Normally, cyclic AMP binds to the regulatory subunit of protein kinase A, which allows the catalytic subunit to phosphorylate the transcription factor CREB (cyclic AMP–responsive element–binding protein), leading to synaptic strengthening and, eventually, to memory formation. Directly or indirectly, toxic Aβ species interfere with the production of cyclic AMP by adenylate cyclase. These fragments aggregate to form relatively soluble oligomers that are thought to damage synapses, perhaps by lodging in the membrane (as shown). The processing of amyloid precursor protein by presenilin and β-secretase generates fragments of the β-amyloid peptide (Aβ) in the neuron. A recent study by Gong et al., 1 however, suggests a new way of thinking about memory deficits in patients with Alzheimer's disease and hints at new therapeutic opportunities. Because of this, we have generated only a few ideas about how to prevent damage to the brain. Although we now know a lot about the biochemistry of the disease, there are some gaps in our knowledge about the links between small changes in molecules at the surface of neurons and the symptoms of disease. We often do not realize how much we need something until it is gone - and Alzheimer's disease shows us how debilitating it is to lose memory. The most trusted, influential source of new medical knowledge and clinical best practices in the world. Information and tools for librarians about site license offerings. Valuable tools for building a rewarding career in health care. The authorized source of trusted medical research and education for the Chinese-language medical community. The most advanced way to teach, practice, and assess clinical reasoning skills. Information, resources, and support needed to approach rotations - and life as a resident. The most effective and engaging way for clinicians to learn, improve their practice, and prepare for board exams. NEW! Peer-reviewed journal featuring in-depth articles to accelerate the transformation of health care delivery.Ĭoncise summaries and expert physician commentary that busy clinicians need to enhance patient care. NEW! A digital journal for innovative original research and fresh, bold ideas in clinical trial design and clinical decision-making.
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Range and card animation (range is more like a conditional trigger, it carries out actions within an area based on if-statements).Detect using formula (can help with matching key points on a graph to values gotten from a formula).Chain and 3D Drag (more like CSS 3D perspective property).These are some of the interesting triggers we have worked with so far:īelow are some cool things that could be done with Protopie: Objects can either be created within Protopie using the basic shape tools or by importing them into Protopie from other design tools. The basic motif here is – interactivity.Īn object changes in state or provides some sort of feedback only if there’s a force acting on it (internally or externally) and this feeds back to “Object + Trigger + Feedback/Response” principle. Trigger is one of the most powerful tools on Protopie because it allows for incredible animation of digital elements/components, whilst keeping them responsive to touch, sound and motion. One of the most useful tools in Protopie is the Trigger. The process flow is simple, we begin the design in Adobe XD, which allows for some micro-interactions, but is limited to just basics and subsequently export to Protopie to do something a little more advanced and realistic. As you can imagine, this does wonders for project management and teamwork. We found that this model serves as the core foundation of ProtoPie’s user interface making it easy to build high-fidelity prototypes while making the learning curve truly interesting and simple and in all this, our designers do not need to learn how to code and developers can focus on actually building the product. Objects are the assets that will be moved or otherwise affected, Triggers are those that will move or change the Objects, and Responses are the changes that the Triggers create” ProtoPie allows users to generate Interactions with Objects, Triggers, and Responses. The prototypes that any designer should make are the ones that resemble the real deal, in regards to the way the user interacts.”Īs high fidelity interactions are key in the design process for modeling user interactions, the golden formula of ProtoPie surrounding interactions is simple:Īccording to the Protopie website “ProtoPie’s concept model is based on how objects move in the world instead of programming. The logic that drives ProtoPie is that high-fidelity prototyping should be done easily and quickly as seen in this quote by Tony Kim, founder of ProtoPie: “I believe in hi-fi prototyping. But First – An introductionĪsides the fact that we love the name Protopie, ProtoPie is a powerful high Fidelity prototyping tool that empowers designers to build the most advanced, highly interactive prototypes easily and quickly deployable and shareable on any device while utilizing smart device sensors. What prototypes do, is help make sure there’s no disparity between your expectation and reality for your product, this especially helps in projects where the endgame is to build a minimum viable product, you want to make sure that you’re making the right design decisions before going headfirst into development. This is where prototyping your products come in, highly interactive prototypes help you share your ideas clearly with your stakeholders to agree on what the end goals should be. You want to be reasonably sure you can bridge the gap of understanding with your stakeholders to make sure everybody involved in the product development is on the same page as to what value is being delivered. 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Two different versions of this rare Beanie Baby were made back in the ’90s: one has a blue-and-green outfit and one wears a rainbow costume. Both plushies go for as much as $40,000 on Etsy as a pair. They were released a few years before the 2008 American Presidential election, with Lefty the Donkey representing the Democratic Party and Righty the Elephant representing the Republican Party. What makes this pair so valuable is the fact that a technician in the United States had Hillary Clinton sign them for his two daughters, which has made them of particular interest to die-hard collectors. Even if you have one in perfect condition with no misprints, it could still fetch you over $1,000. Another was listed on eBay for over $25,000. One version, which included all of these errors, sold for over $42,000 at auction. In some cases, a few Valentinas have different colored noses. Some versions of Valentina the Bear featured misspelled information on the tag, while others were made with different pellets. For example, this ultra-rare Garcia is selling for an impressive $30,000 on Etsy. However, some of the Garcias that were made first - before mass production - or that have tag misprints reel in much more. Although Garcia hasn’t been known to rake in as much money as other celebrity-aligned bears, this Beanie Baby goes for several hundred dollars on average. Unofficially named after the late Grateful Dead lead guitarist and singer Jerry Garcia, Garcia the bear rocks a tie-dye look that’s not unlike the also highly sought-after Peace Bear. Still, we’ve rounded up twenty of the most valuable Beanie Babies out there. Sometimes, prices are driven up on auction sites like eBay, while private sellers or collectors may try to find a more standardized price. There’s no perfect recipe for determining the “real” value of Beanie Babies. 20 of the Rarest and Most Valuable Beanie Babies Much like other collectible items such as baseball cards or vinyl records, other variables that influence the value of a Beanie Baby include the amount produced, misprints on tags or on the plushies themselves, the type of pellet filling, and incorrect or variant colors or designs. It’s worth noting that some of the rarest Beanie Babies are most valuable by themselves, while others garner a high price if they are part of a set or collection (like the collection of Teenie Beanie Boos found in Happy Meals). Photo Courtesy: Bill Greenblatt/Getty Images One might wonder “what’s so special about owning a rare Beanie Baby?” The sheer exclusivity of having something so rare in one’s collection might be the main reason to snag one. Today, collectors are still searching for some of the most elusive and valuable Beanie Babies - and they’re willing to spend quite a bit of cash to do so. What Makes a Beanie Baby Rare or Valuable? released “The Beginning” the Bear on January 1, 2000, and opted to keep the Beanie Baby line alive and strong. However, widespread protests from fans across the world proved that there was still a demand for these toys. originally planned to halt production on the Beanie Baby line - even releasing “The End” the Bear in 1999 to mark the occasion. By the end of the ’90s, the craze began to die down. This was, of course, a significant price jump from the original retail price of $5. The result meant that passionate Beanie Baby buyers, a lot of whom were adults, ended up spending thousands of dollars in some cases to get their hands on rare Beanie Babies. Photo Courtesy: Chris Hondros/ Getty Images This wasn’t because demand was low in fact, the creator randomly pulled certain animals from the production line. In turn, this created substantial rareness in the market and an increase in demand among both casual and avid collectors alike. What contributed to this surge in value and the retirement of so many Beanie Babies? Ty’s warehouse of 370,000 square feet was hoarding over $100 million worth of product. Warner’s series of collectible animals became so sought-after in the mid-to-late-’90s that collectors were forking out thousands of dollars to get their hands on “retired” plushies - that is, ones that weren’t being produced for the general public any longer. The combination of one-to-one motor to leg ratio and advanced collision sensors result in an industry leading anti-collision system. Certifiably sturdy and strong both frames meet the ANSI/BIFMA X5.5-2021 standard for durability and stability. 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