We thank Garvan GWCCG, BTF for technical services. Note = "Funding Information: We thank the patients and their families. These results demonstrate that STAT3 GOF mutations cause effector CD8+ T cell oligoclonal accumulation and that these rogue cells contribute to autoimmune pathology, supporting the hypothesis that somatic mutations in leukemia/lymphoma driver genes contribute to autoimmune disease.", Leukocyte-restricted STAT3 GOF was sufficient and CD8+ T cells were essential for lethal pathology in mice. This subset also expressed genes for granzymes, perforin, interferon-γ, and Ccl5/Rantes and required NKG2D and the IL-15/IL-2 receptor IL2RB for maximal accumulation. STAT3 GOF mutations drove the accumulation of effector CD8+ T cell clones highly expressing NKG2D, the receptor for stress-induced MHC-class-I-related molecules. To investigate whether these mutations are the cause or consequence of CD8+ T cell clonal expansions and autoimmunity, we analyzed patients and mice with germline STAT3 GOF mutations. These results demonstrate that STAT3 GOF mutations cause effector CD8 + T cell oligoclonal accumulation and that these rogue cells contribute to autoimmune pathology, supporting the hypothesis that somatic mutations in leukemia/lymphoma driver genes contribute to autoimmune disease.Ībstract = "The association between cancer and autoimmune disease is unexplained, exemplified by T cell large granular lymphocytic leukemia (T-LGL) where gain-of-function (GOF) somatic STAT3 mutations correlate with co-existing autoimmunity. Leukocyte-restricted STAT3 GOF was sufficient and CD8 + T cells were essential for lethal pathology in mice. STAT3 GOF mutations drove the accumulation of effector CD8 + T cell clones highly expressing NKG2D, the receptor for stress-induced MHC-class-I-related molecules. To investigate whether these mutations are the cause or consequence of CD8 + T cell clonal expansions and autoimmunity, we analyzed patients and mice with germline STAT3 GOF mutations. The association between cancer and autoimmune disease is unexplained, exemplified by T cell large granular lymphocytic leukemia (T-LGL) where gain-of-function (GOF) somatic STAT3 mutations correlate with co-existing autoimmunity.
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The released hormone then has its effect on other organs. The release of hormones is regulated by other hormones, proteins or neuronal signals. One way this is achieved is through ‘feedback loops’. The endocrine system is a tightly regulated system that keeps the hormones and their effects at just the right level. The hormones can set off a cascade of other signaling pathways in the cell to cause an immediate effect (for instance, insulin signaling leads to a rapid uptake of glucose into muscle cells) or a more delayed effect (glucocorticoids bind to DNA elements in a cell to switch on the production of certain proteins, which takes a while to produce). If the hormone fits the cell wall, then it will work. A hormone can be thought of as a key, and its target site (such as an organ) has specially shaped locks on the cell walls. Homeostasis (constant internal balance).Ī hormone will only act on a part of the body if it ‘fits’.Some of the roles of the endocrine system include: The endocrine pancreas also releases hormones such as insulin and glucagon, which are hormones predominantly related to glucose metabolism, into the blood stream. It releases certain enzymes to aid in digestion delivered to the gut via the pancreatic duct. The pancreas is both an endocrine and exocrine organ. Exocrine glandsĪn exocrine gland, unlike an endocrine gland, is a gland that secretes substances (electrolytes, proteins or enzymes) straight to a target site via ducts or tube. The field is rapidly expanding due to understanding of the cellular pathways that hormones stimulate and the discovery of new hormones and their actions. This branch of medicine – relating to the study of the endocrine system – is called endocrinology and is practiced by endocrinologists. The endocrine system works with the nervous system and the immune system to help the body cope with different events and stresses. The hormone can also create changes in the cells of surrounding tissues (paracrine effect). Hormones can be thought of as chemical messages.įrom the blood stream, the hormones communicate with the body by heading towards their target cell to bring about a particular change or effect to that cell. Endocrine glands make chemicals called hormones and pass them straight into the bloodstream. Add to these the dozens of small and not-so-small towns along the coast, with alternating blue-collar ports and up-scale vacation retreats, and you have a great range of food, drink, and accommodations options. Last but certainly not least are the energizing cities- Seattle and Portland in the north, San Francisco in the middle, and Los Angeles and San Diego to the south-that serve as gateways to (or civilized respites from) the landscapes between them. While rarely as old as places on the East Coast, or as impressive as those in Europe, these diverse sites include the Spanish colonial missions of California, Russian and English fur-trading outposts, and the place where Lewis and Clark first sighted the Pacific after their long slog across the continent. The land of palm trees, beach boys, and surfer girls of popular lore really does exist, though only in the southernmost quarter of the state.Īlong with the overwhelming scale of its natural beauty, the West Coast is remarkable for the abundance of well-preserved historic sites-most of which haven’t been torn down, built on, or even built around-that stand as vivid evocations of life on what was once the most distant frontier of a new nation. The phenomenally beautiful coast-line of Northern California is rivaled only by the incredible coast of Big Sur farther south, beyond which stretches the beachfronts of Southern California. At the midway point, you pass through the great redwood forests of Northern California, where the tallest and most majestic living things on earth line the Avenue of the Giants, home also to some of the best (meaning gloriously kitsch) remnants of the golden age of car-borne tourism: drive-through trees, drive-on trees, houses carved out of trees, and much more. Heading south, after the rough-and-tumble logging and fishing communities of Washington State, you cross the mouth of the Columbia River and follow the comparatively peaceful and quiet Oregon coastline, where recreation has by and large replaced industry, and where dozens of quaint and not-so-quaint communities line the ever-changing shoreline. Cape Flattery on Washington’s Olympic Peninsula is the northwesternmost tip of the continental US. Most of the Pacific Coast is in the public domain, accessible, and protected from development within national, state, and local parks, which provide habitat for such rare creatures as mountain lions, condors, and gray whales. This 1,650-mile (2,655 km), mostly two-lane route takes in everything from temperate rainforest to near-desert. Road Trip USA’s Pacific Coast route begins at the northwest tip of the United States at Port Townsend near Olympic National Park, and remains within sight of the ocean almost all the way south to the Mexican border. All this may be true in small pockets, but the amazing thing about the Pacific Coast-from the dense green forests of western Washington to the gorgeous beaches of Southern California-is that it is still mostly wild, open, and astoundingly beautiful country, where you can drive for miles and miles and have the scenery all to yourself. Near the small town of Leggett (home to the famed Chandelier Drive-Thru Tree) US-101 transitions into scenic Highway 1, the most popular portion of this route and the classic Coastal California road trip.įor some reason, when people elsewhere in the country refer to the Pacific Coast, particularly California, it’s apparent that they think it’s a land of kooks, an overbuilt suburban desert supporting only shopping malls, freeways, and body-obsessed airheads. In Washington, Oregon, and at the northern end of California, the Pacific Coast route follows US Highway 101. While many travelers begin in Los Angeles and head north, driving the Pacific Coast Highway from north to south keeps you in the lane closest to the ocean. Before dying, Gus gives Jim and Aurora his ID badge and employee code to access crew-only areas, so he and Aurora can try to repair the ship. Gus attributes it to his hibernation pod's multiple failures. When Gus falls critically ill, the ship's automated medical suite, the Autodoc, diagnoses pansystemic necrosis and gives him hours to live. Gus realizes that Jim awakened Aurora Gus does not condone Jim's actions but understands, and tells Aurora that a "drowning man" (meaning the suicidal Jim) will grab onto any lifeline. If left unrepaired, the ship will inevitably fail, causing the passengers and crew to perish. They discover multiple cascading failures throughout the ship's systems, but the computer does not reveal the cause. Using Gus' personnel code, the group accesses the ship's bridge (which Jim unsuccessfully tried to breach). Sometime later, another pod failure awakens Gus Mancuso, a deck chief officer. She furiously rejects his apologies and avoids contact with him. A distraught and enraged Aurora berates, shuns, and even physically attacks Jim. Just before Jim intends to propose to Aurora, Arthur inadvertently reveals the truth about her awakening. Over the next year, the two fall in love. Resigned to the situation, Aurora, a writer and journalist, begins writing about her experience. Aurora, devastated at having to live out her life on the ship, unsuccessfully tries to re-enter hibernation. He tells Arthur to conceal what he has done. He eventually awakens her, letting her believe it was also a malfunction. He considers reviving her for companionship, but struggles doing so, knowing it is morally wrong and will circumvent her intended life on their destination planet. He views her video profile and is smitten. After only 30 years, an asteroid collision damages the ship despite its defense systems, causing a malfunction that awakens passenger James "Jim" Preston, a mechanical engineer, 90 years too early.Īfter a year of isolation, with only an android barman named Arthur for company, Jim grows despondent and contemplates suicide until he notices Aurora Lane, a beautiful young woman inside a pod. The Avalon, a sleeper ship transporting 5,000 colonists and 258 crew members in hibernation pods, is traveling from Earth to the planet Homestead II, a 120-year journey. It grossed $304 million worldwide and was nominated for Best Original Score and Best Production Design at the 89th Academy Awards. It received mixed reviews, with praise for Lawrence and Pratt's performances, Newman's musical score, and its visual style and production values, but was criticized for its plot and characters. Passengers premiered at the Regency Village Theater in Los Angeles on December 14, 2016, and was released theatrically in the United States by Columbia Pictures on December 21, 2016, in standard format and RealD 3D. It was produced by Village Roadshow Pictures, Start Motion Pictures, Original Film, LStar Capital, Wanda Pictures and Company Films, and was the last film from Columbia Pictures with the involvement of Village Roadshow Pictures. Lawrence, Pratt and Tyldum quickly joined the project, and filming took place from September 2015 to February 2016 in Atlanta. The script was written in 2007 by Spaihts, but languished in development hell with multiple actors attached and detached from it over the years until Sony Pictures Entertainment acquired its rights in late 2014. The film follows two passengers on an immense interstellar spacecraft carrying thousands of people to a colony 60 light years from Earth, when the two are awakened 90 years early from their induced hibernation. The supporting cast features Michael Sheen, Laurence Fishburne and Andy García. Passengers is a 2016 American science-fiction romance film directed by Morten Tyldum, written by Jon Spaihts and starring Jennifer Lawrence and Chris Pratt. Para-Beetle Heavy Parabeetles are larger versions of. The first iteration of the WWW was formed by Dr. Continued abuse of our services will cause your IP address to be blocked indefinitely. Stream Mega Man Zero 4 - Falling Down by Parabeetle X on desktop and mobile. World Three (, Wrudo Sur, written and abbreviated as The name World Three is a nod to the acronym for the World Wide Web. Please fill out the CAPTCHA below and then click the button to indicate that you agree to these terms. If you wish to be unblocked, you must agree that you will take immediate steps to rectify this issue. If you do not understand what is causing this behavior, please contact us here. If you promise to stop (by clicking the Agree button below), we'll unblock your connection for now, but we will immediately re-block it if we detect additional bad behavior. Overusing our search engine with a very large number of searches in a very short amount of time.Using a badly configured (or badly written) browser add-on for blocking content.
When you aren’t editing text, you can click on the text and it will play the audio, starting with the word you clicked on.Once the file is transcribed, click on the title of the file to view the transcript.Note that if you are interested in monitoring the transcription progress, you can click on the title of the file and scroll down to the bottom to find out how much has been transcribed so far.It may take Otter a bit of time to finish processing your episode (for me it took Otter about twenty minutes to transcribe an hour of podcast audio). While they are being transcribed they will say “In Processing…” in gray text below their title. At this point they will probably be in the process of being transcribed. The uploaded files should be listed at the top of Conversations list in the middle of the page.Once the file is uploaded the status will say “Success.” When you have all of your desired files successfully uploaded, exit out of the upload window by clicking on the “x” in the upper right of the window. If this happens, give it a few minuets to go to 100%. Note that the upload may pause for a while at 99%. It will upload the selected file or files.
“Commercial technology, being inherently broadly available, offers no national security advantages by definition.”ĭefense contractors could learn from commercial industry’s ability to take risks and speedily develop a product, but the government also needs to encourage innovation in the defense industrial base. “Commercial solutions, while an important ingredient in much of what gets done, in and of themselves are not the answer to our national security need for technological superiority and therefore should not be an excuse for further reductions in R&D,” he said. Because private companies are interested in profitability rather than meeting the military’s national security needs, they are ill equipped for creating technology such as hypersonic missiles, stealthy aircraft, offensive cyber capabilities or electronic jamming. Throughout his speech, Bush criticized the notion that private sector innovation can replace the research-and-development work done by traditional defense contractors. Instead, he implored the Pentagon to find a middle ground that would facilitate engagement between industry and government on IRAD but would preserve the independence of company projects. “If the fix is to try to put some controls into the front end of it, I think we end up in the wrong place.” Oftentimes when we fix something, we actually impose new costs, and that has a lot of oftentimes unintended consequences,” he said. “I think we have to be careful about the fix. While Bush praised Kendall’s work on BBP, he warned against fixing the IRAD problem with new regulations that could have unexpected results. The Pentagon’s chief acquisition executive and author of Better Buying Power, Frank Kendall, has said that the changes to IRAD arose because some companies had used such funding to grow their own intellectual property or gain a price advantage on a contract bid. You have to be thinking differently sometimes,” he said. “One of the most important principles is: Don’t always just listen to the customer. When companies have that freedom, they can make progress on innovative technologies more quickly. Northrop Grumman CEO Wes Bush agrees that the defense industry and Pentagon need to improve communication so that IRAD funding is focused on the most important areas, but sometimes there is a benefit to companies making decisions independently from government, he said during a May 26 discussion at the Center for Strategic and International Studies. Northrop Grumman Chairman, President and CEO Wes Bush. The Better Buying Power 3.0 guidance released this April would increase Defense Department oversight over government-funded IRAD dollars, requiring companies to have a department sponsor sign off on an IRAD project and submit a written report at its completion. The Pentagon’s new requirements for independent research and development (IRAD) could impede industry’s ability to move quickly on interesting and innovative technologies, Northrop Grumman’s CEO said today. Also, their website claims that you can choose format options based on the device you want the video to play on, but that wasn't true during our tests. For example, neither the history tab that's supposed to show recently formatted files, nor the list of recently used format options, show anything. It also lets you trim videos, pick a new name for the newly formatted video, import your own SRT file for subtitles, include an image or text watermark, convert with or without audio, change the video's resolution, and automatically close the program or shut down the PC after the conversions are finished.Īs great as this app is, there are some small issues we've noticed. You can convert in bulk and pick different settings for each video. Output Formats: MP4, MOV, AVI, WEBM, MKV, MPEG, and MP3 Input Formats: MP4, MOV, AVI, WEBM, MKV, MPEG, MPG, M2TS, WMV, FLV, F4V, M4V, OGV, TS, MTS, and VOB This video converter from Icecream Apps is relatively new, but it's very easy to use, is free from annoying "upgrade" ads, and works with all the typical video formats. Some other things we like are the per-video conversion settings so that you can have each video save to a different format even though you're converting them in bulk, the Device option when choosing a format so that you don't have to know what file type the device supports, the setting that can auto-delete the source file after the conversion, and the ability to work with audio formats too. A timer is at the bottom of the program that lets you choose what should happen when the conversions are finished, like exit the program or shut down the whole computer. There's a folder option so you can import several videos at once if you need to do that. Output Formats: MP4, MOV, MKV, AVI, WMV, M4V, XVID, ASF, DV, MPEG, VOB, WEBM, OGV, DIVX, 3GP, MXF, TS, TRP, MPG, FLV, F4V, SWF, M2TS Input Formats: MP4, MOV, MKV, AVI, WMV, M4V, XVID, ASF, DV, MPEG, VOB, WEBM, OGV, DIVX, 3GP, MXF, TS, TRP, MPG, FLV, F4V, M2TS is super easy to use, and is free from clutter. MiniTool has this free video converter that supports all the important video formats. It also runs on macOS 10.15 through 10.7.Ī bit slower to install than similar programs. This software can be installed on Windows 11, 10, 8, and 7. The only thing we didn't like was the window that appeared after each video conversion, suggesting that you upgrade to enable more output formats. While testing the program, it seemed to convert quickly, and without any troubles. Some other things we like: built-in editor to add subtitles and adjust color, doubles as a video player for discs and ISO-formatted videos, lets you burn videos to a disc, and the editable program settings-they let you do things like convert multiple videos in bulk (up to 5), change default video/audio settings, and define a new default output folder for converted files.Īny Video Converter supports more input video formats than any other video converter program we've used. If you don't know what video format to convert the file to so that it's usable on a specific device, the program handles that for you: just pick the device from a list. This program can be used to convert nearly any file to a variety of high-definition output formats that run on Apple, Android, Windows, and other devices. Output Formats: AAC, AC3, AIFF, APE, ASF, AU, AVI, DTS, FLAC, FLV, GIF, M2TS, M4A, M4V, MKV, MOV, MP2, MP3, MP4, MPG, OGG, OGV, SWF, WAV, WEBM, WMA, and WMV Input Formats: 3GP, ASF, AVI, DIVX, DVR-MS, F4V, FLV, M4V, MKV, MOV, MP4, MPEG, MPV, QT, RM, WMV, and others (over 100 total) If you need them, there are lots of advanced options too like batch conversion, file merging, and frame cropping. Some functions appear free until you try to use them.Īny Video Converter is a really easy to use free video converter-just choose your source file and output format and go. Begs you to upgrade when you convert files.Īttempts to install other programs during setup. Do not remove the cart from your residence.Who repairs a damaged cart or replaces a stolen cart? Be careful not to store it close to a furnace, fireplace, grill or any source of excessive heat. Store the cart in your garage or other location in compliance with your deed restrictions.(Ordinance, Chapter 21, Article II, Section 21-11 (f) for recycling and Section 21-22 (e) for garbage) Carts set out for collection must be removed from the collection location not later than midnight on the designated collection day.Do not allow children to play on, in or around the cart. Never sit, climb or stand on your cart.Simply rinse the inside of your cart with water from time to time to keep it clean.Get information on what and how to recycle, using the blue cart.Do not place anything on top of the cart.Call the Customer Call Center at 311 for proper disposal of dead animals. Do not place dead animals in garbage carts.Hot ashes, flammable or hazardous materials such as asbestos, oil, gas, antifreeze, solvents, brake fluid, transmission fluid, batteries, cleaning solvents, polishes, oven cleaner, pool chemicals, paint, paint thinner, paint stripper, spray paint, weed killer, pesticides, insecticides, sprays, dusts or poisons will NOT be collected with garbage.Construction or other materials such as sheetrock, roofing material, lumber, fencing, concrete, brick, rocks, stone, or dirt will not be collected with garbage.Pet waste should be bagged in order to avoid odor.We encourage you to use plastic bags for wet garbage.You are encouraged to recycle to save landfill space and ensure that your trash will fit into the cart. You must place the cart in the area adjacent to the curb by 7:30 a.m.Please do not place any items outside the cart, as they cannot be picked up. Your regular household garbage must be placed in the cart.What happens if I cannot roll the cart to the curb?įor those who are physically or medically unable to place the cart at the curbside, call the Customer Call Center at 311. On collection days that you set out both Household Trash (green cart) and Recycling (blue cart) simply place your blue cart next to your green cart, five feet apart.On collection days, we ask that you do not park your vehicle at the curb so that the truck can easily approach the cart(s).Corner houses should place carts on street address, not on the side street.The carts must be placed at the street curb, away from mailboxes, low hanging branches, shrubbery or other obstacles.Where should I place my carts and what about parking on collection days? National surveys indicate that a 96-gallon container is adequate for an average household.To verify your cart, call the Customer Call Center at 311. That number is assigned to individual street addresses, not individual customers: If a customer moves, the cart must remain at the assigned address. The cart's number can be found at the front of the cart.For a full list of materials that can be recycled in your Recycling Cart, see here. The blue cart is your Recycling Cart, also called the "smart cart". If you are interested in using grass clippings to help fertilize your lawn, see our Composting page. Yard waste includes grass clippings, weeds, leaves, mulch, small shrubs, limbs or other similar items. Garbage includes food waste, packaging, non-recyclable products found in your home. The green cart is your Garbage Cart, for garbage and yard waste.Which cart is for garbage and which cart is for recycling? Learn how to use and maintain your cart, as well as how to report damaged or stolen carts. Find answers to questions about your garbage or recycling cart. Or rather, the video shows how Radiohead’s “Spectre” might have appeared in the 24th Bond picture. You can hear Radiohead’s theme song as it appears in the opening of 2015’s Spectre (a reference, every Bond fan knows, to the global crime syndicate SPECTRE, or Special Executive for Counter-intelligence, Terrorism, Revenge and Extortion) in the video above. Three Bond pictures later, the producers must have realized that a haunted secret needs a haunted theme song, and so commissioned a piece of the ghostly yet hugely popular, at once cool and uncool work of Radiohead. As soon as he made his debut as Bond in 2006’s Casino Royal e, an adaptation of Fleming’ first novel, Craig immediately earned the distinction of the most troubled Bond yet. Scheduled for release this fall, the 25th Bond film No Time to Die features a theme song by the teenage singer Billie Eilish, whose dark-pop style may neatly suit the return performance by Daniel Craig. But despite all the changes of the leading man and the shifts in audience expectations over the decades, one of the franchise’s tasks has remained constant: to exude this Bondian uncool cool, whose distinctive tone must be set with just the right theme song. Thanks to the long-running Bond film series’ efforts to gradually increase the character’s complexity, the Bond who first appears in Ian Fleming’s 1953 novel Casino Royale may at first look simple, even cartoonish to readers of the 21st century. Though hardly a setter of youthful trends, he has always embodied masculine competence and unflappability of a relatively timeless and quintessentially British kind. Commander James Bond, CMG, RNVR - code name 007 - is both cool and uncool. |
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