![]() In recent years, accumulating evidence has illustrated that Drp1 is implicated in the activation of NLPR3 inflammasome, and plays a crucial role in a variety of inflammatory disorders. Identification of novel therapeutic target is needed to improve the clinical outcomes in gouty arthritis.ĭynamin-related protein 1 (Drp1) is recognized as the master regulator of mitochondrial fission. In addition, the pro-oxidant, in particular mitochondrial reactive oxygen species (ROS), is also known to activate NLRP3 inflammasome. IL-1β further induces neutrophil articular infiltration, leading to joint pain. MSU crystals are taken up by macrophages and trigger the NLRP3 inflammasome activation, as well as the maturation and release of IL-1β. Compelling evidence has illustrated the key roles of NLRP3 inflammasome and the pro-inflammatory cytokine IL-1β in gouty arthritis. MSU crystals elicit inflammatory response which is principally mediated by macrophages and neutrophils. The precipitation of monosodium urate (MSU) crystals within joints is a well-accepted cause of gouty arthritis. Higher prevalence of gout has been observed in China, and the rising incidence and prevalence of gout have been found by each decade of life. Gouty arthritis is the most frequently diagnosed inflammatory arthritis globally. Conclusionĭeubiquitinase USP16 induced gouty arthritis via Drp1-dependent mitochondrial fission and NF-κB/NLRP3 signaling. Functional studies further showed that USP16 was highly expressed in MSU-stimulated macrophages and induced gouty arthritis via Drp1-dependent NLRP3 inflammasome activation. Mechanistically, USP16 mediated deubiquitination and stabilization of Drp1 through its direct interaction with Drp1. In addition, Drp1 activated NF-κB/NLRP3 signaling via modulating mitochondrial fission. Resultsĭrp1 was elevated in MSU-induced gouty arthritis model, and it induced gouty arthritis via NF-κB pathway and NLRP3 inflammasome activation. Co-IP and GST pull-down assay were used to detect the direct interaction between USP16 and Drp1, as well as the ubiquitination of Drp1. Mitochondrial structure and functions were assessed by transmission electron microscopy (TEM) and MitoSOX staining. Cytokine secretion was measured by ELISA assay, and antioxidant enzymes activities and LDH release were monitored using commercial kits. RT-qPCR and western blot were used to detect the expression of Drp1 and the key molecules in joint tissues and macrophages. Histological changes were assessed by H&E and IHC analysis. MethodsĪ mouse model of monosodium urate (MSU)-induced gouty arthritis and MSU-stimulated macrophages were established as in vivo and in vitro models, respectively. However, the biological role of Drp1 in gouty arthritis remains undefined. Dynamin-related protein 1 (Drp1), a regulator of mitochondrial fission, contributes to various inflammatory disorders via activating NLRP3 inflammasome. Gouty arthritis is the most frequently diagnosed inflammatory arthritis worldwide. ![]()
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![]() KeyShot HD now comes with unlimited real-time rendering and output resolution and remains priced at 995 USD. ![]() ![]() Keyshot Network Rendering v12.1.1.11 Free Downloadĭownload Keyshot Network Rendering 11 free latest full version offline direct download link full offline setup by clicking the below button. With the release of KeyShot 6, Luxion introduces new product structure and pricing for KeyShot HD and KeyShot Pro Editions. Processor: Intel Dual Core processor or later download portals for ZWSOFT users and other CAD software users from all. KeyShot is widely recognized as the best 3D rendering software for both Windows and Mac.Free Hard Disk Space: MB of minimum free HDD.Then, I'll guide you through a project beginning-to-end. Through bite-sized, easy-to-follow video courses, you'll get comfortable with KeyShot quickly. This is the course I wish I had 10 years ago. Software File Name: Keyshot-Network-Rendering-v12.1.1.11.rar This beginner-friendly video course is all you need to get started working in KeyShot.Software Name: Keyshot Network Rendering for Windows.Create/Sign in with your KeyShot Account and click ‘Next’ 5. Start KeyShot and select ‘Start a Trial’, then Next 4. Automatic Queue Management: KeyShot Network Rendering automatically manages the render queue, ensuring that jobs are delivered efficiently and completed as quickly as possible. Double-click the installer and follow the prompts 3.3 GPU mode appears on the Ribbon in KeyShot for NVIDIA GPUs built on Maxwell microarchitecture or newer and supports CUDA Compute Capability 5.0 or later found in the Quadro M6000 or GTX 980 and above. Priority Management: KeyShot Network Rendering supports priority management, allowing users to prioritize specific rendering jobs over others based on their importance. 2 For GPU rendering (KeyShot 9 and above) we recommend graphics cards with a minimum of 8 GB memory.Customizable Job Management: Users can customize how render jobs are distributed across the network, specifying which computers are used for rendering and how much processing each computer is assigned to.Simple Setup: Setting up KeyShot Network Rendering is simple and straightforward, with an intuitive user interface that guides users through the process.KeyShot (64-Bit) is an entirely CPU based standalone 3D rendering and animation system for. ![]()
![]() ![]() You assumes the role of the protagonist, a cab driver and your primary objective is to learn about the secret club and struggle to join it. According to the story, a mysterious group of urban street racers rule on the New York City called the Midnight Club. It is the first title in the series of Midnight Club and followed by Midnight Club 2. ![]() The game revolves around competitive street racing based on the movie The Fast and the Furious. Midnight Club: Street Racing is an Action, Racing, Single and Multiplayer video game created by Angel Studios and published by Rockstar Games. Fernbus Simulator includes core features such as Traffic Jams, Repaints, Evaluation Tool, Dynamic Weather, Day/Night Cycle, and more. In Free Play mode, the player can explore the environment freely and can move anywhere he wants. Using the customization, the player can modify his bus and can select the weather condition before starting the game from cloudy, sunny, dynamic, rainy, and snowy. At the beginning of the game, the player selects his bus and set out on an epic mission to make money. The game introduces the variety of buses such as Hannover, Erfurt, Dortmund, Erfurt, Dresden, Munich, Berlin, and more. It is set in the massive environment of the city and put the player in the role of the bus driver, who must drive his bus throughout the city to transport passenger from one place to another to earn money. Fernbus Simulator is a Realistic Driving Simulation supports Single-player mode, developed by TML-Studios and published by Aerosoft GmbH for Microsoft Windows. ![]() ![]() You may have seen Carmax's catchy TV commercials to let private owners know, "We Buy All The Cars" (old cars, new cars, even Purple Wizard Vans) and "We Buy Your Car Even If You Don't Buy Ours" ('WBYCEIYDBO'). A large share of them will be flagged for immediate auction disposal without being offered for sale to the public. That brings in about 22,000 vehicles, but not all them will qualify for resale on their lots due to age, mileage or condition. So, where does Carmax get the 58,000 cars they need every month to feed the machine? Here are their three primary sources: Trade-in OffersĪpproximately 35-40% of the 58,000 vehicles Carmax sells retail each month involves a buyer trade-in. That means on average, Carmax needs to replace (buy) approximately 58,000 vehicles each month to maintain inventory on its lots. A highly efficient used car dealership (like Carmax) will turn its retail inventory every 45 days. There is an old saying in sales, “you can’t sell apples from an empty apple cart.” Carmax the Buyer - Feed the MachineĪ recent search on Carmax’s website showed 86,807 vehicles for sale. Their business model requires a constant inflow of used vehicles from various sources, making Carmax the largest used car buyer in the country too. You may only see your local store in action, but Carmax the company is one huge “used cars for sale” machine that cranks out used vehicles across America.Ĭarmax’s core business is selling late-model cars, trucks, vans and SUVs for a profit. Now, magnify that by 195 corporate-owned large volume locations in dozens of unique retail markets. Keep in mind, running a single point medium-size used car operation is a high risk, capital intensive, process-oriented business. How the Carmax Model WorksĪt the heart of Carmax's success is an obsession with business discipline and process management. There is no question Carmax is good at what they do, but the million dollar question is, "w hen I need to sell my car, is there a way to beat Carmax's offer without giving up convenience?" Before answering that question, it is helpful to understand how Carmax really works. ![]() That makes them America's biggest used car dealer group. In fact, Carmax's annual sales (retail and wholesale) exceeded 1 million units for the first time in 2016. ![]() Since 1993, Carmax has become ‘The Auto Superstore' with 195 locations and more than 8 million used vehicles sold throughout the United States. ![]() ![]() ![]() After all, what is the point in making games people will enjoy if the reviewers will hate them and no one will buy games that the reviewers hate irrespective of their actual worth or potential? The outcome overall is that games will sometimes cater to what developers believe will get them a good review score instead of what fans will like. An even worse case than that is when someone starts an argument with another because the latter likes or dislikes something that a reviewer has given a negative judgment to, and the former does not have an opinion of their own but is making judgments based on what the reviewer said. In some of the more worse cases, this leads to people Praising Shows They Don't Watch or Complaining About Shows They Don't Watch. Not to mention, some reviewers often have a Bias Steamroller, which can also cause them to take points off of a work merely because they have certain pet peeves, or add points because they like the franchise. Oftentimes, reviewers will become rather jaded and tend to be a tad cold towards works that they don't particularly love years down the road. This mentality often hurts some works when people believe a reviewer's word to be law. Unfortunately, many seem to see reviews as the only means to obtain their information, even though far more objective outlets exist, many of which can not be bought like professional reviewers can. This is the reason for the "Nintendo Seal of Quality" - which wasn't supposed to mean "awesome game" so much as "playable game" and "Nintendo has licensed this game to be sold" (the first and second generations also had games that were not licensed by Atari, which was part of the problem as they never had to go through quality control - quality here meaning "playable"). This leads to many upset consumers who had to guess whether a game was any good and quickly became frustrated to discover they just put a lot of cash down for a Porting Disaster or imitation of an arcade game they thought they liked. ![]() One of the big problems of first and second generation video games was the general absence of any detailed information about games. What the critic finds to be So Okay, It's Average, you might find awesome because it is practically tailored to your tastes and desires in a game and the polar opposite happens as well, often leading to Hype Backlash, Critical Dissonance and It's Popular, Now It Sucks! situations.Ĭulturally speaking, this deference has existed for awhile, as aftershocks from The Great Video Game Crash of 1983. It's worth mentioning that reviews are not without biases. Another reason, perhaps, is that video games as a medium demand more time and attention from us than most other entertainment forms, so most of us need to be discriminatory in the games we play. However, over-reliance on reviews is just as common in areas where software piracy is ubiquitous. On the surface, one could say there's some logic behind all this - after all, purchasing a $60 game is a far riskier endeavor than buying a $15-20 book or a $10 movie ticket, so it makes sense that many people might look to something, even if it is a bad source. Naturally, this causes them to often have different tastes than ordinary gamers, and enjoying the product is at best only a small part of their rating and at worst isn't even considered. Worse still, professional reviewers are often just people with a job, and usually view gaming as a burden in order to complete their jobs, instead of a genuine hobby. Not to mention that reviewers are not exactly always trustworthy. Of course, while there's nothing wrong in placing some stock in the opinions of others, review scores shouldn't be regarded as authoritative, simply because reviewers are, like everyone else, human beings with their own personal tastes and preferences. In fact, review scores are just as likely to be used as personal opinions in Console Wars debates or to argue which of the newest killer apps is the best. ![]() Only second to news, reviews of the newest games are the main attraction of most gaming sites and magazines. The Cinema Snob on Rosencrantz and Guildenstern Are Dead (1990), Brows Held Highįor whatever reason, gamers tend to, on the whole, place more stock in professional reviews of works than fans of any other medium. ![]() ![]() ![]() ![]() You can set your browser to refuse all third-party cookies, or to alert you when cookies are being sent. 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Targeting and Advertising cookies: These cookies record visits of a user on our Platform, the pages a user visits and the links a user follows in order to enable us to make our Platform more relevant to the user’s interests and to help us serve ads that might be of interest to the user.Īnalytics, Functionality and Advertising / Targeting cookies can be switched off at any time by accessing the ‘Manage cookies’ option that is located at the footer of our Platform. Additionally, we are using third party session recording technologies that help us better understand our users’ experience, however, the recording data is pseudonymized. These cookies help us to improve our Platform, for example by ensuring that all users are able to find what they are looking for easily. 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Cookies and Automatic Data Collection TechnologiesĪs you navigate through and interact with our Platform, we use automatic data collection technologies, if available in your jurisdiction, to collect Platform activity data. ![]() ![]() ![]() ![]() In order to access downloads on mobile devices you will need to use a web browser (not the app) to log into your account, go to purchases, and download your files. This listing is for digital download files only, NO PHYSICAL ITEMS WILL BE SENT.ĪTTENTION APP USERS on mobile: The Etsy app does not work for downloads. They can also not be sold or distributed as part of a layered image file.Ĭheck our other listings for more digital resources including clipart collections, digital paper designs, and more, many with commercial license included! These images may not be used for the following purposes: they may not be sold or distributed as individual digital files or as part of a collection of digital files. They can be used on websites, blogs, product packaging, physical products and print products including books, magazines, posters, etc. These images can be used for both personal and commercial projects with no limits on the number of print copies. All images are contained in 3 ZIP files for download. Works with any application that can open and edit PNG files. Images are in transparent PNG format with backgrounds removed and are ready to drop into your project. Medieval knight holding sword, royal knight with lance on horseback. Find high-quality stock photos that you wont find anywhere. Preview images have a watermark that will not appear on the actual files. Find Knight stock images in HD and millions of other royalty-free stock photos. Search from 51380 Medieval Knight stock photos, pictures and royalty-free images from iStock. Pictures featuring products should be used with care. Knighthood in the Middle Ages was closely linked with horsemanship (and especially the. Vera Kratochvil has released this Medieval Knight image under Public Domain license. The 20 individual images are between 30 pixels tall each! The lords trusted the knights, who were skilled in battle on horseback. These images are perfect for junk journals, scrapbooks, product packaging, printables, and any other DIY graphics. A curated collection of 20 high-resolution images of knight's suits of armor, swords, shields, axes, and maces, carefully processed to keep all the minute details. ![]() ![]() ![]() Now fill the colours and start your train. Draw wheels on the bottom and connect all these shapes like the way train compartments are connected. Draw small squares inside these shapes like a window. Draw one rectangle and two squares in the straight line. Kline’s portrayal of a young woman aging out of the modern foster care system has also been compared to Vanessa Diffenbaugh’s The Language of Flowers (2011). Draw small one square on top of the rectangle and two rectangles on top of that small square. Other feminist historical novels that, like Orphan Train, focus on the themes of memory, secrets, and overcoming the past, are Jody Picoult’s The Storyteller (2013) and Sue Monk Kidd’s The Secret Life of Bees (2001). In terms of the subject matter of Orphan Train, it has been likened to The Little Immigrants (2000) by Kenneth Bagnell, a work of historical fiction that portrays the history of British orphans who were sent to work in Canada in the 1800s. Kline’s portrayal of Midwestern orphans at the beginning of the twentieth century has also been compared to Willa Cather’s O Pioneers! (1905) and Mail-Order Kid (2010) by Marilyn June Coffey. Like Orphan Train, both of these novels examine the lives and troubles of modern-day women in Maine by exploring their family’s histories. Life in the rural Midwest was deemed better for the children than life in a crowded Eastern city. Orphan Train is also similar to Kline’s other works, a Piece of the World (2017) and The Way Life Should Be (2007). The orphan trains were a humanitarian effort spanning 75 years they served to remove children from slums and get them off the streets by transporting them to good homes out West. Like Orphan Train, Doerr’s novel is a work of historical fiction, portrays the experiences of orphans, has a two-plot structure, and retraces the lives of modern-day characters by telling their stories from the beginning. Orphan Train has most frequently been compared to All the Light We Cannot See (2014 ) by Anthony Doerr, a novel that explores the pasts of a German orphan and a blind French girl in German-occupied France. ![]() ![]() ![]() It also appears when you browse the LinkedIn feed. The headline is listed under their name on the profile page. Now, let’s walk through section by section to identify their relevancy and potential insights. Convenient widgets to check on a user’s profile page include “people you may know” and “people also viewed.” Much the same way a hyperlink in an article takes the reader to a related article, LinkedIn users provide pathways to profiles from the same persona. Use one profile to find more people from the same persona. The bottom of the profile – volunteering, recommendations, publications, and honors and awards – can reveal interesting nuggets. Don’t focus solely on the About or Activity sections at the top. Skim past the underpopulated profiles and spend your time on the detailed ones. Now that you compiled a list of people, you can assess which ones will be most helpful to your research and identify other profiles to add to your tracker. You can create a broad or niche list depending on your filter criteria. To research B2B content marketers, I typed B2B and “content marketers” into the title search field: Then type the job title in quotes, such as “senior procurement manager.” To find people in specific roles, filter for title (under the keywords filter). Pick “current company” to research people at targeted companies. For instance, if you focus on a Middle East-based audience, use the locations filter accordingly. Next to the results view are the filter options – a lot of them, including:Ĭonnections (i.e., degree of connection to your profile)Ĭhoose the filters based on the nature of your research. I usually start with “marketing.”įrom there, click on “people” and “all filters.” It returns over 49.5 million results: Enter a broad descriptive term in the search bar. You first need to generate a list of people to research. In this post, I show you what you can uncover. Researching LinkedIn profiles can provide a wealth of insights. While the process failed to deliver actionable results for my client, it better informed my ability to provide well-developed personas to create more effective content marketing. None of those LinkedIn profiles signaled that type of buying intent. Did they post asking about vendor capabilities? Did they ask for vendor recommendations? Or did they request proposals? The result of my work? Nothing. I analyzed the LinkedIn profiles to identify buying signals. We also had the LinkedIn profiles of those companies’ employees – people who would be likely buyers. We had third-party intent data of companies searching keywords and phrases related to their services. I helped a client with an account-based marketing (ABM) initiative. Unlock Audience Personas With the Power of LinkedIn Profiles ![]() ![]() ![]() Can you combine many isolated interface elements (think: overlapping windows) into a single image? Does it allow you to remove the background manually in this case?. ![]()
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