Podcasts about Karow

Wir lassen im Podcast Jackpot von LOTTO Berlin das Jahr 2024 Revue passieren. Im Laufe des Jahres haben wir tolle Orte besucht, wie zum Beispiel die Trabrennbahn Mariendorf, das Deutsche Technikmuseum oder das Berliner Olympiastadion. Außerdem waren wir zu Gast in großartigen Berliner LOTTO-Läden in Rudow oder in Karow und haben vor Ort über viele der großartigen Produkte aus dem Porte-Folio von LOTTO Berlin gesprochen – TOTO, Eurojackpot oder die Glücksrakete waren Thema. Der große Jahresrückblick mit Christian Friedrich und Till Mildebrath in der aktuellen Episode vom Jackpot dem Podcast von LOTTO Berlin.

Welcome to Part II of our conversation with Tyler Karow. If you missed Part I, I highly recommend checking it out before continuing here.Tyler Karow has built a highly engaged following on YouTube and Instagram, to the point where many might label him as an influencer. While his impact on the climbing community is undeniable, Tyler is quick to distance himself from the typical “influencer” role. Constantly promoting products or leaning into that stereotype is the furthest thing from his goals. He believes that his ability to capture the raw adventure and authentic connections he experiences during his climbs is what ultimately draws people to his content . Tyler takes pride in sharing these stories and feels grateful that they resonate deeply with so many.For Tyler, adventure is the core of his content, but that doesn't always mean taking more risks. He emphasizes that adventure can be found anywhere—whether its a beginner tackling their first 5.7 or a group questing out to rarely accessed boulder fields. It's about pushing beyond your comfort zone into the unknown. For Tyler, these moments are critical to living a fulfilled life—fueling self-improvement, self-discovery, and happiness.We wrap up our conversation with Tyler's future plans to return to Patagonia. With bold objectives like Cerro Torre on his list, he's gearing up for another chapter of wild adventure and plans to bring us all along for the ride.----Don't forget to check out our full video episodes on Youtube!The TCM movement is growing but we need your help to spread the word! Please share this podcast with your friends and family. Word of mouth is one of the best ways to support the show. If you enjoyed the show we'd appreciate it if you could rate and review us on your favorite podcatcher.We are always looking for new guests. If you or someone you know would be a great fit for the show please don't hesitate to reach out. You can reach us on IG or email us directly @ theclimbingmajoritypodcast@gmail.com---ResourcesTyler's WebsiteTyler's Youtube ChannelTyler's InstagramGastronomic Big Wall Climbing in Patagonia

I'm sure we've all been there—the dream of living a life solely dedicated to climbing: sponsorships, life on the road, making a living through our passion for the sport. For many, this represents the ultimate freedom. Often, this grand vision captures us in our early climbing years, yet it seldom holds much reality. Attracting sponsors and dedicating your life entirely to climbing requires something truly special. For most of us, this dream starts to feel one-dimensional, perhaps even a little unrealistic. Climbing, as fulfilling as it is, can sometimes no longer be the clear answer to all of life's questions—because in reality, we have other ambitions, other passions to fulfill, other goals to achieve.But what if you had sponsors and created a thriving climbing YouTube channel? Would you still feel there was something more out there for you, or would you seize the opportunity and dive fully into a life dedicated to climbing?Today, we're sitting down with Tyler Karow, a climber who finds himself at these very crossroads. Despite his success on Youtube and his recently acquired sponsorships, Tyler has chosen to step back from the singular pursuit of climbing to focus on something bigger—a life that balances his passion for climbing with broader ambitions, a life that is truly meaningful and fulfilling for him.For Tyler, climbing has always been about more than just the performance. It's about the adventure, the connection, and the shared experiences that enrich our lives both on and off the rock. From tackling serious alpine routes in Patagonia to bivvying with good food and wine, climbing has fostered deep friendships and unforgettable moments for him. But even with this strong connection to the sport and opportunities most of us could only dream of, he has found himself questioning whether climbing alone is enough. His journey speaks to a broader question that many of us face: How do we balance our love for climbing with our other ambitions, responsibilities, and long-term goals?Tyler's story is a compelling reminder that climbing doesn't have to be the only path. He's finding a way to integrate his passion for the sport with a vision for the future that goes beyond the rock, allowing him to pursue both adventure and purpose in his life.His story also reminds us not to take life or climbing too seriously…because in the end life is short. We might not live tomorrow….so let's be sure to make the most out of today.----Don't forget to check out our full video episodes on Youtube!The TCM movement is growing but we need your help to spread the word! Please share this podcast with your friends and family. Word of mouth is one of the best ways to support the show. If you enjoyed the show we'd appreciate it if you could rate and review us on your favorite podcatcher.We are always looking for new guests. If you or someone you know would be a great fit for the show please don't hesitate to reach out. You can reach us on IG or email us directly @ theclimbingmajoritypodcast@gmail.com---ResourcesTyler's WebsiteTyler's Youtube ChannelTyler's InstagramGastronomic Big Wall Climbing in Patagonia

Sam Karow, founder and CEO of Effective, offers a fresh perspective on marketing, showcasing how strategic approaches can turn marketing into a powerful investment. His insights highlight the importance of aligning consumers, brands, and channels through a triangle model for effective marketing. His approach to integrated marketing is defined by his innovative triangle model, which connects consumers, brands, and channels. This model underscores the importance of thoroughly understanding these elements before implementing marketing tactics. By focusing on deep consumer insights, a clear brand identity, and the right channels, businesses can craft more effective and targeted campaigns. At Effective, Karow has pioneered unique B2B strategies, particularly in complex sectors like healthcare. His methods help businesses reach key decision-makers, and a proactive brand brief approach that ensures clear objectives and budgets from the start. These strategies have proven effective in creating tailored marketing campaigns that drive results. We're happy you're here! Like the pod? Visit our website! Start your trial on Simplified Schedule a consult, get on the mailing list, and learn more about my favorite tools and programs via https://www.yourbrandamplified.com

At 6:00 a.m. on August 28, 1965, Carl and Carmela Coppolino's physician, Dr. Juliette Karow, was awakened by a phone call. Carl Coppolino tearfully described to her how he had just found his 32-year-old wife dead, seemingly from a heart attack. Dr. Karow was concerned when she arrived at the house—young women in their 30s […] The post The Love Triangle Murders appeared first on Tiegrabber.

I'm a little unsure of the best way to frame this introduction. In some ways, this is a story of embracing climbing for all the right reasons. Pursuit of technical mastery and love for the outdoors over the gamification of grades and emphasis on physical training. On the other hand, this is also the story of early adulthood in the modern era. The narrative to pursue something like climbing full-time is strong in the outdoor world. But most I encounter eventually find that climbing alone leaves us yearning for meaning and purpose. My guest today, Tyler Karow, spent nearly three years on the road pursuing climbing. Today he balances considerable climbing achievements with a secondary passion for building and a desire to be a part of the solution to America's affordable housing crisis.Karow is a 29-year-old climber known for his big wall accomplishments in Yosemite, Patagonia, and around the globe. His resume includes a ground-up free ascent of Golden Gate (5.13a) on El Cap, and Yosemite's Triple Crown in under 24 hours, only the eighth time this feat has been achieved. Notably, Karow climbed the Triple while working a full-time (plus) job. He holds a B.S. in Civil Engineering from the University of Southern California and is a licensed civil engineer and general contractor. With this background in engineering and construction, he envisions a career helping to build prefabricated tiny home communities. This emerging approach to construction helps to reduce the cost of new housing and more efficiently add supply to a stressed housing market.This episode is an Oreo of sorts, with a focused discussion of Tyler's climbing achievements and work/life balance in the beginning and end. The middle of this discussion takes a deep dive into the affordable housing crisis, the complex nature of new construction, and Tyler's vision for the future of American affordable housing. Support this project: Buy Me a CoffeeGet the newsletter: SUBSCRIBE ME!Show Notes and Links at Clippingchains.com

Every client is unique.   While some individuals may prefer a scientific approach involving lab testing, others may seek a more emotionally oriented exploration.   As health practitioners, it's crucial for us to consider this as a holistic puzzle and our responsibility to piece it all together.   On today's show we talk with Tonya Karow.   Tonya is an Integrative Health Practitioner from the EquiLife Health Coaching team, who is passionate about integrating the science of health and wellness with emotional well-being.   In this episode, we emphasize the significance of approaching each session and client from a personalized perspective to effectively meet them where they are in their journey.   We also dive into the crucial skill of listening and how it plays a pivotal role in supporting clients by combining what Tonya beautifully refers to as the science and the “woo."   To explore the holistic approach of addressing each client's unique needs, join us on today's episode of the Integrative #HealthCoachSuccess podcast, Episode 281. Enjoy the show!   - - -   Listen or Watch At:  IHP.Coach/281   - - - Dr. Cabral's Book, The Rain Barrel Effect: https://amzn.to/2H0W7Ge - - - Become an Integrative Health Practitioner: https://integrativehealthpractitioner.org

Mark Waschke kommt Anfang März 1972 in Wattenscheid zur Welt, einem Stadtbezirk von Bochum. Seine Mutter ist Krankenschwester, sein Vater Arzt – und er der mittlere von drei Söhnen. Als er acht Jahre alt ist, zieht die Familie nach Bildstock bei Friedrichsthal im Saarland, wo sein Vater eine Stelle im Sulzbacher Krankenhaus antritt. 1981 – also mit neun Jahren – beginnt quasi seine Karriere im Kindertheaterkreis Neuweiler. Später ist er Teil einer Amateur-Theatergruppe und Sänger einer Punk-Band. 1991 zieht er nach Berlin. Dort beginnt er ein Philosophiestudium. 1995 wechselt er jedoch zum Schauspiel an die Ernst Busch Schule. Unter anderem in seiner Klasse: Nina Hoss, Devid Striesow, Fritzi Haberland und Lars Eidinger. Ab 1999 gehört er für vieleJahre zum Ensemble der Schaubühne Berlin. Ab 2007 ist Waschke auch in Kino und TV zu sehen. Etwa als Thomas Buddenbrook unter Regisseur Heinrich Breloer oder an der Seite seiner Klassenkameradin Nina Hoss in Christian Petzolds „Barbara“. Eingeheimst hat er für seine Leistungen bereits den Bayerischen Filmpreis, den Franz-Hofer-Preis und den deutschen Schauspielpreis. Spätestens seit er ab 2015 an der Seite von Meret Becker als Team „Rubin und Karow“ in bisher 18 Fällen ermittelt, ist er tief in der deutschen TV-Kultur verankert. Seit dem Netflix-Hit „Dark“ kennt ihn auch die Streaming-Generation. Waschke lebt in Berlin. Er ist verheiratet und hat eine Tochter. Bei der Initiative #actout des SZ-Magazins hat er sich als einer von 185 Vertreter*innen der Schauspielbranche im Februar 2021 als queer geoutet – passend auch zu seiner Figur im Tatort. Erfahrungen mit Hörspielen hat Waschke schon seit 2002 gesammelt. Für Audible ist er in „Marvel's Wastelanders“ zu hören. Einer Serie, die das Marvel Cinematic Universe als ausproduziertes Audioerlebnis weiterspinnt. Am 29. September 2023 erscheint die zweite Staffel der deutschen Audible Original Podcast-Serie "Marvel's Wastelanders: Hawkeye“ mit Mark Waschke als Clint Barton/ Hawkeye. Hosted on Acast. See acast.com/privacy for more information.

On this in-between episode of the Enormocast, you get the outtakes from Episode 269 with climber, Tyler Karow. After the official interview ended, we kept talking about climbing in Jordan, the social cost of the itinerant climbing lifestyle, and a few more tidbits for your pleasure. And the cops showed up. Enjoy this free “bonus” … Continue reading "Enormocast Tweener: Tyler Karow Saves a Goat (Maybe a Sheep?)"

On Episode 269 of the Enormocast, I catch up with the elusive and prolific climber, Tyler Karow. Though Tyler has a popular presence on Youtube and Instagram, he still remained, for me, an enigma of sorts. Tyler burst on the national scene with a ground up free ascent of Golden Gate on El Cap (5.13) … Continue reading "Enormocast 269: Tyler Karow – Engineering the Stoke"

Jeff Karow took a stand against evangelical culture in the deep south, and it cost him dearly. Advocating for social justice alienated him from his community, his best friends, and his family. The episode starts out as another great, fun, look at an evangelical school, in this case Moody Chicago, but it ended up being a life-changing experience for both of us. No comedy or music segments in this episode, although I did record a parody song, which I apologize for to everyone except Ed Sheeran. If you have a message for Jeff, send it to info@rscottokamoto.com. Let's send some encouragements his way. He's been through the wringer. Chapel Probation is part of the Dauntless Media Collective Join the Dauntless Media Discord for more conversation with all the podcast communities. Asian-American-Apostate- Losing Religion and Finding Myself at an Evangelical University is available now! Music by Scott Okamoto, Jenyi, and Shin Kawasaki and Wingo Shackleford Join the Chapel Probation Patreon  to support Scott and for bonus content.  Join the Chapel Probation Facebook group to continue the conversations. Follow Scott on Instagram and Twitter and Substack You can subscribe to Scott's newsletter and learn more about the book, the blog, and performances at rscottokamoto.com --- Send in a voice message: https://podcasters.spotify.com/pod/show/scott-okamoto/message Support this podcast: https://podcasters.spotify.com/pod/show/scott-okamoto/support

Gutenburg shipped the first working printing press around 1450 and typeface was born. Before then most books were hand written, often in blackletter calligraphy. And they were expensive.    The next few decades saw Nicolas Jensen develop the Roman typeface, Aldus Manutius and Francesco Griffo create the first italic typeface. This represented a period where people were experimenting with making type that would save space. The 1700s saw the start of a focus on readability. William Caslon created the Old Style typeface in 1734. John Baskerville developed Transitional typefaces in 1757. And Firmin Didot and Giambattista Bodoni created two typefaces that would become the modern family of Serif. Then slab Serif, which we now call Antique, came in 1815 ushering in an era of experimenting with using type for larger formats, suitable for advertisements in various printed materials. These were necessary as more presses were printing more books and made possible by new levels of precision in the metal-casting. People started experimenting with various forms of typewriters in the mid-1860s and by the 1920s we got Frederic Goudy, the first real full-time type designer. Before him, it was part of a job. After him, it was a job. And we still use some of the typefaces he crafted, like Copperplate Gothic. And we saw an explosion of new fonts like Times New Roman in 1931. At the time, most typewriters used typefaces on the end of a metal shaft. Hit a kit, the shaft hammers onto a strip of ink and leaves a letter on the page. Kerning, or the space between characters, and letter placement were often there to reduce the chance that those metal hammers jammed. And replacing a font would have meant replacing tons of precision parts. Then came the IBM Selectric typewriter in 1961. Here we saw precision parts that put all those letters on a ball. Hit a key, the ball rotates and presses the ink onto the paper. And the ball could be replaced. A single document could now have multiple fonts without a ton of work. Xerox exploded that same year with the Xerox 914, one of the most successful products of all time. Now, we could type amazing documents with multiple fonts in the same document quickly - and photocopy them. And some of the numbers on those fancy documents were being spat out by those fancy computers, with their tubes. But as computers became transistorized heading into the 60s, it was only a matter of time before we put fonts on computer screens. Here, we initially used bitmaps to render letters onto a screen. By bitmap we mean that a series, or an array of pixels on a screen is a map of bits and where each should be displayed on a screen. We used to call these raster fonts, but the drawback was that to make characters bigger, we needed a whole new map of bits. To go to a bigger screen, we probably needed a whole new map of bits. As people thought about things like bold, underline, italics, guess what - also a new file. But through the 50s, transistor counts weren't nearly high enough to do something different than bitmaps as they rendered very quickly and you know, displays weren't very high quality so who could tell the difference anyways.  Whirlwind was the first computer to project real-time graphics on the screen and the characters were simple blocky letters. But as the resolution of screens and the speed of interactivity increased, so did what was possible with drawing glyphs on screens.  Rudolf Hell was a German, experimenting with using cathode ray tubes to project a CRT image onto paper that was photosensitive and thus print using CRT. He designed a simple font called Digital Grotesk, in 1968. It looked good on the CRT and the paper. And so that font would not only be used to digitize typesetting, loosely based on Neuzeit Book. And we quickly realized bitmaps weren't efficient to draw fonts to screen and by 1974 moved to outline, or vector, fonts. Here a Bézier curve was drawn onto the screen using an algorithm that created the character, or glyph using an outline and then filling in the space between. These took up less memory and so drew on the screen faster. Those could be defined in an operating system, and were used not only to draw characters but also by some game designers to draw entire screens of information by defining a character as a block and so taking up less memory to do graphics.  These were scalable and by 1979 another German, Peter Karow, used spline algorithms wrote Ikarus, software that allowed a person to draw a shape on a screen and rasterize that. Now we could graphically create fonts that were scalable.  In the meantime, the team at Xerox PARC had been experimenting with different ways to send pages of content to the first laser printers. Bob Sproull and Bill Newman created the Press format for the Star. But this wasn't incredibly flexible like what Karow would create. John Gaffney who was working with Ivan Sutherland at Evans & Sutherland, had been working with John Warnock on an interpreter that could pull information from a database of graphics. When he went to Xerox, he teamed up with Martin Newell to create J&M, which harnessed the latest chips to process graphics and character type onto printers. As it progressed, they renamed it to Interpress. Chuck Geschke started the Imaging Sciences Laboratory at Xerox PARC and eventually left Xerox with Warnock to start a company called Adobe in Warnock's garage, which they named after a creek behind his house. Bill Paxton had worked on “The Mother of All Demos” with Doug Engelbart at Stanford, where he got his PhD and then moved to Xerox PARC. There he worked on bitmap displays, laser printers, and GUIs - and so he joined Adobe as a co-founder in 1983 and worked on the font algorithms and helped ship a page description language, along with Chuck Geschke, Doug Brotz, and Ed Taft.  Steve Jobs tried to buy Adobe in 1982 for $5 million. But instead they sold him just shy of 20% of the company and got a five-year license for PostScript. This allowed them to focus on making the PostScript language more extensible, and creating the Type 1 fonts. These had 2 parts. One that was a set of bit maps And another that was a font file that could be used to send the font to a device.  We see this time and time again. The simpler an interface and the more down-market the science gets, the faster we see innovative industries come out of the work done. There were lots of fonts by now. The original 1984 Mac saw Susan Kare work with Jobs and others to ship a bunch of fonts named after cities like Chicago and San Francisco. She would design the fonts on paper and then conjure up the hex (that's hexadecimal) for graphics and fonts. She would then manually type the hexadecimal notation for each letter of each font.  Previously, custom fonts were reserved for high end marketing and industrial designers. Apple considered licensing existing fonts but decided to go their own route. She painstakingly created new fonts and gave them the names of towns along train stops around Philadelphia where she grew up. Steve Jobs went for the city approach but insisted they be cool cities. And so the Chicago, Monaco, New York, Cairo, Toronto, Venice, Geneva, and Los Angeles fonts were born - with her personally developing Geneva, Chicago, and Cairo. And she did it in 9 x 7.  I can still remember the magic of sitting down at a computer with a graphical interface for the first time. I remember opening MacPaint and changing between the fonts, marveling at the typefaces. I'd certainly seen different fonts in books. But never had I made a document and been able to set my own typeface! Not only that they could be in italics, outline, and bold. Those were all her. And she inspired a whole generation of innovation. Here, we see a clean line from Ivan Sutherland and the pioneering work done at MIT to the University of Utah to Stanford through the oNLine System (or NLS) to Xerox PARC and then to Apple. But with the rise of Windows and other graphical operating systems. As Apple's 5 year license for PostScript came and went they started developing their own font standard as a competitor to Adobe, which they called TrueType. Here we saw Times Roman, Courier, and symbols that could replace the PostScript fonts and updating to Geneva, Monaco, and others. They may not have gotten along with Microsoft, but they licensed TrueType to them nonetheless to make sure it was more widely adopted. And in exchange they got a license for TrueImage, which was a page description language that was compatible with PostScript. Given how high resolution screens had gotten it was time for the birth of anti-aliasing. He we could clean up the blocky “jaggies” as the gamers call them. Vertical and horizontal lines in the 8-bit era looked fine but distorted at higher resolutions and so spatial anti-aliasing and then post-processing anti-aliasing was born. By the 90s, Adobe was looking for the answer to TrueImage. So 1993 brought us PDF, now an international standard in ISO 32000-1:2008. But PDF Reader and other tools were good to Adobe for many years, along with Illustrator and then Photoshop and then the other products in the Adobe portfolio. By this time, even though Steve Jobs was gone, Apple was hard at work on new font technology that resulted in Apple Advanced Typography, or AAT. AAT gave us ligature control, better kerning and the ability to write characters on different axes.  But even though Jobs was gone, negotiations between Apple and Microsoft broke down to license AAT to Microsoft. They were bitter competitors and Windows 95 wasn't even out yet. So Microsoft started work on OpenType, their own font standardized language in 1994 and Adobe joined the project to ship the next generation in 1997. And that would evolve into an open standard by the mid-2000s. And once an open standard, sometimes the de facto standard as opposed to those that need to be licensed. By then the web had become a thing. Early browsers and the wars between them to increment features meant developers had to build and test on potentially 4 or 5 different computers and often be frustrated by the results. So the WC3 began standardizing how a lot of elements worked  in Extensible Markup Language, or XML. Images, layouts, colors, even fonts. SVGs are XML-based vector image. In other words the browser interprets a language that displays the image. That became a way to render Web Open Format or WOFF 1 was published in 2009 with contributions by Dutch educator Erik van Blokland, Jonathan Kew, and Tal Leming. This built on the CSS font styling rules that had shipped in Internet Explorer 4 and would slowly be added to every browser shipped, including Firefox since 3.6, Chrome since 6.0, Internet Explorer since 9, and Apple's Safari since 5.1. Then WOFF 2 added Brotli compression to get sizes down and render faster. WOFF has been a part of the W3C open web standard since 2011.  Out of Apple's TrueType came TrueType GX, which added variable fonts. Here, a single font file could contain a number or range of variants to the initial font. So a family of fonts could be in a single file. OpenType added variable fonts in 2016, with Apple, Microsoft, and Google all announcing support. And of course the company that had been there since the beginning, Adobe, jumped on board as well. Fewer font files, faster page loads.  So here we've looked at the progression of fonts from the printing press, becoming more efficient to conserve paper, through the advent of the electronic typewriter to the early bitmap fonts for screens to the vectorization led by Adobe into the Mac then Windows. We also see rethinking the font entirely so multiple scripts and character sets and axes can be represented and rendered efficiently.  I am now converting all my user names into pig Latin for maximum security. Luckily those are character sets that are pretty widely supported. The ability to add color to pig Latin means that OpenType-SVG will allow me add spiffy color to my glyphs. It makes us wonder what's next for fonts. Maybe being able to design our own, or more to the point, customize those developed by others to make them our own. We didn't touch on emoji yet. But we'll just have to save the evolution of character sets and emoji for another day. In the meantime, let's think on the fact that fonts are such a big deal because Steve Jobs took a caligraphy class from a Trappist monk named Robert Palladino while enrolled at Reed College. Today we can painstakingly choose just the right font with just the right meaning because Palladino left the monastic life to marry and have a son. He taught jobs about serif and san serif and kerning and the art of typography.  That style and attention to detail was one aspect of the original Mac that taught the world that computers could have style and grace as well. It's not hard to imagine if entire computers still only supported one font or even one font per document. Palladino never owned or used a computer though. His influence can be felt through the influence his pupil Jobs had. And it's actually amazing how many people who had such dramatic impacts on computing never really used one. Because so many smaller evolutions came after them. What evolutions do we see on the horizon today? And how many who put a snippet of code on a service like GitHub may never know the impact they have on so many?

Sieben Jahre lang haben sie zusammen den Berliner Tatort gedreht, dann stirbt Nina Rubin nach tödlichen Schüssen in Robert Karows Armen. Warum der Ermittler an dem Tod seiner Kollegin nicht zerbrechen durfte und es wichtig ist, dass der Berliner Tatort auch die ganz harten Themen wie rechtsextremistische Gruppen in der Polizei thematisiert, darüber spricht Flo in dieser Special-Folge mit Mark Waschke. Außerdem hört ihr, warum Karow jede Unterstützung seiner neuen Kollegin Bonard gespielt von Corinna Harfouch im Tatort Zweiteiler "Nichts als Wahrheit" gebrauchen kann. Alles zu Karow und Rubin gibt es hier: https://www.daserste.de/unterhaltung/krimi/tatort/kommissare/team-berlin-rubin-karow-100.html Alles über das neue Berliner Tatort Team gibt's hier: https://www.daserste.de/unterhaltung/krimi/tatort/kommissare/team-berlin-bonard-karow-102.html Hier der Link zum Tatort: https://www.ardmediathek.de/tatort

This week Bekah and Dan sat down with Joe Karow, the Lead Engineer at a nonprofit, about his career change from the hospitality industry, his experience with the online bootcamp, 100devs, and about the ADHD experience.Joe KarowJoe is the Lead Engineer at InReach, a 501(c)3 registered non-profit building world's first tech platform matching LGBTQ+ people facing discrimination and persecution with safe, verified resources. Formerly a Director of Finance for a large hotel chain, he made the leap in to tech in 2022. Tech was always a part of Joe's life, it just took a global pandemic for him to decide to start getting paid for it.joekarow.dev@JoeKarow on GitHub@JoeKarow on Twitter@jkarow on LinkedInLinksAll Hands Job Board100devsResilient CodersLeon NoelCedar PointBusch GardensKennywoodcssbattle.devremoSponsor Virtual Coffee! Your support is incredibly valuable to us. Direct financial support will help us to continue serving the Virtual Coffee community. Please visit our sponsorship page on GitHub for more information - you can even sponsor an episode of the podcast! Virtual Coffee: Virtual Coffee: virtualcoffee.io Podcast Contact: podcast@virtualcoffee.io Bekah: dev.to/bekahhw, Twitter: https://twitter.com/bekahhw, Instagram: bekahhw Dan: dtott.com, Twitter: @danieltott

Aus der Spree wird eine Leiche geborgen. Wenig später wird Nina Rubin von einer jungen Frau verfolgt. Julie Bolschakow kannte den Toten und bittet Rubin um Hilfe. Ihr Mann Yasha ist ein führendes Mitglied der russischen Mafia. Der Schutz der Zeugin und die Ermittlungen im kriminellen Umfeld der Familie stellen Rubin und Karow in ihrem letzten gemeinsamen Fall vor ungeahnte Herausforderungen. Aus der Spree wird eine männliche Leiche ohne Kopf geborgen, deren Identität schwer zu ermitteln ist. Wenig später wird Nina Rubin (Meret Becker) von einer jungen Frau verfolgt. Julie Bolschakow (Bella Dayne) erzählt der Kommissarin, dass sie Zeugin eines Mordes geworden ist und bittet Rubin um polizeilichen Schutz. Sie kannte den Toten aus der Spree, er hatte ihr offenbart, dass ihr Mann Yasha (Oleg Tikhomirov) ein führendes Mitglied der russischen Mafia in Berlin ist. Rubin beschließt, der jungen Frau zu helfen und weiht die Kriminaldirektorin (Nadeshda Brennicke) ein. Die will Julie in ein Zeugenschutzprogramm aufnehmen, wenn diese im Gegenzug belastendes Material über ihren Ehemann vorlegen kann. Der Kontakt zu Julie bringt Rubin jedoch in ein Dilemma, weil sie fortan Karow (Mark Waschke) aus den Ermittlungen raushalten muss, um die junge Frau nicht zu gefährden. Karow ermittelt die Identität des Toten, spürt aber mehr und mehr, dass seine Kollegin ihm Dinge verheimlicht. Vertrauen war von Anfang an ein heikles Thema zwischen den beiden und Rubins Verhalten verletzt Karow – zumal sie sich auch privat nähergekommen sind. Umso mehr bricht das alte Problem nun wieder auf. Wird es Nina Rubin in ihrem letzten Fall gelingen, Julie aus den Fängen ihrer kriminellen Familie zu befreien? Foto: rbb/ARD/Hans Joachim Pfeiffer

Aus der Spree wird eine Leiche geborgen. Wenig später wird Nina Rubin von einer jungen Frau verfolgt. Julie Bolschakow kannte den Toten und bittet Rubin um Hilfe. Ihr Mann Yasha ist ein führendes Mitglied der russischen Mafia. Der Schutz der Zeugin und die Ermittlungen im kriminellen Umfeld der Familie stellen Rubin und Karow in ihrem letzten gemeinsamen Fall vor ungeahnte Herausforderungen. Aus der Spree wird eine männliche Leiche ohne Kopf geborgen, deren Identität schwer zu ermitteln ist. Wenig später wird Nina Rubin (Meret Becker) von einer jungen Frau verfolgt. Julie Bolschakow (Bella Dayne) erzählt der Kommissarin, dass sie Zeugin eines Mordes geworden ist und bittet Rubin um polizeilichen Schutz. Sie kannte den Toten aus der Spree, er hatte ihr offenbart, dass ihr Mann Yasha (Oleg Tikhomirov) ein führendes Mitglied der russischen Mafia in Berlin ist. Rubin beschließt, der jungen Frau zu helfen und weiht die Kriminaldirektorin (Nadeshda Brennicke) ein. Die will Julie in ein Zeugenschutzprogramm aufnehmen, wenn diese im Gegenzug belastendes Material über ihren Ehemann vorlegen kann. Der Kontakt zu Julie bringt Rubin jedoch in ein Dilemma, weil sie fortan Karow (Mark Waschke) aus den Ermittlungen raushalten muss, um die junge Frau nicht zu gefährden. Karow ermittelt die Identität des Toten, spürt aber mehr und mehr, dass seine Kollegin ihm Dinge verheimlicht. Vertrauen war von Anfang an ein heikles Thema zwischen den beiden und Rubins Verhalten verletzt Karow – zumal sie sich auch privat nähergekommen sind. Umso mehr bricht das alte Problem nun wieder auf. Wird es Nina Rubin in ihrem letzten Fall gelingen, Julie aus den Fängen ihrer kriminellen Familie zu befreien? Foto: rbb/ARD/Hans Joachim Pfeiffer

In this podcast episode, Sam Karow, President and founder of the marketing and media agency Effective, talks about programmatic paid social for B2B marketing. He touches upon best practices, some future predictions and much more.  If you want to know more or get in touch with Sam, you find more information in the links below:  https://www.linkedin.com/in/sam-karow-39044b5/     https://www.effectivemc.com  

Laura Karow, President of Gunnar Electric, Eden Prairie, Minn., has been involved in the family business for many years. She recognizes the company's greatest advances are in the areas of technology and designing/implementing processes that help to streamline operations. According to Laura, her favorite part of leadership is having the opportunity to work with and learn from other EC leaders in the Twin Cities, and then seeing her own team succeed using new means and methods.

Laura Karow, President of Gunnar Electric joins hosts Luke Kuhl and Andrew Colvard for a discussion about growing the diversity of women and minorities in the electrical industry, how contractors can efficiently utilize data, and the importance of recruiting and retainage of the future workforce. The Lunch Pail Podcast is sponsored by the St. Paul Chapter NECA.

Im Superwahljahr 2021 werden Bundestag, Abgeordnetenhaus von Berlin und Bezirksverordnetenversammlung in Pankow gewählt. In der heißen Phase des Wahlkampfs stellt "Ein Pod Grünes" sämtliche Direktkandidat*innen für die Wahl zum Abgeordnetenhaus in den neun Pankower Wahlkreisen vor. In dieser Folge Christoph Göring für Wahlkreis 1 (Buch, Karow und Französisch-Buchholz Ost).

Hey Welcome to the podcast. This week I was joined by @lilyrakow YouTuber, Health & Wellness coach. We met at a virtual event we both attended back in May. Lily is a breath of fresh air when it comes to living a healthy lifestyle, creating her content to inspire teenagers & young women to live a healthy & happy life while working towards the future. She is the host of the 80/20 podcast and I loved having her on my podcast

Blythe Karow is a medical device veteran who is now the cofounder and CEO of Evren Technologies, a medical device company making a wearable Vagus Nerve Stimulator to help with the problems brought about by Post Traumatic Stress Disorder (PTSD).   Top 3 Takeaways Not only veterans but first responders often get PTSD and 1/9 women will have it at some point in their lives Stimulating the auricular (ear) branch of the Vagus nerve has fewer side effects but with a calming effect on the body Diagnosing and curing PTSD is very difficult and subjective   1:15 "Do you want to introduce yourself and the technology?" 2:30 "You spun out of the University of Florida and then you were able to license it, what did that look like? " 3:30 "So you have some background in medical devices, you saw the potential in this and then you were looking to do something new?  5:00 "What were you looking for and what were the acceptance criteria?" 6:00 "So how does this work? What are some of the effects of vagus nerve stimulation?" 9:00 "So it is this calming effect, you're able to flip that stress response back to normal with the PTSD patients. Is that a one-time thing? Is that a one-time flip or does it have to be re flipped?" 11:00 "PTSD is very hard to quantify, right? How is that currently done?" 13:00 "So what are the current treatments for it?" 15:30 "So what's your device and how does it work? And how do you know that you're stimulating the Vagus nerve? " 19:30 "You guys are still in the prototyping phase and then you have to get FDA approval for this, what are the next steps for the company?" 21:15 "What are some I guess are your biggest challenges?" 23:30 "Would they have to get it as a prescription through a doctor? Would they be able to buy it on Amazon?" 24:15 "Is there anything that we didn't talk about that you wanted to mention?"  

You are in for a treat in this episode... Lidia Karow shares why adoption means so much to her... how her heart is so happy because she is adopted now.  Additionally, there are so many myths surrounding foster and adoption... let us debunk some of them for you!   --- Send in a voice message: https://anchor.fm/becky-khan/message

It's really so much more than orphan care it's Kingdom care.  There are so many ways to contribute to the foster/adoption community.  Join us for a quick glimpse into the Karow's journey and their passion behind the mission. --- Send in a voice message: https://anchor.fm/becky-khan/message

Heute nehme ich euch mit auf eine Etappe der Jubiläumswanderung: Das alpine Berlin, auf 150 km rund um Berlin in sieben Etappen. Diese Berlin-Umrundung haben wir als geführte Touren bereits im letzten Jahr anlässlich des 150-jährigen Jubiläums des Alpenvereins und der Sektion Berlin angeboten. Das kam so gut an, dass wir die Aktion in diesem Jahr wiederholt haben. Diesmal habe ich ein Aufnahmegerät mitgenommen um euch einen kleinen (Hör-)Eindruck zu vermitteln, wie es auf unseren Wanderungen so zugeht.

Die Panke ist nach der Spree und der Havel der drittlängste Fluß auf dem Berliner Stadtgebiet. Ihr Quellgebiet liegt in den Barnimhöhen bei Bernau und fließt einer eiszeitlichen Rinne folgend durch Buch, Karow und das eponyme Pankow bis sie in die Spree mündet. Schon 1920 kannten die Berliner die Panke nur als unter die Erde verlegten Fluß, wenn ihnen überhaupt bewusst war, wo sie langgeführt wurde. Das verhältnismäßig schmale und gemächlich fließende Gewässer, sorgte aber bei starken Regenfällen regelmäßig für Überschwemmungen. Die Hochwasser 1902, 1904, 1915 und 1919 wurden aber noch verstärkt durch die Rieselfelder entlang der Panke. Rieselfelder waren die Vorläufer der Klärwerke. Städtisches Abwasser wurde auf Felder am Stadtrand gepumpt, wo es in riesigen Becken durch Bodenschichten sickerte und sich so reinigte. Am 29. Juli 1920 berichtet die Vossische Zeitung über einen weiteren Anlauf, durch einen Ausbau des Flußbettes, die Gefahr von Überschwemmungen durch die „böse“ Panke zu minimieren. Es liest Paula Leu.

Guest Name and Bio: Dr. David Karow David S. Karow, M.D., Ph.D.,President and Chief Innovation Officer at Human Longevity Inc, is an innovative leader who brings more than 10 years of experience in advance MR Imaging and genomics analytics. Dr. Karow’s primary interest is to develop machine-learning based integrated diagnostics that leverage imaging, genetics, and clinical biomarkers to generate more insightful health assessments and identify disease in early stages when it is most treatable. Before joining HLI, Dr. Karow was the Director of Body MRI and Director of Acute Care Imaging in the Department of Radiology at the University of California, San Diego (UC San Diego), where he still maintains an appointment as an Associate Professor. During his times at UC San Diego he implemented advanced diffusion-based methods that proved beneficial for the detection and in vivo characterization of prostate tumors. The work has yielded multiple published papers and led to multiple federal and private research grants on which Dr. Karow was the Principle Investigator. Dr. Karow is compiling data showing that these techniques may be useful for the screening and staging of cancer across the whole body including breast cancer. Dr. Karow completed his fellowship in advanced body imaging at University of California, Los Angeles. Prior to fellowship, he completed his residency in diagnostic radiology at UC San Diego. His research during residency was recognized with multiple awards, including the 2011 Elliott C. Lasser Award for Excellence in Research; 2009 American Roentgen Ray Society Executive Council Award; the 2008 RSNA Trainee Research Prize; and his work was also featured on the cover of the September 2010 issue of the journal RADIOLOGY. Prior to residency, Dr. Karow completed his medical training at the University of Michigan medical school in the combined M.D./Ph.D. Medical Scientist Training Program, graduating with a distinction in research. What you will learn from this episode: 1) What the true meaning of precision medicine really is 2) Why it is important to look at the whole genome rather than individual genes 3) How you can understand your individualized risk for cancer 4) How you can understand your individualized risk for Alzheimer’s Disease 5) Why learning personalized information about your health can be life changing, help you live longer, and provide you with a higher quality of life How to learn more about our guest: Ready to take control of your health? Learn more about the Health Nucleus and Human Longevity, Inc. https://www.humanlongevity.com/ EMAIL CLIENT SERVICES TO SUBSCRIBE TO HLINSIGHT NEWSLETTER: clientservices@healthnucleus.com Follow: Twitter- https://twitter.com/humanlongevity https://twitter.com/HealthNucleus Linkedin – https://www.linkedin.com/company/human-longevity-inc- Instagram - https://www.instagram.com/humanlongevity/ https://www.instagram.com/health.nucleus/ Facebook - https://www.facebook.com/humanlongevity/ #HLI #health #biotech #healthcare #wellness #dementia #alzheimers #genomics #SanDiego #LaJolla #genetics #science #precisionmedicine #datadriven #preventative #DNA Please enjoy, share, rate and review our podcast and help us bring the message about precision health care to the world!

How do you really know if you're healthy? I've shared this quote more than once in the past, but it's something I stand by, Peter Drucker says, "what gets measured, gets managed." In this Get Yourself Optimized episode, my guest David Karow and I deep dive into the world of genome analytics and MR imaging. If you're interested in biohacking, then you're in for a treat! David is the President and Chief Innovation Officer at Human Longevity, Inc. He is an evangelist for optimizing longevity and personal performance. The show notes, including the transcript and checklist to this episode, are at getyourselfoptimized.com/241

Innerhalb von einer Woche hat das kleine Unternehmen Baltic Windtunnel ein einfaches Beatmungsgerät entwickelt. Es könnte sofort in Serienproduktion gehen. Die medizinische Zulassung fehlt jedoch. Weitere Nachrichten und Hintergründe erfahren Sie jederzeit hier: www.svz.de/corona

JavaScript Remote Conf 2020 May 14th to 15th - register now! Dave Karow is a developer evangelist for Split. He dives into how you can deliver software sustainably without burning out. His background is in performance and he's moved into smooth deliveries. He pushes the ideas behind continuous delivery and how to avoid getting paid to stay late in "free" pizzas. Panel AJ O’Neal Aimee Knight Charles Max Wood Dan Shappir Guest Dave Karow Sponsors G2i | Enjoy the luxuries of freelancing Taiko - free and open source browser test automation CacheFly ____________________________________________________________ "The MaxCoders Guide to Finding Your Dream Developer Job" by Charles Max Wood is now available on Amazon. Get Your Copy Today! ____________________________________________________________ Links Split.io Continuous Delivery zeit.co The Practical Test Pyramid Accelerate The Unicorn Project Ender's Game Ender's Shadow Atlassian Summit DeliveryConf JSJ 418: Security Scary Stories and How to Avoid Them with Kevin A McGrail Feature toggle split.io Dave Karow Progressive Delivery Speaker Deck Dave Karow Learn Enough Command Line to Be Dangerous Beyond Code Bootcamp Picks Aimee Knight: Designing for Performance Early Riser or Night Owl? Dan Shappir: web.dev AJ O’Neal: CineRAID CR-H458 DataCenter 8TB Drives Tiltamax Wireless Follow Focus System Charles Max Wood The Expanse Course Creator PRO Dave Karow: Accelerate Follow JavaScript Jabber on Twitter > @JSJabb

JavaScript Remote Conf 2020 May 14th to 15th - register now! Dave Karow is a developer evangelist for Split. He dives into how you can deliver software sustainably without burning out. His background is in performance and he's moved into smooth deliveries. He pushes the ideas behind continuous delivery and how to avoid getting paid to stay late in "free" pizzas. Panel AJ O’Neal Aimee Knight Charles Max Wood Dan Shappir Guest Dave Karow Sponsors G2i | Enjoy the luxuries of freelancing Taiko - free and open source browser test automation CacheFly ____________________________________________________________ "The MaxCoders Guide to Finding Your Dream Developer Job" by Charles Max Wood is now available on Amazon. Get Your Copy Today! ____________________________________________________________ Links Split.io Continuous Delivery zeit.co The Practical Test Pyramid Accelerate The Unicorn Project Ender's Game Ender's Shadow Atlassian Summit DeliveryConf JSJ 418: Security Scary Stories and How to Avoid Them with Kevin A McGrail Feature toggle split.io Dave Karow Progressive Delivery Speaker Deck Dave Karow Learn Enough Command Line to Be Dangerous Beyond Code Bootcamp Picks Aimee Knight: Designing for Performance Early Riser or Night Owl? Dan Shappir: web.dev AJ O’Neal: CineRAID CR-H458 DataCenter 8TB Drives Tiltamax Wireless Follow Focus System Charles Max Wood The Expanse Course Creator PRO Dave Karow: Accelerate Follow JavaScript Jabber on Twitter > @JSJabb

JavaScript Remote Conf 2020 May 14th to 15th - register now! Dave Karow is a developer evangelist for Split. He dives into how you can deliver software sustainably without burning out. His background is in performance and he's moved into smooth deliveries. He pushes the ideas behind continuous delivery and how to avoid getting paid to stay late in "free" pizzas. Panel AJ O’Neal Aimee Knight Charles Max Wood Dan Shappir Guest Dave Karow Sponsors G2i | Enjoy the luxuries of freelancing Taiko - free and open source browser test automation CacheFly ____________________________________________________________ "The MaxCoders Guide to Finding Your Dream Developer Job" by Charles Max Wood is now available on Amazon. Get Your Copy Today! ____________________________________________________________ Links Split.io Continuous Delivery zeit.co The Practical Test Pyramid Accelerate The Unicorn Project Ender's Game Ender's Shadow Atlassian Summit DeliveryConf JSJ 418: Security Scary Stories and How to Avoid Them with Kevin A McGrail Feature toggle split.io Dave Karow Progressive Delivery Speaker Deck Dave Karow Learn Enough Command Line to Be Dangerous Beyond Code Bootcamp Picks Aimee Knight: Designing for Performance Early Riser or Night Owl? Dan Shappir: web.dev AJ O’Neal: CineRAID CR-H458 DataCenter 8TB Drives Tiltamax Wireless Follow Focus System Charles Max Wood The Expanse Course Creator PRO Dave Karow: Accelerate Follow JavaScript Jabber on Twitter > @JSJabb

Dieser Verein lässt ihn einfach nicht los: Stefan Karow blickt auf eine intensive Zeit beim FC Hansa Rostock zurück. Der 45-Jährige war seit 2014 als Torwart-Trainer der Profis und später als Leiter des Nachwuchsleistungszentrums (NLZ) tätig. Ende des vergangenen war dann plötzlich Schluss. Karow verließ seinen Herzensklub und sucht jetzt in der Bolzarena Bargeshagen eine neue Herausforderung. Im Wellenrauschen Podcast #17 spricht Stefan Karow über seine Zeit bei Hansa, die sportlichen Höhen und Tiefen, seine akribische Arbeit mit den Profikeepern und seinen überraschenden Ausstieg Ende 2019. Und natürlich geht es auch um seine neue Aufgabe in der Bolzarena, wo demnächst viele spannende Projekte auf ihn und die Besucher warten.

In this Fireside Chat, David Karow, MD, PhD, Chief of Radiogenomics & Interim CEO, Human Longevity, Inc., talks to Howard Krein, MD, PhD, Chief Medical Officer, StartUp Health, on "The Longevity Moonshot: A New Plan to Extend Healthy Life" at the 2019 StartUp Health Festival in San Francisco, California. Entrepreneurs: How to get investment from StartUp Health https://www.startuphealth.com/ Investors: How to invest in StartUp Health Moonshots http://www.healthmoonshots.com Want more content like this? You can subscribe to the podcast as well as other health innovation updates at startuphealth.com/content. Sign up for StartUp Health Insider™ to get funding insights, news, and special updates delivered to your inbox.

Chuck and Andrew provide you with first insight thoughts of real life bad boys and what goes on in a daily life of a true bad boy/girl.

Chief of Radiogenomics & Interim Chief Executive Officer David S. Karow, M.D., Ph.D., Chief of Radiogenomics and interim CEO at HLI, is an innovative leader who brings more than 10 years of experience in advanced MR Imaging and genomic analytics. Dr. Karow's primary interest is to develop machine-learning based integrated diagnostics that leverage imaging, genetic, and clinical biomarkers to generate more insightful health assessments and identify disease in early stages when it is most treatable. Before joining HLI, Dr. Karow was the Director of Body MRI and Director of Acute Care Imaging in the Department of Radiology at University of California, San Diego (UC San Diego), where he still maintains an appointment as an Associate Professor. During his time at UC San Diego he implemented advanced diffusion-based methods that proved beneficial for the detection and in vivo characterization of prostate tumors. The work has yielded multiple published papers and led to multiple federal and private research grants on which Dr. Karow was Principal Investigator. Dr. Karow is compiling data showing that these techniques may be useful for the screening and staging of cancer across the whole body including breast cancer. Dr. Karow completed his fellowship in diagnostic and non-vascular interventional radiology, including tumor ablations, at University of California, Los Angeles. Prior to fellowship, he completed his residency in diagnostic radiology at UC San Diego. His research during residency was recognized with multiple awards, including the 2011 Elliott C. Lasser Award for Excellence in Research; 2009 American Roentgen Ray Society Executive Council Award; the 2008 RSNA Trainee Research Prize; and his work was also featured on the cover of the September 2010 issue of the journal Radiology. Prior to residency, Dr. Karow completed his medical training at the University of Michigan medical school in the combined M.D./Ph.D. Medical Scientist Training Program, graduating with a distinction in research. TO LEARN MORE VISIT, https://www.humanlongevity.com/ Cited Resources www.ConciergeMedicineToday.com www.ConciergeMedicineFORUM.com

Want a way to create quicker, more reliable functional tests without the overhead of a full-blown UI test? Do you want to develop functional tests that can also be used as performance tests later in the software development lifecycle? If so, this episode is for you. We’ll be Test Talking with Klaus and Dave from Blaze Meter about API functional testing and the benefits you’ll get by using this approach to software testing.

Próba spektaklu "Rewizor. Będzie wojna!" Artura Pałygi w reż. Anny Augustynowicz w Akademii Teatralnej w Warszawie oraz wywiad ze studentką Wydziału Aktorskiego AT - Elizą Rycembel i studentem Wydziału Wiedzu o Teatrze AT - Janem Karowem.

This episode we have owner of Northern Nineteen and founder of The Check'um Cup Erik karow.  We talk about him meeting his hero Michael Jordan, we talk about the Check'um Cup and the High 5 Foundation and we dive into some stories from back in the day!  

Kreuzberger Nächte sind lang. Berliner TATORTE noch länger. Zumindest wenn man das Handlungskonstrukt der Fälle von Rubin und Karow in Augenschein nimmt. 4 Filme ergeben 1 großen Fall. Doch damit ist jetzt endlich Schluss! Das Rätsel um Maihacks Mörder ist gelöst. So manche_r Zuschauer_in dürfte bei derart langgezogener Handlungsstränge der Geduldsfaden gerissen sein. Die Quote spricht Bände. Doch Gottseidank haben die Podcaster Nerven dehnbar wie Gummiseile. Wie immer sind sie hart am Ball geblieben, wo andere längst abgeschaltet haben. Ihnen bleibt allerdings auch nix anderes übrig. Die Zeit ist also gekommen, nach den 4 ersten Berliner TATORTEN mit der Doppelspitze Rubin/Karow, ein kleines Resümeechen zu ziehen. Und vielleicht etwas Vorfreude aufkommen zu lassen auf das was in Zukunft noch kommen mag. Vielleicht sogar mal wieder ein ganz normaler Krimi. Mit Leiche, Ermittlung, Ergebnis, Ende. Wer weiß.

Our scout this week on the Pipeline Show on TSN 1260 in Edmonton featured our Wisconsin based scout Dusten Braaksma. Dusten spoke about several 2017 NHL Draft [...]

Endlich ein Zwischennutzungskonzept für das unfertige BER-Flughafengelände gefunden: einen TATORT drehen. Genial! Leider ist dabei eine Fensterscheibe kaputt gegangen und ein Mülleimer umgekippt. Deshalb verschiebt sich die Eröffnung um nochmal 10 Jahre. Das neue Berliner Kommissar_innen-Duo Karow/Rubin gibt seinen Einstand und der Podcast begießt das feierlich mit 2 Liter Futschi. Dabei mutet das Sujet dieser TATORT-Folge erst mal nicht so feierlich an. Eine von zwei Drogenkurierinnen wurde zur Entnahme der in ihrem Verdauungstrakt geschmuggelten Drogenpäckchen ausgeweidet und zerstückelt. Die zweite ist verschwunden. Und in Lebensgefahr. Nicht nur, weil jederzeit eines der Päckchen in ihrem Körper platzen könnte. Sondern auch, weil ihr die üblen Gangster dicht auf der Spur sind. So geht's Tag und Nacht durch's Hipster-Berlin mit Karow und Rubin. Und hinten im Anhänger sitzen die Podcast-Atzen und machen sich einen Reim auf die ganze Schose. Watt sacht der Bodycount? Watt sacht die Quote? Und wo kann eine Verbindung zu Eko Fresh hergestellt werden? Berlin, Berlin, dein Herz kennt keine Mauern.  

Der in der Evolution hochkonservierte Wnt-Signalweg spielt in der Embryonalentwicklung, der Stammzellbiologie sowie in der Entstehung von Tumoren eine tragende Rolle. Es werden dabei verschiedene Arten der Wnt-vermittelten Signalübertragung unterschieden: Einerseits der sogenannte kanonische, über β-Catenin vermittelte Wnt-Signalweg und andererseits der Wnt/Ca2+- sowie der planar cell polarity (PCP)-like-Weg, die beide die Signaltransduktion unabhängig von β-Catenin übermitteln. Bislang sind die Mechanismen des Wnt/β-Catenin-Signalweges nur teilweise aufgeklärt, wobei insbesondere das Zusammenspiel von Wnts, Frizzleds und deren Korezeptoren auf funktioneller und struktureller Ebene bis heute nur rudimentär beschrieben wurden. In unserer Arbeitsgruppe konnte in vorangegangenen Arbeiten gezeigt werden, dass der Frizzled-8-Rezeptor (Fzd8) in HT1080-Fibrosarkomzellen im Verhältnis zu den übrigen Fzds sehr stark exprimiert wird und seine erhöhte Expression mit einer Aktivierung des Wnt/β-Catenin-Signalweges sowie mit einer erhöhten Invasivität und Proliferation assoziiert ist (Leitenstern et al., mündliche Mitteilung). Ferner wurde gezeigt, dass die Expression von Fzd8 durch Wnt3a bzw. den kanonischen Wnt-Signalweg negativ reguliert wird (Karow 2008; Kolben, Perobner et al. 2012). Vor diesem Hintergrund sollte nun im Rahmen dieser Arbeit mit Hilfe von Reportergenexperimenten die transkriptionelle Regulation von Fzd8 im Detail untersucht werden. Hierzu wurden die Fzd8-Promotorregion und verschiedene 5’- und 3’-terminale Verkürzungsvarianten in den Vektor pGLuc-Basic kloniert, der eine Quantifizierung der Promotoraktivität mittels des Reporterproteins Gaussia Luciferase erlaubt. Der Fzd8-Promotor konnte durch dieses Verfahren in aktivierende und repressive Elemente unterteilt werden, wobei auch ein putatives Enhancer-Element identifiziert werden konnte. Unter Wnt3a-Stimulation zeigten alle untersuchten Promotorkonstrukte eine verringerte Reporterproteinaktivität, was auf eine negative Regulation von Fzd8 durch Wnt3a hinweist. Interessanterweise aber führten Manipulationen am Wnt/β-Catenin-Signalweg weiter downstream zu entgegengesetzten Ergebnissen. So führte ein APC-Knockdown, der mit einer starken Aktivitätszunahme des Wnt/β-Catenin-Signalweges einhergeht, zu einer Zunahme der Fzd8-Promotoraktivität. Im Gegensatz hierzu ging ein Knockdown von β-Catenin, der einer Inhibierung des Wnt/β-Catenin-Signalweges gleichkommt, mit einer verminderten Fzd8-Promotoraktivität einher. Diese Ergebnisse deuten darauf hin, dass die Wnt3a-vermittelte Repression von Fzd8 auch unabhängig vom kanonischen Wnt/β-Catenin-Signalweg erfolgen könnte. Des Weiteren wurde die Fzd8-Promotorregion einer in silico-Analyse mit der Software MatInspector unterzogen, um mögliche Transkriptionsfaktoren zu identifizieren, die für die Fzd8-Regulation maßgeblich sein könnten. Dabei zeigte sich, dass der Transkriptionsfaktor ZF5, der sowohl aktivierend als auch reprimierend an verschiedenen Promotoren wirken kann, aufgrund des Verteilungsmusters seiner Bindungsstellen am Fzd8-Promotor als möglicher Regulator fungieren könnte. ZF5 konnte dabei als putativ positives Wnt/β-Catenin-Zielgen charakterisiert werden. Es konnte ferner gezeigt werden, dass Fzd8 indirekt über ZF5 durch den Wnt/β-Catenin-Signalweg induziert werden kann. Da ZF5 wie auch Fzd8 in HT1080-Fibrosarkomzellen stark exprimiert wird und die ZF5-Überexpression mit einer Zunahme des Wnt/β-Catenin-Signals einhergeht, könnte hier ein positiver feedback loop vorliegen. Somit könnte diese Amplifikation des Wnt/β-Catenin-Signals von maßgeblicher Bedeutung für die verstärkte Proliferation und Invasivität von mesodermalen Tumoren sein.

Mit der intensiven Erforschung von Stammzellen soll zukünftig die Möglichkeit eröffnet werden durch Manipulation von Stammzellpopulationen das regenerative Potential des Organismus zu verstehen und zu nutzen. Darüber hinaus soll mittels genetisch modifizierter Stammzellpopulationen die Grundlagen dafür geschaffen werden schwere Gen- und Immundefekte zu therapieren. Humane mesenchymale Stammzellen (hMSC) versprechen hierbei großes Potential, da sie bereits für systemische Therapieansätze eingesetzt werden. Allerdings sind die theoretischen Grundlagen der Stammzelleigenschaften der hMSC wie Proliferation, Invasion bzw. Migration und die Differenzierungskapazität nur rudimentär verstanden. Aufbauend auf den Ergebnissen von Dr. Marisa Karow und Dr. Thomas Kolben, die eine Beteiligung des Wnt/β-Catenin-Signalweges an der Steuerung dieser Stammzelleigenschaften in ihren Arbeiten nachweisen konnten (Karow 2008; Kolben et al. 2012), sollten in der vorliegenden Arbeit die Rezeption des spezifischen Wnt-Signals und die dabei beteiligten Frizzled (Fzd)-Rezeptoren näher untersucht werden. Da aus den vorigen Arbeiten schon hervorging, dass alle 10 Fzd-Rezeptoren in den hMSC exprimiert werden, sollte über eine qualitative PCR die Expression potentieller Wnt-Liganden sowie der beiden Inhibitoren des Wnt-Weges sFRP1 und WIF1 geprüft werden. Dabei zeigte sich, dass 8 der 19 Wnts sowie der Inhibitor sFRP1 exprimiert werden. Das Wnt-Expressionsmuster der Krebszelllinie HT1080 unterschied sich dagegen nur in der Expression zweier Wnts, was wahrscheinlich auf den mesodermalen Ursprung dieser Krebszelllinie zurückzuführen ist. Im Gegensatz hierzu zeigte sich eine umfangreichere Wnt-Expression in der immortalisierten Zelllinie HEK293, in der 13 der 19 Wnts sowie auch die beiden Inhibitoren sFRP1 und WIF1 nachgewiesen wurden. Für eine detailliertere Aufschlüsselung der Beteiligung einzelner Fzds an der Rezeption eines Wnt-Signals sowie an der basalen Aktivität des Wnt/β-Catenin-Signalweges in hMSC wurde ein TCF/LEF-Reporter-Vektorsystem in die hMSC eingebracht. Als Reportergen kam die sekretierte Form einer Luciferase aus dem Tiefsee-Cephalopoden Gaussia princeps zum Einsatz. Vorteil dieser Luciferase ist, dass die Sekretion in den Überstand eine Evaluierung der Wnt/β-Catenin-Aktivität über die Zeit hinweg erlaubt, ohne die Zellen zerstören zu müssen. Hierbei wurden transient und stabil-transfizierte TCF/LEF-(T-cell-specific transcription factor/lymphoid enhancer-binding factor)-Reporter-hMSC generiert und die Zellkulturbedingungen für nachfolgende Experimente optimiert. Die Evaluierung unterschiedlicher Aktivatoren des Wnt/β-Catenin-Signalweges ergab die stärkste Aktivierung nach Knockdown des Tumorsuppressorgens APC, während ein Knockdown des β-Catenins, dem zentralen Mediator des Wnt-Weges, zu einer signifikanten Reduktion der Gaussia-Luciferase-Aktivität führte. Bei Knockdown-Studien mit den verschiedenen Fzds mittels RNA-Interferenz (RNAi) in den TCF/LEF-Reporter-hMSC zeigte sich, dass Fzd5 und Fzd7 an der Weiterleitung eines Wnt-Signals sowohl unter unstimulierten Bedingungen als auch nach Applikation von Wnt3a beteiligt sind. Weiter zeigte nur noch der Knockdown von Fzd1, dass dieser Rezeptor an der Weiterleitung eines Wnt3a-Signals partizipiert. Um diese Ergebnisse über einen reversen Ansatz in Form einer Überexpression der Fzds zu untersuchen, wurde ein flexibles Klonierungssystem entwickelt, das einen einfachen Austausch von Protein-tags ermöglichen sollte. Nach Bestätigung der Überexpression der Fzds auf mRNA-Ebene und Proteinebene wurde die Wirkung der Überexpression in den TCF/LEF-Reporter-hMSC ohne und mit Wnt3a-Aplikation untersucht. Hier zeigte sich, dass neben der Überexpression von Fzd5 auch Fzd3 und Fzd6 eine Erhöhung der Gaussia-Luciferase-Aktivität und damit eine gesteigerte Aktivität des Wnt/β-Catenin-Signalweges sowohl unter unstimulierten als auch unter stimulierten Bedingungen nach sich zogen. Bei vergleichender Überexpression von Wnt3 oder Wnt3a konnte gezeigt werden, dass Wnt3 – welches hMSC auch endogen exprimieren – sehr viel stärker den Wnt-Weg aktivieren kann als Wnt3a. Um die Auswirkung des kanonischen Wnt-Rezeptors Fzd5 auf die Stammzelleigen-schaften der hMSC zu prüfen, wurde die Expression des Wnt-Zielgens Cyclin D1 und die Proliferation nach Knockdown sowie transienter Überexpression von Fzd5 quantitativ erfasst. Hierbei zeigte sich nach Knockdown von Fzd5 eine signifikante Abnahme der Proliferation, die auch auf Ebene der Wnt-Zielgene mit einer Abnahme der Cyclin D1-Expression einherging. Umgekehrt konnten stabil Fzd5-transfizierte hMSC-Populationen generiert werden, die eine signifikante Steigerung der Cyclin D1-Expression aufwiesen. Zusammenfassend konnte im Rahmen der hier vorliegenden Arbeit gezeigt werden, dass die verschiedenen Fzds in unterschiedlichem Maße an der Weiterleitung eines Wnt-Signals beteiligt sind. Besonders scheinen hier Fzd5 und Fzd7 eine wichtige Rolle in hMSC zu spielen, da sie auch an der Vermittlung eines endogenen Wnt-Signals innerhalb der Stammzellpopulation beteiligt sind. Weiter wurde im Fall von Fzd5 auch die maßgebliche Beteiligung dieses Rezeptors am Erhalt der Proliferationskapazität der hMSC-Population nachgewiesen.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.04.21.038737v1?rss=1 Authors: Herrero-Navarro, A., Puche-Aroca, L., Moreno-Juan, V., Sempere-Ferrandez, A., Espinosa, A., Susin, R., Torres-Masjoan, L., Leyva-Diaz, E., Karow, M., Figueres-Onate, M., Lopez-Mascaraque, L., Lopez-Atalaya, J. P., Berninger, B., Lopez-Bendito, G. Abstract: Neuronal cell diversity is essential to endow distinct brain regions with specific functions. During development, progenitors within these regions are characterised by specific gene expression programs, contributing to the generation of diversity in postmitotic neurons and glia. While the region-specific molecular diversity of neurons and astrocytes is increasingly understood, whether these cells share region-specific programs remains unknown. Here, we show that in the neocortex and thalamus, neurons and astrocytes express shared region-specific transcriptional and epigenetic signatures. These signatures not only distinguish cells across brain regions but are also detected across substructures within regions, such as distinct thalamic nuclei, where clonal analysis revealed the existence of common nucleus-specific progenitors for neurons and glia. Consistent with their shared molecular signature, regional specificity was maintained following astrocyte-to-neuron reprogramming. A detailed understanding of these regional-specific signatures may thus inform strategies for future cell-based brain repair. Copy rights belong to original authors. Visit the link for more info