If there is something in all your images that you don't include in your tags, it will become part of your Lora. Let me describe how tags work in your dataset: You need to be detailed, as the Lora will reference what's going on by using the base model you use for training. For anime you'll need to use booru tags ( 1girl, blonde hair, full body, on chair, etc.). You can train a mediocre Lora with a bare minimum of 5 images, but I recommend 20 or more, and up to 1000.Īs for the descriptions, for general images you want short and detailed sentences such as " full body photograph of a woman with blonde hair sitting on a chair". For example a character may then be generated in new poses and in different clothes. As you add more variety, the concept will be better understood, allowing the AI to create new things that weren't in the training data. If all your images are face close-ups for example, your Lora will have a hard time generating full body shots (but it's still possible!), unless you add a couple examples of those. The quality of your dataset is essential: You want your images to have at least 2 examples of: poses, angles, backgrounds, clothes, etc. "1.png" and "1.txt"), and they all have something in common which you want the AI to learn. A dataset is (for us) a collection of images and their descriptions, where each pair has the same filename (eg. This is the longest and most important part of making a Lora. I won't cover them as I don't think they're very useful. LoHa, LoKR, (IA)^3: These use novel mathematical algorithms to process the training data. LoCon: Has more layers which learn more aspects of the training data. LoRA: The classic, works well for most cases. However there are also different types of Lora now: However I won't help you if you want to copy real people's faces without their consent.Īs you may know, a Lora can be trained and used for: This guide focuses on anime, but it also works for photorealism. We'll also be using a little bit of Google Drive storage. You can also pay $10 to get up to 50 extra hours, but you don't have to. We won't be doing that in this guide though, we'll be using Google Colab, which lets you borrow Google's powerful computers and graphics cards for free for a few hours a day (some say it's 20 hours a week). You could of course train a Lora in your own computer, granted that you have an Nvidia graphics card with 6 GB of VRAM or more. All while keeping some advanced settings you can use later on. Well, I've streamlined the process such that anyone can make their own Lora starting from nothing in under an hour. So many options and nobody explains what any of them do. Just try to read carefully, use critical thinking, and don't give up if you encounter errors. I'll try to explain these new concepts in an easy way. Knowledge about what Loras are and how to use them. You can even do this from your phone if you want to (as long as you can prevent the tab from closing). I just do it for fun.Īlso here's a page where I collect Hololive loras.Īn internet connection. However I do not support you if you want to use AI to trick people, scam people, or break the law. ![]() I believe all information should be free for everyone, including image generation software. I'm making this guide for the joy it brings me to share my hobbies and the work I put into them. If you're new to Stable Diffusion I also have a full guide to generate your own images and learn useful tools. In this guide we'll be using resources from my GitHub page. Click "Show more" below.Įven if you don't know where to start or don't have a powerful computer, I can guide you to making your first Lora and more! "im babby" to "hello, babby" don't need to download anything, this is a guide with online tools. The tweet later on garnered 112 retweets and 470 likes. Twitter user posted a tweet on January 7th, 2020 with the caption " ema skye really went from 'im babby' to 'hello, babby' " featuring 2 pictures of her concept art, one from the first game in the series Phoenix Wright: Ace Attorney and the other from the sixth game in the series Ace Attorney: Spirit of Justice. One of the first mentions of her on the Internet was from the Ace Attorney Court Records fansite, and one of the first memes about her, featuring a hentai quote was posted by (((Richard Cheese 妹妹 Master))) onto Know Your Meme on October 14th, 2014. The new episode mentioned featured aforementioned character Ema Skye. On September 15th, 2005 a rerelease of the first game (Gyakuten Saiban) was released for the Nintendo DS in Japan, with a new episode, Rise from the Ashes. Gyakutensaiban, character, ace attorney, gyakuten saiban, video games, gamesĮma Skye is a character from the Ace Attorney game franchise who is portrayed as a lazy forensic detective.
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Every box includes a Halo 5 Req Pack code that can be submitted in the game to unlock the ASTRO emblem and other in-game content. Still a wonderful and beautiful controller. The result of a deep collaboration between ASTRO, 343 Studios and Xbox, the A40 headset and MixAmp M80 feature colors, materials and finishes that match the Halo 5 Xbox One console and controller. I’m unsure how this can be fixed or if it can be. Chan ging to 5 stars again because everything is perfect!Įdit 3: It’s unfortunate to say, but it seems like the analog stick flaw is permanent. Hopefully nothing else goes wrong with it, but this was a steal for the product received.Įdit: The req pack included did work! Unfortunately for us, we didn’t check to see if he already had gotten that promotion from something else and it got wasted.Įdit 2: After about 12 matches, the analog stick started working correctly. Xbox One Limited Edition Halo 5: Guardians Wireless Controller (Renewed) Usb. I’m really sore about this because it does impede on our ranking progress. Xbox-One Controller Skin, BRHE Anti-Slip Silicone Cover Protector Case Accessories Set for Microsoft Xbox 1 Wireless/Wired Gamepad Joystick with 2 Thumb Grips Caps (Red). Going up or forward on it seems to be really slow and takes a couple seconds to make it to a jog. Improve Your Play Whether you’re racking up Killtaculars in Halo online play or taking cover in Gears, our custom Xbox controllers provide the performance, comfort and customization you. ![]() Custom SCUF controllers help you game like a pro. This product includes: An Xbox Elite Wireless Controller, a carrying case, a set of 4 paddles, a set of 6 thumbsticks, a set of 2 D pads: faceted and standard, a USB cable, AA batteries and a quick set up guide and product manual. Features: Exclusive design inspired by Halo 5: Guardians Unique laser etched design inspired by Spartan Locke. Customize your Xbox One & Series X/S controller with remappable paddles, thumbsticks, triggers, & more. We’re in the process of testing it out with competitive matchmaking in halo 5 and everything seems to be fine except the left analog stick. Official Xbox One Halo 5 Guardians Controller. I bought this for my boyfriend so we could eventually get both sets of the limited edition controllers/headsets. ![]() And the KnitPosite 2.0 upper provides a secure fit to help you move with confidence. They have a full-length Zoom Air unit and Max Air in the heel to absorb impact and return energy. Nike LeBron shoes are all about speed and power.From LeBron James orchestrating an attack to Giannis Antetokounmpo leading a fast break, the next generation of players needs shoes that have a little bit of everything: balanced support, traction in any direction and energy return without unnecessary weight. In today's game, the distinction between guards and forwards is disappearing. The lightweight shoe minimises ground contact for stability and control. The Nike Air Zoom low-top basketball shoes are made for the players who use their skills to create and close space on the court.Be kind to the planet, not the opposing team. Its Air Zoom Strobel unit, partially composed of recycled materials, provides efficient acceleration off the dribble. The Nike Cosmic line makes rubbish on the court a good thing.These shoes benefit from a variety of traction patterns to help keep you from slipping on the court. When you're pulling up for a jumper or driving to the basket off a pick and roll, a high level of grip and traction for those sudden, sharp cuts is essential. With two stacked Zoom Air units in the forefoot for responsive cushioning, they help you harness more of your own speed to change the game. The Jordan 'Why Not?' line proves that speed is the most important factor on the court.Run stacks a React footbed on top of a React midsole and Zoom Air in the forefoot to provide shock absorption and a responsive ride. Nike Max Air helps keeps your legs fresh late into the fourth quarter for better individual performances and team wins.The Nike Zion kicks off Zion Williamson's line with an understated design that channels his athleticism and power. Nike Air Zoom technology provides explosive performance and comfort that lasts the whole game.Proper support keeps your feet and ankles secure and locked in so you can make quick, lateral movements and constant vertical jumps. ![]() Ankle support and stability are important for front-court players-you need a stable base when fighting to grab a rebound or exploding to the rim for a putback. ![]() Halo has a rich history with powerful pistols like the Magnum, but it also has as strong a legacy with rifles like the Battle Rifle. For Halo Infinite, we felt it was important for the utility weapon to be in the form of a rifle. If you remember, this is something that was very important to us on Halo 5: Guardians as well, and is why the Magnum played such a key role as the starting utility weapon for that title. First, the importance of nailing the classic need for a starting utility weapon. But from a sandbox perspective, there are two ideologies that matter most to us when crafting our gameplay features. Quinn: For competitive Halo there is a strong handful of tenets that we strive to understand and follow. Any item that can be earned can also be taken away through combat resolution, positioning, and tactical actions. Scavenging gameplay within a map/mode combo pushes teams to contest the acquisition of items within the Sandbox.This meant to bolster tactical decision making. When a mode’s state is progressed then all players should be informed of the change and have a window of opportunity to react to it. Arena game states are communicated efficiently and urgently.A match with two teams of equal skill should be determined by the teams’ tactical decision making as the mode’s state is continued by player action. Mechanical skill expression will get players far in the Arena ecosystem, but mastery comes from macro gameplay decision making within a map and mode’s framework.Mastery = Mechanical Depth + Tactical Decision Making.Players feel like they can have a high impact on the game individually through their skill expression within the combat sandbox and mode ruleset, but the team with the better coordination, communication, and reactive skills will seize the most victories. ![]() The Lone Wolf Survives but the Pack Thrives.Players start the match with fair and balanced gameplay mechanics. King Solomon says it is the “wellspring of life.” In other words, it is the source of everything else in your life. Because your heart is the source of everything you do.This is why Solomon says, “Above all else.” He doesn’t say, “If you get around to it” or “It would be nice if.” No, he says, make it your top priority. It is that part of you that connects with God and other people.Just like your physical body, if your heart-your spiritual heart-dies, your leadership dies. It is where all your dreams, your desires, and your passions live. It is your authentic self-the core of your being. Why? Because it is worthless.Not so with your heart. It sits on the sidewalk all night, completely unguarded. I take my garbage to the street every Wednesday night. Because your heart is extremely valuable.This is necessary for at least three reasons: King Solomon said it best: “Above all else, guard your heart, for it is the wellspring of life” (Proverbs 4:23). This is why, I think, as leaders we must be diligent to guard our hearts. In fact, as I have grown older, the conflict has intensified. In my journal, I have cataloged almost twenty distinct situations where I was ready to quit and throw in the towel. That experience wouldn’t be the last time I experienced an assault on my heart. We were disappointed, angry, and ready to quit. We were left high and dry, with only $12.00 in our checking account. We made the fatal mistake of putting all of our eggs in one basket.Īfter months of back-and-forth, the investor decided not to make the investment after all. We really didn’t have time to court anyone else. The due diligence process was all-consuming. We had one investor who promised to make a sizable investment. Your heart is your most important leadership tool. It is not your experience, knowledge, or skills. My partner and I left big corporate jobs, developed a business plan, and began raising money for our new venture. It is your heart that matters most of all.īack in the mid-80s, I started my own business. 2 Rare Takes & Radio Cuts Honky Tonk Man Hank Williams Revealed: The Unreleased Recordings Country Collection The Hank Williams Story All-American Country Your Cheatin' Heart Your Cheatin' Heart Essential Hank Williams: Hillbilly Legend Hank Williams: The Complete Mother's Best Recordings.Plus! Hank Williams: The Complete Mother's Best Recordings.Your heart is the most important leadership tool you have. 2 Moanin' the Blues 1947-1951 I'm So Lonesome I Could Cry The Best of Hank Williams I Saw the Light/I'm So Lonesome I Could Cry The Hillbilly Shakespeare The Honky Tonk Man Gold No More Darkness Settin' the Woods on Fire Hall of Fame You Win Again: 26 Great Original Recording Very Best of Hank Williams Country Music Legends Famous Country Music Makers The Immortal Hank Williams The Immortal Hank Williams The Collector's Edition Hank Williams The Unreleased Recordings Hey, Good Lookin King of Hillbilly Country Legends Collected Rockin' Chair Money 20 Greatest Hits, Vol. 1 Long Gone Lonesome Blues Ultimate Collection Honky Tonkin' Collection Great Country Legends 48 Original Recordings Long Gone Lonesome Blues: Hillbilly Hero Hillbilly Hero Hank Williams Story Golden Greats The Hank Williams Story Honky Tonkin' I Won't Be Home No More Kaw-Liga and Other Humorous Songs The Very Best of Hank Williams, Vol. 1: Honky Tonkin' Blues Come Around Prodigal Son Lovesick Blues Best of Hank Williams, Vol. 2 Original Singles Collection.Plus 24 Greatest 40 Greatest Hits Honky Tonkin' Commemorative Collection Honky Tonkin' Best of Hank Williams Hank Williams His Greatest Hits, Vol. ![]() Lost Highway (And Other Folk Ballads) 24 of Hank Williams' Greatest Hits A Legendary Collection The Complete Hank Williams Hits, Vol. If you mind your own business, you'll stay busy all the time I got all that I can do just to mind my own Mindin' other people's business seems to be high-toned If you mind your business, then you won't be mindin' mine ![]() Now, brother that's my headache, don't you worry 'bout me If I want to honky tonk around 'til two or three Well, if you mind your own business, you sure won't be minding mine I got a little gal that wears her hair up high ![]() Well, if you mind your business, then you won't be mindin' mine She picks up her receiver when she knows it's my ring Oh, the woman on our party line's the nosiest thing 'Cause if you mind your business, then you won't be mindin' mine 'Cause me and that sweet woman's got a license to fight If the wife and I are fussin', brother that's our right ![]() 11 In normal individuals, the TCR repertoire is polyclonal and non-static. 10 The clonotype of a TCR population is a molecular description of the unique sequences (typically described from the amino acid perspective) required to produce the antigen specificity of TCRs, as well as the specific V and J genes involved in the composite rearrangements. The ability of human T cells to recognize a vast range of pathogens and initiate specific adaptive immune responses depends on the versatility of the TCR population. 1, 9 Thus, the sequence of CDR3 and the identity of the flanking V and J gene segments are widely used to classify TCR variants. 7, 8 The vast majority of TCR variation is within complementarity-determining region 3 (CDR3), which encompasses the VDJ recombination junctions and encodes the portion of the TCR that directly contacts peptide-bound major histocompatibility complex molecules. 3, 6 Because this somatic rearrangement occurs only in the T-cell genome and produces an extremely diverse repertoire of TCRs as a hallmark of the cellular adaptive immune system, it can be effectively used as a unique tag to enumerate and quantify T-cell clonality. 4, 5 An individual’s TCR repertoire is shaped by biases during the process of VDJ recombination and by the subsequent expansion and deletion of certain T-cell clones upon antigen recognition during T-cell development in the thymus and later in the periphery. ![]() 3 The TCR consists of a heterodimer of two chains (αβ or γδ), both of which are products of V(D)J recombination. 1, 2 This process is directly analogous to the generation of antibody diversity by somatic VDJ recombination of the B-cell receptor locus in B lymphocytes. The T-cell receptor (TCR), which is generated through random rearrangement of genomic V(D)J-variable(diversity)joining-segments, is the mediator of specific antigen recognition by T lymphocytes. Thus, determining monoclonal architecture and clonal diversity by RNA sequencing might be useful for prognostic purposes and for personalizing ATL diagnosis and assessment of treatments. CDR3 sequence length distribution, amino acid conservation and gene usage variability for ATL patients resembled those of peripheral blood cells from ACs and healthy donors. ACs, CD4 -positive samples and smoldering patients showed significantly higher TCR diversity compared with chronic, acute and lymphoma subtypes. Expression of TCRα and TCRβ genes in the dominant clone differed among the samples. Based on these TCR profiles, CD4-positive cells and ACs showed polyclonal patterns, whereas ATL patients showed oligo- or monoclonal patterns (with 446 average clonotypes across samples). We analyzed 62 sets of high-throughput RNA sequencing data from 59 samples of HTLV-1−infected individuals-asymptomatic carriers (ACs), smoldering, chronic, acute and lymphoma ATL subtypes-and three uninfected controls to evaluate TCR distribution. Here we examined the diversity of TCR clonality and its association with pathogenesis and prognosis in adult T-cell leukemia/lymphoma (ATL), a malignancy caused by infection with human T-cell leukemia virus type-1 (HTLV-1). The TCR repertoire can be altered in the context of infections, malignancies or immunological disorders. High-throughput sequencing technologies now allow examination of antigen receptor repertoires at single-nucleotide and, more recently, single-cell resolution. Particularly, we discuss several aspects of challenges in this field and highlight the efforts to develop potential solutions, in the era of high-throughput sequencing of the immune repertoire.īCR High-throughput sequencing Immune repertoire TCR.The diversity of T-cell receptor (TCR) repertoires, as generated by somatic DNA rearrangements, is central to immune system function. In this article, we review the history of immune repertoire studies, in terms of technologies and research applications. The massive paralleled sequencing technology suits perfectly the researches on immune repertoire. Before the emergence of high-throughput sequencing, the studies on immune repertoire were limited by the underdeveloped methodologies, since it was impossible to capture the whole picture by the low-throughput tools. Immune repertoire is defined as the sum of T cell receptors and B cell receptors (also named immunoglobulin) that makes the organism's adaptive immune system. The diversity of T and B cells in terms of their receptor sequences is huge in the vertebrate's immune system and provides broad protection against the vast diversity of pathogens. Find out more about our advertising opportunities. Advertise Advertising on is well-targeted, has unique benefits, and is highly successful. Looking for something lighter? Read our funny complaints to see people who found humor in a bad situation. ![]() Vehicle Problems Find out what cars to avoid, view the latest problem trends, or keep up-to-date with the most recently reported problems. ![]() Contact us with any comments or concerns. Car Problem Resources Around the Site Information Find out more about us in the press or read stories from drivers who praise our work.The complaints are organized into groups with data published by vehicle, vehicle component, and specific problem. Shop from brands including Chevrolet Performance, Ford Performance, Mopar Performance, BluePrint Engines, VEGE Remanufactured Engines, First Mate, ATK, and more.Pontiac 2010 Vibe 2008 Vibe 2007 Vibe Scion 2011 tC 2010 tC 2009 tC Subaru 2008 Forester 2007 Forester 2005 Forester 2004 Forester 2011 Legacy 2007 Legacy 2006 Legacy 2017 Outback 2012 Outback 2011 Outback 2010 Outback 2009 Outback 2008 Outback 2007 Outback 2006 Outback Toyota 2014 4Runner 2013 4Runner 2012 4Runner 2011 4Runner 2010 4Runner 2009 4Runner 2008 4Runner 2007 4Runner 2006 4Runner 2005 4Runner 2004 4Runner 2003 4Runner 2016 Avalon 2015 Avalon 2012 Avalon 2010 Avalon 2009 Avalon 2015 Camry 2014 Camry 2013 Camry 2010 Camry 2006 Camry 2004 Camry 2017 Camry Hybrid 2016 Camry Hybrid 2015 Camry Hybrid 2014 Camry Hybrid 2013 Camry Hybrid 2012 Camry Hybrid 2011 Camry Hybrid 2010 Camry Hybrid 2016 Corolla 2012 Corolla 2011 Corolla 2008 Corolla 2007 Corolla 2004 Corolla 1999 Corolla 1998 Corolla 1997 Corolla 2005 Echo 2004 Echo 2009 Highlander 2007 Highlander 2013 Matrix 2012 Matrix 2011 Matrix 2010 Matrix 2008 Matrix 2007 Matrix 2019 Prius 2018 Prius 2017 Prius 2015 Prius 2009 Prius 2004 RAV4 2000 RAV4 2017 Sequoia 2016 Sequoia 2015 Sequoia 2014 Sequoia 2013 Sequoia 2012 Sequoia 2011 Sequoia 2010 Sequoia 2009 Sequoia 2008 Sequoia 2007 Sequoia 2006 Sequoia 2005 Sequoia 2004 Sequoia 2003 Sequoia 2010 Sienna 2009 Sienna 2008 Sienna 2003 Sienna 2002 Sienna 2001 Sienna 2015 Tacoma 2014 Tacoma 2017 Tundra 2016 Tundra 2015 Tundra 2014 Tundra 2013 Tundra 2017 Yaris 2016 Yaris 2015 Yaris 2014 Yaris 2013 Yaris 2012 Yaris 2011 Yaris 2010 Yaris 2009 YarisĬ ® is an online automotive complaint resource that uses graphs to show automotive defect patterns, based on complaint data submitted by visitors to the site. Research the 2016 GMC Sierra 2500 at and find specs, pricing, MPG, safety data, photos, videos, reviews and local inventory. A crate engine can be a significant investment, so we only carry manufacturers we’d use for our own projects. Since 1968, Summit Racing has been helping back yard tinkerers and professional builders find the right parts for their build. Summit also carries other popular crate engine designs, including the Chevy small block 350, the Ford 302 and Coyote, and, of course, the Hemi. Refer to your vehicle’s service manual for complete information on the scheduled maintenance recommended by the. Maintenance tasks and schedules can vary between different engines/trims. One of the most popular engine swap projects today uses the versatile LS design. 2018 GMC Sierra 1500 Maintenance Schedule Note: The maintenance schedule described in this article is specifically for the 2018 GMC Sierra 1500 5.3L V8. For more detailed information about selecting a crate motor for your project, check out this article on our official blog, which includes a helpful video. These terms aren’t that precise, and can mean different things to different manufacturers, so make sure the crate engine you buy comes with everything you need and nothing you don’t. You can also decide how much finishing and customizing you want to do:Ī short block includes a balanced rotating assembly and little else.Ī long block usually comes with cylinder heads, oil pan, camshaft, and valve covers, along with horsepower and torque ratingsĪ fully dressed engine includes everything except front drive accessories (like alternators and power steering pumps), and even a warranty! 2000 GMC Safari SLE Van Like Chevy Astro Low 91k miles NO RESERE. Whether you just want a proven and convenient solution for your project vehicle, or your racing class mandates one, shop at Summit Racing Equipment for crate engines!īuilding a new engine (or restoring an older one) takes time, tools, and lots of tuning, so buying a crate engine can be a wise investment. 2016 Chevy Express Van For Sale - Stock K4008A, 2010 Chevy You are looking. ![]() DUMP Episode 3: BFG Edition is a collaborative mod for Doom II for ZDoom. When the projectile hits an enemy or wall, it will create a cone-shaped field of damage. The BFG's appearance in Doom 64 is slightly different compared to other versions of the game, having a darker appearance and making whirring sounds. I searched for 20 minutes earlier and was unable to find him.The BFG9000 is a large gun which fires balls of plasma. in one of the rooms there is an upper torso you can pick it up and use it at the retinal scanner. there is a body in one of those room and you use his eye to open the room, look on the floor for the body. The gun fires a blue (rather than green) blast of plasma, which obliterates the target and burns away at. It has no apparent magazine, suggesting that it is recharged in its special storage system. The BFG is depicted as a futuristic black-colored rifle. The BFG, or known as the Bio Force Gun version 3.14, is an experimental energy weapon developed by the UAC and depicted in the 2005 film Doom. The port is based on the Doom Classic codebase, but. It was initially announced on stage during the QuakeCon 2019 (DoomCon) keynote presentation. I searched for 20 minutes earlier and was unable to find him.The Doom Classic Unity port is a series of official ports of Doom and Doom II initially developed by Nerve Software in cooperation with id Software and first published by Bethesda on Jas part of the "Year of Doom" promotional campaign. It appears as a large, silver metallic gun with a dark gray aperture similar to the plasma gun, and fires large spheres of green plasma.there is a body in one of those room and you use his eye to open the room, look on the floor for the body. The BFG9000 is the ultimate weapon to be found in Doom. The game is also know as Doom 2016 according to the official doom discord. ![]() It is currently available on PC, PS4, and Xbox One, and was released on the Nintendo Switch on November 10, 2017. ![]() Legal issues in Germany According to the German Strafgesetzbuch §86a, the usage of unconstitutional symbols is forbidden outside of certain contexts such as research, teaching and others.Doom (known as Doom 4 during development) is a soft reboot (see shared universe) of the Doom franchise produced by id Software and published by Bethesda Softworks. Doom II was re-released in the Doom 3 BFG Edition however, this version is different in that the Nazi references were removed from MAP31 and MAP32. These models are usually divided into two main categories: The diet-induced models and the genetically modified models (transgenic or knockout models). Historically, several animal models have been developed to represent the pathophysiology, morphological findings, biochemical changes, and clinical features of human NAFLD/NASH. A likely contributor to the absence of therapeutics is the paucity of preclinical models resembling human NAFLD/NASH. There are currently no pharmacological agents specifically approved for the treatment of NASH and disease management is consequently focused on the correction of underlying risk factors ( e.g., obesity, insulin resistance and dyslipidemia). The pathogenesis of NASH is described by the “two-hit” hypothesis, the first hit being fat accumulation in hepatocytes, while the “second hit”, e.g., oxidative stress, apoptosis or mitochondrial dysfunction, causes development of inflammation and fibrosis. NAFLD is considered the hepatic manifestation of the metabolic syndrome and covers a variety of pathologies ranging from simple hepatic steatosis (accumulation of triglycerides in hepatocytes) to nonalcoholic steatohepatitis (NASH), characterized by inflammation, cellular ballooning and fibrosis in varying degrees. It is generally accepted that along with increasing rates of obesity, type 2 diabetes and metabolic syndrome, the incidence and prevalence of patients with nonalcoholic fatty liver disease (NAFLD) continues to rise. Notably, fibrosis stage was significantly ( P < 0.001) increased in ob/ ob-NASH mice, when compared to DIO-NASH mice.ĬONCLUSION: These data introduce the obese diet-induced DIO-NASH and ob/ ob-NASH mouse models with biopsy-confirmed individual disease staging as a preclinical platform for evaluation of novel NASH therapeutics. ![]() Furthermore, fibrosis stage was significantly elevated for DIO-NASH mice (0 vs 1.2 ± 0.2, P < 0.05 compared to lean chow) and ob/ ob NASH (0.1 ± 0.1 vs 3.0 ± 0.2, P < 0.001 compared to ob/ ob chow). Histopathological scoring demonstrated significantly increased NAS of DIO-NASH mice (0 vs 4.7 ± 0.4, P < 0.001 compared to lean chow) and ob/ob-NASH mice (2.4 ± 0.3 vs 6.3 ± 0.2, P < 0.001 compared to ob/ ob chow), respectively. During the eight week repeated vehicle dosing period, the metabolic phenotype was sustained in DIO-NASH and ob/ ob-NASH mice in conjunction with hepatomegaly and increased hepatic lipids and collagen accumulation. Overall, the metabolic NASH phenotype was more pronounced in ob/ ob-NASH vs DIO-NASH mice. The diet also induced clear histological features of NASH including hepatosteatosis and fibrosis. RESULTS: Diet-induction for 26 and 12 wk in DIO-NASH and ob/ ob-NASH mice, respectively, elicited progressive metabolic perturbations characterized by increased adiposity, total cholesterol and elevated plasma liver enzymes. Steatosis and fibrosis were also quantified using percent fractional area. Non-alcoholic fatty liver disease activity score (NAS) (steatosis/inflammation/ballooning degeneration) and fibrosis were scored. Metabolic parameters, plasma liver enzymes and lipids (total cholesterol, triglycerides) as well as hepatic lipids and collagen content were measured by biochemical analysis. Global gene expression in liver tissue was assessed by RNA sequencing and bioinformatics. Mice were then stratified into groups counterbalanced for steatosis score and fibrosis stage and continued on diet and to receive daily PO dosing of vehicle for 8 wk. After the diet-induction period, mice were liver biopsied and a blinded histological assessment of steatosis and fibrosis was conducted. A normal chow diet served as control in C57 mice (lean chow) and ob/ ob mice ( ob/ ob chow). ![]() METHODS: Male wild-type C57BL/6J (C57) mice (DIO-NASH) and male Lep ob/ Lep ob ( ob/ ob) mice ( ob/ ob-NASH) were maintained on a diet high in trans-fat (40%), fructose (22%) and cholesterol (2%) for 26 and 12 wk, respectively. AIM: To characterize development of diet-induced nonalcoholic steatohepatitis (NASH) by performing liver biopsy in wild-type and genetically obese mice. In June 2019, both sites were removed from Google, per the company's policy of de-listing websites that violate the Digital Millennium Copyright Act. Access to Exhentai requires an existing E-Hentai account for individuals without an account, Exhentai appears as a blank page with an illustration of a crying panda, and has consequently has earned the nickname "Sad Panda" among users of the site. ![]() Existing galleries containing this content were deleted from the site, amounting to the removal of approximately 30,000 of the website's 150,000 galleries this content was later spun off onto Exhentai, a sister site to E-Hentai. On March 27, 2010, E-Hentai announced that in response to pressure from advertisers, it would no longer host artwork depicting underage characters ( lolicon and shotacon) and bestiality. net domain lapsed and was purchased by another party. org domain in 2005 after ownership of its. net domain in 2001 before moving to its current. Its sister site Exhentai (colloquially known as Sad Panda) was spun off from E-Hentai in 2010 to host artwork that depicts material that is illegal in certain jurisdictions, such as lolicon, shotacon, and bestiality.Į-Hentai launched as a Yahoo! Group on July 1, 1999. ![]() The site hosts user-generated image galleries primarily of pornographic content originating or derived from anime, manga, and video games, such as fanart, scanlations of manga and dōjinshi, and cosplay photographs. E-Hentai is an image-hosting and file-sharing website focused on hentai (Japanese cartoon pornography). |
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