Podcasts about cdta

Do you love hiking and exploring the outdoors? Then hear about Nature Bus, a great FREE service offered each Saturday by the Capital District Transportation Authority (CDTA) that takes folks on routes from downtown Albany to parks and trails in the region. The "Beaver" route goes to Five Rivers Environmental Education Center in Bethlehem (pictured), Six Mile Waterworks, and other locations each Saturday through 9/27. The new "Warbler" route heads from downtown Albany and on to Thacher Park each Saturday through 10/4. For details on the routes, the many other nature destinations, and the many points where you can get on, check the bus 872 schedule at cdta.org. The Nature Bus is run in conjunction with the Mohawk Hudson Land Conservancy (www.mohawkhudson.org). Jonathan Scherzer, CDTA Director of Business Development, also notes three other special CDTA services: Flex on Demand, bike sharing, and electric-car sharing. Produced by Brea Barthel for Hudson Mohawk Magazine.

Recently, in coordination with New York Congressman Paul Tonko, the Rockefeller Institute hosted the Locally Sourced Capital Region Climate Policy conference, which examined ways local governments and organizations within New York's capital region are addressing climate change through policy and practice. As part of the Rockefeller Institute's ongoing look at municipal solutions to improving our climate and environmental sustainability, Carm Basile, CEO of the Capital District Transit Authority (CDTA) and a panelist during the Locally Sourced conference, joins the podcast to detail what programs and initiatives CDTA is embarking on that help reduce the regional carbon footprint by increasing access to and use of public transportation, as well as reduce its own carbon footprint by increasing green transit infrastructure. Guest: Carm Basile, CEO, Capital District Transit Authority Learn More: Locally Sourced Capital Region Climate Policy | An Integrated Approach to Zero Emissions, Carm Basile, CEO, Capital District Transit Authority Locally Sourced Capital Region Climate Policy | Entire Conference

Today, Gary discusses the proposal for the Capital District Transit Authority's acquisition of Greater Glens Falls Transit, and what it would cost local taxpayers. Also, power outages caused by yesterday's snow storm, scholarships offered by the Glens Falls Zonta Club, the DEC's call for summer workers, the status of a proposed merger study between Johnsburg and Minerva school districts, and the upcoming ADK Tabletop Day. 00:02 - Intro 00:39 - Ad Break 1 01:34 - Story 1: Winter Storm: Power Outages 02:42 - Story 2: Zonta Club Scholarships 03:53 - Ad Break 2 04:17 - Story 3: CDTA Acquisition: Taxpayer Costs 07:21 - Story 4: DEC Hiring Summer Park Workers 08:20 - Story 5: Johnsburg/Minerva Merger Study 09:49 - Story 6: ADK Tabletop Day 10:59 - Outro Stories Cited: Winter Storm: Power Outages – News 10 Zonta Club Scholarships – Post Star CDTA Acquisition: Taxpayer Costs – Sun Community News DEC Hiring Summer Park Workers – News 10 Johnsburg/Minerva Merger Study – Post Star ADK Tabletop Day – News 10

In this episode, we are joined by professional service dog trainer Leslie Horton to talk about all things service dogs, including what they are, legal protections, and training. We try to clear up some common misconceptions and touch on how they differ from emotional support animals, behavior standards in public, and being a “Certified” service dog.She owns Most Fine Canine in Frederick, Maryland, where she has spent over 20 years training and specializing in service dogs. She is certified as a dog trainer and service dog trainer and was inducted into the International Association of Canine Professionals (IACP) Hall of Fame.Leslie is also an R.N. and the Coordinator of Inova Fairfax Hospital's Animal Assisted Care (AAC) program overseeing teams of handlers and dogs at the health system's four facilities.Leslie's experiences as a dog trainer, medical professional, and patient give her incredible insight on a topic where there is a lot of confusion and can be pretty emotional for people.ABOUT US:The Demystifying NMO and MOG podcast is a Sumaira Foundation (TSF) project and was made possible with the generous support of Genentech.STAY CONNECTED:Leslie Horton, IACP CDT, CDTA, PDTI, CSDTWebsite - https://www.mostfinecanine.netFacebook - https://www.facebook.com/HortonLeslieLDemystifying NMO podcastInstagram - https://www.instagram.com/demystifying_nmomogTwitter - https://twitter.com/DemystifyingNMOThe Sumaira FoundationWebsite - https://www.sumairafoundation.orgFacebook - https://www.facebook.com/TheSumairaFoundationTIMESTAMPS/TOPICS:00:00:58 Leslie Horton00:02:14 Service Dogs Vs. Emotional Support Animals00:02:58 Where Can Service Dogs Go?00:07:06 What Can A Business Ask?00:08:32 "Certification"00:08:51 Standards Of Behavior00:10:55 Fake Service Dogs00:18:24 What Is The Process Of Getting A Service Dog?00:26:57 Training A Service DogLINKS:ADA Requirements: Service Animals https://www.ada.gov/resources/service-animals-2010-requirements/ADA Service Animal FAQhttps://www.ada.gov/resources/service-animals-faqs/IACP - Service Dogs Overview https://www.canineprofessionals.com/service-dogs-overviewIACP - Business Resources Regarding Service Dogs https://www.canineprofessionals.com/business-resources-regarding-service-dogsCREDITS:Executive Producer -Host - Brian DawsonMusic - Denys Kyshchuk from Pixabay

This week's episode recaps the Buttonista's sold out live show at the Misfit, the legendary gift Jack got for his 30th, and one Reddit Rat calls into the show to express his dismay about our company and explain why Albany Reddit has beef with 2BD. This show is best enjoyed with a Sam Adams beer. Notes:- Peaks of the week (2:05)- The Buttonista Live Show (9:10)- Jack's legendary 30th birthday gift (15:55)- A Reddit Rat calls in to the show (19:50)- Peek into the week: What we will be giving away next week on CDTA busses (44:00) Follow Two Buttons Deep for more stuff worth talking about from the Great Upstate & Beyond... 

This week's episode marks our official transition to winter and not because of the snow, but because Sam Adams Winter Lager is officially on tap at The Bunker in North Greenbush... We also recap Park Albany doing Drew dirty, we watch our Spectrum News story live on the show, brainstorm the Buttonista's next live show, her giveaway with The Plant Hatch in Clifton Park, plus a jam-packed peak into the week, presented by Slip 12. Notes:- Peak or pit of the week (4:40)- Park Albany strikes again (10:35)- Why Drew might convert to full-time CDTA rider (15:50)- Watching the 2BD Spectrum News story (16:41)- The Buttonista's next live Podcast (26:55)- The Buttonista's hand-made giveaway from The Plant Hatch (29:30)- Peek into the week: Presented by Slip 12 (33:35)

Today's show comes to you from the one-of-a-kind June Farms, where the Buttonista announces her next live show, Jack's concerning message he received before the adult spelling bee, how Dronah dropped the ball on the bus, and our next big idea for a new series on Two Buttons Deep which will take us all back to our roots here in the Capital Region... This episode is brought to you by the Albany Times Union. Peak of the week (0:55)Drew meets our President, Gary Dake (6:51)The Buttonista's next live show on her birthday, 9/20 (9:45)Recapping the adult spelling bee and Back 9 Bri's performance (15:15)Our idea for a new series on Two Buttons Deep (23:10)Jack's inaugural CDTA bus ride in Montgomery County with Paul Tonko (26:45)Post of the week: The Glenville Bridge saga (Presented by Crossgates Mall, The place to go for everything back to school) (33:30)

Dr. Diwakar Davar and Dr. Jason Luke, both of the University of Pittsburgh's Hillman Cancer Center, share the latest news on immunotherapy trials KEYNOTE-A10, LIBRETTO-001, and other key IO studies across tumor types featured at the 2022 ASCO Annual Meeting.  Transcript Dr. Diwakar Davar: Hello, and welcome to the ASCO Daily News Podcast. I am Dr. Diwakar Davar, and I'm an assistant professor of Medical Oncology in phase 1 therapeutics, at the University of Pittsburgh's Hillman Cancer Center, and the guest host of today's podcast. I'm delighted to welcome Dr. Jason Luke to this podcast. He's the director of the Cancer Immunotherapeutic Center at the Hillman Cancer Center, University of Pittsburgh, and a great colleague and friend.  Today we'll be discussing some key posters that highlight some advances in immunotherapy that will be featured and the 2022 ASCO Annual Meeting. You will find our collective disclosures in the show notes and the disclosures of all guests on the podcast are available on our transcripts at asco.org/podcasts.  So, Jason, thank you for coming on the podcast today.  Dr. Jason Luke: Well, thanks very much for the invitation. I always love doing these podcasts for ASCO, and never love anything more than hanging out with my friend Diwakar Davar.  Dr. Diwakar Davar: Well, thank you! Below are the abstracts we've selected. We will start with Abstract 2504. This is a phase 1 trial of the TIM-3 inhibitor cobolimab monotherapy, singly and in combination with the PD-1 inhibitors nivolumab or dostarlimab. Phase 1 data from the AMBER trial with the presenting author being Dr. Gerald Falchook. And this is a trial that initially started several years ago. And I know Jason, that you were involved with the inception of this agent, that TIM-3 inhibitor. So, walk us through, TIM-3. It's a third-generation checkpoint, we now have TIGIT LAG coming into the landscape. Definitely a first indication for LAG-3 melanoma with a positive trial, RELATIVITY 047. So, where are we with TIM-3? Why should we be excited about TIM in general, and this data in particular?  Dr. Jason Luke: It is quite exciting, especially building off the recent data that we saw for relatlimab or LAG-3 because it's becoming clearer that a number of these other immune checkpoints that we have been talking about for many years, actually really can be effective when used in the right setting.  So, this drug, this anti-TIM-3 antibody cobolimab monotherapy, as you mentioned, started out in a phase 1 clinical trial dating all the way back to I think about 2015. And that was at the time in immuno-oncology when everybody was so excited, [and] they thought everything was going to work immediately.  Subsequent to that, obviously, we've had some hurdles that we've had to come over. But we're coming back to some of these agents now, which are looking very exciting. So, just in the same way we think about blocking PD-1 or now blocking LAG-3 to reinvigorate T cells in the tumor microenvironment, there's a good chance and a high probability based on preclinical data that blocking TIM-3 could be just as effective as blocking LAG-3, so to say.  Now, one thing that I note in this abstract is really the safety finding and early PK analysis. And so, this is the important work we do early on to understand the drug. It's important to be aware that in a study like this, it's very hard to seek efficacy signals.  So, when you see this poster, really, you probably shouldn't be thinking, ‘Oh, this is a frontline phase 3 trial,' but rather that the efficacy is going to be a secondary consideration. Rather, what's quite important is looking at the properties of the drug and looking at the safety signals around that. And what we can see here is that TIM-3 appears to be quite safe when blocking it in conjunction with anti-PD-1 across several different tumor types. And that really sets the stage then to think about moving this into earlier lines of therapy across many different cancers.  And so, here we see advanced solid tumors but focused on lung cancer and melanoma and kind of the usual tumors we think about, and people can keep their eyes open because there are other posters of this molecule with PD-1 in some of the other sections outside of developmental therapeutics.  Now, one thing I would like to get your opinion on because your group has focused a lot on TIM-3, as I described it as this T cell centric mechanism to reinvigorate exhausted T cells. But it's possible that TIM-3 does other things as well. And I don't know if you want to comment on that or give any other feedback that you've had when thinking about this AMBER Trial.  Dr. Diwakar Davar: That was an excellent summary, Jason, of really what is a truncated 8-year track record of developing this agent all the way from 2015. But you bring up a very interesting point, which is: exactly what does this drug does in the non-T-cell compartment?  Some very interesting data from Brian Ruffell in a paper that was published about 3 years ago now suggested that TIM-3 was actually potentially a myeloid checkpoint, meaning that, in a tumor model in which Dr. Ruffell was studying this in the context of breast cancer, the drug primarily appeared to work on the effect of antigen-presenting cells and augment the presentation of antigen to T cells suggesting that it may be, in addition to being a chronicle T cell exhaustion marker, it may also be reinvigorating antigen-presenting cells. And the question of whether or not the role of TIM-3 on APCs as well as the role of TIM-3 on T cells, and which of these compartments are more important, and how these compartments segregate in any given cancer across many different lines of therapy will hopefully be something that we disengage, and understand a little bit better as we look at biomarkers of this drug across different settings.  And especially to that point, Jason, the biomarker question, you'll notice that very interestingly, that was a signal in which that drug had a certain response rate. Again, as you correctly point out, we cannot read too much into response rates in very small patient numbers. But very interestingly, there was a slightly higher response rate at the 300 milligrams, which is not the top dose level of the drug, and a slightly lower response rate at the ceiling dose of the drug that was tested, 900 milligrams, leading the investigators to conclude that the RP2D, was actually 300 milligrams every 3 weeks and not 900 milligrams.  What are your thoughts on dose in the context of immunotherapy (IO) drug development? And why might it be that 300 is the optimal dose as opposed to 900?  Dr. Jason Luke: That's a complicated question. I mean, when we think about checkpoint blockade, we classically think about it as only blocking on T cells. But to your point, if there are multiple mechanisms in play, sort of modulating other cell compartments actually may start to do different things at different doses that maybe weren't our primary intent as we went into the trial.  That's a little bit of hand waving, immunologic hand waving, but I think the data are the data and once we hit an effective dose level, there's really no need to really push the dose that much further. But that really emphasizes the importance of these kinds of early phase clinical trials.  So, I'm really looking forward to seeing this data. For disclosure, obviously, we have both been investigators on this trial. But we're very excited about the idea that there may be hope for a fourth checkpoint to come forward in the field beyond just PD-1 CTLA-4, and LAG-3, maybe now here with TIM-3.  Dr. Diwakar Davar: So, with that we'll go to the next abstract and that is Abstract 2516, “Phase I trial of adjuvant autogene cevumeran, an individualized mRNA neoantigen vaccine, for pancreatic ductal adenocarcinoma.”  So, this is an mRNA vaccine from our good friend, BioNTech. And that's been essentially evaluated in the context of highly lethal cancer, pancreatic ductal cancer, and specifically in the context of adjuvant vaccines, specifically in the setting of patients who had followed definitive pancreatic cancer surgery.  So, Jason, you know a lot of neoantigen vaccines, you've led some of these trials, really, the neoantigen vaccine is really the primary reason we are actually having an in-person meeting this year, because if not for this company and others like this, really this pandemic would not be behind us.  What are your thoughts on the role of neoantigen vaccines in cancer therapeutics, and also, particularly this particular trial in the data, the immunological data, and the clinical data regarding the development of neoantigen-specific T cells in this setting, and what this means for you?  Dr. Jason Luke: Right. So, the idea of targeting neoantigens as cancer immunotherapy was really all the rage a few years back, and it was thought based on preclinical animal models that this was just going to be the secret sauce, and this would be the new targeted therapy for immunotherapy. And it isn't to say that that's not true, but the first generation of neoantigen, peptide-based vaccines for the most part, unfortunately, just kind of didn't end up moving the needle the way we had hoped.  The question then was raised: is that because targeting neoantigens isn't reasonable, or is that because the setting where we were trying to do it in the refractory disease area was not the optimal way to leverage this?  And so, a couple of different companies and trials now are coming forward looking at targeting neoantigen in a minimal residual disease setting where the idea could be that immunologic responses that you could generate wouldn't be hampered by all the immunosuppression associated with the tumor microenvironment.  And so, here we have this molecule, which you eloquently pronounced, ‘autogene cevumeran.' It's an RNA-lipoplex neoantigen vaccine. So, it's not a peptide. It's more like the COVID-19 vaccines actually. And it's being given after surgery, followed by anti-PD-L1 followed by chemotherapy.  So, it's a complicated regimen, but it's very intriguing these early data, which do show that the patients who got the vaccine seemed to have better and longer-term outcomes. But then as you emphasize, really, I think probably what's at the heart of this that really makes it exciting is their ability to immune monitor the patients, meaning to look for antigen-specific immune cells from the peripheral blood in these patients to be able to identify those immune responses as being specific to cancer. Because this kind of a clinical trial, it's still signal seeking and proof of concept kind of trial.  In order to actually establish that a vaccine approach in a post-surgical setting would have efficacy, we need to do a large randomized trial. And so, this is not that yet. But I think these data really point in the direction that that could be a reasonable thing to try. And when you think about pancreatic cancer, where we've made no success with immunotherapy, really in a meaningful way in terms of checkpoint blockade, at least, that's pretty exciting actually to think about.  I would actually marry this dataset with another that we actually saw at the American Association for Cancer Research (AACR) meeting that also looked at neoantigen targeting and antigen-specific responses in colorectal cancer, again, and in a similar setting with the minimal residual disease setting.  And so, I think this highlights that we may need to start thinking about using immunotherapy in different ways than we had before. Obviously, everybody knows about using PD-1 blockade in lots of different cancer types that are really for metastatic disease, or maybe even for adjuvant now in melanoma a little bit. But maybe there's this space, which is the minimal residual disease setting where you might be able to detect by ctDNA after surgery, the patients are still positive. And maybe you could treat that before there's visible cancer, and maybe certain immunotherapies could be more valuable in that setting than others. And that's where I think maybe some of these mRNA technologies really might find their sweet spot.  So, coming back to this abstract, I think really, the emphasis point here is the novelty of generating patient-specific neoantigen vaccines, and then being able to track linearly over time the immune response against those vaccines.  I think with that kind of technology and being able to leverage that, I think we're really headed towards a real shift in the way we think about managing cancer in a post-surgical setting, again, thinking about MRD, or minimal residual disease, maybe in a way that our leukemia colleagues have been thinking it about for a long time.  Dr. Diwakar Davar: That's an excellent summary of a very, very complicated, both setting, and in this case, a therapeutic landscape. So, well said, well summarized, and we'll now pivot to Abstract 2514. So, this is ‘Efficacy and safety of NT-I7, long-acting interleukin-7, plus pembrolizumab in patients with advanced solid tumors: Results from the phase 2a study' [and] the presenting author is Dr. Aung Naing from [The University of Texas] MD Anderson [Cancer Center].  So, Jason, you know, with checkpoints, we've got so many thoughts about checkpoints, particularly given the rather unfortunate failure of BEMPEG in the context of melanoma.  So, we've got lots of interesting cytokines that we think of as important in the context of immuno-oncology 2, certainly 12, 15. You've been very involved with IO-15. We've got a lot of clinical trials studying IL-12. And now we've got one studying IL-7. So, tell us what do you think of this IL-7 targeting approach in the context of cytokine-based therapeutics?  Dr. Jason Luke: I think it's really important to emphasize on first principles, for those that are listening, who don't think about immunology all the time that not all cytokines are the same thing.  So, interleukin 2 that many people have heard of is very different actually than interferon. And that's very different from many of the other cytokines, the ILs, and everything, right?  So, IL-7 is a very potent cytokine that's associated with the expansion of immune responses, and that can drive interferon gamma-dependent effects. And you should hear whenever I say interferon-gamma is sort of a link through to PD-1 responsiveness. Because we think the mechanism that underpins anti-PD-1 effectiveness in patients really is interferon gamma biology.  So, IL-7 has been a molecule, it's been of a lot of interest but really was too toxic to try to deliver. But now we have novel drug delivery sorts of approaches that are being developed to try to bring the drug in, in a way that doesn't cause such systemic toxicity.  So, in this clinical trial, this NT-I7 molecule is given intramuscularly, every 6 weeks in conjunction with pembrolizumab, and very interestingly, in a small number of patients, but there were resist responses observed across a series of tumors that you really wouldn't expect should be responsive in any way to pembrolizumab alone. And so, we're talking about microsatellite stable colorectal cancer, pancreatic cancer, and some others as well.  And in conjunction with that, they were able to identify some of the biomarker effects we would think we would see with IL-7, such as expansion of peripheral immune compartments. And the toxicity profile was really consistent with what we've seen with fevers and chills, but manageable in a way that previous approaches really weren't.  So, I think this is really exciting because I think the idea here then is with this IL-7 approach, we might expand the kinds of cancers that we could go after, in conjunction with anti-PD-1 again, pancreas, colorectal cancer. I think that's really where the unmet need lies in oncology.  So, I really applaud these kinds of approaches and several of these cytokine approaches, and what we're going to talk about them, I think, have the potential to do that over the next couple of years.  Dr. Diwakar Davar: Excellent! Pivoting now to a different cytokine, but one that was alluded to before IL-12. So, Abstract 2518 is ‘Phase II evaluation of the combination of PDS0101, M9241, and bintrafusp alfa in patients with HPV 16+ malignancies,' and the presenting author here is Dr. Julius Strauss of the NCI Cancer Center and the Clinical Center of the National Cancer Institute at the National Institutes of Health.  So, what do you think, Jason, about the role of the HPV targeting vaccine, in this case, that was added to IL-12 immune-cytokine and bintrafusp alpha contextualizing the recent data that we have of bintra along with what is a very interesting result here?  Dr. Jason Luke: Yes, I think building on the last abstract where we talked about IL-7 as some novel biology now we move to IL-12, which again introduces other biology. So, interleukin-12 is a complicated cytokine, but one that's strongly associated with initial immune responses or immune priming, as well as enhancement of anti-tumor effects in the tumor microenvironment.  So, here we have sort of a 3-legged approach. So, the vaccination approach against HPV really can generate a strong immune response initially, and that can be supported with the IL-12. And then you come in with anti-PD-L1 and to whatever extent the TGF data is relevant here. And so, you have this cocktail where you're generating tumor-specific responses with a vaccine, you're supporting them with IL-12, and then blocking PD-L1.  And as we go back even a couple of abstracts we talked about, now we sort of have a cocktail right of approaches. And so, I think this is very exciting. It's unique in that, in these tumors, obviously, HPV is the driving force of cancer. So, developing a vaccine against that is fairly straightforward. But I really like this concept of bringing forward sort of a multi-dimensional immunotherapy approach. And we'll note they have previously presented data on this trial, I think last year at ASCO, actually. But what they see are pretty strong response rates, almost 30% range in PD-1 refractory tumors.  Again, that's our area of really high unmet need. It's hard to read through how useful a PD-1 naive treated patient here, although the response rates were high. But to me, it's really those patients who had progressed on PD-1 where they're getting these responses that tells me that this really could be something that's useful and potentially could be expanded beyond just say head neck cancer to any HPV relevant malignancy.  Dr. Diwakar Davar: Excellent! Now on to our last abstract. Abstract 2520, ‘Effect of intratumoral INT230-6 on tumor necrosis and promotion of a systemic immune response: Results from a multicenter phase 1/2 study of solid tumors with and without pembrolizumab (PEM) [Intensity IT-01; Merck KEYNOTE-A10].' The first author is Dr. Jacob Thomas.  Jason, we've seen a lot of interesting intratumoral therapies. You and I have both done a lot of studies in looking at intratumoral agents from toll-like receptor agonists, TLR-9, TLR 7-8, and more recently, oncolytic viruses.  So, contextualizing IT230-6 in the spectrum of intratumoral therapies, how do you feel about this drug, which is actually a very interesting novel drug. It's not just a TLR agonist, or for that matter, an OV, very interestingly, it's an intratumoral therapy that has actually got chemotherapy in it. So, how do you feel about this drug? How do you feel about the responses that we've seen? And particularly how do you feel about the setting in neoadjuvant breast cancer?  Dr. Jason Luke: Yeah. I would pick up where you said that this drug INT230-6 is just a really interesting concoction. So, it's cisplatin mixed with vinblastine, in a specific amphiphilic molecule that allows it to diffuse in through the cancer.  And so, if you had said that to me a few years ago, I would have looked at you and been like, ‘What are you talking about?' But I think the data that's been emerging for this is just really interesting because something about this chemotherapy cocktail actually drives immune responses. And really what the focus of this abstract is on is showing that you get an influx of CD foreign CDTa cells into the tumor microenvironment that's associated with a therapeutic benefit.  I think that's just really, really interesting to think about. It sort of makes one wonder when we're doing these intratumoral injections, how much of it is just the injection, and how much of it is the therapeutic agent, but I think it's a really novel therapy, and one that appears to be very well tolerated as well. And that's also the exciting part. When you hear cisplatin and vinblastine, you think, ‘Oh, well, that's not going to work.'  But apparently, it stays right in the tumor and generates these immune effects. I think it's very exciting. I think their approach here—going after what we usually call cold tumors, ones that don't respond to immunotherapy, you mentioned breast cancer—I think it's really interesting. I'm really looking forward to seeing the actual data from this abstract because, on first pass, it wouldn't have been what I thought about in terms of driving immune responses, but maybe it just goes to show that there's a lot more to understand there about immunogenic cell death and some of these other concepts that we bandy about. But I think this will be one of the most interesting abstracts actually to see the data for once it's available.  Dr. Diwakar Davar: Great! Taking a slight pivot from that. You've been involved in the development of novel response endpoints. One of the issues that we have with intratumoral therapies is that you're measuring a lesion that you inject, so now you inject something and it gets a little bigger. Is it getting bigger because it's growing? Is it getting bigger because the drug is working? We don't know. We have now itRECIST, which you have been working on.  What's very interesting is that whether you look at itRECIST, or RECIST, irRECIST, or imRECIST, when you have the monopoly of different response endpoints we have to deal with these days, these patients have monotherapy responses in non-injected tumors. How do you feel about that as a drug developer and somebody who's giving patients drugs like that? What is your impression of having shrinkage in the non-injected tumor?  Dr. Jason Luke: I think it's really exciting about this concept of the abscopal effect that we've bandied about for years. Despite being an investigator in this space, I'm really excited to actually see the data and to understand what these out of field responses are. If it's really true that this is robust, I mean, it could potentially be like a game-changer kind of thing. But I'll reserve judgment until I see the actual scans of the tumors that actually shrank that weren't injected.  Dr. Diwakar Davar: Fantastic insights, Jason. So, thank you for taking the time to join us on this podcast and to highlight these extraordinarily important advances in immunotherapy.  Dr. Jason Luke: I appreciate the opportunity to participate today.  Dr. Diwakar Davar: So, thank you, and thank you to our listeners for your time today, you will find the links to the abstracts that we discussed today in the transcript of the episode.  Finally, if you're enjoying the content on the ASCO Daily News podcast, please take a moment to rate review and subscribe wherever you get your podcasts.  So, thank you, Jason. And thank you to the team for putting this together.      Disclosures:   Dr. Diwakar Davar:   Honoraria: Merck, Tesaro, Array BioPharma, Immunocore, Instil Bio, Vedanta Biosciences  Consulting or Advisory Role: Instil Bio, Shionogi (Immediate Family Member), Vedanta Biosciences  Research Funding: Merck, Checkmate Pharmaceuticals, CellSight Technologies, Zucero Therapeutics (Inst), GSK, Merck, Arcus Biosciences  Patents, Royalties, Other Intellectual Property: Application No.: 63/124,231, and Enteric Microbiotype Signatures of Immune-related Adverse Events and Response in Relation to Anti-PD-1 Immunotherapy  Dr. Jason Luke:  Stock and Other Ownership Interests: Actym Therapeutics, Mavu Pharmaceutical, Pyxis, Alphamab Oncology, Tempest Therapeutics, Kanaph Therapeutics, Onc.AI, Arch Oncology, Stipe, NeoTX   Consulting or Advisory Role: Bristol-Myers Squibb, Merck, EMD Serono, Novartis, 7 Hills Pharma, Janssen, Reflexion Medical, Tempest Therapeutics, Alphamab Oncology, Spring Bank, Abbvie, Astellas Pharma, Bayer, Incyte, Mersana, Partner Therapeutics, Synlogic, Eisai, Werewolf, Ribon Therapeutics, Checkmate Pharmaceuticals, CStone Pharmaceuticals, Nektar, Regeneron, Rubius, Tesaro, Xilio, Xencor, Alnylam, Crown Bioscience, Flame Biosciences, Genentech, Kadmon, KSQ Therapeutics, Immunocore, Inzen, Pfizer, Silicon Therapeutics, TRex Bio, Bright Peak, Onc.AI, Stipe, Codiak Biosciences, Day One Therapeutics, Endeavor, Gilead Sciences , Hotspot Therapeutics, SERVIER , STINGthera, Synthekine  Research Funding (Inst): Merck, Bristol-Myers Squibb, Incyte, Corvus Pharmaceuticals, Abbvie, Macrogenics, Xencor, Array BioPharma, Agios, Astellas Pharma, EMD Serono, Immatics, Kadmon, Moderna Therapeutics, Nektar, Spring bank, Trishula, KAHR Medical, Fstar, Genmab, Ikena Oncology, Numab, Replimmune, Rubius Therapeutics, Synlogic, Takeda, Tizona Therapeutics, Inc., BioNTech AG, Scholar Rock, Next Cure  Patents, Royalties, Other Intellectual Property: Serial #15/612,657 (Cancer Immunotherapy), and Serial #PCT/US18/36052 (Microbiome Biomarkers for Anti-PD-1/PD-L1 Responsiveness: Diagnostic, Prognostic and Therapeutic Uses Thereof)  Travel, Accommodations, Expenses: Bristol-Myers Squibb, Array BioPharma, EMD Serono, Janssen, Merck, Novartis, Reflexion Medical, Mersana, Pyxis, Xilio  Disclaimer:   The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions.  Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. 

Listen live weekday mornings 5:30am-9:00am on WGY

Today, on the Hudson Mohawk Magazine, We begin with talking to Liz Moran of NYPIRG about the new International Panel of Climate Change report Then, for our peace bucket, I talk with Rev. Felicia Parasaider of the Revolution of Love Ministry Later on, we hear about the CDTA and the Mohawk Hudson Land Conservancy's partnership called the Nature Bus After that, we hear about Thomas Indian School, the Native American boarding school that was in Buffalo. Finally, we finish with a segment by Willie Terry on Black August

Hudson Mohawk Magazine Producer, Sally Becker talks with Jaime Watson, the Director of Cooperate Communication at the CDTA, about the CDTA and the Mohawk Hudson Land Conservancy's partnership called the Nature Bus which launched in June. The Nature Bus runs every Saturday from 9 AM to 7 PM from now until September, 25th and anyone can ride for free. You can find the schedule for the Nature Bus here: https://www.cdta.org/sites/default/files/news_files/dx_naturebus_june21_0.pdf

Today, on the Hudson Mohawk Magazine, We begin with an interview with Blair Horner of NYPIRG about Governor Cuomo and the AG report on sexual harassment Then, for our peace bucket we talk about the 76th anniversary of the atomic bombing of Hiroshima on August 6, Later on, we hear about CDTA's newest mode of transportation, SCOOT, electric scooters. After that, in a Reclaiming History segment, Lovonia Mallory interviews artist and author Brandon Pilcher Finally, We finish with Willie Terry speaking to Margaret Kimberley of Black Agenda Report about the origins of Black August. A Black August event take place at Freedom Square on August 6.

Hudson Mohawk Magazine producer Sally Becker talked to Lindsey Garney the mobility manager at CDTA about the capital regions newest mode of transportation SCOOT, electric scooters. Garney talks about safety, traffic rules, how to use the scooters and more! You can find out more about CDTA's SCOOT on their website: https://scootcdta.com/

Did you know that Acrobatic Arts has a Maureen Johnson Professional Development Scholarship? This scholarship is awarded annually to one dance teacher who exemplifies a passion for professional development. The recipient of this scholarship receives full tuition to the Acrobatic Arts Module One Teacher's Certification Course. In this episode, Maureen talks about her life as a dance teacher, a studio owner and also provides some interesting information about the scholarship. Maureen Johnson owned and directed Martin School of Dance and Baton Twirling for 54 years. Throughout her extensive career, Maureen never stopped learning. Her drive for ongoing professional development is evident in the many organizations from which she achieved accreditation. These include RAD, ADAPT, CDTA, and WBTF, to name a few. Maureen encourages her students to always strive to further their education. As a result, she has created dance instructors who, like herself, value life long learning. www.acrobaticarts.com martindance.com

The Buttonista's Spicy Tuesday -  0:49 Behind the Scenes of Behind the Buttons - 6:55   “Can you post butts to Instagram?” - 9:38 A NEW Saratoga tradition? - 11:23 10 years later, could the TBD crew graduate high school today? - 14:51 CDTA's Two Wheels Deep  - 17:22 All Buttons Deep at the Saratoga Track? - 20:06

Albany County Legislator Sam Fein (Dist. 6) wants the CDTA to do a pilot to allow people to ride buses for free. He also discusses the ongoing problems with the Norlite hazardous waste incinerator. With Mark Dunlea for Hudson Mohawk Radio Network.

Mornings 5:30am-9:00am on WGY

Hello Capital Region! This is the Hudson Mohawk Magazine on WOOC-LP 105.3 FM Troy and WOOS-LP 98.9 FM Schenectady broadcasting from The Sanctuary for Independent Media in Troy. Today, on the Hudson Mohawk Magazine, First, Paul Smart brings us coverage of the CDTA’s new rapid bus line along the river between Albany's South End, Troy, Cohoes and Waterford. Then, we have another Reclaiming History segment at Chas G Burch Supply Co of Schenectady, a company that was founded in 1890. After that, Black Lives Matter activist Lukee Forbes joins Erika Diggs to discuss an event happening this weekend Then, Alexis Goldsmith interviews Lee Harris, the managing editor for the brand new nonprofit digital journalism publication, New York Focus. And to close out the show, Spencer Keable continues his series on controversial public health issues, in an interview with Masters of Public Health student Cecelia Guthrie on the topic of premature puberty But first, here are the headlines.

Representatives of CDTA have been attending community meetings of late, explaining their new rapid bus line along the river between Albany's South End, Troy, Cohoes and Waterford.

Registrovan još jedan slučaj infekcije korona virusom, ukupno 273. Crna Gora pristupila mehanizmu EU za brzu nabavku lijekova i medicinske opreme. Od ponoći jeftiniji benzin i lož ulje. Španija popušta mjere uvedene zbog epidemije, građevinska preduzeća i male prodavnice od danas mogu da nastave rad Povodom jučerašnje liturgije Srpske pravoslavne crkve u Podgorici, Milica Kovačević iz CDTa kaže da mjere za sprječavanje širenja korona virusa moraju da poštuju svi, pa i crkva. Poslušajte priču Slavena iz Sarajeva koji tvrdi da je preležao sve simptome korona virusa, ali doktori nijesu htjeli da ga testiraju.

It's wet February, and we finally talk about the peach mint, take a look at morning news explaining wealth inequality with pie, and discuss the dystopian ramifications from our totally democratic and effectual institution, The Supreme Court, ruling in favor of Trump’s Wealth Test for immigrants. For our wildflower, we bring some wonderful news though - the Capital District Transit Authority is using eminent domain to force the sale of a parking garage from a slumlord to be made into a bus station. Then, because we love you and all of humanity, we bring you Chapter 4 of Peter Kropotkin's Conquest of Bread: Expropriation.Bus Links: (https://www.timesunion.com/business/article/Funds-in-place-for-CDTA-s-new-bus-rapid-transit-15029404.php) & (https://www.bizjournals.com/albany/news/2020/01/30/cdta-troy-transit-center-eminent-domain-won.html)Let them eat Pie: (https://slate.com/news-and-politics/2020/02/watch-cbs-journalist-use-pie-illustrate-inequality.html)Support us on Patreon: (https://www.patreon.com/ironweeds)

This week the gang is #blessed with a guest: Justin Roczniak of Do Not Eat YouTube fame and acclaim. We discuss Tesla under-delivering their electric Ford Pintos, cars being just the absolute worst, some light history on urban transit is sprinkled throughout, and we ask: nuclear energy - hot or not? Wildflowers for the week are about how strikes are dope, and what soothing media opiates we consume to get through stressful work sessions.  Justin's YouTube: (https://www.youtube.com/user/donoteat01/featured)Justin's Patreon: (https://www.patreon.com/donoteat)CDTA electric buses: (https://www.metro-magazine.com/zero-emissions/news/735134/new-york-s-cdta-to-add-40-foot-new-flyer-battery-electric-buses)Tesla stock tanking: (https://www.marketwatch.com/story/tesla-stock-reels-after-electric-car-makers-missed-sales-2019-10-03)Tesla batteries are a fire risk: (https://www.cnbc.com/2019/10/04/tesla-battery-fire-issues-under-investigation-by-us-traffic-safety-agency.html)Amazon workers walking out: (https://www.vice.com/en_us/article/pa7qny/60-amazon-workers-walked-out-over-warehouse-working-conditions)Outro music - On Strike by GmacCash: (https://www.youtube.com/watch?v=uJOHvQ9cL38)Bonus content for those who review us or throw us a hammy! (https://www.buymeacoffee.com/ironweeds)

In today's episode of Backpacker Radio, we sit down with Teresa Martinez, the executive director at the Continental Divide Trail Coalition.  We talk all things CDT, including the future of the trail, the biggest threats to its continued development, Teresa's favorite stretch of trail, and way more.  We also talk through some layering strategies for the Appalachian Trail, and Chaunce gives us a primer on vlogging etiquette.  We close out the show by featuring your questions via Instagram. Subjects discussed in today's show include: Gossamer Gear Anniversary Video Use code "TREK15" at GossamerGear.com to save 15% Sawyer Permethrin Sawer Micro vs. Sawyer Squeeze Recommended AT base layer options for guys and ladies.  Interview with Teresa Martinez of the Continental Divide Trail Coalition Worked at the ATC Transition from the CDTA to CDTC The CDT is 3100 miles long, starts in boot heel of New Mexico to Glacier National Park in Montana - Mexico to Canada Logistics of entering Canada after CDT vs PCT What does job look like as executive director of CDTC Why there are fewer people on the CDT than on the PCT or AT Differences between the ATC and CDTC “Focus on protecting the corridor and everything else will follow” The CDT Corridor: congress created the CDT and said from the physical 18-24 inch tread of the trail, a 1/2 mile from either side of it - 1 mile wide - 1.9 million acres of land to protect experience around CDT What percent of the trail is complete today What are the threats to the trail  Teresa's favorite section of CDT That time Teresa had a gun pulled on her CDT Kickoff - April 26-28 Favorite book: Desert Solitaire by Edward Abbey Head to continentaldividetrail.org to donate or learn how you can volunteer Land and Water Conservation Fund New sponsor! Greenbelly.co  Use code "TREK15" at checkout to save 15% Trek Propaganda Vlogging Etiquette (by Chaunce!): Tips to not let your vlog affect other hikers’ experiences Emergency Q&A Mail Bag  5 Star Reviews KEEP AN EYE OUT FOR TRAIL CORRESPONDENTS TO DROP ON 2/8/19!!!   Have any praise, questions, praise, comments, praise or praise for Backpacker Radio?  Reach out to podcast@thetrek.co. Subscribe to this podcast on iTunes (and please leave us a review)!  Find us on Stitcher and Google Play. Support us on Patreon! A super big thank you to our Chuck Norris Award winner(s) from Patreon: Sawyer Products, Travis Smith, and S11N. A big thank you to our Cinnamon Connection Champions from Patreon: Gregory Gardner, Andre Oosthuizen, Randy Harter, and Peter Leven Follow The Continental Divide Trail Coalition, Backpacker Radio, The Trek, Chaunce, Badger, and Trail Correspondents on Instagram. Follow The Trek and Chaunce on YouTube. Follow The Trek on Facebook, Twitter and sign up for our newsletter. Intro music via.

Peter chats with CDTA CEO Carm Basile with leadership/management style, regionalization. Tune in to hear Peter and Carm.

The Context of White Supremacy welcomes the return of Dr. Amanishakete Ani. With research investigating pathological culture and thought in European systems, Dr. Ani uses her scholarship to resist White Supremacy and support black liberation. She last visited with us in February of this year to discuss the ongoing conflict involving three former University of Albany students. Alexis Briggs, Ariel Agudio and Asha Burwell were at the center of a 2016 melee on a CDTA bus. The young ladies reported being assaulted by a gang of intoxicated Whites. However, the three black females were the only people charged with criminal offenses. Judge Roger McDonough, one of the judges involved with this case, offers another example of White judicial power over Black lives. After a year of court cases and punitive action from the school, none of the ladies are enrolled at the University of Albany. We'll discuss the aftermath of this event and how it impacted their lives. We'll also review how the University allegedly retaliated against Dr. Ani - who advocated relentlessly for these young ladies and indicted the schools Racist conduct. #AnswersForMiriamCarey INVEST in The COWS - http://paypal.me/GusTRenegade CALL IN NUMBER: 641.715.3640 CODE 564943#

The Context of White Supremacy welcomes Dr. Amanishakete Ani. An assistant professor at the University of Albany in New York, Dr. Ani examines pathological culture and thought in European systems, resistance against Racism/White supremacy, and women's health and child birth. Dr. Ani is just one of the University of Albany faculty members who mobilized to support a trio of black female scholars who reported being verbally and physically attacked by a drunken White mob on a CDTA public bus in January of 2016. The incident received a large amount of attention; Hillary Clinton spoke about the matter during her run for president. But weeks later, the three black females were charged with assault and filing a false report. We discussed this case in detail with one of the filmmakers of, INDEFENSIBLE: The Wrongful Prosecution of the Albany Three. We'll ask Dr. Ani about the case and if her public support of these accused black scholars has caused her any problems. #AnswersForMiriamCarey INVEST in The COWS - http://paypal.me/GusTRenegade CALL IN NUMBER: 641.715.3640 CODE 564943# The C.O.W.S. archives: http://tiny.cc/76f6p

We’re talking about coping with diabetes, depression and feelings of shame during the holidays on December’s Diabetes Late Nite with musical inspiration from Leona Lewis. ‘Tis the season for family, festivity, and temptations that may disrupt daily diabetes health routines. That means it's also the season when eating healthy, staying active, and taking medication on schedule is harder to do.  The added stress and anxiety of staying on track with your diabetes health may cause even those who are usually content to experience loneliness, anxiety and a lack of fulfillment. Studies show that people with diabetes have a greater risk of depression than people without diabetes. Just like denial, depression can get you into a vicious cycle. It can block good diabetes self-care. “I have a best friend who has severe depression, who takes medication and still struggles, so I know how bad it can be,” says Leona Lewis. She describes herself as having “highs and lows” brought on by circumstance, not a clinical illness. In retrospect, frustrated and anxious might have been better terms to use, but she declines to dwell on it. If you are feeling symptoms of depression, don't keep them to yourself. First, talk them over with your doctor. Guests include Diabetes Alert Dog expert, Debby Kay CDT, CDTA, PDTI, Megrette Fletcher, MEd, RD, CDE, the Charlie’s Angels of Outreach, Janis Roszler RD, CDE, LDN, Emmy winning Producer, Linda Bracero Morel, Poet Lorraine Brooks and Mama Rose Marie. Plus, we’re giving away 6 months access to mySugr Pro in our INSTANT WINNER challenge.   Throughout the podcast we will be featuring music from Leona Lewis’ “Christmas, with Love” album courtesy of SONY Music.

The Context of White Supremacy reviews the film, INDEFENSIBLE: The Wrongful Prosecution of the Albany Three. The filmmakers will join us to re-examine an important incident from the beginning of 2016. Three black female University of Albany students, Ariel Agudio, Asha Burwell, and Alexis Briggs, reported that a mob of drunken White passengers assailed them on a CDTA public bus. Many expressed outrage about the incident, including presidential candidate Hillary R. Clinton, who posted, "There's no excuse for racism and violence on a college campus." However, weeks after the incident, university police publicized segments of video. Officials concluded the footage absolved the White passengers of any wrongdoing and proceeded to charge the three black females with assault and filing a false report. The three were indicted in May. "The University of Albany expelled Agudio and Burwell and suspended Briggs for two years. INDEFENSIBLE "examines the ways both race and racism are viewed," and highlights "the inherent problems in allowing the benefactors of racism to define and legitimize what constitutes a racially motivated act." We'll interrogate how this case has been reported and where things currently stand. #AnswersForMiriamCarey INVEST in The COWS - http://paypal.me/GusTRenegade CALL IN NUMBER: 641.715.3640 CODE 564943# The C.O.W.S. archives: http://tiny.cc/76f6p

Eukaryotic gene transcription is highly complex and regulation occurs at multiple stages. RNA Polymerase II (Pol II) is recruited to promoter regions of the DNA to initiate transcription. Shortly after initiation, Pol II exchanges initiation factors for elongation factors. After Pol II passes termination signals, the RNA is cleaved and Pol II eventually released from the DNA template. pre-mRNAs are polyadenylated and exported to the cytosol for translation and ultimately degradation. Mechanisms regulating transcription have been studied extensively, but mechanisms of mRNA degradation are less well understood. To monitor mRNA synthesis and degradation, we developed the comparative dynamic transcriptome analysis (cDTA). cDTA provides absolute rates of mRNA synthesis and decay in Saccharomyces cerevisiae Sc cells with the use of Schizosaccharomyces pombe Sp cells as internal standard. We show that Sc mutants can buffer mRNA levels and that impaired transcription causes decreased mRNA synthesis rates compensated by decreased decay rates. Conversely, impairing mRNA degradation causes decreased decay rates, but also decreased synthesis rates. Thus, although separated by the nuclear membrane, transcription and mRNA degradation are coupled. In addition to regulated mRNA synthesis, pervasive transcription can be found throughout the genome, governed by an intrinsic affinity of Pol II for DNA. These divergent noncoding RNAs (ncRNAs) stem to a large extent from bidirectional promoters. However, global mechanisms for the termination of ncRNA synthesis that could act as a transcriptome surveillance mechanism are not known. It is also unclear if such a surveillance system protects the transcriptome from deregulation. Here we show that ncRNA transcription in Sc is globally restricted by early termination which relies on the essential RNA-binding factor Nrd1. Depletion from the nucleus results in Nrd1-unterminated transcripts (NUTs) that originate from nucleosome-depleted regions (NDRs) throughout the genome and can deregulate mRNA synthesis by antisense repression and transcription interference. Transcriptome-wide Nrd1-binding maps reveal divergent NUTs at essentially all promoters and antisense NUTs in most 3’-regions of genes. Nrd1 preferentially binds RNA motifs which are enriched in ncRNAs and depleted in mRNAs except in some mRNAs whose synthesis is controlled by transcription attenuation. These results describe a mechanism for transcriptome surveillance that selectively terminates ncRNA synthesis to provide promoter directionality and prevent transcriptome deregulation

So far, much attention has been paid to regulation of transcription. However, it has been realized that controlled mRNA decay is an equally important process. To understand the contributions of mRNA synthesis and mRNA degradation to gene regulation, we developed Dynamic Transcriptome Analysis (DTA). DTA allows to monitor these contributions for both processes and for all mRNAs in the cell without perturbation of the cellular system. DTA works by non-perturbing metabolic RNA labeling that supersedes conventional methods for mRNA turnover analysis. It is accomplished with dynamic kinetic modeling to derive the gene-specific synthesis and decay parameters. DTA reveals that most mRNA synthesis rates result in several transcripts per cell and cell cycle, and most mRNA half-lives range around a median of 11 min. DTA can monitor the cellular response to osmotic stress with higher sensitivity and temporal resolution than standard transcriptomics. In contrast to monotonically increasing total mRNA levels, DTA reveals three phases of the stress response. In the initial shock phase, mRNA synthesis and decay rates decrease globally, resulting in mRNA storage. During the subsequent induction phase, both rates increase for a subset of genes, resulting in production and rapid removal of stress-responsive mRNAs. In the following recovery phase, decay rates are largely restored, whereas synthesis rates remain altered, apparently enabling growth at high salt concentration. Stress-induced changes in mRNA synthesis rates are predicted from gene occupancy with RNA polymerase II. Thus, DTA realistically monitors the dynamics in mRNA metabolism that underlie gene regulatory systems. One of the technical obstacles of standard transcriptomics is the unknown normalization factor between samples, i.e. wild-type and mutant cells. Variations in RNA extraction efficiencies, amplification steps and scanner calibration introduce differences in the global intensity levels. The required normalization limits the precision of DTA. We have extended DTA to comparative DTA (cDTA), to eliminate this obstacle. cDTA provides absolute rates of mRNA synthesis and decay in Saccharomyces cerevisiae (Sc) cells with the use of Schizosaccharomyces pombe (Sp) as an internal standard. It therefore allows for direct comparison of RNA synthesis and decay rates between samples. cDTA reveals that Sc and Sp transcripts that encode orthologous proteins have similar synthesis rates, whereas decay rates are five fold lower in Sp, resulting in similar mRNA concentrations despite the larger Sp cell volume. cDTA of Sc mutants reveals that a eukaryote can buffer mRNA levels. Impairing transcription with a point mutation in RNA polymerase (Pol) II causes decreased mRNA synthesis rates as expected, but also decreased decay rates. Impairing mRNA degradation by deleting deadenylase subunits of the Ccr4–Not complex causes decreased decay rates as expected, but also decreased synthesis rates. In this thesis, we provide a novel tool to estimate RNA synthesis and decay rates: a quantitative dynamic model to describe mRNA metabolism in growing cells to complement the biochemical protocol of DTA/cDTA. It can be applied to reveal rate changes for all kinds of perturbations, e.g. in knock-out or point mutation strains, in responses to stress stimuli or in small molecule interfering assays like treatments with miRNA or siRNA inhibitors. In doing so, we show that DTA is a valuable tool for miRNA target validation. The DTA/cDTA approach is in principle applicable to virtually every organism. The bioinformatic workflow of DTA/cDTA is implemented in the open source R/Bioconductor package DTA.