Podcasts about NANOG

Michael Costello shares his career journey on today’s Total Network Operations. Currently on the Board of Directors at NANOG and a Distinguished Engineer at Saviynt, Michael talks about his early days learning the ropes as a junior network engineer, trying to start an ISP, his stint in graduate school, and a very interesting role at... Read more »

Michael Costello shares his career journey on today’s Total Network Operations. Currently on the Board of Directors at NANOG and a Distinguished Engineer at Saviynt, Michael talks about his early days learning the ropes as a junior network engineer, trying to start an ISP, his stint in graduate school, and a very interesting role at... Read more »

In this episode of PING, APNIC's Chief Scientist, Geoff Huston explores bgp "Zombies" which are routes which should have been removed, but are still there. They're the living dead of routes. How does this happen? Back in the early 2000s Gert Döring in the RIPE NCC region was collating a state of BGP for IPv6 report, and knew each of the 300 or so IPv6 announcements directly. He understood what should be seen, and what was not being routed. He discovered in this early stage of IPv6 that some routes he knew had been withdrawn in BGP still existed when he looked into the repositories of known routing state. This is some of the first evidence of a failure mode in BGP where withdrawal of information fails to propagate, and some number of BGP speakers do not learn a route has been taken down. They hang on to it. Because BGP is a protocol which only sends differences to the current routing state as and when they emerge (if you start afresh you get a LOT of differences, because it has to send everything from ground state of nothing. But after that, you're only told when new things come and old things go away) it can go a long time without saying anything about a particular route: if its stable and up, nothing to say, and if it was withdrawn, you don't have it, to tell people it's gone, once you passed that on. So if somehow in the middle of this conversation a BGP speaker misses something is gone, as long as it doesn't have to tell anyone it exists, nobody is going to know it missed the news. In more recent times, there has been a concern this may be caused by a problem in how BGP sits inside TCP messages and this has even led to an RFC in the IETF process to define a new way to close things out. Geoff isn't convinced this diagnosis is actually correct or that the remediation proposed is the right one. From a recent NANOG presentation Geoff has been thinking about the problem, and what to do. He has a simpler approach which may work better.

In this Telemetry News Now episode, hosts Phil Gervasi and Justin Ryburn discuss the latest in AI and networking, including the game-changing release of DeepSeek R1, a Chinese open-source AI model that rivals OpenAI and sent NVIDIA's stock plunging 17%. They also talk Cisco's new AI security solution, the stalled HPE-Juniper acquisition, TikTok's brief U.S. ban and reinstatement, and proposed tariffs on AI chip-making equipment. Plus, they highlight upcoming industry events like NANOG and APRICOT. Tune in for expert insights on AI's global impact, cybersecurity, and networking trends.

AWS Morning Brief for the week of January 27, with Corey Quinn. Links:Amazon Bedrock Flows announces preview of multi-turn conversation supportAmazon CloudWatch allows alarming on data up to 7 days oldAmazon S3 Tables are now available in five additional AWS RegionsAWS Client VPN announces support for concurrent VPN connectionsAWS CodeBuild now supports test splitting and parallelismAWS Marketplace introduces 8 decimal place precision for usage pricingAnnouncing AWS User Notifications GA on AWS CloudFormationEnhance the resilience of critical workloads by architecting with multiple AWS RegionsIntroducing cross-account targets for Amazon EventBridge Event BusesDiving deep into the new Amazon Aurora Global Database writer endpointAWS and NANOG join forces: Unlocking IPv6 potential with the IPv6 Clinic at NANOG 93Issue with AWS Sign-in IAM User Login Flow – Possible Username Enumeration (CVE-2025-0693)

Today, Calvin Smith of Answers in Genesis Canada, goes through all of the latest evidence for evolution. Either that or he goes through some of the evidence for evolution from the last century...there's a bit of a disconnect between the title and the actual content.Cards:AiG Canada is Lying for Clicks!

Today we chat with Leslie Daigle, CTO at Global Cyber Alliance, where she works on addressing cyber security challenges that require collective action and coordination among different stakeholders in the internet ecosystem.We peek into Leslie's career journey from being a computer science student to a programmer, a manager, a leader, and a collaborator in various internet-related organizations and projects, such as Bunyip, IETF, World IPv6 Day, and MANRS.In this talk, we will hear some of Leslie's insights and challenges in her work, such as how to frame problems in ways that matter to others, how to balance technical and human aspects, how to deal with imposter syndrome and career transitions, and how to support network operator groups like NANOG.-Individual contracts and consulting kept me entertained but really got to the point where I was like “well, this is fun, but I can't do big things on my own”It's much more interesting to be part of something.-Links: LinkedInTwitterFediverseThinking CatTechSequences--Thanks for being an imposter - a part of the Imposter Syndrome Network (ISN)! We'd love it if you connected with us on LinkedIn: https://www.linkedin.com/company/the-imposter-syndrome-network-podcast Make it a great day.

In this episode, we chat with Dave Siegel, a visionary technology leader who specializes in product strategies, network planning, business planning, network architecture and design, and leadership and management. Dave has been helping build the Internet since 1993 and has been self-employed since 2018.Dave shares his journey from starting his own ISP in Tucson to working at Global Crossing and Level 3, and how he became a consultant and a board member of NANOG. We also discuss Dave's passion for learning new things and how he applies his technical skills to different domains such as marketing, audio engineering, and video editing. He also gives us some tips and advice on how to deal with imposter syndrome and how to keep learning and growing.-Keep learning. Never stop learning.You just don't know how learning a thing is going to translate into whatever task you have to do next.-Dave's Links: LinkedInTwitterInstagramWebsiteNANOG--Thanks for being an imposter - a part of the Imposter Syndrome Network (ISN)! We'd love it if you connected with us at the links below: The ISN LinkedIn group (community): https://www.linkedin.com/groups/14098596/ The ISN on Twitter: https://twitter.com/ImposterNetwork Zoë on Twitter: https://twitter.com/RoseSecOps Chris on Twitter: https://twitter.com/ChrisGrundemann Make it a great day.

In this episode, we feature Matt Vitale, Sr. Network Automation Consultant at Network to Code with 13 years of experience in the networking field. Matt shares his personal journey of dealing with impostor syndrome, from landing his first network engineering job at Finish Line to presenting at NANOG 87 on overcoming impostor syndrome in network automation.  Join us as we hear the story of how a simple configuration error led to a major outage at Rackspace and about the importance of being open to making mistakes as also recognizing and celebrating your own mistakes.  -“I realized that more people felt imposter syndrome than I realized. I always thought I was alone, or it was just me and one other person that I'm close with. And it turns out that a lot of people do. I think even just bringing that kind of awareness, really can at least help open conversations” -Matt's Links:  LinkedIn  NANOG 87 Presentation (video)  NANOG 87 Presentation (slides) --Thanks for being an imposter - a part of the Imposter Syndrome Network (ISN)! We'd love it if you connected with us at the links below: The ISN LinkedIn group (community): https://www.linkedin.com/groups/14098596/ The ISN on Twitter: https://twitter.com/ImposterNetwork Zoë on Twitter: https://twitter.com/RoseSecOps Chris on Twitter: https://twitter.com/ChrisGrundemann Make it a great day.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.01.20.524871v1?rss=1 Authors: Fojtik, P., Senfluk, M., Holomkova, K., Salykin, A., Gregorova, J., Smak, P., Pes, O., Raska, J., Stetkova, M., Skladal, P., Sedlackova, M., Hampl, A., Bohaciakova, D., Uldrijan, S., Rotrekl, V. Abstract: Precise control of pluripotency is a requirement for the safe and effective use of hPSCs in research and therapies. Here we report that pyruvate dehydrogenase upregulates histone H3 pan acetylation and levels of pluripotency marker NANOG in 5% O2. Pyruvate dehydrogenase (PDH) is an essential metabolic switch and a bottleneck for the glycolytic production of acetyl-CoA. Silencing of gene expression showed that PDH is regulated by the activity of its phosphatase PDP1. We show that PDP1 is sensitive to reactive oxygen species-mediated inactivation, leading to the downregulation of H3 pan acetylation and NANOG levels. Furthermore, we show that FGF2, a cytokine commonly used to maintain pluripotency activates pyruvate dehydrogenase through MEK1/2-ERK1/2 signaling pathway-mediated downregulation of ROS in 5% O2, thus promoting histone acetylation. Our results show the importance of pyruvate dehydrogenase in regulating energy metabolism and its connection to pluripotency. Furthermore, our data highlight the role of reactive oxygen species and redox homeostasis in pluripotency maintenance and differentiation. Highlights- PDP1-induced activation of PDH leads to increased histone H3 pan acetylation and NANOG levels in hPSCs - Reactive oxygen species (ROS) inactivate PDP1 and decrease histone H3 pan acetylation and NANOG levels in hPSCs - MEK1/2-ERK1/2 signaling-mediated downregulation of ROS in 5% O2 activates PDH in hPSCs Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=129 SRC="FIGDIR/small/524871v1_ufig1.gif" ALT="Figure 1" greater than View larger version (39K): org.highwire.dtl.DTLVardef@1d4717forg.highwire.dtl.DTLVardef@678234org.highwire.dtl.DTLVardef@195576borg.highwire.dtl.DTLVardef@19e5684_HPS_FORMAT_FIGEXP M_FIG C_FIG Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Welcome back to the Tech Policy Grind Podcast by the Internet Law and Policy Foundry. In this episode, Joe Catapano, ILPF Class 4 fellow interviews Edward McNair, Executive Director of the North America Network Operators Group (NANOG). We all know the role that lawyers and government officials play in contributing to tech policy, but how do the people that “make it work” (e.g. network operators, software engineers) help develop the rules of the road? NANOG is just one of many organizations that bring technical expertise to the table, whether it's feeding into formal policymaking processes at global multi-stakeholder bodies, or raising awareness with lawmakers. Hear how NANOG works to represent the needs and views of the Internet's technical communities. You can read Edward's full bio on the NANOG website. Coming soon from the Foundry: keep an eye out for the next round of applications to become a Foundry Fellow! If you'd like to sponsor an episode or propose a guest for the show, get in touch with us: foundrypodcasts@ilpfoundry.us If you'd like to support the show, consider donating to the Foundry; you can do so here.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.10.17.512504v1?rss=1 Authors: Meyer, K., Lammers, N. C., Bugaj, L. J., Garcia, H. H., Weiner, O. D. Abstract: YAP is a transcriptional regulator that controls pluripotency, germ layer specification, and proliferation. Different subsets of YAP target genes are engaged in each physiological setting, but how YAP selectively regulates different effectors in different contexts is not known. Here we use optogenetics to investigate how the levels and dynamics of YAP activation control its pluripotency effectors Oct4 and Nanog. We observe different thresholds for repression of Oct4 and Nanog, enabling differential control of both genes through YAP levels. Pluripotency factors also decode YAP dynamics. Oct4 preferentially responds to oscillatory YAP inputs that mimic endogenous pulsatile YAP dynamics. Using single-cell live imaging of Oct4 transcription and computational-theoretical analysis of transcriptional regulation, we demonstrate that YAP dynamics are decoded by an adaptive change sensor that modulates Oct4 transcription burst frequency. Our results reveal how the levels and timing of YAP activation enable multiplexing of information transmission for key regulators of cellular differentiation and pluripotency. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

MIT Engineers Test An Idea For A New Hovering Rover | Brighter Side News (01:28) Due to the lack of atmosphere, the moon and other airless bodies such as asteroids can build up an electric field.Because of direct exposure to the sun and surrounding plasma. Moon's electric charge is strong enough to levitate dust more than 1 meter above the ground. Engineers at NASA and elsewhere have recently proposed harnessing this natural surface charge to levitate a gliderMylar wings, which is a material that holds the same charge as surfaces on airless bodies.  Thinking of magnets, the same charged sides would repel causing a levitation effect  A design would likely be limited to small asteroids, as larger planetary bodies would have a stronger, counteracting gravitational pull. Or would it?MIT's rover could get around this The concept resembles a retro-style, disc-shaped flying saucer, and uses tiny ion beams to both charge up the vehicle and boost the surface's natural charge.Generates a relatively large repulsive force between the vehicle and the ground with a small amount of power  In an initial feasibility study, the researchers show that such an ion boost should be strong enough to levitate a small, 2-pound vehicle on the moon and large asteroids. Large asteroid using a 10-kilovolt ion source The Moon the same rover would need a 50-kilovolt source Design relies on the use of miniature ion thrusters, called ionic-liquid ion sources Using a basic disc model with ion thrusters Could achieve levitation of about one centimeter off the ground Co-author Paulo Lozano explains why levitation on a rover would be good:“With a levitating rover, you don't have to worry about wheels or moving parts … An asteroid's terrain could be totally uneven, and as long as you had a controlled mechanism to keep your rover floating, then you could go over very rough, unexplored terrain, without having to dodge the asteroid physically.”   MIT unveils the world's longest flexible fiber battery. You can weave and wash it in fabrics | ZME Science (08:01) Engineers at MIT have created a rechargeable lithium-ion battery in the form of very long fiber.Could be used to 3D print batteries in any shape. The proof of concept is 140 meters long, making it the longest flexible fiber battery thus far.Length is arbitrary according to the engineers since they could do much longer lengths. Fiber batteries are not new, however previously they have all the lithium and other key materials outside the fiber, which would leave them unprotected.This Fiber is the opposite with the new system embedding the battery inside the fiber  This provides a protective outside coating, which gives the fiber both stability and waterproofing. The thickness of the fiber device is only a few hundred microns, much thinner than any previous attempts at a fiber battery. To demonstrate the functionality of this proof of concept, the researchers used the fiber battery to power a “Li-Fi” communications system, the kind that uses pulses of light to transmit data rather than radio waves. Includes a microphone, pre-amp, transistor, and diodes The 140-meter-long battery fiber has a rated energy storage capacity of 123 milliamp-hours  Enough to power a smartwatch or phone.  Battery fibers could be woven to produce two-dimensional fabrics like those used for clothing, but could also be used in 3-D printing to create solid objects, such as casings.Because the system creates it all without having to add anything else it would be one-step printing.   Scientists Can Now Print Metal Objects That Are Only 25 Nanometers Long | Interesting Engineering (13:08) A group of scientists has set a new benchmark in 3D printing by succeeding in fabricating ultrasmall metal objects using a new technique. According to the team, their system can be used to make objects out of copper just 25 billionths of a meter in diameter (equivalent to 25 nanometres).Equivalent to 195 copper atoms in a row. Their electrochemical 3D printing technique fabricates complex conductive structures with nanometer resolution, and it could have potential applications in battery technology, microelectronics, and sensor technology. The new electrochemical technique could be used to print far smaller metal objects that have never been printed before. Dr. Dmitry Momotenko of a chemist at the University of Oldenburg talked on the printing method with Phys.org:“The technology we are working on combines both worlds — metal printing and nanoscale precision … 3D-printed catalysts with high surface area and special geometry to allow particular reactivity could be prepared for the production of complex chemicals.” Momotenko and his team are currently working towards improving the efficiency of electrical energy storage through three-dimensional electrodes.     Smart sutures to monitor deep surgical wounds | MedicalXPress (17:24) Monitoring surgical wounds after an operation is an important step to prevent infection, wound separation and other complications. However, when the surgical site is deep in the body, monitoring is normally limited to clinical observations or costly radiological investigations that often fail to detect complications before they become life-threatening. To detect wound complications as soon as they happen, a team of researchers from National University of Singapore (NUS) have invented a smart suture that is battery-free and can wirelessly sense and transmit information from deep surgical sites. The NUS team's invention has three key components: a medical-grade silk suture that is coated with a conductive polymer to allow it to respond to wireless signals; a battery-free electronic sensor; and a wireless reader used to operate the suture from outside the body. These smart small sensors can monitor multiple problems (i.e. Wound integrity, gastric leakage and tissue micromotions), while also providing healing outcomes which are equivalent to medical-grade sutures.For example, if the suture is broken, an external reader picks up a reduced signal due to a reduction in the length of the smart suture's antenna, alerting the attending doctor to take action. One advantage of these smart sutures is that their use involves minimal modification of the standard surgical procedure.  Similar to existing sutures, clips and staples, the smart sutures may be post-operatively removed by a minimally invasive surgical or endoscopic procedure when the risk of complications has passed. Assistant Professor John Ho, who lead the team, commented on the smart sutures capability & the effect it would have: "Currently, post-operative complications are often not detected until the patient experiences systemic symptoms like pain, fever, or a high heart rate. These smart sutures can be used as an early alert tool to enable doctors to intervene before the complication becomes life-threatening, which can lead to lower rates of re-operation, faster recovery, and improved patient outcomes."  In future, the team is looking to develop a portable wireless reader to replace the setup currently used, enabling surveillance of complications even outside of clinical settings. Additionally they want to increase the detection capabilities for detecting wound bleeding and leakage after gastrointestinal surgery.   Researchers uncover protein that reverses muscle aging | Brighter Side News (23:13) A University at Buffalo-led research team has shown that a protein, NANOG, is effective at reversing aging in skeletal muscle cells. Skeletal muscles are organs of the vertebrate muscular system that are mostly attached by tendons to bones of the skeleton.Longer than in the other types of muscle tissue, and are often known as muscle fibers. In a series of experiments with mice, researchers overexpressed NANOG in myoblasts, which are the embryonic precursors to muscle tissue. The myoblasts were senescent, meaning they were no longer able to divide and grow. The overexpression improved some of the primary characteristics associated with age-related deterioration of cells, including autophagy, energy homeostasis, genomic stability, nuclear integrity and mitochondrial function.Autophagy - Bodies' way of clearing out damaged cells Additionally there was an increase in the number of muscle stem cells in the muscle of prematurely aging mice.Demonstrating the feasibility of reversing cellular aging in the body The study's corresponding author Stelios T. Andreadis, PhD stated:“Our work focuses on understanding the mechanisms of NANOG's actions in hopes of discovering druggable targets in signaling or metabolic networks that mimic the anti-aging effects of NANOG. Ultimately, the work could help lead to new treatments or therapies that help reverse cellular senescence, and aid the many people suffering from age-related disorders.”  ----more---- Podcast Links: Website: https://thatscoolnews.com/ Review The Podcast: https://thatscoolnews.com/review Email List: https://thatscoolnews.com/email Follow On Social Media: Instagram: https://www.instagram.com/thatscoolnews/ Twitter: https://twitter.com/Thats_Cool_News  Join the Community: Discord: https://thatscoolnews.com/discord Facebook Group: https://thatscoolnews.com/group  

Jezzibell Gilmore is passionate about the internet as a vehicle for communication and collaboration. In this inspiring #NomadFuturist podcast, she shares an inspiring and entrepreneurial story that took her from fine arts to technology and the co-founding of PacketFabric. Gilmore hails from Beijing, China where one side of her family was deeply rooted in theater and the performing arts, and the other side was involved in academia and the sciences. As a teenager Gilmore came to the United States and was dropped off by her mother at a boarding school with her suitcases and dictionaries and told “I'll see you in six months and I hope you will be able to speak English.” In retrospect, Gilmore appreciates how this challenging experience increased her resilience.  After studying fine arts in college, Gilmore worked at a law firm. In the late 90's a friend invited her to join AboveNet, a fledgling internet company, describing the internet as “the printing press of today's world…allowing us to distribute information and proliferate it worldwide.” Gilmore was hooked. “I knew nothing about technology. I didn't know anything about the internet but what could be better than allowing people to gain access to information! I just jumped in with both feet and started in the industry.” After AboveNet, Gilmore worked at several tech companies in the networking space, in operations and then in business development. She immediately understood the tremendous potential of the internet to provide information and empower people throughout the world. This understanding has inspired her throughout her career. In 2015, Gilmore co-founded PacketFabric and received support for her Network-as-a-Service vision. “I felt that the Internet needed to be global, to be accessible for everyone…that access to infrastructure needed to happen automatically, flexibly, and on demand.” The company now operates in three continents with Gilmore serving as Chief Commercial Officer. She discusses the passion that drives her and her colleagues. “I'm very lucky. I surround myself with people who are equally passionate about what we are doing…my spouse and all my friends and the people that I work with, we all circle around the axis of making the internet and the world a better place.” Gilmore is always engaging with new technologies and platforms, reading, and listening, learning, and absorbing information.  She encourages others to reach out, to not be held back by self-doubt. Despite being a natural introvert, Gilmore has pushed beyond her natural proclivities and is constantly communicating with friends and colleagues.  “Pushing your boundary as an individual is really important…We're not alone. Nobody succeeds by themselves. Again, it goes back to collaboration, communication, exchange of ideas. When we win, we win together!” Her advice to the young: “Believe in yourself. Whether you think something is right or wrong, follow your instinct.” Jezzibell Gilmore, co-founder and Chief Commercial Officer at PacketFabric, has over 20 years of experience working in the telecommunications industry. PacketFabric redefines how companies build and use network services. The PacketFabric Network-as-a-Service platform provides instant connectivity between colocation facilities, to major cloud providers, and internet exchanges. Prior to co-founding PacketFabric in 2015, Jezzibell was an early-stage employee of AboveNet Communications and Akamai Technologies. She has also previously served as VP of Business Development for GTT, and as a NANOG board member.

«Una hecatombe poblacional pone en peligro a toda la especie. ¿Quién pensaría en aprovechar un desastre semejante para manipular a todos sus individuos?». En el programa de hoy, con el que iniciamos nuestra primera temporada de pódcast, ofrecemos a ustedes la interpretación actoral del microrrelato «Nanogénesis» y entrevistamos a su particular autor: Carlos Felipe Acevedo.

В 68-м выпуске подкаста для связистов гости из Arista Networks и «Плотность Света», уже докладывавшие в linkmeup. В гостях: Андрей Нуштаев. Системный инженер. Arista Networks.Леонид Ермилов. Системный инженер. Arista Networks.Сергей Панасюк. Коммерческий директор. Плотность Света.Про что: SDN в ЦОД,Сказ про строительство взрослых сетей,EOS. 1. Конференция solutions.arista.com/cloud-builders-emea 2. Презентация с NANOG про новые протоколы pc.nanog.org/static/published/meetings/NANOG74/1763/20181003_Martin_Routing_In_Dense_v1.pdf Скачать файл подкаста Url podcast:https://archive.org/download/linkmeup-V068/linkmeup-V068.mp3

В 68-м выпуске подкаста для связистов гости из Arista Networks и «Плотность Света», уже докладывавшие в linkmeup. В гостях: Андрей Нуштаев. Системный инженер. Arista Networks.Леонид Ермилов. Системный инженер. Arista Networks.Сергей Панасюк. Коммерческий директор. Плотность Света.Про что: SDN в ЦОД,Сказ про строительство взрослых сетей,EOS. 1. Конференция solutions.arista.com/cloud-builders-emea 2. Презентация с NANOG про новые протоколы pc.nanog.org/static/published/meetings/NANOG74/1763/20181003_Martin_Routing_In_Dense_v1.pdf Скачать файл подкаста Url podcast:https://archive.org/download/linkmeup-V068/linkmeup-V068.mp3

В 68-м выпуске подкаста для связистов гости из Arista Networks и «Плотность Света», уже докладывавшие в linkmeup. В гостях: Андрей Нуштаев. Системный инженер. Arista Networks.Леонид Ермилов. Системный инженер. Arista Networks.Сергей Панасюк. Коммерческий директор. Плотность Света.Про что: SDN в ЦОД,Сказ про строительство взрослых сетей,EOS. 1. Конференция solutions.arista.com/cloud-builders-emea 2. Презентация с NANOG про новые протоколы pc.nanog.org/static/published/meetings/NANOG74/1763/20181003_Martin_Routing_In_Dense_v1.pdf Скачать файл подкаста

Chemotherapeutic treatment of hepatocellular carcinoma often leads to chemoresistance during therapy or upon relapse of tumors. For the development of better treatments, a better understanding of biochemical changes in the resistant tumors is needed. Therefore, especially in vivo models are very important tools to generate standardized cell-material, which can be examined by high throughput techniques. Thus, it should be possible to find new targets for therapy or even for diagnostic. This thesis focusses on the characterization of the in vivo chemoresistant human hepatocellular carcinoma HUH-REISO established from a metronomically cyclophosphamide (CPA) treated HUH7 xenograft mouse model. First step of the work was the establishment of the xenograft mouse model. SCID mice bearing subcutaneous HUH7 tumors were treated i.p. with 75 mg/kg CPA every six days. After 10 weeks of response to the therapy, the tumor growth relapsed and tissue grew with very fast doubling time again, despite of ongoing treatment. This aggressive manner of growth under therapy could be also observed in a re-implantation study where the reisolated CPA chemoresistant HUH-REISO tumors grew without a lag phase, indicating an endogenous imprinted component. To evaluate this, tumors were examined by immunohistochemistry, a functional blood-flow Hoechst dye assay, and qRT-PCR for ALDH-1, Notch-1, Notch-3, HES-1, Thy-1, Oct-4, Sox-2 and Nanog mRNA levels. Histochemical analysis of HUH-REISO tumors revealed significant changes in host vascularization of tumors and especially in expression of the tumor-derived human endothelial marker gene PECAM-1/CD31 in HUH-REISO in comparison to parental HUH-7 cells and in vivo passaged HUH-PAS cells (in vivo grown without chemotherapeutic CPA pressure). The pronounced network of host murine vascularization in parental HUH-7 tumors was completely substituted by a network of human and murine vessel-like structures in HUH-REISO tumors under therapy. In addition, cell lines of these tumors were analyzed in endothelial trans-differentiation studies on matrigel. In those studies with limited oxygen and metabolite diffusion, followed by a matrigel assay, only the chemoresistant HUH-REISO cells exhibited tube formation potential and expression of human endothelial markers ICAM-2 and PECAM-1/CD31. Such a trans-differentiation capacity requires a lineage of cells with pluripotent capacities like so called tumor stem cells. Indeed, I could show in a comparative study on stemness and plasticity markers that Thy-1, Oct-4, Sox-2 and Nanog were upregulated in resistant xenografts. Furthermore, under therapeutic pressure by CPA, tumors of HUH-PAS and HUH-REISO displayed regulations in Notch-1 and Notch-3 expression, which I could also show by qRT-PCR. Notch-1 raised in HUH-PAS under therapeutic pressure, meanwhile it was conversely regulated in comparison to Thy-1, Oct-4, Sox-2 and Nanog in HUH-REISO. In both groups Notch-3 was inducible by 2 times CPA treatment and fell back on base level after further four therapeutic cycles in HUH-REISO. To conclude all these finding: chemoresistance of HUH-REISO was not manifested under standard in vitro, but only under in vivo conditions. HUH-REISO cells showed increased pluripotent capacities and the ability of trans-differentiation to endothelial like cells in vitro and in vivo. These cells expressed typical endothelial surface marker and functionality. Although the mechanism behind chemoresistance of HUH-REISO and involvement of plasticity remains to be clarified, we hypothesize that the observed Notch regulations and upregulation of stemness genes in resistant xenografts are involved in the observed cell plasticity.

Over the past year the Government has unveiled an audacious programme under the banner of Genomics England, aiming to sequence the genomes of 100,000 people affected by cancer and rare genetic diseases. We take a look at some of the practical and ethical issues around the project. Plus, our gene of the month comes from the land of the forever young. Like this podcast? Please help us by supporting the Naked Scientists

Slides here: https://defcon.org/images/defcon-22/dc-22-presentations/Mahjoub-Toonk-Reuille/DEFCON-22-Mahjoub-Reuille-Toonk-Catching-Malware-En-Masse-DNS-IP-Style-UPDATED.pdf Additional Materials available here: https://defcon.org/images/defcon-22/dc-22-presentations/Mahjoub-Toonk-Reuille/DEFCON-22-Mahjoub-Reuille-Toonk-Catching-Malware-En-Masse-DNS-IP-Style-WP.pdf Catching Malware En Masse: DNS and IP Style Dhia Mahjoub SENIOR SECURITY RESEARCHER, OPENDNS Thibault Reuille SECURITY RESEARCHER, OPENDNS INC Andree Toonk MANAGER OF NETWORK ENGINEERING, OPENDNS The Internet is constantly growing, providing a myriad of new services both legitimate and malicious. Criminals take advantage of the scalable, distributed, and rather easily accessible naming, hosting and routing infrastructures of the Internet. As a result, the battle against malware is raging on multiple fronts: the endpoint, the network perimeter, and the application layer. The need for innovative measures to gain ground against the enemy has never been greater. In this talk, we will present a novel and effective multi-pronged strategy to catch malware at the DNS and IP level, as well as our unique 3D visualization engine. We will describe the detection systems we built, and share several successful war stories about hunting down malware domains and associated rogue IP space. At the DNS level, we will describe original methods for tracking botnets, both fast flux and DGA-based. We use a combination of fast, light-weight graph clustering and DNS traffic analysis techniques and threat intelligence feeds to rapidly detect botnet domain families, identify new live CnC domains and IPs, and mitigate them. At the IP level, classical reputation methods assign “maliciousness” scores to IPs, BGP prefixes, or ASNs by merely counting domains and IPs. Our system takes an unconventional approach that combines two opposite, yet complementary views and leads to more effective predictive detections. (1) On one hand, we abstract away from the ASN view. We build the AS graph and investigate its topology to uncover hotspots of malicious or suspicious activities and then scan our DNS database for new domains hosted on these malicious IP ranges. To confirm certain common patterns in the AS graph and isolate suspicious address space, we will demonstrate novel forensics and investigative methods based on the monitoring of BGP prefix announcements. (2) On the other hand, we drill down to a granularity finer than the BGP prefix. For this, we zero in on re-assigned IP ranges reserved by bad customers within large prefixes to host Exploit kit domains, browlock, and other attack types. We will present various techniques we devised to efficiently discover suspicious smaller ranges and sweep en masse for candidate suspicious IPs. Our system provides actionable intelligence and preemptively detects and blocks malicious IP infrastructures prior to, or immediately after some of them are used to wage malware campaigns, therefore decisively closing the detection gap. During this presentation, we will publicly share some of the tools we built to gather this predictive intelligence. The discussion of these detection engines and “war stories” wouldn’t be complete without a visualization engine that adequately displays the use cases and offers a graph navigation and investigation tool. Therefore, in this presentation, we will present and publicly release for the first time our own 3D visualization engine, demonstrating the full process which transforms raw data into stunning 3D visuals. We will also present different techniques used to build and render large graph datasets: Force Directed algorithms accelerated on the GPU using OpenCL, 3D rendering and navigation using OpenGL ES, and GLSL Shaders. Finally, we will present a few scripts and methods used to explore our large networks. Every concept is intended to detect and highlight precise features and will be presented with its corresponding visual representation related to malware detection use cases. Dhia Mahjoub works on research and development problems involving DNS, security, big data analysis, and networks. He focuses on building fast predictive threat detection systems based on the monitoring and analysis of traffic and hosting infrastructures. Dhia holds a PhD in Computer Science from Southern Methodist University, Dallas with a specialty in graph theory applied on Wireless Sensor Networks. He has a background in Computer Networks with experience in writing sniffers and port scanners among other things. Dhia presented his research at BSides NOLA, APWG eCrime, BSides Raleigh, BotConf, BSides San Francisco, ISOI 13, SOURCE Boston and will be talking at the upcoming BSides NOLA and VirusBulletin. He is also member of the non-profit security research group MalwareMustDie helping track botnets and other malicious sources on the Internet. Twitter: @DhiaLite Thibault Reuille is a Security Researcher at OpenDNS Inc. His research is mainly focused on big data visualization. At a very young age, Thibault fell in love with the demo scene and everything related to computer generated art. He started to teach himself 3D graphics and went to EPITA school in Paris, France. He later joined the LSE, the computer security laboratory, for a total period of 4 years where he spent a lot of time breaking everything he could. He built a solid knowledge of reverse engineering, pen-testing, secure programming, exploit writing and many other (in)security related techniques. After obtaining his master's degree in 2010. Thibault decided to move to California and accepted a position at Nvidia Corporation. This is where he had the chance to refine his 3D graphics knowledge and to dig deep inside the GPU mechanisms and the OpenGL API. He stayed at this position for 4 years. Finally, Thibault found a new job at OpenDNS Inc. as a Security Researcher and has been working there since June 2013. He is developing a 3D engine capable of rendering large amount of data and extract intelligent patterns from it using advanced graph theory. He believes the combination of visualization, distributed computing and machine learning is the key to take computer intelligence to the next level. Thibault has given several presentations in world renowned conferences, such as: CanSecWest Vancouver (March 14, 2014) BSides SF (February 23, 2014) BayThreat 4 (December 6, 2013) You can consult some of his work here: http://labs.umbrella.com/author/thibault/ And some of his artsy work here : http://thibaultreuille.tumblr.com/ Twitter: @ThibaultReuille Andree Toonk is the manager of network engineering at OpenDNS. At OpenDNS Andree is responsible for the OpenDNS global Network architecture, development, implementation and operations of the OpenDNS infrastructure. Managing all aspects:transit, peering, anycast, DDOS mitigation, facilities, routing, switching, firewalls, etc. Andree is the founder and lead developer of BGPMon.net, where he specializes in BGP routing and BGP security incidents such as routing hijacks and large scale outages. Andree received his M.Sc. degree in System and Network Engineering from the University of Amsterdam. He has presented about network security at network engineering conferences around the world such as Nanog and Terena and Canheit. Twitter: @atoonk

Background: Chemotherapeutic treatment of hepatocellular carcinoma often leads to chemoresistance during therapy or upon relapse of tumors. For the development of better treatments a better understanding of biochemical changes in the resistant tumors is needed. In this study, we focus on the characterization of in vivo chemoresistant human hepatocellular carcinoma HUH-REISO established from a metronomically cyclophosphamide (CPA) treated HUH7 xenograft model. Methods: SCID mice bearing subcutaneous HUH7 tumors were treated i.p. with 75 mg/kg CPA every six days. Tumors were evaluated by immunohistochemistry, a functional blood-flow Hoechst dye assay, and qRT-PCR for ALDH-1, Notch-1, Notch-3, HES-1, Thy-1, Oct-4, Sox-2 and Nanog mRNA levels. Cell lines of these tumors were analyzed by qRT-PCR and in endothelial transdifferentiation studies on matrigel. Results: HUH-REISO cells, although slightly more sensitive against activated CPA in vitro than parental HUH-7 cells, fully retained their in vivo CPA chemoresistance upon xenografting into SCID mice. Histochemical analysis of HUH-REISO tumors in comparison to parental HUH-7 cells and passaged HUH-PAS cells (in vivo passaged without chemotherapeutic pressure) revealed significant changes in host vascularization of tumors and especially in expression of the tumor-derived human endothelial marker gene PECAM-1/CD31 in HUH-REISO. In transdifferentiation studies with limited oxygen and metabolite diffusion, followed by a matrigel assay, only the chemoresistant HUH-REISO cells exhibited tube formation potential and expression of human endothelial markers ICAM-2 and PECAM-1/CD31. A comparative study on stemness and plasticity markers revealed upregulation of Thy-1, Oct-4, Sox-2 and Nanog in resistant xenografts. Under therapeutic pressure by CPA, tumors of HUH-PAS and HUH-REISO displayed regulations in Notch-1 and Notch-3 expression. Conclusions: Chemoresistance of HUH-REISO was not manifested under standard in vitro but under in vivo conditions. HUH-REISO cells showed increased pluripotent capacities and the ability of transdifferentiation to endothelial like cells in vitro and in vivo. These cells expressed typical endothelial surface marker and functionality. Although the mechanism behind chemoresistance of HUH-REISO and involvement of plasticity remains to be clarified, we hypothesize that the observed Notch regulations and upregulation of stemness genes in resistant xenografts are involved in the observed cell plasticity.

Embryonic development represents a sophisticated multistep process. Hereby, specification, patterning and differentiation of cells and tissue need to be extremely well regulated in a temporo-spatial manner. This is based on repression and activation of a vast number of cell-type specific genes, but only a small number of transcription factors seem to be responsible for their regulation. The transcription factor network of Oct4, Sox2 and Nanog are thought to play an essential role in the maintenance of pluripotency and in timing the onset of differentiation. The importance of mouse Oct4 in the regulation of pluripotency is underscored by recent findings providing evidence that Oct4 is essential for reprogramming somatic cells. Nevertheless, little is known on the molecular function of this transcription factor during normogenesis. Given the extra uterine development of the embryos, the well-studied early development and the established manipulation methods like injection of RNA or DNA, Xenopus leavis offers an ideal model organism to study the role of Oct4 homologs in early development. In Xenopus laevis three Oct4 paralogs – Oct25, Oct60 and Oct91 – are known, which are similar in size and have a high sequence homology compared to mammalian Oct4. There are strong evidences that Xenopus Oct proteins and mammalian Oct4 share similar functions. To gain further insights into the function of Oct proteins I generated dominant activating- (VP16-Oct60), dominant repressing- (EnR-Oct60) and hormone inducible (GR-Oct60) transcription factor variants for all three Xenopus Oct proteins. Protein expression was verified in vitro as well as in vivo. Oct60 shows a unique expression pattern among Xenopus Oct proteins: Oct60 is maternally transcribed and its RNA is detectable in mature oocytes. Expression is downregulated in the gastrula, when the expression of other Xenopus POU proteins begins. Therefore, it is one of the earliest genes to be expressed. I decided to concentrate first efforts on Oct60. The transactivating functions of the Oct60 G.o.F. variants were tested in a luciferase assay on two different Oct4 reporter constructs in vivo. Oct60 and VP16-Oct60 acted as strong activators whereas EnR-Oct60 repressed both reporter constructs. By overexpression of Oct60 and its G.o.F. variants, several phenotypes were observed that affected distinct parts of the body. Beside impaired head differentiation, observed by overexpression of VP16-Oct60 and Oct60, a strong hyperpigmentation was observed by injection of EnR-Oct60 and Oct60. Additionally, EnR-Oct60 injected embryos showed hyperpigmented outgrowths in the trunk region. All injected embryos possessed a shortened body axis that was specifically curved depending on the injected mRNA. In situ hybridizations were performed to investigate the molecular mechanism of the observed phenotypic changes. Experiments revealed that all examined constructs promote neuroectodermal fate while repressing mesoderm formation. These results indicate that Oct60 plays an important role in the induction and specification of germ layer formation. By cloning and testing these different G.o.F. variants I accomplished to obtain important tools for further dissecting the molecular function of Oct4 homologs in Xenopus embryos.

Osteogenic differentiation of hMSC into osteoblasts is a prerequisite for subsequent bone formation. Numerous studies have explored osteogenic differentiation under standard tissue culture conditions, which usually employ 21% of oxygen. However, bone precursor cells such as hMSC reside in stem cell niches of low oxygen atmospheres. Furthermore, they are subjected to low oxygen concentrations when cultured on three dimensional scaffolds in vitro for bone tissue engineering purposes, and even more so after transplantation when vascularisation has yet to be established. Similarly, hMSC are exposed to low oxygen in the fracture microenvironment following bony injury. Recent studies revealed that hypoxic preconditioning improves cellular engraftment and survival in low oxygen atmospheres. In the present study we therefore investigated the osteogenic differentiation potential of hMSC under 2% O2 (hypoxia) in comparison to a standard tissue culture oxygen atmosphere of 21% (normoxia). The success of differentiation was validated through Alizarin red staining and RT-PCR analysis of osteoblast markers ALP and OPN. We assessed osteogenic differentiation of hMSC following hypoxic preconditioning to address whether this pretreatment is beneficial for subsequent differentiation under low oxygen tension. To validate our findings we carefully characterised the extent of hypoxia exerted on cells with respect to cell survival (WST assay) and proliferation (growth curve). Furthermore we also tried to elucidate the role of HIF-1 alpha with respect to osteogenic differentiation under hypoxia via silencing RNA and DFO, a pharmacological agent. Finally we tested whether an immortalized hMSC-line (SCP-1) would serve as a model system for hMSC. We found that hMSC proliferate better if cultured under 2% of oxygen. We confirmed that osteogenic differentiation of hMSC is indeed inhibited under hypoxia. We showed for the first time that hypoxic preconditioning of hMSC prior to osteogenic induction restores osteogenic differentiation of hMSC under hypoxia. HIF-1 alpha seemed not to play a significant role in osteogenic differentiation under hypoxia, as transiently knocking down of HIF-1 alpha in preconditioned samples did not show any differences in their osteogenic differentiation. Moreover stabilising Hif-1 alpha in hypoxic samples did not yield any osteogenic differentiation either substantiating the notion that HIF-1 alpha does not have a direct role in the osteogenic differentiation of hMSC under hypoxia. Together our data suggest that hypoxia favours stemness over differentiation by upregulating embryonic stem cell markers like OCT-4 and NANOG. Hypoxic preconditioning may help to restore the otherwise reduced osteogenic potential of hMSC, either within a hypoxic fracture environment or at the site of implantation of tissue engineered bone constructs. We therefore believe that hypoxic preconditioning is a helpful tool for successful regenerative cell-based therapies in bone tissue engineering. SCP-1 cells might be used as a model system for hMSC as they are easy to handle, can be cultured to a desired cell number within a very short period of time, are relatively inexpensive and above all do not go into senescence as seen with hMSC after approximately 20 passages. Apart from their distinct advantages SCP-1 cells still maintain the specific CD markers characteristic for hMSC and are able to differentiate into adipogenic, osteogenic and chondrogenic lineages. However for in vivo experiments in animals a constant monitoring of neoplastic transformation is mandatory

The hallmark of embryonic stem (ES) cells is their ability for self-renewal (capability of unlimited cell division without the loss of pluripotency) as well as for differentiation into all cell types of the adult organism. One factor supposed to be involved in self-renewal is the rapid proliferation rate of ES cells, which is coupled to an unusual cell cycle distribution with the majority of cells in S-phase and a very short G1-phase. This is linked to the lack of a functional G1/S-phase checkpoint, which allows the cells to enter the S-phase almost directly after mitosis. Generally, cells have to closely coordinate growth and cell cycle progression during proliferation to prevent premature division. One important factor for cell growth is ribosome biogenesis. In mature cells, disruptions in ribosome biogenesis are directly linked to the cell cycle machinery by a p53-dependent activation of the G1/S-phase checkpoint, leading to an arrest of cells in G1-phase. During this work, the function of the proteins Pes1, Bop1 and WDR12, which were shown previously to be involved in ribosome biogenesis of mature cell lines, was investigated in mouse ES cells. Moreover, a putative crosstalk between ribosome biogenesis and proliferation of ES cells was assessed. A high expression of Pes1, Bop1 and WDR12 was observed in ES cells, which strongly decreased during in vitro differentiation. Localization of the proteins was predominantly nucleolar and the formation of a stable complex (PeBoW-complex), including all three proteins, was experimentally validated in mature mouse cells as well as in mouse ES cells. The function and stability of the proteins seems to be dependent on incorporation into the PeBOW-complex, as protein levels were interdependent on each other and no free, non-incorporated proteins were observed, except for WDR12. According to their nucleolar localization, depletion of Pes1 and Bop1 were shown to inhibit maturation of the 28S rRNA and thereby the large 60S ribosomal subunit. Further, impaired proliferation of ES cells was observed. Thus, the PeBoW-complex seems to be an essential factor for the rapid proliferation of ES cells and might therefore also be involved in self-renewal. However, first results suggest that the complex is not directly involved in the maintenance of pluripotency. No changes in the expression levels of pluripotency-genes like Nanog, KLF4 and Sox2 were observed. Moreover, alkaline phosphatase activity was equally detectable after depletion of Pes1 or Bop1 and no morphological changes within the ES cell colonies were observed. Impaired ribosome biogenesis is known to activate a p53-dependent checkpoint in mature cell lines, which leads to an arrest of cells in G1-phase. Treatment of mouse NIH3T3 cells with 5FU, a potent inhibitor of rRNA maturation, confirmed an activation of this checkpoint, leading to weak induction of the tumor suppressor p53, induction of the Cdk-inhibitor p21, an increase in active, hypo-phosphorylated Rb, and to accumulation of cells in the G1- and S-phase with an increase of cells in G1-phase. In contrast, ES cells showed strong induction of p53, but no induction of its target gene p21. The overall levels of Rb were strongly induced, but the ratio between inactive, hyper-phosphorylated Rb and active, hypo-phosphorylated Rb was not changed towards the active form. These results were observed upon 5FU treatment and upon depletion of Pes1 or Bop1. Hence, ribosomal stress does not lead to checkpoint activation via the p53-p21-Rb pathway in ES cells. Moreover, no robust accumulation of cells in G1-phase was observed. 5FU treated ES cells showed an accumulation of cells in S-phase instead. Whether this effect is regulated by the induced p53 needs further investigation. Overall, the results suggest that ES cells use different mechanisms as mature cells to coordinate their proliferation rate with ribosome biogenesis.

Ron Sheridan is Director of Business Development for DomainSponsor. Ron has deep experience in internet and online/new media sales and marketing, affiliate marketing and business development for technology companies. He also served as Vice President, Marketing and Sales of DSR Software and founded RGP to provide channel development services to microcomputer consumer software and hardware companies. Jothan leads a wrapup of the Domain Roundtable. Jothan Frakes is the Vice President of Business Development for Name Intelligence, operators of whois.sc and is the executive event producer for the current 2006 Domain Roundtable and 2005 Domain Roundtable Conferences. He has specialized in Domain Name technical operations and DNS since 1993, with a particular career focus on ccTLD and gTLD operations and the ccTLD industry, NANOG, and the ICANN process.