal scales, orchestrating neuronal activity in the brain. This proportionality, referred to as E-I balance, is thought to be critical for neuronal functions because its disruption was observed in many neurological disorders. However, the causal evidence demonstrating its significance is scarce. Here we show that deleting Neuroligin-2 (Nlgn2), a postsynaptic adhesion molecule at inhibitory synapses, from mouse glutamatergic or GABAergic neurons reduces inhibition cell-autonomously without affecting excitation, thereby disrupting E-I balance and causing lethality. In contrast, deleting Nlgn2 constitutively or simultaneously from both glutamatergic and GABAergic neurons results in viable mice. A neural network model shows that reducing inhibition in either neuronal type is detrimental to network activity, but in both types partially re-establishes E-I balance and activity. Together, our results provide evidence for an essential role of E-I balance in brain functions and organism survival. Copy rights belong to original authors. Visit the link for more info Podcast created by PaperPlayer
(00:32):Before we jump in, would each of you share a little bit about your background and yourselves? (01:18):Dr. Marcou. could you provide us with an overview of what the WESDX test is? (01:50):Marissa, would you help explain why this test is important? (03:10):In your experience who would benefit from WESDX,(05:12):How does a provider order A WES DX and secondarily what type of samples are accepted?(06:24):What types of variants are detected by the test? (07:47):There are a lot of exome tests available. What are some other unique features that set WESDX apart? (09:52):Last question, could you summarize the benefits of doing WESDX at Mayo?
Read it with your eyeballs instead! https://medium.com/doctor-funny/accidental-deletions-e08c297b9f62 Have a funny story regarding accidental deletions that you're comfortable sharing on air? Record an audio message and you could be a part of my next podcast episode! ♥ --- Send in a voice message: https://anchor.fm/lucy-dan/message
Owner of Koality, 1/2 of Puff N Chat, singer, entrepreneur and so much more - the incredible Koala Puffs! We got to sit down and talk everything from her creative process to why she was deleted and so much more. She has created an incredible community of fellow smokers and keeps everyone stocked up with her favorites through her Koality boxes. Learn what she has coming up and how she was able to forge her own path in a very male-dominated industry. Connect with Koala and stream her new song! https://open.spotify.com/track/01iwr67cDw3l6QvHnBxnx2?si=b8eef163b6cf4c51 https://twitter.com/koalapuffss https://www.snapchat.com/add/koala.puffs https://www.instagram.com/koala.puffss/?hl=en https://www.koalapuffs.com/
Nothing to see here! Simon Miller presents 10 Changes WWE Hoped You Wouldn't Notice...ENJOY!Follow us on Twitter:@SimonMiller316@WhatCultureWWEFor more awesome content, check out: whatculture.com/wwe See acast.com/privacy for privacy and opt-out information.
Your thoughts affect your feelings, your feelings affect your actions, your actions make your life. If you want to have a great life you have to develop biblical thinking. Tune In the next three nights as we discover how to think biblically Our Podcast, Blog and YouTube Links https://linktr.ee/rttbros Be sure to Like, Share, Follow and subscribe it helps get the word out. RSS feed https://anchor.fm/s/127be410/podcast/rss
#Adrian #health #AmandhaVollmer Make sure to sign up for my newsletter so you never miss any new content and offers: https://fortheloveoftruth.co.uk/newsletter-signup/To listen to the entire episode:Bitchute: https://www.bitchute.com/video/IAffYVUOoCSz/Brighteon: https://www.brighteon.com/04f7f744-e7a1-4f2e-b442-9b3f6d795b9dOddysey: https://odysee.com/@adrianr:8/ep.247_Dr_amandha_vollmer:7Podcast: https://fortheloveoftruth.co.uk/podcast/ or https://fortheloveoftruth.buzzsprout.com/Dr Amandha Dawn Vollmer holds a bachelor of science in Agricultural Biotechnology from the University of Lethbridge (2000) in Alberta, Canada and a degree of Doctor of Naturopathic Medicine from the Canadian College of Naturopathic Medicine (2008) in Toronto. She also has previous experience as a certified lab animal technician at the University of Alberta. Most of her life she has taken an interest in botanical medicine: self-educating on the topic many years before becoming her formal medical training. Having developed many of her extra senses with martial arts & dance, she realized a natural gift for sensing illness and a laying on of hands. She soon sought answers via the energetic healing arts and became a registered reiki practitioner & teacher, among other modalities.After much scholarly & independent study, her passion for the elegant and effective sub-molecular medicine known as homeopathy, brought her to study in South India under Rajan Sankaran. She also volunteered for a month-long intensive medical program in Northern India shadowing cardiologists, obstetricians, Ayurvedic practitioners and homeopathic doctors alike. Afterward, she took a 10 day silent Vippassana retreat in the Himalayan mountains. Originally training to be a veterinarian, she took courses through the British Institute of Homeopathy for veterinary homeopathic medicine. During naturopathic college, she was certified both in IV therapy and with Dr. David Leaf in Applied Kinesiology.We covered a lot of topics in this delightful conversation. You can reach Amandha here:Blog: https://yummy.doctor/video/Bitchute: https://www.bitchute.com/channel/6DNCVpNofW5k/Vimeo: https://vimeo.com/user74902399Lbry: https://lbry.tv/@yumnaturals:0YouTube: https://www.youtube.com/channel/UCVgrhHSEj6XySgEcqeQr_AwTelegram: https://t.me/amandhavollmerWebsiteshttps://yumnaturals.store/https://yummy.doctor/https://healingwithdmso.com/Patreon:https://www.patreon.com/yumnaturals---My book:I have written a book on health and well-being. Nothing mainstream in here, just things I've observed and worked out that have helped me and others who have used the ideas.You can read more about it here:http://alternativeprinciplesforhealth.info/—Support the show (https://www.patreon.com/adrianr)
In this week's episode, we'll review a study providing new insights on megakaryocyte diversity and function, including a unique subpopulation that may act as immune cells. Next, we'll review research that intriguingly reveals a putative role for the PD1 gene in cutaneous T-cell lymphoma. Lastly, we'll conclude with a report demonstrating a lack of cross-reaction between the antibodies that cause vaccine-induced thrombocytopenia and thrombosis, and the COVID-19 spike protein.
Today on Like It Matters Radio, Mr. Black talks about communication. Communication is the foundation for a relationships both personal and professional. As human beings we have so much information coming at us all the time. An article in Fast Company magazine posed the following statement: 'We’ve created a world with 300 exabytes of human-made information. Try processing all that'. We can't so we naturally use three filters: distortions, generalizations and Deletions. These filters are also the key to, Miscommunication. Tune into Like It Matters Radio for an hour of Power as Mr. Black discusses: Miscommunicating well! See omnystudio.com/listener for privacy information.
The brain requires a lot of energy generated by mitochondria to function properly. Researchers suspect that mutations and deletions in the mitochondrial genome have a bigger effect than previously appreciated, with implications for neurological disorders, such as major depressive disorder, Alzheimer's disease, and beyond. Niki Spahich from The Scientist's Creative Services team spoke with Brooke Hjelm, assistant professor of clinical translational genomics at the Keck school of medicine at the University of Southern California, to learn more. The Scientist Speaks is a podcast produced by The Scientist's Creative Services team. Our podcast is by scientists and for scientists. Once a month, we bring you the stories behind news-worthy molecular biology research.
This week @kingdavidlane, @chrisbest99, & @brockbza are all here! We discuss what Peacock has scrubbed from WWE Network, what we imagine will have to be, & what's left. Plus the new WWE HOF members, Impact's move to a nw night, & Ronda Rousey's connection to Black History Month. Plus what NOT to say in your UFC promo, a DX member has health issues, & Sting has it rough for his Revolution match. ROH's Women Of Honor division gets a reboot & more! VOC Nation takes you behind the scenes of your favorite moments in pro wrestling history. Notable show hosts include legendary pro wrestling journalist Bill Apter, former WWE/TNA star Shelly Martinez, former WWE and AWA broadcaster Ken Resnick, former WCW performer The Maestro, former TNA Impact talent Wes Brisco, Pro Wrestling Illustrated's Brady Hicks, independent pro wrestling and Fireball Run star Sassy Stephie, and more! Since 2010, VOC Nation has brought listeners into the minds of the biggest stars in pro wrestling and entertainment. Subscribe to the podcasts for free on most major directories, and visit vocnation.com for live programming. Subscribe on YouTube for the video version of the show: https://www.youtube.com/vocnationradionetwork Learn more about your ad choices. Visit megaphone.fm/adchoices Learn more about your ad choices. Visit megaphone.fm/adchoices
Today on Like It Matters Radio, Mr. Black talks about communication. Communication is the foundation for a relationships both personal and professional. As human beings we have so much information coming at us all the time. An article in Fast Company magazine posed the following statement: 'We’ve created a world with 300 exabytes of human-made information. Try processing all that'. We can't so we naturally use three filters: distortions, generalizations and Deletions. These filters are also the key to, Miscommunication. Tune into Like It Matters Radio for an hour of Power as Mr. Black discusses: Miscommunicating well! www.likeitmatters.net www.likeitmattersradio.com See omnystudio.com/listener for privacy information.
The Twilight Saga from a guy's perspective! In this fifth episode of this brand new podcast your host, Jez, focuses on a special issue facing the Twilight fandom world on Instagram: hundreds and hundreds of Twilight / Twihard accounts being deleted without warning or explanation. Today, you'll get some explanations and some analysis. This is a special episode - I hope you enjoy it and find it educational and informative. Next episode will be back to our usual journey through the Twilight Saga novels.In every episode of Bella Goodness 143 - it's commonly called "Bella's Goodness" - you'll learn something about the Twilight saga that I hope you've never heard or thought much about before. This is a Twilight podcast where I hope it feels like you're sitting back relaxing with a friend talking about your favorite fandom: the love of Edward Cullen for one Bella Swan.Be sure to find me on Instagram @BellaGoodness143Also feel free to email me directly at bellagoodness143@gmail.comCome say hello - let me know your thoughts about the podcast - and share your questions or insight for future episodes.
Volume 11, Issue 28 of Oncotarget features "Genetic analysis of the cooperative tumorigenic effects of targeted deletions of tumor suppressors Rb1, Trp53, Men1, and Pten in neuroendocrine tumors in mice" by Xu et, al. which reported that the authors examined whether the TSGs Rb1, Trp53, Pten, and Men1 have cooperative effects in suppressing neuroendocrine tumors in mice. By monitoring growth and examining the histopathology of the pituitary and pancreas in these mice, the authors demonstrated that pRB had the strongest cooperative function with PTEN in suppressing Pit NETs and had strong cooperative function with Menin and TRP53, respectively, in suppressing Pit NETs and Pan NETs. TRP53 had weak cooperative function with PTEN in suppressing pituitary lesions. Collectively, the data indicated that pRB and PTEN pathways play significant roles in suppressing Pit NETs, while the Menin-mediated pathway plays a significant role in suppressing Pan NETs. Understanding the molecular mechanisms of these genes and pathways on NETs will help us understand the molecular mechanisms of neuroendocrine tumorigenesis and develop effective preclinical murine models for NET therapeutics to improve clinical outcomes in humans. Dr. Eugenia Y. Xu from Rutgers and Princeton University as well as Dr. Daniel A. Notterman from Princeton University said, "Human pituitary neuroendocrine tumors (PitNETs) are the third most common intracranial neoplasms and represent approximately 10–25% of all primary intracranial tumors." Additionally, in rare cases, RB1 has been found with epigenetic mutations in the promoter region in Pit NETs suggesting that inactivation of the RB pathway contributes to the development of Pit NETs. Compound mice with concomitant deletions of Men1 and Pten develop Pit NETs and Pan NETs and mice with p18–/– Pten+/– mutations develop Pit NETs, suggesting that PTEN plays a role in pituitary and pancreatic islet tumorigenesis. However, Men1 deletion mice develop pars distalis prolactinomas and Rb1 deletion mice develop pars intermedia tumors of the pituitary, suggesting that the functions of Menin and pRB may not fully overlap. Here they investigate the question of whether Men1 and Rb1 have cooperative tumorigenic effects on NETs using tissue-specific double homozygous deletions of Men1 and Rb1 in mice. The Oncotarget authors report that the characterization of Pit NETs and Pan NETs with double homozygous deletions of TSGs and illustrate that pRB has the strongest cooperative function with PTEN in suppressing Pit NETs and has a strong cooperative function with Menin and TRP53, respectively, in suppressing Pit NETs and Pan NETs in mice. The Xu/Notterman Research Team concluded in their Oncotarget Research Paper, "our data clearly demonstrate that TSGs Rb1, Pten, Men1, and Trp53 have distinct tissue specificity in neuroendocrine tumorigenesis in mouse and likely in man. The mouse models here and deletion of these TSGs in MIP-Cre mice will help further our understanding the molecular function of these TSGs and their pathways in PitNET and PanNET pathogenesis, which will help develop targeted novel therapeutic options in treating human patients." Sign up for free Altmetric alerts about this article DOI - https://doi.org/10.18632/oncotarget.27660 Full text - https://www.oncotarget.com/article/27660/text/ Correspondence to - Eugenia Y. Xu - exu@princeton.edu and Daniel A. Notterman - dan1@princeton.edu Keywords - neuroendocrine tumors, RB1, Trp53, PTEN, Men1 About Oncotarget Oncotarget is a weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.22.393108v1?rss=1 Authors: Loewenthal, G., Rapoport, D., Avram, O., Moshe, A., Itzkovitch, A., Israeli, O., Azouri, D., Cartwright, R. A., Mayrose, I., Pupko, T. Abstract: Insertions and deletions (indels) are common molecular evolutionary events. However, probabilistic models for indel evolution are under-developed due to their computational complexity. Here we introduce several improvements to indel modeling: (1) while previous models for indel evolution assumed that the rates and length distributions of insertions and deletions are equal, here, we propose a richer model that explicitly distinguishes between the two; (2) We introduce numerous summary statistics that allow Approximate Bayesian Computation (ABC) based parameter estimation; (3) We develop a neural-network model-selection scheme to test whether the richer model better fits biological data compared to the simpler model. Our analyses suggest that both our inference scheme and the model-selection procedure achieve high accuracy on simulated data. We further demonstrate that our proposed indel model better fits a large number of empirical datasets and that, for the majority of these datasets, the deletion rate is higher than the insertion rate. Finally, we demonstrate that indel rates are negatively correlated to the effective population size across various phylogenomic clades. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.13.381475v1?rss=1 Authors: Pabis, K. Abstract: The "theory of resistant biomolecules" posits that long-lived species show resistance to molecular damage at the level of their biomolecules. Here, we test this hypothesis in the context of mitochondrial DNA (mtDNA) as it implies that predicted mutagenic DNA motifs should be inversely correlated with species maximum lifespan (MLS). First, we confirmed that guanine-quadruplex (GQ) and direct repeat (DR) motifs are mutagenic, as they associate with mtDNA deletions in the human major arc of mtDNA, while also adding mirror repeat (MR) and intramolecular triplex motifs to a growing list of potentially mutagenic features. What is more, triplex motifs showed disease-specific associations with deletions and an apparent interaction with GQ motifs. Surprisingly, even though DR, MR and GQ motifs were associated with mtDNA deletions, their correlation with MLS was explained by the biased base composition of mtDNA. Only triplex motifs negatively correlated with MLS and these results remained stable even after adjusting for body mass, phylogeny, mtDNA base composition and effective number of codons. Taken together, our work highlights the importance of base composition for the comparative biogerontology of mtDNA and suggests that future research on mitochondrial triplex motifs is warranted. Copy rights belong to original authors. Visit the link for more info
America's confrontation grows even more intense. Massive evidence and witnesses confirm systemic fraud. POTUS is making memories for history. Patriots approach the fight with humility. Real journos talked about election fraud long ago, and described details. All the left's tally machines had network connections. PIN code voting. Hard evidence aplenty for those that want it. Think message over messenger. When it's most difficult, practice doing things with love. Learn more about your ad choices. Visit megaphone.fm/adchoices
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.08.332478v1?rss=1 Authors: Wang, Q., Gong, Y., He, Y., Xin, Y., Lv, N., Du, X., Li, Y., Jeong, B.-r., Xu, J. Abstract: Industrial microalgae are promising photosynthetic cell factories, yet tools for targeted genome engineering are limited. Here for the model industrial oleaginous microalga Nannochloropsis oceanica we established a method to precisely and serially delete large genome fragments of ~100 kb from its 30.01-Mb nuclear genome. We started by identifying the "non-essential" chromosomal regions (i.e., low-expression region or LER) based on minimal gene expression under N-replete and N-depleted conditions. The largest such LER (LER1) is ~98 kb in size, located near the telomere of the 502.09 kb-long Chromosome 30 (Chr 30). We deleted 81 kb and further distal and proximal deletions of up to 110 kb (21.9% of Chr 30) in LER1 by dual targeting the boundaries with the episome-based CRISPR/Cas9 system. The telomere-deletion mutants showed normal telomeres consisting of CCCTAA repeats, revealing telomere regeneration capability after losing distal part of Chr 30. Interestingly, the deletions caused no significant alteration in growth, lipid production or photosynthesis (transcript-abundance change for < 3% genes under N depletion). We also performed double-deletion of both LER1 and LER2 (from Chr 9) that totals ~214 kb, and phenotypes are essentially normal. Therefore, loss of the large yet "non-essential" regions does not necessarily sacrifice important traits. Such serial targeted deletions of large genomic regions have not been reported in plants or microalgae, and will accelerate crafting minimal genomes as chassis for photosynthetic production. Copy rights belong to original authors. Visit the link for more info
Have you ever thought about your Monday routine, and realized that how you live that one day was setting up how you live your life? Imagine waking up on Monday morning so refreshed and excited that you don't need to have a cup of coffee to help you make it to 10 a.m. What would you accomplish with that level of energy? Communication is one of the largest determinates of how we function in the world. And in our minds, we create a map, which determines the type of world we live in. So if we create a faulty map based on negative filters or improper truths, then we create a pathway for our lives to continuously be steered down ways that keep us away from the goals or places we wish to be. This part 3 of 3 for the Neuro Linguistic Communication Model and in this episode we will be talking about Deletions in our language. So if you haven't listened to 668 and 669, go back and listen to them to get the full picture of Generalizations, Distortions, and then Deletions in this episode. Your subconscious doesn't know the difference between fact or fiction and in this episode, I talk about something in our brains called the reticular activating system that guides us towards where our attention is focused. So join me, and let me help you create ways to craft a better internal map that guides your life. If you are getting something out of the podcast, share a favorite episode with someone who you think might benefit from it. Help Support The Strong Within Affirmation Podcast By Going To: www.strongwithin.com/support (You can also get the transcripts there) Thanks for listening. I'm sending great energy your way as we become Strong Within together, Holistic Performance and Personal Development Coach- Chris O'Hearn My links: https://linktr.ee/strongwithin Contact info- email: chris@strongwithin.com phone:865-219-3247follow me on social media: www.facebook.com/thechrisohearn www.instagram.com/thechrisohearn Music by: - Zest by basematic (c) copyright 2011 Licensed under a Creative Commons Attribution (3.0) license. - I Have Often Told You Stories (guitar instrumental) by Ivan Chew (c) copyright 2013 Licensed under a Creative Commons Attribution (3.0) license. Location: Knoxville, Tennessee USA but available worldwide
Let's just say at least one network won't be happy with this week's episode.Each week the TV Blackbox team take you behind the scenes, wade through the PR spin and launch into the reality that is the Australian television business.In this episode:1.27 - Seven goes to war with Cricket Australia5.59 - Social media turns on Studio 1014.17 - OzTam to change the ratings game19.33 - How does 10 News First have one presenter hosting two bulletins at the same time?23.25 - Plate of Origin a real stinker for Seven28.49 - Hatches & Dispatches31.32 - A new plan for drama content39.45 - TV BlackvaultFollow the @TVBB_podcast crew:@rob_mcknight@shrimptank@viscountbrooky@BenjaminJNorris@SteveMolkFollow us on Twitter: https://twitter.com/tv_blackboxFind us on Facebook: https://facebook.com/TVBlackbox/Visit our website: https://tvblackbox.com.au Support this show http://supporter.acast.com/tv-blackbox. See acast.com/privacy for privacy and opt-out information.
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.18.256065v1?rss=1 Authors: Pedebos, C., Verli, H. Abstract: Oligosaccharyltransferases (OSTs) are enzymes that catalyze the transfer of a glycan chain to an acceptor protein. Their structure is composed by a transmembrane domain and a periplasmic / C-terminal domain, which can be divided into structural units. The Archaeoglobus fulgidus OST, AfAglB, has unique structural units with unknown functions. Here, we evaluate the stability role proposed for AfAglB units by employing molecular modelling and molecular dynamics simulations, to examine the effect of single and double deletions in the enzyme structure. Our results show a strong effect on the dynamics of the C-terminal domain for the mutated systems with increased fluctuations near the deleted areas. Conformational profile and stability are deeply affected, mainly in the double unit deletion, modifying the enzyme behavior and binding interfaces. Coordination at the catalytic site was not disrupted, indicating that the mutated enzymes could retain activity at some level. Hotspots of variation were identified and rationalized with previous data. Our data shows that structural units may provide stabilization interactions, contributing for integrity of the wild-type enzyme at high temperatures. By correlating our findings to structural units mutagenesis experimental data available, it was observed that structural units deletion can interfere with OSTs stability and dynamics but it is not directly related to catalysis. Instead, they may influence the OST structural integrity, and, potentially, thermostability. This work offers a basis for future experiments involving OSTs structural and functional characterization, as well as for protein engineering. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.05.216739v1?rss=1 Authors: Kosicki, M., Allen, F., Bradley, A. Abstract: Repair of Cas9-induced double-stranded breaks results primarily in formation of small indels, but can also cause potentially harmful large deletions. While mechanisms leading to the creation of small indels are relatively well understood, very little is known about the origins of large deletions. Using a novel library of clonal mouse embryonic stem cells bona fide deficient for 32 DNA repair genes, we have shown that large deletion frequency increases in cells impaired for non-homologous end joining and decreases in cells deficient for the central resection gene Nbn and the microhomology-mediated end joining gene Polq. Across deficient clones, increase in large deletion frequency was closely correlated with the increase in the extent of microhomology and the size of small indels, implying a continuity of repair processes across different genomic scales. Furthermore, by targeting diverse genomic sites, we identified examples of repair processes that were highly locus-specific, discovering a novel role for exonuclease Trex1. Finally, we present evidence that indel sizes increase with the overall efficiency of Cas9 mutagenesis. These findings may have impact on both basic research and clinical use of CRISPR-Cas9, in particular in conjunction with repair pathway modulation. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.07.23.217976v1?rss=1 Authors: Bigio, B., Seeleuthner, Y., Kerner, G., Migaud, M., Rosain, J., Boisson, B., Nasca, C., Puel, A., Bustamante, J., Casanova, J.-L., Abel, L., Cobat, A. Abstract: The detection of copy number variations (CNVs) in whole-exome sequencing (WES) data is important, as CNVs may underlie a number of human genetic disorders. The recently developed HMZDelFinder algorithm can detect rare homozygous and hemizygous (HMZ) deletions in WES data more effectively than other widely used tools. Here, we present HMZDelFinder_opt, an approach that outperforms HMZDelFinder for the detection of HMZ deletions, including partial exon deletions in particular, in typical laboratory cohorts that are generated over time under different experimental conditions. We show that using an optimized reference control set of WES data, based on a PCA-derived Euclidean distance for coverage, strongly improves the detection of HMZ deletions both in real patients carrying validated disease-causing deletions and in simulated data. Furthermore, we develop a sliding window approach enabling HMZDelFinder-opt to identify HMZ partial deletions of exons that are otherwise undiscovered by HMZDelFinder. HMZDelFinder_opt is a timely and powerful approach for detecting HMZ deletions, particularly partial exon deletions, in laboratory cohorts, which are typically heterogeneous. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.06.25.172262v1?rss=1 Authors: Urresti, J., Zhang, P., Moran-Losada, P., Yu, N.-K., Negraes, P. D., Trujillo, C. A., Antaki, D., Amar, M., Chau, K., Pramod, A. B., Diedrich, J., Tejwani, L., Romero, S., Sebat, J., Yates, J. R., Muotri, A. R., Iakoucheva, L. M. Abstract: Reciprocal deletion and duplication of 16p11.2 is the most common copy number variation (CNV) associated with Autism Spectrum Disorders, and has significant effect on brain size. We generated cortical organoids to investigate neurodevelopmental pathways dysregulated by dosage changes of 16p11.2 CNV. We show that organoids recapitulate patients' macrocephaly and microcephaly phenotypes. Deletions and duplications have "mirror" effects on cell proliferation, neuronal maturation and synapse number, consistent with "mirror" effects on brain development in humans. Excess neuron number along with depletion of neural progenitors in deletions, and "mirror" phenotypes in duplications, demonstrate dosage-dependent impact of 16p11.2 CNV on early neurogenesis. Transcriptomic and proteomic profiling revealed synaptic defects and neuron migration as key drivers of 16p11.2 functional effect. Treatment with the RhoA inhibitor Rhosin rescued neuron migration. We implicate upregulation of small GTPase RhoA as one of the pathways impacted by the 16p11.2 CNV. This study identifies pathways dysregulated by the 16p11.2 CNV during early neocortical development. Copy rights belong to original authors. Visit the link for more info
We discuss the recent PS5 console reveal and analyze what it means for the upcoming next gen console war. Nerd News we go over Twitch clip deletions and the Star Wars: Squadron. 8:30 Nerd News 25:00 PS5
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.06.16.155523v1?rss=1 Authors: Benitez-Burraco, A., Fernandez-Urquiza, M., Jimenez-Romero, M. S. Abstract: Copy-number variations of the distal region of the short arm of chromosome 9 are associated with learning disabilities and behavioral disturbances. Deletions of the 9p are more frequent than duplications. We report in detail on the cognitive and language features of a child with a duplication in the 9p24.3 region (arr[hg19] 9p24.3(266,045-459,076)x3). He exhibits marked expressive and receptive problems, which affect to both structural aspects of language (notably, inflectional morphology, complex syntax, and sentence semantics), and to functional aspects (pragmatics). These problems might result from a severe underlying deficit in working memory. Regarding the molecular causes of the observed symptoms, they might result from the altered expression of selected genes involved in procedural learning, particularly, some of components of the SLIT/ROBO/FOXP2 network, strongly related to the development and evolution of language. Dysregulation of specific components of this network can result in turn from an altered interaction between DOCK8, affected by the microduplication in 9p24.3 borne by our proband, and CDC42, acting as the hub component of the network encompassing language-related genes. Still, some genes found strongly upregulated in the subject and not related to these genes, particularly NRCAM, can contribute to the observed problems in the language domain, as well as to specific features of the proband, particularly, his impulsivity. Copy rights belong to original authors. Visit the link for more info
Love this episode? Make sure you leave us a review!! Today Natasha shares with you a follow up coaching session she had with one of her members, Sheila. Sheila still has some things holding her back, and we dig deep today to find out what the root cause of her fear is (hint: it's not of falling off her horse - it's much deeper than that!) If you have any suggestions for future podcast content, people you would like Natasha to interview or if you are an equestrian that loves our message and would be interested in being interviewed, contact the team at support@yourridingsuccess.com Loving Natasha's message and wanting more? Check out www.yourridingsuccess.com for free videos, web classes, our online programs and more!
Love this episode? Make sure you leave us a review!! In our very first podcast episode, Natasha shares with you some tools and techniques, looking at a new way of experiencing your world, specifically aimed at horse riders of all disciplines (but it can also be applied to any area of your life), so you can experience your horse riding in a dramatically different way, and start to notice why you are fearful, anxious, worried or having any negative emotional reaction to whatever is going on in your life and in your horse riding, and how you can change it to become confident, happy and ready to take your horse riding and your life to the next level. If you have any suggestions for future podcast content, people you would like Natasha to interview or if you are an equestrian that loves our message and would be interested in being interviewed, contact the team at support@yourridingsuccess.com Loving Natasha's message and wanting more? Check out www.yourridingsuccess.com for free videos, web classes, our online programs and more!
Ep #33 - In this week's episode we discuss how we internalize our life and our experiences. These memories become the building blocks for our belief and values systems throughout our lives. What we discuss: How are we processing our external, main life events? How our beliefs in life stem from our interpretation of past life events: how good we are, our role in the world, skilled enough, loveable enough, good looking enough, what people have said about us, or how they have treated us. Empowerment in life comes via responsibility No one in life can make me feel anything; I am responsible for my own emotions. Mental filtering: how we perceive the information, person, etc. will determine our mindset about what we're experiencing. Generalizations Deletions Distortions 1. Generalizations: the characteristics of one person gets prescribed to all of them 2. Deletions: imperfect people (all of us) will conveniently remember the bad/hurtful things done to us and we will delete what we are doing to others. 3. Distortions: jumping to an assumption or presumption. Reacting to our perception of reality and not reality itself. Distorting what others say and do. When we look at life this way we might think we are broken, but we are not. All 3 impact how we perceive our reality thus the stories we tell ourselves about the events that occur - good, bad, right, wrong - all based on how we react or others react to what we have done. Thank you so much for listening and being a part of this community. I truly appreciate your support. Also, please subscribe, rate and review the show to help us spread the word about this awesome free content. Your simple action of rating and reviewing does wonders in helping others find the show. If you have questions you'd like addressed on the show, want to book me to speak at an event, or want to recommend or be a guest on this show, please contact me through any of the social media links below or via email. Feel free to contact me here for any other reason as well: Facebook: https://facebook.com/jessemogle Twitter: https://twitter.com/jessemogle Instagram: https://instagram.com/jessemogle LinkedIn: https://www.linkedin.com/in/jessemogle/ Email: jesseisinteresting@gmail.com
Most social platforms offer mechanisms allowing users to delete their posts, and a significant fraction of users exercise this right to be forgotten. However, ironically, users' attempt to reduce attention to sensitive posts via deletion, in practice, attracts unwanted attention from stalkers specifically to those (deleted) posts. Thus, deletions may leave users more vulnerable to attacks on their privacy in general. Users hoping to make their posts forgotten face a "damned if I do, damned if I don't" dilemma.In this talk, we will look into two new proposed deletion mechanisms that provide privacy for the deletion of users.In the first approach, in the form of intermittent withdrawals, we present, Lethe, a novel solution to this problem of (really) forgetting the forgotten. If the next-generation social platforms are willing to give up the uninterrupted availability of non-deleted posts by a very small fraction, Lethe provides privacy to the deleted posts over long durations. Furthermore, we introduce Deceptive Deletion, a new decoy mechanism that minimizes the adversarial advantage. Our mechanism creates a two-player min-max game between, an adversary that seeks to classify damaging content among the deleted posts, and a challenger that employs decoy deletions to masquerade real damaging deletions.We evaluate the systems using the Twitter data samples and show that in the presence of a strong adversary our systems protect the privacy of the users' deletions. About the speaker: Mohsen Minaei is a Ph.D. candidate at Purdue University working with Professor Aniket Kate. His research focuses on designing and implementing better privacy-enhancing mechanisms for content deletion and using cryptocurrencies as covert channels to bootstrap the censor circumvention tools. Prior to joining Purdue, he received his bachelor's degree from Sharif University in Tehran.He has completed three internships with the fraud detection and Xbox teams at Microsoft and one with the blockchain team at Visa Research.
Most social platforms offer mechanisms allowing users to delete their posts, and a significant fraction of users exercise this right to be forgotten. However, ironically, users’ attempt to reduce attention to sensitive posts via deletion, in practice, attracts unwanted attention from stalkers specifically to those (deleted) posts. Thus, deletions may leave users more vulnerable to attacks on their privacy in general. Users hoping to make their posts forgotten face a “damned if I do, damned if I don’t” dilemma. In this talk, we will look into two new proposed deletion mechanisms that provide privacy for the deletion of users. In the first approach, in the form of intermittent withdrawals, we present, Lethe, a novel solution to this problem of (really) forgetting the forgotten. If the next-generation social platforms are willing to give up the uninterrupted availability of non-deleted posts by a very small fraction, Lethe provides privacy to the deleted posts over long durations. Furthermore, we introduce Deceptive Deletion, a new decoy mechanism that minimizes the adversarial advantage. Our mechanism creates a two-player min-max game between, an adversary that seeks to classify damaging content among the deleted posts, and a challenger that employs decoy deletions to masquerade real damaging deletions. We evaluate the systems using the Twitter data samples and show that in the presence of a strong adversary our systems protect the privacy of the users' deletions.
Tom Barbalet talks with Anton Mikhailov on a variety of topics. Will they continue the podcast after the meeting? Time will tell.
Tom Barbalet talks with Anton Mikhailov on a variety of topics. Will they continue the podcast after the meeting? Time will tell.
Tom Barbalet talks with Anton Mikhailov on a variety of topics. Will they continue the podcast after the meeting? Time will tell.
Tom Barbalet talks with Anton Mikhailov on a variety of topics. Will they continue the podcast after the meeting? Time will tell.
July 2018 See acast.com/privacy for privacy and opt-out information.
Jane Ferguson: Hello, welcome to Getting Personal: Omics of the Heart. It is June 2018, and this is podcast episode 17. I'm Jane Ferguson, an assistant professor of medicine at Vanderbilt University Medical Center, and a proponent of precision medicine, genomics, and finding ways to prevent and treat heart disease. Jane Ferguson: This podcast is brought to you by Circulation: Genomic and Precision Medicine, and the AHA Council on Genomic and Precision Medicine. Jane Ferguson: For our interview this month, early career member, Jennie Lin talked to Beth McNally about science and careers in genomic medicine. We'll have more on that later but first I want to tell you about the cool papers we published in the journal this month. Jane Ferguson: First up, Orlando Gutierrez, Marguerite Irvin, Jeffrey Kopp, Cheryl Winkler, and colleagues from the University of Alabama at Birmingham, and the NIH, published an article entitled APOL1 Nephropathy Risk Variants and Incident Cardiovascular Disease Events in Community-Dwelling Black Adults. This study was conducted in over 10 thousand participants of the Reasons for Geographic and Racial Differences in Stroke, or, REGARDS Study. They examined associations between APOL1 variants and incident coronary heart disease, ischemic stroke, or composite CVD outcome. Because there are coding variants in the APOL1 Gene that are only found in individuals of African ancestry, these are hypothesized to contribute to the disparities in cardiovascular and renal disease in African Americans. Jane Ferguson: The authors found that carrying the risk variants was associated with increased risk of ischemic stroke, but only in individuals who did not have diabetes, or chronic kidney disease. They hypothesize that because diabetes and kidney disease already increase CVD risk, the variant does not have an additional effect on risk in individuals with existing comorbidities. But, it contributes to small vessel occlusion and stroke in individuals without diabetes. Jane Ferguson: They also found that the magnitude and strength of the association became stronger in a model adjusted for African ancestry, suggesting an independent effect of the APOL1 risk variants. Jane Ferguson: While future work is needed to study this more, this is an important step in understanding the complex relationship between APOL1 and disease. Jane Ferguson: Next up, Daniela Zanetti, Erik Ingelsson, and colleagues from Stanford, published a paper on Birthweight, Type 2 Diabetes, and Cardiovascular Disease: Addressing the Barker Hypothesis with Mendelian Randomization. The Barker Hypothesis considers that low birthweight as a result of intrauterine growth restriction, causes a higher future risk of hypertension, type 2 diabetes, and cardiovascular disease. However, observational studies have been unable to establish causality or mechanisms. Jane Ferguson: In this paper, the authors used Mendelian Randomization as a tool to address causality. They used data from the UK Biobank, and included over 237,000 participants who knew their weight at birth. They constructed genetic predictors of birthweight from published genome wide association studies, and then looked for genetic associations with multiple outcomes, including CAD, stroke, hypertension, obesity, dyslipidemia, dysregulated glucose and insulin metabolism, and diabetes. Jane Ferguson: The Mendelian randomization analysis indicated that higher birthweight is protective against CAD type 2 diabetes, LDL cholesterol, and high 2 hour glucose from oral tolerance test. But, higher birthweight was associated with higher adult BMI. This suggests that the association between low birthweight and higher disease risk is independent of effects on BMI later in life. While the study was limited to a well nourished population of European ancestry, and would need to be confirmed in other samples, and through non-genetic studies, it suggests that improving prenatal nutrition may be protective against future cardiometabolic disease risk. Jane Ferguson: Laura Muino-Mosquera, Julie De Backer, and co-authors from Ghent University Hospital, delved into the complexities of interpreting genetic variants, as published in their manuscript, Tailoring the ACMG and AMP Guidelines for the Interpretation of Sequenced Variants in the FBN1 Gene for Marfan Syndrome: Proposal for a Disease- and Gene-Specific Guideline. Jane Ferguson: With a large number of variants being uncovered through widespread sequencing efforts, a crucial challenge arises in their interpretation. The American College of Medical Genetics and Genomics, and the Association for Molecular Pathology put forward variant interpretation guidelines in 2015, but these were not tailored to individual genes. Because some genes have unique characteristics, the guidelines may not always allow for uniform interpretation. Jane Ferguson: In their manuscript, the authors focused on variants in fibrillin-1 that cause Marfan Syndrome, and reclassified 713 variants using the guidelines, comparing those classifications to previous in-depth methods which had indicated these variants' causal or uncertain significance. They find 86.4% agreement between the two methods. Jane Ferguson: Applying the ACMG, AMP guidelines without considering additional evidence may thus miss causal mutations. And it suggests that adopting gene specific guidelines may be helpful to improve clinical decision making and accurate variant interpretation. Jane Ferguson: Delving deeper into FBN1 and Marfan Syndrome, Norifumi Takeda, Ryo Inuzuka, Sonoko Maemura, Issei Komuro, and colleagues from the University of Tokyo examined the Impact of Pathogenic FBN1 Variant Types on the Progression of Aortic Disease in Patients With Marfan Syndrome. They evaluated 248 patients with pathogenic, or likely pathogenic, FBN1 variants, and examined the effect of variant subtype on severe aortopathy, including aortic root replacement, type A dissections, and related death. They found that the cumulative aortic event risk was higher in individuals with haploinsufficient type variants, compared with dominant negative variants. Jane Ferguson: Within individuals with dominant negative variants, those that affected Cysteine residues, or caused in-frame deletions, were associated with higher risk compared with other dominant negative mutations, and were comparable to the risk of the haploinsufficient variants. These results highlight the heterogeneity and risk of the FBN1 variants, and suggest that individuals with haploinsufficient variants, and those carrying dominant negative variants affecting Cysteine residues or in-frame Deletions, may need more careful monitoring for development of aortic root aneurysms. Jane Ferguson: Lydia Hellwig, William Klein, and colleagues from the NIH, investigated the Ability of Patients to Distinguish Among Cardiac Genomic Variant Subclassifications. In this study, they analyzed whether different subclassifications of variants of uncertain significance were associated with different degrees of concern amongst recipients of genetic test results. 289 subjects were recruited from the NIH ClinSeq Study, and were presented with three categories of variants, including variants of uncertain significance, possibly pathogenic, and likely pathogenic variants. Participants were better able to distinguish between the categories when presented with all three. Whereas, a result of possibly pathogenic given on its own, produced as much worry as a result of likely pathogenic. The authors conclude that multiple categories are helpful for subjects to distinguish pathogenicity subclassification, and that subjects receiving only a single uncertain result, may benefit from interventions to address their worry and to calibrate their risk perceptions. Jane Ferguson: Erik Ingelsson and Mark McCarthy from Stanford, published a really nice review article entitled Human Genetics of Obesity and Type 2 Diabetes: Past, Present, and Future. Over the past decade, we've had a lot of excitement, optimism, and also disappointment in what genome-wide association studies can deliver. Doctors Ingelsson and McCarthy do a great job laying out the history and the successes in the field of genetic interrogation of obesity and diabetes, as well as acknowledging where reality may not live up to the hype, what challenges remain, and what the future may hold. They also have a figure that uses an analogy of a ski resort to emphasize the importance of taking a longitudinal perspective. And I would argue that any paper that manages to connect apres-ski with genomics is worth reading, for that alone. Jane Ferguson: Robert Roberts wrote a perspective on the 1986 A.J. Buer program, pivotal to current management and research of heart disease. Highlighting how the decision by the AHA in 1986 to establish centers to train cardiologists and scientists in molecular biology, has led to huge advances in knowledge and treatment of heart disease. Jane Ferguson: Finally, rounding out this issue, Kiran Musunuru and colleagues, representing the AHA Council on Genomic and Precision Medicine, Council on Cardiovascular Disease in the Young, Council on Cardiovascular and Stroke Nursing, Council on Cardiovascular Radiology and Intervention, Council on Peripheral Vascular Disease, Council on Quality of Care and Outcomes Research, and the Stroke Council, published a scientific statement on Interdisciplinary Models for Research and Clinical Endeavors in Genomic Medicine. Jane Ferguson: This paper lays out the field of cardiovascular research in the post genomic era, highlights current practices in research and treatment, and outlines vision for interdisciplinary, translational research and clinical practice, that could improve how we understand disease, and how we use those understandings to help patients. Jane Ferguson: Our guest interviewer today is Dr. Jennie Lin, an Assistant Professor at Northwestern Universities Feinberg School of Medicine, and the incoming Vice Chair of the Early Career Committee of the AHA Council on Genomic and Precision Medicine. As an aside, Jennie is a great person to follow on Twitter for insights into genomics and kidney disease, and as a bonus, she also posts the occasional dog photo. So she's well worth following just for that. You can find her on Twitter @jenniejlin. As you'll hear, Jennie talked to Dr. Beth McNally about her view on genomic medicine, and Beth also shared some really great practical tips for early career investigators building their independent labs. So make sure you listen all the way to the end. Take it away Jennie. Dr. Lin: Thank you for tuning in to this edition of Getting Personal: Omics of the Heart, a podcast by the Genomic and Precision Medicine Council of the American Heart Association, and by Circulation: Genomic and Precision Medicine. Today I am joined by Dr. Elizabeth McNally, the Elizabeth J Ward Professor of Genetic Medicine, and director of the Center for Genetic Medicine at Northwestern University. Beth, thank you for taking time to chat with all of us. Dr. McNally: Happy to be here. Dr. Lin: As a successful physician scientist, you have been interviewed in the past about your life, your scientific interests, and advice for budding investigators. I don't want to rehash everything you have already stated beautifully in an interview with Circ Res, for example. But instead wanted to focus more on your views of genetic medicine and genome science today. Dr. Lin: So you mentioned in that prior Circ Res interview that you started your laboratory science training and career during college, when you participated in a project focused on genetic variation among children with muscular diseases. What have you found to be most interesting about the process of identifying functional genetic variants back then, and also that on-going work now. Dr. McNally: Well, I think over the years I've been doing this is the tools have gotten so much better, to be able to actually define the variants much more comprehensibly than we ever could in the past. And then also to be able to study them, and very much to be able to study them in context. And so I look at the revolutions in science that will cause people to look back on this era as the era of genetics. It began obviously with PCR, we couldn't have gotten anywhere without that. Dr. Lin: Right. Dr. McNally: And then you leap forward to things like next generation sequencing, and IPS cells, and now CRISPR/Cas gene editing. And to realize that the last three happened within a decade of each other, is going to be so meaningful when you think about the next few decades, and what will happen. So being able to take an IPS cell and actually study a mutation or a variant in context of that patient, the rest of their genome, is really important to be able to do. Dr. Lin: Okay, Great. And so, where do you envision ... with taking say for example, this next gen. technology, CRISPR/Cas9, studying variants in an IPS cell, for example. How do you envision this really revolutionizing the study of human genetics for patients? And how far do you think we've come in fulfilling that vision, and what do you think should be our focus going forward? Dr. McNally: I think broadly thinking about human genetics we're really very much still at the beginning, which I know is hard to say and hard to hear. But, we've spent a lot of the last 15 years very focused on that fraction of the genome that has high frequency, or common variation, through a lot of the GWA studies. With those common variants, we had a lot of associations, but relatively small effects of a lot of those, causing a lot of people to focus on the missing heritability and where we might find that hiding. And of course, now that we have deep sequencing, and we have deep sequencing where we've really sampled so much more of the genome, and from so many more people, I think we're just at the beginning of really appreciating that rare variation. And beginning again to really appreciate that 80-85% of the variation that's in each of our genomes is really characterized as rare. Dr. McNally: And so we really each are quite unique, and that when we understand a variant we do have to understand it in the context of all that other variation. So computationally that's very challenging to do. Obviously requires larger and larger data sets. But even in doing that, you are not going to find exact replicates of the combinations that you see in any one individual. While I know everybody would love that we're going to have the computational answer to all of this, it's still going to come down to a physician and a patient and making what you think is that best decision for the patient, based hopefully on some genetic data that helps inform those decisions. Dr. Lin: Right, right. So it kind of gets into this whole concept of precision medicine, which has gained a lot of popularity and buzz in recent years, and Obama has really brought it to the forefront in the public arena. You mention rare variants in ... finding rare variants in each patient, for example. And moving a little bit away from some of the common variants that we find in GWAs. What does it mean for a patient to have a rare variant and come see you in your cardiomyopathy clinic, is it going to be precision for that patient, or suing rare variants among many different individual patients to try to find function for a gene? Dr. McNally: It's a great question. So I think the first way we approach it is, it depends who's asking the question. So if it's somebody who comes to me who has cardiomyopathy, or has a family history of cardiomyopathy and sudden death, that's a very different question to ask what's going on with their rare variants, for example in cardiomyopathy genes. Now if you translate that over to, I have a big population of people, I don't particularly know what their phenotype is, and I see rare variants for cardiomyopathy, those are two fundamentally different questions. So we very much know a lot about how to interpret rare variants for cardiomyopathy in the context of a patient or a family who has disease, and I do emphasize the latter part of that, the family, working with families and seeing how variants segregate within families. We interpret that very differently, and I think it's appropriate to interpret that very differently in that context. And that's completely different than again, going against what is the regular population, notice I'm not calling it normal population- Dr. Lin: Right. Dr. McNally: ... but the general population that's out there. The first step in doing that is the list of the ACMG, American College of Medical Genetics, actionable genes. So this is an interesting question in and of itself. It's 59 genes, of course that list is too small, and it should be bigger than that, and ultimately that will happen. But to take a population based approach to those actionable genes, and looking across the population, finding someone who's got variants in, lets say our favorite genes MYH7, MYBPC3. Knowing what that risk means on a population level is very different than knowing what that means in the context of a patient who comes to you, who has that variant, runs in their family, and has clear disease. Those again, really two different questions, and we have to come up with what's the best practices on that, how to answer either of those questions. Dr. McNally: I think the first step working with patients and families who have known disease and have clear variants that segregate with disease, I think its very powerful. I think we've probably got close to a good decade of doing that already. It's incredibly useful for those patients and families. It helps us reduce their risk. It helps us treat them early, it helps us manage their arrhythmias. There's no question that that information is incredibly valuable, but we're still learning how to process that across the population, and how to answer that question for people who are coming who don't already have disease. Dr. Lin: Right, right. That makes sense. And I guess that kind of plays into a follow up question about whether or not we need to test, or think about every variant of unknown significance in lab, and ... the- Dr. McNally: It's a great ... You know again, you always have to very carefully consider the context in which the question's being asked. So again, if you're talking about a relatively normal population, well, walking, healthy person, and you're seeing variants of uncertain significance, that's a very different question than somebody who's coming in to you with cardiomyopathy and has a highly suspicious variant of uncertain significance that falls right within the head domain of MYH7. We know a lot about that, and we can do a lot of interpretation in that case. Dr. McNally: However, I would say that to put too much value on what we do in the research lab ... Just putting a regulatory hat on for a second and thinking about it, there's nothing from a regulatory standpoint that really validates what we do in the research lab, to say that we can really fairly adjudicate a VUS or not. We can't do that, that's over-valuing what we do in research lab. Dr. McNally: So I think, how do we consider variants among certain significance? I think it's really important to recognize that it's exactly that, it's a variant of uncertain significance. And so when you're a clinician taking that to a patient, you have to approach it from the standpoint of saying, this is a variant of uncertain significance. Which means we don't know whether it's pathogenic, but we also don't know that its benign. Because I think right now what we've seen, a lot of clinicians, and even researchers, fall into the path of this believing that variant of uncertain significance is the equivalent of benign. That's not true. It is simply ... That is a rare variant, and we don't know whether it's pathogenic or non-pathogenic. And hopefully overtime we will learn more to better assess that, and better provide the interpretation of what that means in the context of that patient. Dr. McNally: It's a good conversation to have. It's important to recognize they're not necessarily pathogenic, but they're also not necessarily benign. Dr. Lin: Mm-hmm (affirmative). So do you see a role, for example, when you see this variant of uncertain significance, is there a role to go back into lab, for example, and try to knock that mutation to IPSC's and test to see if its pathogenic? Or is that going a step too far? Dr. McNally: In some cases, that is the right thing to do. Because genetics is so powerful, genetics doesn't only give you the association of a gene with an outcome, and GWAs was fabulous at doing that ... giving us a lot of variants, and often nearby genes, sometimes far away genes, but linking genes to phenotypes, and that's very powerful. But specific variants can actually tell you a lot about mechanism, about how a gene and protein actually function, and how it functions when it's broken. And so, particularly where you can gain a lot from the research front in understanding mechanism, then I think it's really powerful to take those things to the laboratory and to use that to learn about mechanism. Dr. McNally: Sometimes you can do it to help adjudicate whether something's pathogenic or not, but again, I think we want to be cautious in doing that. Because what we do in the res ... I always like to say, "What we do in the research lab isn't exactly CLIA certified." Dr. Lin: Right. Dr. McNally: There isn't anything magical about what we do, but we definitely ... It is so powerful what's available out there in terms of the genetic variants, and teaching us about how genes and proteins interact. And so I think it is such a rich resource of information right now. The things I bring back to the laboratory, and get my students and trainees excited about working on, is usually where I think we can gain something new about mechanism. Dr. Lin: Right, right, right. Since you are a role model physician scientist, and you think about questions in lab that will ultimately benefit your patients, and you are a genetic cardiologist. What are your thoughts on doing genome editing as a possible therapy for your patients? It's a little bit of a loaded question [crosstalk 00:21:51], it's a little bit controversial. Dr. McNally: So I think, no doubt CRISPR/Cas9 gene editing is transforming what we do in the research setting. It's a fantastic tool. Is it a perfect tool? No. Anybody who has been using it a lot in the lab knows that it is much better than anything we've had before, but still quite limited in fidelity and efficiency. And so imagining that we are going to do that in patients is still pretty daunting to me. We do enough gene editing in cells to know that you have to select through an awful lot of cells before you get the one that has the exact variant you are trying to make. So that's not something we can tolerate in the human setting. But we're not there yet, we know that. Dr. McNally: Many of the disorders I see clinically are things that are autosomal dominant due to very precise single base-pair changes. And so envisioning how we're going to correct only one copy of an allele and do in a very precise manner, we don't have those tools available yet. Now on the other hand, if you look at a disease like one of the diseases I spend a lot of time on, Duchenne muscular dystrophy, where the majority of mutations are deletions. It's X-linked, it's male, so there's only one copy of the gene, and we know a whole lot about the structure and function of the gene. We know that if we take out this other part we can skip around that mutation and make an internally truncated protein. That's actually a very good use of gene editing, because it only requires making deletions. They don't need to be very precise, and there's only one copy of it that you have to do the gene editing on. Dr. McNally: So I see that being something in the near term that will happen, simply because the genetics positions it well to be something where that could be successful. The hard part is still how are we going to get the guides, and how are we going to get the Cas9 in safely into all the cells that need to be treated? And ultimately that lands us back at looking at what our delivery vehicles are. Which at this point in time is still viral delivery, and still has a lot of issues around can we make enough of it? Are people immune to it? So all those questions that come with viral delivery. So still lots of hurdles, but you can see some paths where it makes sense to go forward. Dr. Lin: Very interesting. Okay great. Well thank you for providing your thought on human genetics and genome science. We're going to switch gears for the last portion of this podcast, and talk about your thoughts on career development issues for young investigators. At a recent AHA Scientific Sessions meeting, you participated on a panel that was assembled to provide advice to early career scientists. When you were starting out, what were some of the biggest challenges you faced when you were transitioning to independence and building your own lab, and what's your advice to those facing the same challenges today? Dr. McNally: Well, even though I did it quite a few years ago, many of the things are still the same. Transitioning to independence, I think is easier if you pick up and move and start in a new place. I think it's much easier to establish your independence when you're not in the same place as your mentor. That said, we have many more people who now stay in the same place as where their mentors were and we have many more approaches towards doing that. So I think people are much more open to both possibilities as being ways of doing that. But at some level it still comes down to starting your own lab, and you hopefully have been given some start-up resources and you have to think about how to wisely spend them, and how to really get things going. I don't think this is changed either. Dr. McNally: I usually tell people, don't just start in one area, if you can, start in two areas because things don't work, and sometimes things do work. In reality when you look at people who are successful, they're often working in more than one area. And so the sooner you start getting comfortable working in more than one area, that's a good thing. Now ideally, they should be areas that have some relationship to each other, and then feed each other in terms of information so that they grow off each other. But what does that practically mean? I always say, "Well if you can hire two people and start them on two different paths, that's a really good way to get going." And practical things like look at all different kinds of private foundations and things like that for getting some good pilot start up money to help develop new projects in the lab. And always be looking at how can these projects help me develop a bigger data package, that's going to put me in a good competitive position for example bigger grants and federal funding, and things along those lines. Dr. McNally: Very much a stepwise process. People want to shoot for the moon and get the biggest things first, but sometimes just focusing on the smaller steps which are definitely achievable and building your path towards those bigger steps is the smarter way of doing it. Dr. Lin: That's great advice. You also mentioned recently that young investigators should try to have as many mentors as possible. What advice would you have for, in particular, early career genomics investigators, for finding these mentors passed the postdoc phase? Some of us get introduced at the postdoc phase to maybe some other collaborating labs, but those are really collaborations of our mentors per se. Dr. McNally: Well I think especially in the field of genetics and genomics, collaboration is key, and I will say one of the things that has changed over since I started doing this is there is a lot more understanding of the need to collaborate. Not so many years ago, it wasn't really an independent investigator went and started a lab, and it would be your trainees and the papers would have only those people on it. Dr. McNally: I think these days, the best science is where you've tackled a problem from multiple different directions, one or two of those being genetics, genomics directions. And then sometimes there's other ways that you've approached that scientific problem. And by necessity, that usually involves collaborating with other people. And your role is sometimes to be the coordinator of all those collaborators, and that's where again you might be in a senior author position then doing that. But your role sometimes is to be the good collaborator. And so when I look at people being successful right now, seven, eight years in to running their own lab, I like to see that they've been the organizer of some of those, that they've collaborated with people who are even senior to them, and that they've established those good collaborations, but that they've taken the leading role in doing that. But also that they've had middle author contributions, that they've been a good collaborator as well. Dr. McNally: And so, part of that is not being afraid to collaborate, and to recognize the value of doing that. And what's so great about doing that is you can collaborate with people at your same institution where you are, but you can also collaborate with people all over the world, and I think that's what we do. You go to where you need somebody who is using a technique or an approach that really helps answer the question you want to have answered. And so that's reaching out to people and really establishing again that network and good collaborators which you can do by a whole bunch of ways. You can do it by meeting somebody at a meeting, scientific meeting. You can do it through emails, phone calls, Skype, all sorts of different ways that you can reach out and collaborate with people. Dr. McNally: It is easier than ever to share data and share ideas, but that negotiation of how to establish the terms of the collaboration and how to make it be successful is a critically important part of being a scientist. And what we now know when we look at the promotion process, is people who do that effectively, that's a really important mark of being a successful scientist, and marks them as somebody who should be promoted through the process. So great. Dr. Lin: Yeah. No I agree. Certainly with the direction science is moving, it's definitely very difficult to work in a siloed manner. Dr. McNally: Yeah. Well you won't get very far. You'll be able to have some really good first ideas, and show some proof of principle approaches. But to really, really address an important scientific problem, we know that you have to see those signals using multiple different methods. And once you have five different ways showing you that that's the right answer, then you're much More confident that you've gotten to the right answer. Dr. Lin: Right. Alright, so I think we're going to wrap up. Do you have any other final thoughts for any other young investigators or genomics researchers listening to this podcast? Dr. McNally: It's a great time to be doing genetics and genomics, and particularly human genetics, where we now finally have all this information on humans, and we'll have even more of it in the future. So I think humans are coming close to becoming a real experimental system. Dr. Lin: Excellent. Alright well thank you so much for your time. It was a pleasure having you on this podcast. Dr. McNally: Great. Thank you for doing this. Jane Ferguson: As a reminder, all of our original research articles come with an accompanying editorial, and these are really nice to help give some more background and perspective to each paper. To read all of these papers, and the accompanying commentaries, log on to circgenetics.ahajournals.org. Or, you can access video summaries of all our original articles from the circgen website, or directly from our YouTube channel, Circulation Journal. And lastly, follow us on Twitter @circ_gen, or on Facebook, to get new content directly in your feed. Jane Ferguson: Okay, that is it from us for June. Thank you for listening, and come back for more next month.
Prof. Rudi Wiesner talks with Dr Julie Ann Lough about his recently published research: Catecholamine metabolism induces mitochondrial DNA deletions and leads to severe adrenal degeneration during ageing
NLP In Action - Mike Sweet - 10 Minute Coach - Rapid Practical NLP
There are 3 areas that I'll separate out for Deletions. These are Nominalisations, Unspecified verbs and Simple deletions. For clarity, the purpose of understanding deletions is to get to the heart of another person map. We are deletions machines, it allows us to simplify and fast track through life, but this means we miss so much of what actually is going on for a person. The first sections we can take a deep dive into is Nominalisations, I have written a post, podcast and video on this, but in the interest of keeping it all together, here's another summary.
Samra Turajlic discusses the contribution of small insertions and deletions to tumour-specific antigen analyses.
Mothers who smoke during pregnancy and after birth put their children at increased risk of a common type of childhood cancer. This, according to a new University of California, San Francisco study. Adam de Smith says their work is the first to find an association between maternal smoking and acute lymphoblastic leukemia. “In the mothers who are exposed to tobacco smoke, there was a higher rate of deletion in the fetal cells that was likely caused by a particular mechanism. It is an innate mechanism in our immune system, which functions to create antibodies to particularly create diversity in our antibodies. And we think when this mechanism goes wrong, or goes into overdrive and has abnormal effects, it can increase the risk of causing deletions in genes around across the genome.” Deletions are genetic mutations that can lead to cancer and other diseases. “We think that the tobacco smoke maybe increasing the abnormal effects of this immune mechanism, that lead to increased deletions. And this maybe through inflammation, because we know tobacco smoke has inflammatory properties.”
IT'S THE ULTIMATE THRILL RIDE!!! Join Kyle & Duncan as they relive the ups and downs of the biggest spectacle in sports entertainment, filled with hellos, goodbyes and DELETIONS.
Es wird Zeit, wieder einmal über Ring Of Honor zu reden. Wir hatten einen Geburtstag, wir hatten viele Gerüchte, wir hatten Ladder Matches, Deletions und einen neuen ROH World Champion. Zeit, gemeinsam wieder auf den aktuellsten Stand zu kommen! Außerdem besprechen wir ab ca. einer Stunde über Sakura Genesis von New Japan, weil wir es einfach nicht mehr ausgehalten haben. Hört rein!
Es wird Zeit, wieder einmal über Ring Of Honor zu reden. Wir hatten einen Geburtstag, wir hatten viele Gerüchte, wir hatten Ladder Matches, Deletions und einen neuen ROH World Champion. Zeit, gemeinsam wieder auf den aktuellsten Stand zu kommen! Außerdem besprechen wir ab ca. einer Stunde über Sakura Genesis von New Japan, weil wir es einfach nicht mehr ausgehalten haben. Hört rein!
This week The Truepenny Show previews Bound For Glory as James is joined by resident TNA expert Marcus Green. They look back at the start of the Corgan era, the things that are going right for the company, and how they have managed to stablise the company. They also look at the fall out from the numerous Deletions taking place in TNA. Bobby Lashley's championship reign, Gail Kim's Hall of Fame run and Maria Kannelis Bennet as heel in chief.
The 186th of a series of weekly radio programmes created by :zoviet*france: First broadcast 30 January 2016 by Resonance 104.4 FM Thanks to the artists included here for their fine work. track list 01 Tauchsieder - Laika – Long Version 02 Thomas F Newell - Tremble 03 Tomas Phillips - Limit_Fold [extract] 04 Toy Bizarre - [untitled – 'kdi dctb 180' side A] 05 :zoviet*france and Fossil Aerosol Mining Project - Kinesic Remnant 1987 06 Moljebka Pvlse - You Are Alone 07 Quatroconnection - Endless Circle (If You Want It To) 08 France Jobin - 2_t
A Great REPLAY ---99 Weeks: When Unemployment Benefits RUN OUT,(Bloomberg) Treasury Shields CitiGroup as Deletions undercut Disclosure, France: Strikes Costing up to $557 Million per day, France Braces itself for Another week of Protests as France drowning in waste. Look at us today, Please pass the Show Around. Thanks Rich Marla and Mark
CARTA - Center for Academic Research and Training in Anthropogeny (Audio)
Evolution of Human Duplications: Genomic Instability and New Genes (Evan Eichler); Human Accelerated Regions in the Genome (Katherine S. Pollard) Series: "CARTA - Center for Academic Research and Training in Anthropogeny" [Science] [Show ID: 21956]
CARTA - Center for Academic Research and Training in Anthropogeny (Video)
Evolution of Human Duplications: Genomic Instability and New Genes (Evan Eichler); Human Accelerated Regions in the Genome (Katherine S. Pollard) Series: "CARTA - Center for Academic Research and Training in Anthropogeny" [Science] [Show ID: 21956]
Background: Deletions of the mitochondrial DNA (mtDNA) accumulate to high levels in dopaminergic neurons of the substantia nigra pars compacta (SNc) in normal aging and in patients with Parkinson's disease (PD). Human nigral neurons characteristically contain the pigment neuromelanin (NM), which is believed to alter the cellular redox-status. The impact of neuronal pigmentation, neurotransmitter status and brainstem location on the susceptibility to mtDNA damage remains unclear. We quantified mtDNA deletions (Delta mtDNA) in single pigmented and non-pigmented catecholaminergic, as well as non-catecholaminergic neurons of the human SNc, the ventral tegmental area (VTA) and the locus coeruleus (LC), using laser capture microdissection and single-cell real-time PCR. Results: In healthy aged individuals, Delta mtDNA levels were highest in pigmented catecholaminergic neurons (25.2 +/- 14.9%), followed by non-pigmented catecholamergic (18.0 +/- 11.2%) and non-catecholaminergic neurons (12.3 +/- 12.3%; p < 0.001). Within the catecholaminergic population, Delta mtDNA levels were highest in dopaminergic neurons of the SNc (33.9 +/- 21.6%) followed by dopaminergic neurons of the VTA (21.9 +/- 12.3%) and noradrenergic neurons of the LC (11.1 +/- 11.4%; p < 0.001). In PD patients, there was a trend to an elevated mutation load in surviving non-pigmented nigral neurons (27.13 +/- 16.73) compared to age-matched controls (19.15 +/- 11.06; p = 0.052), but levels where similar in pigmented nigral neurons of PD patients (41.62 +/- 19.61) and controls (41.80 +/- 22.62). Conclusions: Catecholaminergic brainstem neurons are differentially susceptible to mtDNA damage. Pigmented dopaminergic neurons of the SNc show the highest Delta mtDNA levels, possibly explaining the exceptional vulnerability of the nigro-striatal system in PD and aging. Although loss of pigmented noradrenergic LC neurons also is an early feature of PD pathology, mtDNA levels are not elevated in this nucleus in healthy controls. Thus, Delta mtDNA are neither an inevitable consequence of catecholamine metabolism nor a universal explanation for the regional vulnerability seen in PD.
"Merry What? Deletions, Dilutions, and Delusions" Selected Passages Introduction Deletions Dilutions Delusions The True Christmas Information, Transformation, Reformation:
1-99 Weeks: When Unemployment Benefits RUN OUT,(Bloomberg) Treasury Shields CitiGroup as Deletions undercut Disclosure, France: Strikes Costing up to $557 Million per day, France Braces itself for Another week of Protests as France drowning in waste.
This is the third and last podcast on the Meta-Model in this language series, to be followed by Sleight of Mouth patterns, and the Milton Model patterns, each a small series in itself. In this last Meta-Model talk, we cover the following deletions: Ambiguous nouns Ambiguous verbs Ambiguous adjectives and adverbs Unspecified referential index Implicit […]
Fakultät für Biologie - Digitale Hochschulschriften der LMU - Teil 03/06
Rad5 is a decisive protein in S. cerevisiae due to its role in the Post-replication repair (PRR) pathway, in which Rad5 is necessary for at least one error-free and one error-prone repair subpathway. In addition, Rad5 plays a role in other repair pathways; for instance, Rad5 regulates the balance between the double strand break (DSB) repair pathways, favoring the Rad52-dependent Homologous Recombination (HR) over the yKu70-dependent Non-Homologous-End Joining (NHEJ). Furthermore, since UV-induced damages are substrates for Rad5 but also for Base Excision Repair (BER) proteins, Rad5 is possibly involved directly or indirectly in the BER pathway. To get a deeper insight into the interaction of Rad5 with HR, NHEJ and BER proteins, survival curves, plasmid assays, and mutagenicity experiments were carried out in this work. In addition, a new software tool has been developed for the quantification of DSB. This software, called Geltool, allows the quantification of DSB in haploid cells from PFGE gels, even if the number of DSB is small. This represents a decisive advantage in comparison with previous programs. The sensitivity of Geltool has permitted the quantification of DSB repair during the stationary growth phase in haploid cells, detecting a repair of 46 %- 57 % of the gamma-induced DSB in HR proficient strains against 6 % - 16 % in HR deficient strains. Studies of the functional interactions of Rad5 with HR and NHEJ proteins revealed a synergistic effect between Rad5 and Rad52 proteins for the repair of DSB at chromosomal and plasmidial level. Differences in the repair of plasmids from the rad52 and the rad5 mutants revealed different end joining mechanisms for gap repair. Severe degradations found in plasmids from rad52 and rad52rad5 mutants could indicate an end protection function for Rad52 and also for Rad5, when Rad52 is absent. Moreover, the regulatory role of the Rad5 protein is confirmed, since the additional deletion of YKU70 suppresses the rad5 phenotype and forces the yku70rad5 mutant to repair by HR. The further study of the interplay of Rad5 with BER proteins shows that while BER only plays a minor role for the repair of gamma-induced damage, the rad5 phenotype is suppressed in the BER deficient apn1ntg1ntg2rad5 mutant. The same phenotype of suppression is also found for survival after UV irradiation. An enhanced mutagenicity of the apn1ntg1ntg2rad5 mutant indicates a possible repair through the REV3-dependent Translesion Synthesis Repair (TLS) pathway, suggesting that an error-prone tolerance of UV-induced damage can be very effective for survival.
Medizinische Fakultät - Digitale Hochschulschriften der LMU - Teil 03/19
Peroxisomales Targeting und Import von Proteinen in Peroxisomen sind für die Entstehung, Wachstum und Funktion von Peroxisomen entscheidend. Ziel dieser Dissertation war, die Region und das Aminosäure-Motiv innerhalb des Adrenoleukodystrophie-Proteins (ALDP) zu identifizieren, welches für das peroxisomale Targeting erforderlich ist. Dieses peroxisomale Membran-Protein ist defekt oder fehlend bei der X-gebundenen Adrenoleukodystrophie, einer überwiegend in der Kindheit auftretenden letalen neurodegenerativen Erkrankung. Unter Verwendung von Deletions- und GFP-Fusionsprotein-Konstrukten konnte die für das peroxisomale Targeting notwendige Region des humanen ALDP auf die Aminosäuren 67-110 eingegrenzt werden. Dabei sind die NH2-terminalen 66 Aminosäuren des ALDP für das peroxisomale Targeting zwar nicht notwendig, sie erhöhen jedoch die Targeting-Effektivität insgesamt. Die für das Targeting notwendige Region ist allerdings alleine nicht auseichend, um ein Fusionsprotein an das Peroxisom zu leiten. Zusätzliche Aminosäuren scheinen für die Stabilisierung und Insertion in die peroxisomale Membran notwendig zu sein, da die Aminosäure-Regionen 1-110 und 67-164 ein Fusionsprotein an das Peroxisom dirigieren können. GFP-Fusionsproteine der dem 67-164 ALDP entsprechenden Regionen des humanen peroxisomalen Membran-Proteins 69 und des Pxa1 der Hefe wurden ebenfalls an das Peroxisom geführt. Damit konnte eine partielle Konservierung der Targeting-Region innerhalb der humanen peroxisomalen ABC-Transporter und zwischen Hefe und Mensch gezeigt werden. Die Targeting-Region beinhaltet ein 14 Aminosäuren (71-84) umfassendes konserviertes Motiv. Eine Deletion des gesamten Motivs oder von Teilen dieses Motivs führt zu einem Verlust des peroxisomalen Targetings des ALDP. Von den getesteten Mutationen einzelner Aminosäuren bewirkt lediglich die Substitution L78F eine signifikante Verminderung der Targeting-Effektivität. Dagegen führt die bei zwei X-ALD Patienten beobachtete Deletion von drei Aminosäuren innerhalb des Motivs zu einem Verlust des peroxisomalen Targetings mit einer partiellen Anreicherung des GFP-Fusionsproteins in Mitochondrien und gibt somit Aufschluss über die molekulare Ätiologie ihrer Erkrankung.
We report on multicolor fluorescence in situ hybridization protocols for the simultaneous visualization of deletion-prone regions for carrier detection of Duchenne/ Becker (DMD/BMD) muscular dystrophy. Cosmid and yeast artificial chromosome (YAC) clones specific for preferentially deleted subregions of the dystrophin gene were labeled differentially and detected with three different fluorochromes using digital imaging microscopy. This approach allows for an assessment of the carrier status of female relatives even in families where no index patient is available. Cosmid and YAC clones, and different probe-generation protocols are compared with respect to their feasibility for carrier detection. The use of histone-depleted interphase nuclei (Halo-preparations) for deletion mapping is demonstrated and shown to have a resolution power of 5 kb.
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