Podcasts about il2

Welcome back to Rinse And Repeat Radio! On this week's guest mix we DJ/Producer Duo - FAED! FAED consists of LA Based DJ's Eric D Lux & DJ Five.FAED took over the first half of the episode and put together a mix just for us including some of their original records, remixes, edits, & more.Episode 247, turn it up! **Tracklisting****FAED Guest Mix**1.) Faed - Id2.) Yeah Yeah Yeahs, A-trak - Heads Will Roll  (Rick Wonder Go Down Edit) 3.) Chris Lorenzo - U Should Be Doing This4.) Future, Metro Boomin, Kendrick Lamar - Like That (Gz Edit)5.) Sosa - White Girl (Id Edit)6.) A$ap Ferg - Work (Omar Duro Afro Edit)7.) Keem Vent (Booty Bass Edit)8.) Black Eyed Peas - My Humps (Sein Edit)9.) Pawsa - Dirty Cash (Gainz And Novacane Edit)10.) Haddaway X Fisher - What Is Love (Crg Edit)11.) Diplo - Express Yourself (Pickle Remix) 12 - Skrillex - Bangarang ( Alboa Edit)13.) Weeknd Vs Tobehonest - Cry For Me (Hmc ‘hey Ya' Edit)14.) Don Toliver - Bandit (Dzeko Edit)15.) Beltran - Smack Yo16.) M3b8 - Monkey Riddim - M3b817.) Peggy Gou - Nanana (Egnever & Marco Pedro Edit)18. Faed - My Way**Cazes Mix**19.) Cloonee, Young M.a, Inntraw X Hntr X Fomo - Stephanie (Cazes Edit)20.) Chachi X Bobby Shmurda X Joy Orbison - Hot Boy (Chachi Edit)21.) Rosé & Bruno Mars X Pickle - Apt (Cazes Edit)22.) Bad Bunny - Dtmf (Hills Remix)23.) Alok & Firebeatz X Icona Pop X Matt Guy, Club De Combat - I Love It X Higher State Of Conciousness (Cazes Party Of The Year' Vip Edit)24.) Dom Dolla Ft. Daya - Dreamin25.) Layton Giordani, Linney & Sarah De Warren Vs. Lucas & Steve, Maynamic, Edd Blaze - Act Of God (Rick Wonder Edit)Find Me On My Socials! - @cazesthedjwww.cazesthedj.comUpcoming Dates2/21 - Good Night John Boy - Chicago, IL2/22 - Good Night John Boy - Cleveland, OH2/28 - Green Light Social - Austin, TX3/1 - Green Light Social - Dallas, TX3/2 - Sunset Sessions @ Ruby Room - Dallas, TX

Welcome back to Rinse And Repeat Radio! On this week's guest mix we have Blake Horstmann. Blake is 1/2 of the DJ/Producer duo 'Roadhouse' as well as being known for his appearances on ABC's - The Bachelorette & Bachelor in Paradise Blake took over the first half of the episode and put together a mix just for us with some of his favorite current house records, remixes, edits, & moreEpisode 246, turn it up! **Tracklisting****Blake Horstmann Guest Mix**1.) Raury, Jaden Smith X Tiësto X Zonderling & Don Diablo - Losing Your Mind X Split (Only U) X Tunnel Vision (Aurelios Mashup)2.) Pawsa - Dirty Cash (Money Talks) (Rick Wonder 'merther' Edit)3.) Duke Dumont - Need U (100%) (Squared 2024 Edit)4.) Sigma - Nobody To Love (Pizzata & Klein X Salvatore Mancuso Remix)5.) Underwold X Timothy Allen - Can't Stop Born Slippy (Jean Luc Mashup)6.) Robin S Vs. Gala Vs. Crystal Waters - Show Me Love X Freed From Desire X Gypsy Woman (Aurelios Mashboot)7.) Adele - Rolling In The Deep X Pilka (Waldo X Funk D Mashup)8.) Eurythmics Vs. Corona Vs. James Hype - Sweet Dreams Vs. The Rhythm Of The Night V.s Dancing (Aurelios Mashup)9.) Fleetwood Mac - Landslide (Mister Gray & Ruen Remix)10.) Diplo & Sleepy Tom X Goles Be Right There (Cazes Edit)11.) Omnom & Sven Lochenhoer - That's The Spot12.) Nate Dogg - I Got Love (Marshall James Edit)13.) Blake Horstmann - Table Dancing14.) Kylie Minogue Vs. Dj Jackum - Can't Get You Out Of My Head (Squared Edit)15.) Young M.a - Ooouuu (Micah Baxter & Alec Cortez Remix)16.) Alex Guesta - Diamonds Rolex Champagne (Vip Extended)17.) Danny Avila, Sam Wolfe & Hntr Feat. Rome Fortune - Yes B!tch (Nxsty & Cheyenne Giles Remix)18.) Faed - Bout To Go Dumb Again19.) Dillon Francis & Longstoryshort - Take Me Away20.) Faed - Make Em Bounce **Cazes Mix**21.) Dom Dolla ft. Daya - Dreamin'22.) Max Styler - Inferno23.) Gorillaz - Clint Eastwood (Codeko Remix)24.) Waka Flocka Flame x Yves V & Chester Young - Hard In Da Paint (Cazes Edit)25.) Fancy Inc, Teamworx - Rock The Floor26.) Cloonee, Young M.A, InntRaw - Stephanie (HNTR Remix)27.) Matroda - Good GirlsFind Me On My Socials! - @cazesthedjwww.cazesthedj.comUpcoming Dates2/15 - Bounce - Delray Beach, FL2/21 - Good Night John Boy - Chicago, IL2/22 - Good Night John Boy - Cleveland, OH2/28 - Green Light Social - Austin, TX3/1 - Green Light Social - Dallas, TX3/2 - Sunset Sessions @ Ruby Room - Dallas, TX

Covering the latest military flight simulation news for the week of 24 Feb 2024. Topics include major updates for IL-2 and DCS, a new free Typhoon campaign is in development for IL-2 BoN owners, FlightSimForge released an F-16 ICP on their Etsy store, SimFab announced a mounting pattern update for new Winwing/Virpil products, a ton of community updates including news from Enigma's Cold War server and a variety of tutorials, and Cheli777 earning the week's SimpitSpotlight! Timestamps: 00:00 The Hangar Bay: Episode 5 00:48 The Fly-By The Week's Military Flight Sims News in 60 seconds or less 02:34 Developer News IL-2 update 5.202 is live! IL2 "Wings over Caen" free campaign is in development for BoN owners DCS update 2.9.3.51704 is live with the game now unified to one version (no more open beta) Grinnelli Designs shows off an interesting time-lapse visualization of their F-100D code base 13:06 Hardware News FlightForgeSim debuts their F-16 ICP on their Etsy store https://www.etsy.com/shop/FlightForgeSim) SimFab announces mounting pattern plate updates for Collective and Rudder Pedal plates (https://simfab.com/services/) 17:28 Community News Enigma Cold War Server announces a 3rd campaign set on the Persian Gulf map as well as introduction of "intermission" scenarios Enigma interviews the developer of a new DCS PVP server "The Coop" Fox3 Managed Solutions announces the "Ultimate DCS Skills Showdown" in support of K9sForWarriors AviationPlus has a terrific F-15C tutorial for BMS on their YouTube page JetPilot walks us through using VoiceAttack for the F-16C using the JanJan plugin in DCS/BMS on their YouTube page Notso teaches DCS players how to use the MGRS in the F-15E Strike Eagle on their YouTube page 35:46 User Content of the Week Skyward Flight Media (@skykwardfm) shares a Syria COIN CO-OP multiplayer mission for DCS Sedlo updates his OIR missions on DCS to support the new Muwaffaq Salti airbase on the DCS: Syria map Sedlo gives us a walkthrough of some new DCS Mission Editor functionality on his YouTube page 40:58 Simpit Spotlight Cheli777's F-16/F-18/Racing Home Cockpit https://www.reddit.com/r/homecockpits/comments/1au8fxu/f16fa18racing_home_cockpit/ Episode notes: https://thehangarbay.notion.site/Episode-5-You-Get-a-Patch-b2606839f01f4f84bb6c4cd7061b380e?pvs=4 email: feedback@thehangarbaypod.com Show Notes: https://www.thehangarbaypod.com Twitter (X): https://www.twitter.com/thehangarbaypod Instagram: https://www.instagram.com/thehangarbaypod Facebook: https://www.facebook.com/hangarbaypod Spotify: https://podcasters.spotify.com/pod/show/thehangarbaypod --- Send in a voice message: https://podcasters.spotify.com/pod/show/thehangarbaypod/message

Welcome back to Rinse And Repeat Radio! On this week's guest mix we have special guest JRoc! He took over the first half of the episode and shared a bunch of his favorite records/remixes/& moreEpisode 195, turn it up! **Tracklisting****JRoc Guest Mix**1.) Tiesto - Lay Low (Arem Ozguc & Arman Aydin Remix) [Jroc Orchestral Intro]2.) Loud Luxury Vs David Guetta Vs Sesco - Body Vs Love Is Gone Vs Feel Good (Sell Out Mc Mashup)3.) Fred Again.., Swedish House Mafia, Future Vs. Lucas & Steve - Turn On The Lights (Andrew Marks "Warp" Edit)4.) Tiesto, Tears For Fears, Niiko X Swae & Gudfella  - Rule The World (Everybody)5.) Kenya Grace - Strangers (Bvrnout Remix)6.) Gunna X Tujamo & Sick Individuals - Fukumean X Lose Control (Joe Maz Edit)7.) Ian Carey Ft. Michelle Shellers - Keep On Rising (Fancy Inc And Bruno Be Remix)8.) Ship Wrek & Disco Lines - Where Do I Belong?9.) Zerb & Sofiya Nzau - Mwaki (Tiesto Vip Mix)10.) La Roux Vs. Choujaa & Joanna - Bulletproof (Cazes 2023 Edit)11.) Dom Dolla - Saving Up (Meda Extended Remix)12.) Rufus Du Sol - Innerbloom (Ship Wrek X L.a. X Gabriel Boni & Raphael Siqueira) [Jroc Mega Edit]13.) Corona Vs. Westend & Max Styler - Rhythm Of The Night (Kupyd 'Rhythm Machine' Edit)14.) Jack Harlow Vs. David Guetta & Hypaton - Lovin On Me (Kastra "Be My Lover" Edit)15.) Sian Evans - Hide U (Tinlicker Extended Remix)16.) Jamek Ortega X The Weeknd - Lunar Power X Nothing Is Lost (Varon Junior Bootleg)**Cazes Mix**17.) Gotye, Kimbra, Fisher, Chris Lake & Sante Sansone - Somebody (2024)18.) Deeper Purpose & Guz Feat. Dope Earth Alien - That Sound19.) David Guetta, Mason & Princess Superstar - Perfect (Exceeder) 20.) Dombresky & Jaded - Sound Of The Drums21.) Anyma - Pictures Of You22.) The Temper Trap - Sweet Disposition (John Summit & Silver Panda 2024 Remix)Find me on my socials! @cazesthedjwww.cazesthedj.comUpcoming Dates 2/14 - The Warehouse - Tallahassee, FL2/16 - Good Night John Boy - Cleveland, OH2/17 - Good Night John Boy - Chicago, IL2/24 - Strawberry Moon - Miami Beach, FL2/24 - Swan - Miami, FL2/25 - Food & Wine Festival - Miami Beach, FL

On this episode of The Business of Biotech, Obsidian Therapeutics CEO Paul Wotton, Ph.D. takes us behind the scenes to reveal what precipitated the FDA's clearance of its IND application for a novel, engineered tumor-infiltrating lymphocyte therapy called OBX-115.  Learn how the company navigated the regulatory path for a first-of-its-kind biologic therapy developed in partnership with the University of Texas MD Anderson Cancer Center that Dr. Wotton says, should it succeed, will eliminate the patient risk associated with concomitant IL2 therapy and improve clinical outcomes for certain patients with metastatic melanoma. We also get an update on outcomes from Obsidian's unique approach to solving COVID-19 challenges covered on episode 9 of the Business of Biotech.

In this episode, William R. Short, MD, MPH, AAHIVS, explores recommendations and data on strategies to address suboptimal CD4+ cell count response in people with HIV on suppressive ART.Listen as he gives his perspectives on:The consequences of suboptimal CD4+ cell count responseART intensificationART switch strategies with data from the SPIRAL studyData on the addition of interleukin-2 from the SILCAAT and ESPIRIT studiesDHHS guideline recommendationsPresenter:William R. Short, MD, MPH, AAHIVSAssociate Professor of MedicineDivision of Infectious DiseasesDepartment of MedicinePerelman School of Medicine at the University of PennsylvaniaPhiladelphia, PennsylvaniaFollow along with the slides at: https://bit.ly/3DC2bkPSee the entire program at: https://bit.ly/2TXTYWx

This is the tenth of a series of short videos on Low dose Medicine and in particular Cytokines. This video introduces the cytokine Interleukin 12. IL 12 is also known as a T cell-stimulating factor because it can stimulate the growth and function of T cells and especially the differentiation of naive T cells into Th1 cells (cell mediated immunity). IL-12 enhances the cytotoxic activity of NK cells and CD8+ cytotoxic T lymphocytes and also induces the synthesis of IFN-gamma, IL2, and TNF-alpha (TNF-α). IL-12 inhibits the synthesis of IgE induced by IL-4 and can therefore be useful in allergic diseases. IL 12 has anti-angiogenic (it can block the formation of new blood vessels), anti-tumoral and anti-metastatic activity, and because of this, it has been proposed by immunologists as a possible anti-cancer drug (although in pharmacological doses it can cause many side-effects). IL 12 is the most important cytokine with IL 2 and interferon gamma (IFN-gamma) in neoplastic pathologies (cancer support therapy) in general and especially melanomas and kidneys carcinoma. More information about this and other health topics can be found in my books "Low Dose Medicine" and "Cure Without Side effects" by following these links: ►►►https://amzn.to/3Bbx8fd ►►►https://amzn.to/36iaqDU To check the Low dose Medicine health kit follow this link: ►►►https://kit.co/cureswithoutsideffect/low-dose-medicine DISCLAIMER: Nothing contained in this video is intended nor can be taken to diagnose, treat, or cure any disease. It is for informational purposes only. This episode is also available as a blog post: https://cureswithoutsideffects.wordpress.com/2021/11/17/cytokines-series-interleukin-12-the-allergy-support-cytokine/ --- Send in a voice message: https://anchor.fm/cureswithoutsideeffects/message

This is the ninth of a series of short videos on Low dose Medicine and in particular Cytokines. This video introduces the cytokine Interleukin 10. IL10 regulates the reactivity of the organism and inhibits the synthesis of most pro- inflammatory cytokines such as IL1, IL6, IL8, IL12, IL23 and tumor necrosis factor (TNF) and also the Th1 sub populations of T-cells such as IFN-gamma and IL2. IL 10 regulates cell cycles and prevents nitric oxides and oxidative stress, it suppresses metastasis and tumor invasion. Since it inhibits the release of IL 1 and TNF it is able to slow down cartilage erosion. IL-10 can stimulate the synthesis of IgE antibodies and acts synergically with IL 4 to inhibit cell mediated immunity. It also prevents insulin resistance and insulin sensitivity. More information about this and other health topics can be found in my books "Low Dose Medicine" and "Cure Without Side effects" by following these links: ►►►https://amzn.to/3Bbx8fd ►►►https://amzn.to/36iaqDU To check the Low dose Medicine health kit follow this link: ►►►https://kit.co/cureswithoutsideffect/low-dose-medicine This episode is also available as a blog post: https://cureswithoutsideffects.wordpress.com/2021/11/12/cytokines-series-interleukin-10-the-master-anti-inflammatory-cytokine/ DISCLAIMER: Nothing contained in this video is intended nor can be taken to diagnose, treat, or cure any disease. It is for informational purposes only. --- Send in a voice message: https://anchor.fm/cureswithoutsideeffects/message

Investigating the anti-hypertensive effects of pumpkin seed oil Marymount University and University of Guilan (Iran), September 29, 2021 In a study, researchers from Iran and the U.S. found that pumpkin seed oil can potentially treat hypertension in postmenopausal women. Their report was published in Complementary Therapies in Clinical Practice. Postmenopausal women are more likely to develop hypertension than men of the same age. In vivo studies reveal that pumpkin seed oil has anti-hypertensive activity. The team investigated the effects of pumpkin seed oil supplementation on vascular function and heart rate variability in postmenopausal women with elevated blood pressure. Participants were assigned to take either a pumpkin seed oil supplement or a placebo for the six-week study. Those in the experimental group took 3 grams of pumpkin seed oil every day. Brachial and central blood pressure, wave reflection (augmentation index, AIx), arterial stiffness (SI) and various HRV parameters were measured at baseline and at the end of the study. Those who took pumpkin seed oil had significantly lower AIx, brachial and systolic blood pressure after treatment. SI and HRV parameters remained unchanged for the treatment group and the placebo group at the end of the study. In sum, taking pumpkin seed oil may improve arterial hemodynamics in postmenopausal women.     Health benefits of evening classes revealed   Oxford University, September 20, 2021    Those with a taste for adult education classes have long known it, but now Oxford University scientists have confirmed that taking part in the weekly sessions can boost wellbeing – regardless of the subject studied.   In partnership with the Workers' Educational Association (WEA), the largest voluntary sector provider of adult education in England and Scotland, a team from Oxford's department of experimental psychology studied attendees at seven separate day-time adult education classes. Their findings are published in a series of papers.   Each class took place over seven months and included a break in the middle. Attendees completed questionnaires before and after their class three times over the seven months: at the beginning of their courses, after 3 months, and at the end of the seven months. Participants were involved in one of three activities: singing, crafts or creative writing.   Overall, attendees at all seven classes had improved mental and physical health and reported more satisfaction with their lives at the end of their courses.   Dr Eiluned Pearce led the research. She said: 'The students reported benefits including increased self-confidence, a greater feeling of control over their lives and more willingness to take on new challenges. Some said the classes made them more motivated to be more active, despite the classes not specifically involving physical activity.   'Participants also said that the classes broadened their networks of friends and gave them an increased sense of belonging. We also found that the more someone felt part of their group, the more their health and wellbeing improved.' An intriguing finding was in the singing and creative writing classes. Building on the results of an earlier paper from the same study, which found that people in singing classes felt closer to their group more quickly than those in the other classes, the team looked at how relationships formed between individuals in the classes.   Each person was asked to name those other people in the class whose name they could remember, whether or not they felt connected to each person they named, and whether they had talked to that person during class.   Dr Pearce said: 'The results showed that those in the singing and creative writing groups built up relationships with other individuals more quickly than the crafters, and singers felt more connected to the class as a whole more quickly than both the other groups. 'While this confirms our earlier finding that singing has an 'ice-breaker effect' compared to other activities, it shows that other activities may enable people to increase their social networks just as much, even if it takes them longer to feel connected to their group as a whole.'   Co-author Dr Jacques Launay adds: 'While much of our previous work has demonstrated the importance of music, it is likely that the most socially bonding activities are always those that are personally chosen and enjoyed. This research adds to growing support for the relevance of creative activities in creating happy communities and improving health and well-being, with consequent benefits for public services and society.'   Dr Pádraig Mac Carron, Dr Anna Machin and Professor Robin Dunbar were also involved in the research.   Howard Croft, WEA Regional Education Manager, said: 'The findings reiterate the feedback that we have had from our students over the years: learning is a fantastic way to boost your self-esteem and confidence. Also of note, is its therapeutic effect. For many students, creative courses are a means of finding a new outlet for expressing their feelings. This can be of immense help during times of personal difficulty or emotional upheaval, such as divorce or bereavement. Simply going to a course can offer much-needed respite.   'For others, learning can be an opportunity to reignite a former passion. This could be anything from a subject which you enjoyed at school to an area which you are interested in. Whatever your reason, there are so many benefits to be gained by signing up to a course.'       Want to live forever? Theoretically, you could, study says Swiss Federal Institute of Technology, September 29, 2021 Humans can probably live to at least 130, and possibly well beyond, though the chances of reaching such super old age remain vanishingly small, according to new research. The outer limit of the human lifespan has long been hotly debated, with recent studies making the case we could live up to 150 years, or arguing that there is no maximum theoretical age for humans. The new research, published Wednesday in the Royal Society Open Science journal, wades into the debate by analyzing new data on supercentenarians—people aged 110 or more—and semi-supercentenarians, aged 105 or more. While the risk of death generally increases throughout our lifetime, the researchers' analysis shows that risk eventually plateaus and remains constant at approximately 50-50. "Beyond age 110 one can think of living another year as being almost like flipping a fair coin," said Anthony Davison, a professor of statistics at the Swiss Federal Institute of Technology in Lausanne (EPFL), who led the research. "If it comes up heads, then you live to your next birthday, and if not, then you will die at some point within the next year," he told AFP. Based on the data available so far, it seems likely that humans can live until at least 130, but extrapolating from the findings "would imply that there is no limit to the human lifespan," the research concludes. The conclusions match similar statistical analyses done on datasets of the very elderly. "But this study strengthens those conclusions and makes them more precise because more data are now available," Davison said. The first dataset the team studied is newly released material from the International Database on Longevity, which covers more than 1,100 supercentenarians from 13 countries. The second is from Italy on every person who was at least 105 between January 2009 and December 2015. 'One in a million' The work involves extrapolating from existing data, but Davison said that was a logical approach. "Any study of extreme old age, whether statistical or biological, will involve extrapolation," he said. "We were able to show that if a limit below 130 years exists, we should have been able to detect it by now using the data now available," he added. Still, just because humans can theoretically reach 130 or beyond, doesn't mean we're likely to see it anytime soon. For a start, the analysis is based on people who have already achieved the relatively rare feat of making it to well over 100. And even at age 110, your chances of making it to 130 are "about one in a million... not impossible but very unlikely," said Davison. He thinks we could see people reaching 130 within the century, as more people make it to supercentenarian status, increasing the chances of one becoming that one in a million. "But in the absence of major medical and social advances, ages much over this are highly unlikely ever to be observed," he added. For now, the oldest person on record is Frenchwoman Jeanne Calment, who died in 1997 at the confirmed age of 122. Her true age was the subject of some controversy, with claims of a possible fraud, but in 2019 several experts said a review of the evidence confirmed her age. Other pretenders to the throne of oldest person ever have a long way to go. The oldest verified living person in the world is Japan's Kane Tanaka, a comparatively youthful 118.     Psychological treatment shown to yield strong, lasting pain relief, alter brain networks University of Colorado, September 29, 2021 Rethinking what causes pain and how great of a threat it is can provide chronic pain patients with lasting relief and alter brain networks associated with pain processing, according to new University of Colorado Boulder-led research. The study, published Sept. 29 in JAMA Psychiatry, found that two-thirds of chronic back pain patients who underwent a four-week psychological treatment called Pain Reprocessing Therapy (PRT) were pain-free or nearly pain-free post-treatment. And most maintained relief for one year. The findings provide some of the strongest evidence yet that a psychological treatmentcan provide potent and durable relief for chronic pain, which afflicts one in five Americans. "For a long time we have thought that chronic pain is due primarily to problems in the body, and most treatments to date have targeted that," said lead author Yoni Ashar, who conducted the study while earning his Ph.D. in the Department of Psychology and Neuroscience at CU Boulder. "This treatment is based on the premise that the brain can generate pain in the absence of injury or after an injury has healed, and that people can unlearn that pain. Our study shows it works." Misfiring neural pathways Approximately 85% of people with chronic back pain have what is known as "primary pain," meaning tests are unable to identify a clear bodily source, such as tissue damage. Misfiring neural pathways are at least partially to blame: Different brain regions—including those associated with reward and fear—activate more during episodes of chronic pain than acute pain, studies show. And among chronic pain patients, certain neural networks are sensitized to overreact to even mild stimuli. If pain is a warning signal that something is wrong with the body, primary chronic pain, Ashar said, is "like a false alarm stuck in the 'on' position." PRT seeks to turn off the alarm. "The idea is that by thinking about the pain as safe rather than threatening, patients can alter the brain networks reinforcing the pain, and neutralize it," said Ashar, now a postdoctoral researcher at Weill Cornell Medicine.or the randomized controlled trial, Ashar and senior author Tor Wager, now the Diana L. Taylor Distinguished Professor in Neuroscience at Dartmouth College, recruited 151 men and women who had back pain for at least six months at an intensity of at least four on a scale of zero to 10. Those in the treatment group completed an assessment followed by eight one-hour sessions of PRT, a technique developed by Los Angeles-based pain psychologist Alan Gordon. The goal: To educate the patient about the role of the brain in generating chronic pain; to help them reappraise their pain as they engage in movements they'd been afraid to do; and to help them address emotions that may exacerbate their pain.  Pain is not 'all in your head' "This isn't suggesting that your pain is not real or that it's 'all in your head'," stressed Wager, noting that changes to neural pathways in the brain can linger long after an injury is gone, reinforced by such associations. "What it means is that if the causes are in the brain, the solutions may be there, too." Before and after treatment, participants also underwent functional magnetic resonance imaging (fMRI) scans to measure how their brains reacted to a mild pain stimulus. After treatment, 66% of patients in the treatment group were pain-free or nearly pain-free compared to 20% of the placebo group and 10% of the no-treatment group. "The magnitude and durability of pain reductions we saw are very rarely observed in chronic pain treatment trials," Ashar said, noting that opioids have yielded only moderate and short-term relief in many trials. And when people in the PRT group were exposed to pain in the scanner post-treatment, brain regions associated with pain processing—including the anterior insula and anterior midcingulate —had quieted significantly. The authors stress that the treatment is not intended for "secondary pain"—that rooted in acute injury or disease. The study focused specifically on PRT for chronic back pain, so future, larger studies are needed to determine if it would yeild similar results for other types of chronic pain.  Meanwhile, other similar brain-centered techniques are already ememrging among physical therapists and other clinicians who treat pain. "This study suggests a fundamentally new way to think about both the causes of chronic back pain for many people and the tools that are available to treat that pain," said co-author Sona Dimidjian, professor of psychology and neuroscience and director of the Renee Crown Wellness Institute at CU Boulder. " It provides a potentially powerful option for people who want to live free or nearly free of pain."     Citicoline (CDP-choline) and Memory Function in Healthy Older Adults: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial  Kyowa Hakko Bio (Japan), September 2021 Supplementation of citicoline (CDP-choline), a naturally occurring mononucleotide, has shown beneficial effects on memory function and behavior in populations with a wide range of impairments. However, few studies have investigated its effect in healthy older populations. Objective The objective of this study was to investigate the effects of citicoline, on memory in healthy elderly populations with age-associated memory impairment (AAMI). Methods A total of 100 healthy men and women aged between 50 and 85 y with AAMI participated in this randomized, double-blind, placebo-controlled trial. Participants were randomized to receive placebo (n = 51) or citicoline (n = 49; 500 mg/d) for 12 wk. Memory function was assessed at baseline and end of the intervention (12 wk) using computerized tests (Cambridge Brain Sciences, Ontario, Canada). Safety measurements included adverse events query, body weight, blood pressure, and hematology and metabolic panel. Intent-to-treat analysis was conducted using ANCOVA for the primary and secondary outcome variables with Bonferroni correction for multiple comparisons. Results A total of 99 out of 100 participants completed the study in its entirety. After the 12-wk intervention, participants supplemented with citicoline showed significantly greater improvements in secondary outcomes of episodic memory (assessed by the Paired Associate test), compared with those on placebo (mean: 0.15 vs. 0.06, respectively, P = 0.0025). Composite memory (secondary outcome), calculated using the scores of 4 memory tests, also significantly improved to a greater extent following citicoline supplementation (mean: 3.78) compared with placebo (mean: 0.72, P = 0.0052). Conclusions Dietary supplementation of citicoline for 12 wk improved overall memory performance, especially episodic memory, in healthy older males and females with AAMI. The findings suggest that regular consumption of citicoline may be safe and potentially beneficial against memory loss due to aging.      Sleep may strengthen long-term memories in the immune system   University of Tuebingen (Germany) September 29, 2021   More than a century ago, scientists demonstrated that sleep supports the retention of memories of facts and events. Later studies have shown that slow-wave sleep, often referred to as deep sleep, is important for transforming fragile, recently formed memories into stable, long-term memories. Now, in an Opinion article published  in Trends in Neurosciences, part of a special issue on Neuroimmunology, researchers propose that deep sleep may also strengthen immunological memories of previously encountered pathogens.   "While it has been known for a long time that sleep supports long-term memoryformation in the psychological domain, the idea that long-term memory formation is a function of sleep effective in all organismic systems is in our view entirely new," says senior author Jan Born of the University of Tuebingen. "We consider our approach toward a unifying concept of biological long-term memory formation, in which sleep plays a critical role, a new development in sleep research and memory research."   The immune system "remembers" an encounter with a bacteria or virus by collecting fragments from the bug to create memory T cells, which last for months or years and help the body recognize a previous infection and quickly respond. These memory T cells appear to abstract "gist information" about the pathogens, as only T cells that store information about the tiniest fragments ever elicit a response. The selection of gist information allows memory T cells to detect new pathogens that are similar, but not identical, to previously encountered bacteria or viruses.   Studies in humans have shown that long-term increases in memory T cells are associated with deep slow-wave sleep on the nights after vaccination. Taken together, the findings support the view that slow-wave sleep contributes to the formation of long-term memories of abstract, generalized information, which leads to adaptive behavioral and immunological responses. The obvious implication is that sleep deprivation could put your body at risk.   "If we didn't sleep, then the immune system might focus on the wrong parts of the pathogen," Born says. "For example, many viruses can easily mutate some parts of their proteins to escape from immune responses. If too few antigen-recognizing cells [the cells that present the fragments to T cells] are available, then they might all be needed to fight off the pathogen. In addition to this, there is evidence that the hormones released during sleep benefit the crosstalk between antigen-presenting and antigen-recognizing cells, and some of these important hormones could be lacking without sleep."   Born says that future research should examine what information is selected during sleep for storage in long-term memory, and how this selection is achieved. In the end, this research could have important clinical implications.   "In order to design effective vaccines against HIV, malaria, and tuberculosis, which are based on immunological memory, the correct memory model must be available," Born says. "It is our hope that by comparing the concepts of neuronal and immunological memory, a model of immunological memory can be developed which integrates the available experimental data and serves as a helpful basis for vaccine development."         Standardized astragalus extract for attenuation of the immunosuppression induced by strenuous physical exercise: randomized controlled trial University of Physical Sciences (Poland), September 3, 2021 This paper aimed to verify how a supplementation of rower's diet with Astragalus Membranaceus Root (AMR) modulated their immune system response to maximal physical exertion. Methods The double-blind study included 18 members of the Polish Rowing Team assigned to the supplemented group (n = 10), and the placebo group (n = 8). The participants performed a 2000 m test on a rowing ergometer at the beginning and at the end of the six-week of intensive training camp during which the supplemented group received 500 mg of AMR. Blood samples were obtained prior to, 1 min after completing, and 24 h after the exertion test. The levels of interleukin 2 (IL2), interleukin 4 (IL4), interleukin 10 (IL10), interferon ɤ (IFN-ɣ), and lactic acid were determined. Subpopulations of T regulatory lymphocytes [CD4+/CD25+/CD127−] (Treg), cytotoxic lymphocytes [CD8+/TCRαβ+] (CTL), natural killer cells [CD3−/CD16+/CD56+] (NK), and TCRδγ-positive cells (Tδγ) were determined with flow cytometry. Results After the camp, the initial NK and Treg levels sustained at the baseline, while Tδγ counts increased relative to the levels in the placebo group. In the supplemented subgroup, a decrease in IL2 level in reaction to maximal exertion clearly deepened while the change in IL-2/IL-10 level induced by the recovery after this exertion clearly increased, relative to the changes in the placebo group. Conclusions AMR restored the immunological balance in strenuously trained athletes through a stabilization of NK and Treg cells with a positive trend in Tδγ towards Th1 response during restitution by cytokine IL2 modulation.

Summary: My tenacious interlocutor returns to discuss his lively Street Epistemology Discord server engagements that occurred in the interim. I do some more "messaging" than normal in this one, likely in response to them asking me questions. Watch video of talk here: https://youtu.be/HQWeRF0OBG4 Note: I found in interesting how "importance" of the claim was being viewed differently by both parties here. The students seem to be using it as "needed" while I seem to be viewing it as "fantastic." If only I had asked something like, "Are you saying that, the more necessary a claim is to a person, the more likely the attestations of others from a long time ago are true?", or something to that effect. IL2 at one point asks, "What happens to me?," as if that should be a factor in assessing the truth of a claim. I was later reminded about a discussion I had about differences in adjective meanings, like we might see with a word like "important" or "extraordinary". In their view, it seems, if a claim is "important" to them personally (like "Jesus rose from the dead," it's less likely someone would lie or be mistaken about the claim, and therefore you can accept what they stated as true to a high degree of confidence. Whereas from my perspective (and perhaps others who might be more skeptically-minded) we see "importance" as a biasing factor to control for; the more important or impactful one might find a claim to them personally is a reason to apply more—not less—scrutiny to the supporting reasons. Check out Pinecreek on YouTube and his more advanced "Flying Man" ( https://youtu.be/2ZNiCpeF_Jg?t=4789 ) example, which is further along than I was here with my off-the-cuff car metaphor in 2019. I'd like to see this idea of how we might be using adjectives differently explored further in future SE discussions. Location: San Antonio, Texas Recorded: 25 November 2019 Released: 27 May 2021 Anthony's Social Media: https://linktr.ee/magnabosco Street Epistemology Resources: https://tinyurl.com/abm-se-resources Street Epistemology Communities: https://tinyurl.com/abm-se-community Street Epistemology Discord Server: https://discord.gg/sKap3zM (recommended) Street Epistemology Survey: https://se-survey.web.app/en Skip ahead to a desired point in the talk: -- Intro: 00:01 Carolina: 00:16 Best Entrance Ever: 00:44 Interruption: 01:05 Start: 03:07 Opting Out: 03:32 Staying Cool?: 07:44 Faith: 08:07 Testing: 12:49 Peace Out: 14:28 Elon's Tesla: 18:14 What Happens to Me?: 20:36 Handshakes: 24:40 Have a Blessed Day: 24:55, 26:30 Equipment Change: 25:09 Closing Thoughts: 25:47 Consent: 26:58 Get Right Back in There: 27:39 End Screen: 27:42 Bonus Footage: 28:05 -- Note: Add 35 seconds to these timestamps if listening to the podcast version of this talk. Audio correction provided by Philipp Grzemba. Intro Music '19th Floor' by Bobby Richards, provided by YouTube. Audio Clip: 'Say Good Night' by Joakim Karud, Unported— CC BY-SA 3.0 Music provided by Jim Rhodes, with Dan Harris on lap steel. Links to References in Video: IL1's YouTube Channel: https://www.youtube.com/channel/UCuhe7b8v1lgHQCppxEEI_uw Watch 1st talk w/IL1: https://youtu.be/DBBW-ZUjKEM Watch 2nd talk w/IL1: https://youtu.be/w3bu-yc8sRI Watch 3rd talk w/IL1: https://youtu.be/HQWeRF0OBG4 Watch more faith talk: https://youtu.be/hxDD3sajaxw (How Faith Ends) Watch talk w/Jenna (ACA Host): https://youtu.be/S_0JhCv1mTs Mistakes: Please let me know if you spot any. Recorded w/Go-Pro. Edited w/PowerDirector. The views addressed here are mine and mine alone, and are not necessarily shared by members of my family and friends. The intro and outro of this episode was narrated by AZ.

Trevor Bauer had another dominant outing on Monday, and he could be among the biggest risers from 2020 to 2021. Kwang-hyun Kim has the right schedule to be a fantasy baseball hero over the next two weeks. Meanwhile, Aaron Judge and Giancarlo Stanton could be getting back into the Yankees' lineup just in time to make one final push for their fantasy mangers. Al Melchior and Michael Beller discuss all that, and more, on this episode of Fantasy Baseball in 15.Rundown1:17 Rhys Hoskins (Elbow) on the IL2:19 Any Love for Phil Gosselin?4:42 Scott Kingery in Position to Contribute5:47 Giancarlo Stanton and Aaron Judge Expected Back Later This Week10:29 Trevor Bauer's 2021 Fantasy Value13:30 Kwang-hyun Kim Has a Great Remaining Schedule14:52 Josh Bell and Ke'Bryan Hayes Turning it OnFeatured Read: 'Meet the cigar-loving, nearly 33-year-old rookie without a baseball card' by Brittany GhiroliFollow Al on Twitter: @almelchiorBBFollow Beller on Twitter: @MBeller Get a subscription to The Athletic for $1/month by visiting theathletic.com/baseballin15 Learn more about your ad choices. Visit megaphone.fm/adchoices

22 January 2020 - Episode 11: Welcome to 2020 pilots, it's good to be back!  Sport, Dutt, & Tricker catch up with everything that has been going on in their lives and launch into the new year with discussions on DCS and IL2.  Included on this episode are discussions on the F-16, F-18, A-10C, IL-2, and a special review of the F-16 from Dutt himself.  Pardon the clipping on Trickers microphone, the issue has been addressed for future episodes.  Stay Alert!   iTunes | Spotify | Overcast | Google Play | Podbean    Join our Discord! Alert 5 Discord   Contact Us! Email | Twitter | Facebook   Come Watch Us on Twitch and YouTube: Tricker | Sport | Dut   Time Stamps: 01:30 Catching Up 15:17 A-10C News 17:36 F-18C Updates 21:33 DCS WW2 Talk (Corsair, Mosquito, Essex) 25:00 Landing on a WW2 Carrier Discussion 28:45 Razbam F-15, MIG-27 31:54 Kiowa Talk 39:24 New Maps 47:16 Channel Map 50:04 Super Carrier News 58:08 What we look forward to in 2020 1:01:09 Highlights of 2019 1:04:26 IL-2 News 1:10:22 Dutt’s F-16 Review   Link Dump: F/A-18C TWS Mode Wags Video Redkite F-18 Walleye Tutorial P-47, Mosquito WIP Pictures Corsair WIP Pictures VFAT Demo F-8J Crusader DCS Super Carrier Battle of Bodenplatte Battle of Normandy B-25 Rumors

This JCO Podcast provides observations and commentary on the JCO article “Maintaining Outstanding Outcomes Using Response and Biology-Based Therapy for Intermediate-Risk Neuroblastoma: A Report From the Children's Oncology Group Study ANBL0531” by Twist et al. My name is Javed Khan, and I am Deputy Chief and Senior Investigator at the Genetics Branch and an Attending for the Pediatric Oncology Branch of the National Cancer Institutes of the NIH in Bethesda, Maryland. My oncologic specialty is Pediatric Hematology Oncology. Childhood cancer is a life-threatening disease where survival rates have increased exponentially to over 75% over the past three decades. However, this has come at a considerable cost with significant incidence of late effects including hearing loss, scoliosis, hypothyroidism, growth and development delay, infertility, psychological, emotional, cognitive and neurological sequelae, and secondary malignancies. Most of these late effects have been attributed therapy including chemotherapy, surgery and radiation. In the manuscript that accompanies this podcast, Twist et al report on the results of the Children’s Oncology Group study ANBL0531, whose primary aim was to reduce therapy for subsets of children aged =95% for the entire cohort. Neuroblastoma is an extracranial pediatric malignancy of neural crest origin that has often been described as an enigmatic cancer due to its significant clinical, molecular and biological heterogeneity. For example, some patients with widely metastatic disease are cured with minimal or no therapy whereas others have relentless progression to death despite intensive therapies.  There has been considerable progress in dissecting out the causes of this heterogeneity and developing prognostic biomarkers to stratify the risk based on several clinical, histological and molecular markers. At the time this clinical study was performed, and the manuscript written, the authors stratified patients using several clinical and biologic parameters including age, the International Neuroblastoma Staging System, MYCN amplification status, the International Neuroblastoma Pathology Classification of histopathology, and tumor DNA index. An additional marker utilized in this study was loss of heterozygosity determination of the tumors at chromosome bands 1p36 and 11q23. This stratification strategy has led to the identification of low and high-risk groups where therapy is more clearly defined and patients with low risk have excellent outcome for most patients with surgery alone and watchful waiting. For high-risk disease, significant strides have been made using a combination of surgery, aggressive chemotherapy, radiation followed by Chimeric Antibody 14.18 anti GD2 therapy, GM-CSF, IL-2 and Isotretinoin, however the five-year survival remains guarded at 40-50%. In the intermediate-risk group, the subject of this study, although the 5-year survival rates of 90-95% have been achieved, this group is significantly heterozygous raising the possibility of reducing therapy for subsets of patients within this group. This was the motivation for this study. Thus, the goal of this clinical protocol, ANBL0531, was to refine the minimal therapy needed to achieve excellent outcomes for patients with intermediate-risk neuroblastoma, with the aim to maintain an overall 3-year OS rate of > 95% for the entire cohort. Patients were stratified into Groups 2, 3, or 4, who were assigned to receive a minimum of 2, 4, or 8 cycles of chemotherapy, respectively. Chemotherapy was identical to that used on a previous study A3961. Reduction of therapy was planned to be achieved for patients with biologically favorable tumors (Groups 2 and 3) by using the achievement of Partial Response (PR) to chemotherapy +/- surgery to be the endpoint of therapy, rather than the achievement of Very Good Partial Response (VGPR) as was previously used on A3961. If the treatment endpoint was not achieved after completion of the scheduled chemotherapy courses, additional cycles of therapy could be administered, and patients re-evaluated following every 2 cycles to determine if the treatment endpoint has been achieved. VGPR, a more stringent response criteria, was used for Group 4 patients which includes those with age< 365 days, stage 4 disease, MYCN-not amplified, and either Unfavorable Histology (UH) or DNA Index or Ploidy (DI)=1. Patients within this subgroup received 8 cycles of chemotherapy on A3961, which was a reduction in therapy for these patients compared to prior studies. Group 4 patients also includes 2 subgroups who were previously stratified as high risk including those who had stage 3 disease, age 365- < 547days, stage 3, MYCN-NA, UH, any ploidy and also those with stage 4 disease, age 365 - < 547 days, MYCN-NA, FH, DI>1). These patients also received Isotretinoin (13-cis-retinoic acid, Accutane) for maintenance therapy, as they would have previously received this treatment on high-risk protocols. Thus, these patients would receive a significant reduction in therapy compared to prior studies.  These patients were closely monitored by interim stopping rules. Rescue therapy for this study for patients with an inadequate response to initial therapy and for patients with progressive, non-metastatic disease utilized standard cyclophosphamide and topotecan. Reduction of therapy was also planned and achieved on their study by reducing potential surgical morbidity for patients with stage 4S disease, who would no longer be required to undergo resection of their primary tumor. In the manuscript, the authors report that 404 evaluable patients were enrolled between 2007 and 2011, They found that compared to legacy COG studies, subsets of patients with locoregional disease, infants with stage 4 or 4S tumors, and toddlers with stage 3 or 4 disease had a reduction in treatment. The 3-year event-free survival (EFS) and OS were 83.2±1.9% and 94.9±1.1%, respectively. Infants with stage 4 favorable biology tumors (n=61) had superior 3-year EFS compared to patients with >= unfavorable biological feature (n=47; 86.9±4.4% versus 66.8±7.0%; p=0.02), with a trend towards OS advantage (95.0±2.8% and; 86.9±5.1% respectively p=0.08. For patients with localized disease OS was 100%. They conclude that comparable/excellent survival was achieved with this biology- and response-based algorithm, with reduction of therapy for subsets of intermediate-risk neuroblastoma patients. However, more effective treatment strategies are still needed for infants with unfavorable biology stage 4 disease. For the 32 infants with hyperdiploid, favorable histology (FH) stage 4 tumors with LOH at 1p36 or 11q23, or missing LOH data, intensification of treatment on ANBL0531 compared to A396110 did not reduce the risk of relapse previously reported for infants with tumors that harbor these genetic anomalies. Three-year EFS for this cohort was 68.6% (95% CI: 52.2-85.1%) versus 86.9% (95% CI: 78.3-95.4%) for stage 4 infants with favorable biology (p=0.04). Overall survival was not significantly different, indicating that many of the infants with 1p36/11q23 aberrations were successfully salvaged. Of the 20 patients who received CPM/TOPO due to an inadequate response to initial therapy, 9 achieved ≥VGPR. However, 6 of the 20 patients developed PD or relapsed, and 1 died, indicating that more effective treatment is needed for patients who do not meet the defined treatment endpoint after 8 cycles of chemotherapy. Take home messages: This is an important study with clinical implications for intermediate-risk neuroblastoma where the authors show that it is possible to reduce therapy based on a clinical Partial Response (PR) endpoint compared to Very Good Partial Response (VGPR). This most likely reflects the biology of the disease such that tumors that are responding to therapy will continue to involute. However, more effective therapy is needed for those patients who develop progressive disease (PD) or relapse or do not meet the defined treatment endpoint after 8 cycles of chemotherapy as these patients continue to have poor outcome. This will await the result of current biological and genomic studies and the development of novel therapies targeting ALK or RAS, or epigenetic targeting of MYC or MYCN activated tumors, or immunotherapeutic approaches such as adoptive cell therapies consisting of chimeric antigen receptor (CAR T cell) or, NK cells, or the use of immunocytokines such as hu14.18-IL2 or antibody drug conjugates. All these holds promise for future sub-stratification and new therapies for children with intermediate and high-risk neuroblastoma. This concludes this JCO Podcast. Thank you for listening.

3 May 2019 - Episode 8:  The guys are back at it (finally!)  In this episode, they catch up with each other on their lives, cover the mountain of news over the last month, and talk about some of the exciting things coming to DCS, IL2, and more. Thanks for listening and Stay Alert! iTunes | Spotify | Overcast | Google Play | Podbean     Join our Discord! Alert 5 Discord   Contact Us! Email | Twitter | Facebook   Come Watch Us on Twitch and YouTube: Tricker | Sport | Dut   Time Stamps: 16:00 Talking Tomcat 25:15 SATAL Talk 26:20 DCS Changelogs 30:45 SA-5 Coming to DCS 35:55 F-18C Changes/Updates 38:30 F-14 Changes/Updates 43:04 RAZBAM Harrier Changes/Updates 45:40 DCS News 54:00 MIG-19 54:30 Nimitz Class Carrier for DCS 59:00 IL-2 News 1:03:00 Warthunder 1:05:00 Outro

Man, I hope my internet comes back at some point. Guess I'll watch Cabin Boy on DVD while I'm waiting. Topics - Catherine, anime is still gay, Guacamelee! 2, consistently goofy, overpowered powers, Mortal Kombat 11, clay people, Hitman 2, mission stories, IL-2 Sturmovik: Battle of Stalingrad. Music - Catherine OST - Yo, Peter Chapman/Michelle Frey/Rom Di Prisco/Mariachi Entertainment System - Infierno, Horse the Band - Cloudwalker

07 December 2018 - Episode 04:  Today the guys talk about some of the news that has been released for DCS and IL2 over the last few weeks, including some exciting updates to the DCS: F/A-18 Hornet, AJS-37 Viggen, as well as the early-access release of IL2: Battle of Bodenplatte.  This week’s interview is once again with Heatblur, talking about the powerful weapon system users will be enjoying in the F-14 Tomcat!   We welcome your feedback!   iTunes | Spotify | Overcast | Google Play | Podbean     Join our Discord! Alert 5 Discord   Contact Us! Email | Twitter | Facebook   Come Watch Us on Twitch and YouTube: Tricker | Sport | Dut     Time Stamps: 00:40 - Introduction 01:19 - Opening Discussion 11:20 - Dutt bought some new modules! 13:18 - Community A-4 First Impressions 16:30 - Hornet Updates 21:22 - Viggen Updates from Heatblur 23:54 - F-14 Tomcat livestream 25:39 - DCS VR Optimizations 26:50 - VR Touch control 31:57 - DCS WWII 32:44 - DCS Damage Model Update 33:32 - IL2 Battle of Bodenplatte 37:56 - Heatblur Weapons Systems Interview 1:34:22 - Final Thoughts 1:34:50 - Announcements     Link Dump: CPDLC - https://bit.ly/2bWRz6N ANGLL4 Arrival - https://bit.ly/2L1aOuN Community A-4 Download - https://bit.ly/2EfSJJb Hornet Mini-Updates - https://bit.ly/2E5RISS F-14 Livestream Replay - https://youtu.be/awqmQT1jaSs VR Tech - https://bit.ly/2Ox5apz Smarter Every Day: https://youtu.be/OK2y4Z5IkZ0 DCS: Fw-190A-5 WIP Pictures - https://bit.ly/2EeZMBC DCS Damage Model Update - https://bit.ly/2PnTuRb IL2 Battle of Bodenplatte - https://bit.ly/2RE1ijV DCS: F-14 by Heatblur Pre-Purchase - https://bit.ly/2EjGKdw Virtual Festival of Aerobatic Teams - https://www.virtual-airshows.com/ Top Gun 2019 - https://bit.ly/2rqb3Xj  

In a packed episode, your favorite Maniacs put over The 2018 Super Bowl Champion Philadelphia Eagles, Monster Hunter World, The Gaming Historian, The Solo trailer, and the life and legacy of J Dilla and Nujabes, oh, and talk a little wrestling.Does Uncle Dave REALLY KNOW what's going on? The Usos cut the promo of the year, 2nd week in a row.Catch Mega Ran live this week! 2/10/18 at Emporium Arcade Bar, Chicago, IL2/11/18 at Icehouse, Minneapolis, MN 2/12/18 at 2720 Cherokee, St. Louis, MO

Bienvenidos a la segunda parte de simuladores. En este nuevo podcast nos pondremos serios pero no por ello aburridos: hablaremos de físicas, motores, submarinos, clanes y temas armamentísticos. Contaremos con 5 jugones que surcan desde las alturas de los cielos con DCS World a las profundidades de los océanos con la saga Silent Hunter, pasando por tierra con el simulador terrestre por excelencia: el Arma2 y Arma3. Leta, Bandura, Camaleon, Silverdragon y Waldemarne, nos cuentan sus experiencias en el mundo de la simulación. Veteranos y jugones a la vez, nos explicarán además las quedadas de sus clanes, como la 12BDI y las quedadas del Il2. Vente a la simulación más realista que puedas esuchar en toda la red, vente al podcast de simuladores de PDL !

Immunotherapy Forum Video #30: Immunotherapy for cancer has rewritten the rules for what we consider a successful response to treatment. Some tumors grow before they regress. Dr. Jedd Wolchok discusses why a new measurement criteria was developed.

Immunotherapy Forum Video #30: Immunotherapy for cancer has rewritten the rules for what we consider a successful response to treatment. Some tumors grow before they regress. Dr. Jedd Wolchok discusses why a new measurement criteria was developed.

Immunotherapy Forum Video #30: Immunotherapy for cancer has rewritten the rules for what we consider a successful response to treatment. Some tumors grow before they regress. Dr. Jedd Wolchok discusses why a new measurement criteria was developed.

Immunotherapy Forum Video #28: Doctors are still weighing the pros and cons of giving a cancer patient immunotherapy before or after resection surgery. In part 1 of 2 videos, Dr. Jason Luke details those risks and benefits.

Immunotherapy Forum Video #28: Doctors are still weighing the pros and cons of giving a cancer patient immunotherapy before or after resection surgery. In part 1 of 2 videos, Dr. Jason Luke details those risks and benefits.

Immunotherapy Forum Video #28: Doctors are still weighing the pros and cons of giving a cancer patient immunotherapy before or after resection surgery. In part 1 of 2 videos, Dr. Jason Luke details those risks and benefits.

Immunotherapy Forum Video #27: Immunotherapies work well in some, but not in others. Who benefits, and why? Dr. Sumanta (Monty) Pal explains what doctors are learning.

Immunotherapy Forum Video #27: Immunotherapies work well in some, but not in others. Who benefits, and why? Dr. Sumanta (Monty) Pal explains what doctors are learning.

Immunotherapy Forum Video #27: Immunotherapies work well in some, but not in others. Who benefits, and why? Dr. Sumanta (Monty) Pal explains what doctors are learning.

Immunotherapy Forum Video #22: Drs. Lauren Harshman and Sumanta (Monty) Pal answer questions from the audience following their presentations on immunotherapy for kidney cancer. Moderated by Dr. Marianne Davies.

Immunotherapy Forum Video #22: Drs. Lauren Harshman and Sumanta (Monty) Pal answer questions from the audience following their presentations on immunotherapy for kidney cancer. Moderated by Dr. Marianne Davies.

Immunotherapy Forum Video #22: Drs. Lauren Harshman and Sumanta (Monty) Pal answer questions from the audience following their presentations on immunotherapy for kidney cancer. Moderated by Dr. Marianne Davies.

Immunotherapy Forum Video #21: Dr. Sumanta (Monty) Pal reviews the past, present, and future of immunotherapy for kidney cancer and expresses concern about early study results of newer treatments. 

Immunotherapy Forum Video #21: Dr. Sumanta (Monty) Pal reviews the past, present, and future of immunotherapy for kidney cancer and expresses concern about early study results of newer treatments. 

Immunotherapy Forum Video #21: Dr. Sumanta (Monty) Pal reviews the past, present, and future of immunotherapy for kidney cancer and expresses concern about early study results of newer treatments. 

More than 50% of the world's population harbor Helicobacter pylori in their stomach mucosa. The chronic gastric infection is associated with several diseases including peptic ulcer disease and gastric carcinoma. One of the most thoroughly studied virulence factors produced by H. pylori is the Vacuolating Cytotoxin A (VacA). All isolated H. pylori strains possess the vacA gene, although significant sequence diversity was noticed in vacA genes across H. pylori isolates. VacA protein is produced and secreted as an 88 kD mature toxin. The protein binds to the host cells and is internalized. Inside the host cells, it causes “vacuole”-like membrane vesicles in the cytoplasm of gastric epithelial cells. Besides vacuolation, VacA exerts various other effects on target cells. VacA also forms membrane-embedded pores at the inner-mitochondrial membrane, resulting in mitochondrial dysfunction by cytochrome c release and apoptosis induction. VacA suppresses nuclear translocation of nuclear factor of activated T-cells (NFAT) resulting in down regulation of interleukin-2 (IL2) gene transcription to efficiently block proliferation of T-cells. The aim of this work was to understand the effects of VacA on intracellular calcium signalling in T-lymphocytes by considering the fact that VacA inhibits the Ca2+-calmodulin-dependent phosphatase calcineurin and induces cell cycle arrest. However, the exact mechanism how VacA exerts this response in T-cells is not known. Therefore, in this thesis various cell lines were used to study the effects of VacA on calcium influx. Calcium influx was found to be affected in the presence of VacA protein in the human Jurkat E6.1 T-cell line and primary human CD4+ T-cells activated by phorbol myristate acetate (PMA). Once inside T-cells, it could be shown that VacA suppresses the increase of the cytosolic free calcium concentration after stimulation by the calcium ionophore ionomycin and thapsigargin. Ionomycin forms pores in the cytoplasmic membrane, whereas thapsigargin blocks the sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA) and thereby causes depletion of the endoplasmic reticulum (ER) calcium store. In contrast, a VacA mutant, which was constructed by deletion of the hydrophobic region (amino acids 6-27), was unable to induce vacuolation activity and to block Ca2+ influx. A major result of this work was to demonstrate that one of the main components of store operated calcium entry (SOCE), the ER localized calcium sensor protein STIM1, is a target of VacA. Using co-localization studies and yeast two-hybrid (YTH) assays, it was found that VacA localizes to the lumen of the ER where it binds to the cEF-hand domain of STIM1. Furthermore, these data show that VacA strongly reduced the movements of the STIM1 towards the plasma membrane localized calcium channel ORAI1 after Ca2+ store depletion by thapsigargin. A YTH screen identified cEF-hand domain of STIM1 as the target of VacA to inhibit calcium influx. The results obtained in this work showing involvement of VacA in the modulation of intracellular calcium signalling will provide new insights that are required to understand how VacA inhibits T-cell proliferation and signalling.

May 07, 2012 In this interesting episode, host Dr. Tim Cripe (Nationwide Children's) and co-hosts Dr. Lionel Chow (Cincinnati Children's), Dr. Andy Kolb (AI DuPont), and Donna Ludwinski (Solving Kids' Cancer) quiz Dr Paul Sondel and Dr. Ken DeSantes (both from University of Wisconsin - Madison) on NK cells and the implications of KIR/KIR-ligand mismatch (killer immunoglobulin-like receptor) with regard to immunotherapy treatment of neuroblastoma. References: Delgado DC, Hank JA, Kolesar J, Lorentzen D, et al. Genotypes of NK cell KIR receptors, their ligands, and Fcγ receptors in the response of neuroblastoma patients to Hu14.18-IL2 immunotherapy. Cancer Res. 2010 Dec 1;70(23):9554-61. Epub 2010 Oct 8. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2999644/ . Venstrom JM, Zheng J, Noor N, Danis KE, et al. KIR and HLA genotypes are associated with disease progression and survival following autologous hematopoietic stem cell transplantation for high-risk neuroblastoma. Clin Cancer Res. 2009 Dec 1;15(23):7330-4. Epub 2009 Nov 24. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2788079/ . Alderson KL, Sondel PM. Clinical cancer therapy by NK cells via antibody-dependent cell-mediated cytotoxicity. J Biomed Biotechnol. 2011;2011:379123. Epub 2011 May 24. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3110303/

Dr. Sumanta (Monty) Pal, medical oncologist at City of Hope Cancer Center in Duarte, CA, explains the range of options and his approach to first line treatment of metastatic kidney cancer.

Dr. Sumanta (Monty) Pal, medical oncologist at City of Hope Cancer Center in Duarte, CA, explains the range of options and his approach to first line treatment of metastatic kidney cancer.

Dr. Sumanta (Monty) Pal, medical oncologist at City of Hope Cancer Center in Duarte, CA, explains the range of options and his approach to first line treatment of metastatic kidney cancer.

Dr. Sumanta (Monty) Pal of City of Hope Cancer Center discusses the current role of interleukin-2 (IL-2) in the context of many other treatment alternatives for metastatic renal cell carcinoma.

Dr. Sumanta (Monty) Pal of City of Hope Cancer Center discusses the current role of interleukin-2 (IL-2) in the context of many other treatment alternatives for metastatic renal cell carcinoma.

Dr. Sumanta (Monty) Pal of City of Hope Cancer Center discusses the current role of interleukin-2 (IL-2) in the context of many other treatment alternatives for metastatic renal cell carcinoma.

Background/Aims: The chromosome 4q27 region harboring IL2 and IL21 is an established risk locus for ulcerative colitis (UC) and various other autoimmune diseases. Considering the strong coincidence of primary sclerosing cholangitis (PSC) with UC and the increased frequency of other autoimmune disorders in patients with primary biliary cirrhosis (PBC), we investigated whether genetic variation in the IL2/IL21 region may also modulate the susceptibility to these two rare cholestatic liver diseases. Methods: Four strongly UC-associated single nucleotide polymorphisms (SNPs) within the KIAA1109/TENR/IL2/IL21 linkage disequilibrium block were genotyped in 124 PBC and 41 PSC patients. Control allele frequencies from 1,487 healthy, unrelated Caucasians were available from a previous UC association study. Results: The minor alleles of all four markers were associated with a decreased susceptibility to PSC (rs13151961: p = 0.013, odds ratio (OR) 0.34; rs13119723: p = 0.023, OR 0.40; rs6822844: p = 0.031, OR 0.41; rs6840978: p = 0.043, OR 0.46). Moreover, a haplotype consisting of the four minor alleles also had a protective effect on PSC susceptibility (p = 0.0084, OR 0.28). A haplotype of the four major alleles was independently associated with PSC when excluding the patients with concomitant inflammatory bowel disease (p = 0.033, OR 4.18). Conclusion: The IL2/IL21 region may be one of the highly suggestive but so far rarely identified shared susceptibility loci for PSC and UC. Copyright (C) 2011 S. Karger AG, Basel

Die adoptive T-Zelltherapie ist eine attraktive Alternative zu konventionellen Therapien zur Behandlung von malignen Erkrankungen. So konnten bereits Tumorremissionen bei Melanompatienten nach adoptivem T-Zelltransfer erreicht werden (Dudley et al, 2002b; Morgan et al, 2006). Während im autologen System jedoch oft nur unzureichende Antitumorantworten zu generieren sind, zeigt der Erfolg der allogenen Stammzelltransplantation, dass im allogenen System T-Zellen hoch effektiv Tumorzellen bekämpfen können. Die allogene Stammzelltransplantation konnte auch bei B-Zell-Non-Hodgkin-Lymphomen, wie beispielsweise der chronischen lymphatischen Leukämie (CLL), mit Hilfe eines Transplantat-gegen-Leukämie-Effektes (Graft-versus-Leukemia, GvL) lang andauerndes, krankheitsfreies Überleben bewirken. Sie birgt aber ein sehr hohes Morbiditäts- und Mortalitätsrisiko auf Grund der Transplantat-gegen-Wirts-Erkrankung (Graft-versus-Host-Disease, GvHD) in sich. Die im Transplantat enthaltenen T Zellen sind hierbei sowohl für den erwünschten GvL-Effekt verantwortlich, gleichzeitig aber auch für die unerwünschte GvHD (Horowitz et al, 1990; Kolb et al, 2004). Zur Minimierung des Risikos einer GvHD könnten T Zellen eingesetzt werden, die spezifisch und allorestringiert Peptide von tumorspezifischen Antigenen erkennen und somit bevorzugt Tumorzellen angreifen. Die Reaktivität der T Zellen kann durch einen T Zellrezeptor (TZR)-Transfer auf sekundäre Zellen übertragen werden. Diese transgenen Zellen können dann mittels adoptivem T Zelltransfer im Patienten zur selektiven Bekämpfung von Tumorzellen zum Einsatz kommen. In Vorarbeiten wurde FMNL1 (formin related protein in leukocytes 1) als hoch attraktives tumorassoziiertes Antigen identifiziert, das in der chronischen lymphatischen Leukämie (CLL) und in anderen Lymphomen, sowie in Zelllinien solider Tumoren stark überexprimiert wird, während es in gesunden Zellen fast ausschließlich in hämatopoetischen Zellen vorkommt. Ziel der vorliegenden Arbeit war es, allorestringierte FMNL1-peptidspezifische T-Zellen zu isolieren, zu charakterisieren und den T-Zellrezeptor dieser T-Zellen in sekundäre Zellen zu transduzieren. Hierzu wurden Peptide des tumorassoziierten Antigens FMNL1 mit Hilfe von Prädiktionsalgorithmen vorhergesagt und in T Zell-Stimulationsansätzen eingesetzt. Unter Einsatz von HLA-A2-positiven T2-Zellen als antigenpräsentierende Zellen, die mit dem prädizierten synthetischen Peptid FMNL1-PP2 beladen waren, ist es gelungen allorestringierte, FMNL1-PP2-spezifische T Zellen eines gesunden HLA-A2-negativen Spenders zu isolieren. Von 67 T-Zellklonen bzw. oligoklonalen T-Zellen konnte bei neun T-Zellklonen Allorestriktion und FMNL1-PP2-Peptidspezifität nachgewiesen werden. Der T-Zellklon SK22 war für diese neun T-Zellklone, die auf Sequenzebene einen identischen T-Zellrezeptor aufwiesen, repräsentativ. Der T-Zellklon SK22 zeigte in Reaktion auf peptidbeladene T2-Zellen eine hohe Peptidspezifität für FMNL1-PP2 im Kontext mit dem für SK22 allogenen HLA-A2. Nach Zielzellerkennung sezernierte der T-Zellklon Zytokine wie IFNγ, TNFα, GM-CSF und teilweise IL2. Der T Zellklon zeigte eine hohe Aktivität und mittlere Avidität gegen FMNL1 PP2-beladene T2-Zellen. Des Weiteren wurde die Reaktivität gegen unbeladene native Zellen getestet. Der T-Zellklon SK22 erkannte verschiedene Zellen, wenn sie HLA-A2-positiv waren und gleichzeitig FMNL1 exprimierten. Hierzu zählten zum einen maligne Zellen, darunter verschiedene Epstein-Barr-Virus (EBV)-positive und EBV-negative Lymphomzelllinien und die Nierenzellkarzinomzelllinie RCC26, die gut erkannt wurden sowie CD40-aktivierte CLL-Zellen, die schwächer erkannt wurden. Bei der Untersuchung von gesundem Gewebe wurden FMNL1-exprimierende HLA-A2-positive periphere Blutleukozyten (PBL) schwach und B-Zellen in mittlerer Stärke erkannt. HLA-A2-positive Zellen, die FMNL1 nicht exprimieren, wie beispielsweise Lungenfibroblasten, wurden vom T-Zellklon SK22 nicht erkannt. Der T Zellklon zeigte Kreuzreaktivität gegen neun verschiedene lymphoblastoide Zelllinien (LCL), die Allelvarianten von HLA-A2 exprimierten. Zusätzlich wurden 4 von 18 HLA-A2-negativen LCL-Zelllinien erkannt. Jeweils zwei dieser vom T Zellklon SK22 erkannten HLA-A2-negativen LCL-Zelllinien trugen ein gemeinsames MHC-Klasse-I-Molekül. Eines davon war HLA-A*3303, welches durch die Erkennung der HLA-A*3303-positiven Transfektante der C1R-Zelllinie bestätigt werden konnte. Das andere war HLA-A*6802, welches zur HLA-A2-Superfamilie gehört. Der T-Zellrezeptor des T-Zellklons SK22 wurde identifiziert, sequenziert und kloniert, sowie mit Hilfe von Retroviren in sekundäre Zellen eingebracht. Durch den Transfer des T Zellrezeptors von SK22 in sekundäre Zellen konnte nachgewiesen werden, dass dieser T Zellrezeptor für die spezifische Reaktivität des T-Zellklons SK22 verantwortlich war. Dies zeigte sich in der T-Zellrezeptor-Oberflächenexpression nach Transduktion in Jurkat76-CD8α-Zellen und in der Übertragung der Funktionalität des T-Zellklons in PBL. Der T Zellrezeptor von SK22 ist ein „schwacher“ Rezeptor, da er in der Konkurrenzsituation mit einem weiteren Rezeptor nur in geringem Grade an der Zelloberfläche von PBL exprimiert wurde. Durch einen Austausch der jeweiligen konstanten Regionen der T-Zellrezeptor-SK22-Sequenzen durch die konstanten Bereiche eines murinen T-Zellrezeptors konnten in der Summe verbesserte Expressionswerte in Jurkat76-Zellen und eine verbesserte Funktionalität in PBL erreicht werden. Der T-Zellklon SK22 zeigte Allorestriktion, FMNL1-PP2-Peptidspezifität und Zytotoxizität gegen FMNL1-exprimierende Zellen, insbesondere gegen Tumorzellen. Die beobachtete Kreuzreaktivität ist Fokus weiterführender Untersuchungen. Im Fall des T-Zellrezeptors von SK22 bedeutet es, dass Spender und Patienten sorgfältig nach Analyse des gesamten MHC-Klasse-I-Expressionsmuster ausgewählt werden müssen. Im Rahmen einer haploidentischen Stammzelltransplantation ist jedoch der klinische Einsatz dieses spezifischen T-Zellrezeptors zur Behandlung von B-Zell-Non-Hodgkin-Lymphomen und anderen FMNL1-überexprimierenden Tumorerkrankungen vielversprechend.

The general feasibility of chimerization of monoclonal antibodies (mAbs) has already been shown for a large number of them. In order to evaluate in vitro parameters relevant to immunosuppressive therapy, we have chimerized and synthesized two anti-CD4 mAbs recognizing two different epitopes on the human T-lymphocyte antigen, CD4. The chimerized mAbs are produced at levels corresponding to those of the original hybridoma cell lines. With respect to activation of human complement, the individual Abs are negative; however, when used in combination, complement activation was performed. When applied in combination, they were found to modulate the CD4 antigen, whereas the individual mAb do not display this property. Individually they mediate an up to 60% inhibition of the mixed lymphocyte reaction (MLR). However, by combination of an anti-CD4 mAb with one directed against the a-chain of the human IL2 receptor, nearly 100% inhibition of the MLR was achieved, even with reduced dosage of the mAbs. Our data suggest that the combination of an anti-CD4 mAb and an anti-IL2Rcc chain mAb is more effective with respect to immunosuppression than each mAb by itself, indicating that this mAb cocktail could be a new strategy for immunosuppressive therapy.