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![]() ![]() B Morphological changes induced by a 100 ng/ml TNF-α treatment (photographs). Protein expressions were analysed by western blot. HMVECs were treated for 96 h with 0, 20, 50 or 100 ng/ml of TNF-α. 1B).Ī TNF-α decreases the protein expression of vascular endothelial marker (CD31) and increases the protein expression of mesenchymal markers (S100A4, α-SMA). Furthermore, FACS analysis demonstrates that the TNF-α-induced decrease of CD31 protein expression affects a large majority of endothelial cells (Supplemental Fig. Analysis of additional endothelial and mesenchymal markers confirmed these results (Fig. For further experiments, we chose the concentration of 100 ng/ml. Results show that TNF-α-treated cells are much more elongated than untreated cells (Fig. To quantify these morphological differences between TNF-α-treated and untreated cells, we measured the elliptical form factor EFF. At 100 ng/ml, we observed a strong morphological change, from epithelioid to an elongated and spindle-shaped fibroblast-like appearance (Fig. Dose-dependent these effects were very strong already from 20 ng/ml of TNF-α. Results show that TNF-α reduced the protein expression of the vascular endothelial marker CD31 and reciprocally augmented the expression of the mesenchymal markers α-SMA and S100A4. After 96 h, cells were lysed and protein expression was analysed by western blot. 1A) or daily for 4 days (Supplemental Fig. Human microvascular endothelial cells (HMVECs) were treated with 20, 50 or 100 ng/ml of TNF-α added once (Fig. TNF-α induces endothelial–mesenchymal transition We especially focus on the pro-inflammatory cytokine tumour necrosis factor-α (TNF-α) because it induces an acute and chronic inflammation directly linked to various steps involved in tumorigenesis and, explore the hypothesis that the TNF-α, abundantly present in PDAC, induces EndMT. We investigate the factors that, in PDAC, induce EndMT and CAF production. EndMT plays an important role in embryonic heart formation and is involved in a variety of tissue fibrosis and other uncommon diseases such as fibrodysplasia ossificans progressive (FOP) and cerebral cavernous malformation. EndMT, a form of epithelial –mesenchymal transition (EMT), is a process in which cells lose their polarity and expression of endothelial markers and instead acquire mesenchymal markers and invasive and migratory properties. We have previously demonstrated that EndMT occurs in human tumours. demonstrated, in mouse models of cancer, that endothelial –mesenchymal transition (EndMT) is an important source of CAFs. CAFs are also responsible for suboptimal drug delivery to tumour cells and equally involved in drug resistance. CAFs are key components of PDAC because they facilitate tumour progression by secreting ECM and soluble factors that stimulate cancer progression, invasion and metastasis. Īpart from the extracellular matrix (ECM), infiltrated immune cells and endothelial cells, the most abundant cells present in this tumour microenvironment (TME) are cancer-associated fibroblasts (CAFs). PDAC is characterised by a desmoplastic stroma that represents 90% of the tumour and compresses blood vessels leading to hypovascularisation and poorly perfused tumours, thereby preventing efficient delivery of chemotherapeutic drugs. Although the use of combined chemotherapies has improved responses, survival gains in patients remain limited, underlining the urgent requirement of new therapeutic targets to improve PDAC patient survival. It is the fourth leading cause of cancer-related death, with 5-year survival rates remaining less than 8%. Pancreatic ductal adenocarcinoma (PDAC) represents >90% of all pancreatic tumours. With the aim of restoring normal angiogenesis and better access to drugs, our results support the development of therapies targeting CAFs or inducing the EndMT reversion process in PDAC. Finally, secretome analysis identified TNFSF12, as a regulator that is also present in PDAC patients. Furthermore, TNF-α treatment of orthotopic mice resulted in an important increase in the stroma, including CAFs. We also show that TNF-α-induced EndMT is reversible. Interestingly, TNF-α strongly downregulates the expression of the endothelial receptor TIE1, and reciprocally TIE1 overexpression partially prevents TNF-α-induced EndMT, suggesting that TNF-α acts, at least partially, through TIE1 regulation in this process. Here, we show that TNF-α strongly induces human endothelial cells to undergo EndMT. PDAC is characterised by abundant CAFs and tumour necrosis factor-α (TNF-α). Endothelial–mesenchymal transition (EndMT) is an important source of cancer-associated fibroblasts (CAFs), which facilitates tumour progression. ![]() ![]() ![]() Earning himself a shameful spanking for forgetting that a maid must put his mistress's needs before his own, Max finds himself falling even further behind when Amber insists he redo his work - this time with a painfully paddled posterior! Will this humiliated husband ever be free to leave the house? Find out in The List. With his lacy uniform locked in place, he knows he'll first have to finish a long list of chores, but worse is in store for this reluctant sissy maid when he keeps his wife waiting while cleaning the toilet. Max has other things on his mind as he half-heartedly does the housework, longing to leave his domestic duties behind in favour of watching the match with his friends. Discover how Kevin gets on in Keeping His Hands to Himself. That turns into the most humiliating of punishments when he's expected to wait upon her friends later on, suffering the shameful taunts of three women who can't help noticing his disgrace while he's serving them tea. His efforts to sort himself out only get this male maid into even hotter water when his wife catches him with his hands where they shouldn't be, insisting that her housemaid husband humble himself by keeping them on his head henceforth. When a feminized husband is caught fooling around in frillies, he has no choice but to face the consequences of his crimes - however humiliating that may be! Follow the misadventures of four sissy maids as they find out all about disobedience, discipline and duty.įorced to endure the tight embrace of old-fashioned foundation wear while he washes his wife's sexy lingerie, Kevin soon finds himself in an uncomfortable situation when one of Lauren's bras makes him become hard in his girdle. Faced with a disobedient domestic, their dominant wives know there's only one way to keep a housemaid husband from falling into bad habits - discipline, and plenty of it! Knowing exactly how to teach a man his place, these women won't stop until they receive the devotion they deserve, employing psychological humiliation along with physical chastisement to make sure he learns his lesson.Ĭleaning and chores should stay at the forefront of every male maid's mind, sparing no effort when it comes to domestic service no matter how distracted he may be by a sexy uniform. Visit Mistress Dede at is the lot of a male maid who misbehaves, as the submissive husbands in these stories discover to their cost when they disappoint their mistresses. ![]() tease and denial, humiliation, forced feminization, sissy maids. She is the founder and CEO of the "Sissy Feminization Academy" and currently oversees various online training programs aimed at male transformation and feminization/sissification at Her interests include: panty perverts, forced bi, chronic masturbation, Goddess worship, virtual dominant girlfriend, forced crossdressing, sissy training, feminization, sissification, crossdressing stories, sissy maid, sissy stories, sissy boys, sissy slave, forced sissy, forced crossdressing, sissy humiliation, forced feminization stories, sissy husband, forced womanhood, forced feminisation, feminization hypnosis, sissy school, sissy maids, sissy crossdresser, forced feminization captions, forced sissification, feminization stories, facial feminization surgery, sissy maid training, forced feminization videos, etc. MISTRESS DEDE is not only an accomplished author but also a passionate practitioner of the art of female dominance. Completing these sissy training tasks may be at first difficult but they should also be fun in their own way for you. You are to follow their instructions to the letter, without questioning their methods. Remember that everything your Mistress/ Master has you do is to help you achieve your end goal of becoming who you truly are. You may find that some of these sissy assignments are more difficult than others but you must always push yourself to the absolute limits so that your sissy transformation can become a reality. Reading these progress reports will be a good way for your Mistress/Master to figure out where you need to proceed next in your training. During the process of completing these tasks, it is a good idea to keep both a progress report and progress photos. ![]() After finishing these X-rated sissy assignments, you will be broken and fully accepting of anything and everything your Mistress/Master has you do to please them. Becoming a perfect little sissy boi is a difficult task that requires dedication, perseverance, and constant practice. These tasks are perfect for the self-training sissy or a Mistress/ Master that would like to give their sissy boi's some extra training to whip them into shape. Welcome to your X-rated sissy training exercises. ![]() ![]() Alfred Radcliffe-Brown (1881–1955), a social anthropologist, defined the function of any recurrent activity as the part it played in social life as a whole, and therefore the contribution it makes to social stability and continuity (Radcliffe-Brown 1952). He believed that to study society, a sociologist must look beyond individuals to social facts such as laws, morals, values, religious beliefs, customs, fashion, and rituals, which all serve to govern social life (Durkheim, 1895). ![]() Durkheim believed that society is a complex system of interrelated and interdependent parts that work together to maintain stability (Durkheim, 1893), and that society is held together by shared values, languages, and symbols. Émile Durkheim applied Spencer’s theory to explain how societies change and survive over time. The parts of society that Spencer referred to were the social institutions, or patterns of beliefs and behaviors focused on meeting social needs, such as government, education, family, healthcare, religion, and the economy. He argued that just as the various organs of the body work together to keep the body functioning, the various parts of society work together to keep society functioning (Spencer, 1898). Functionalism grew out of the writings of English philosopher and biologist, Herbert Spencer, who saw similarities between society and the human body. Functionalismįunctionalism, also called structural-functional theory, sees society as a structure with interrelated parts designed to meet the biological and social needs of the individuals in that society. Table 1.1 Sociological Theories or Perspectives Different sociological perspectives enable sociologists to view social issues through a variety of useful lenses. Three paradigms have come to dominate sociological thinking because they provide useful explanations: structural functionalism, conflict theory, and symbolic interactionism. Paradigms are philosophical and theoretical frameworks used within a discipline to formulate theories, generalizations, and the experiments performed in support of them. In sociology, a few theories provide broad perspectives that help explain many different aspects of social life, and these are called paradigms. Classic sociological theories are still considered important and current, but new sociological theories build upon the work of their predecessors and add to them (Calhoun, 2002). Sociological theory is constantly evolving and should never be considered complete. Grand theories attempt to explain large-scale relationships and answer fundamental questions such as why societies form and why they change. Macro-level theories relate to large-scale issues and large groups of people, while micro-level theories look at very specific relationships between individuals or small groups. Theories vary in scope depending on the scale of the issues that they are meant to explain. His work supports the utility of theory in sociological research. Durkheim gathered a large amount of data about Europeans and found that Protestants were more likely to commit suicide than Catholics. ![]() He studied social solidarity, social ties within a group, and hypothesized that differences in suicide rates might be explained by religious differences. In sociology, a theory is a way to explain different aspects of social interactions and to create a testable proposition, called a hypothesis, about society (Allan 2006).įor example, although suicide is generally considered an individual phenomenon, Émile Durkheim was interested in studying the social factors that affect it. Sociologists study social events, interactions, and patterns, and they develop theories to explain why things work as they do. Figure 1.7 Sociologists develop theories to explain social occurrences such as protest rallies. ![]() ![]() ![]() ![]() This should be largely transparent to you and shouldn't affect anything, but it's something to be aware of. All images will be passed through the Roll20 image proxy to prevent security attacks.All classes that don't start with "attr_", "repeating_", or "roll_" will be prefixed with "sheet-".All inputs (and selects, and text areas, etc.) should have a unique attribute name. Attribute names are case-insensitive when checked for uniqueness.Some tags like, ,, doesn't work either.Doing so will prevent your character sheet from loading in the virtual tabletop. Do not use reserved HTML tags such as or in your character sheet HTML.(Any ID attributes on one character's sheet would affect another character's sheet in the same campaign when opened. In the browser, the character sheet is basically wrapped inside a giant tag. There are a few caveats to be aware of in regards to the security filtering that Roll20 applies to your HTML as well: HTML: Generally speaking, character sheets are created with HTML, CSS, and JavaScript (for Sheet Workers), but there exist some constraints that are good to know for the intermediate and advanced user. The editor has four tabs: HTML Layout, CSS Styling, Translation, and Preview. Select Custom from the Character Sheet Template menu.Under the Settings menu, select Game Settings.Select the game to go to the campaign details page.Select the Games menu, and select My Games. ![]() To edit a custom character sheet for a game: To build a sheet, you must have access to a Pro account. ![]() ![]() ![]() Much of the resort is over the tree line which is lower in the Jura than the. Family members can then contribute to your family tree. I know both, weve a flat in Morillon and my office is in foothills of the Jura. MyHeritage has a feature that lists your immediate family and lets you send an invitation to those family members you wish to include. You can share your family tree on MyHeritage with your family members. ![]() Continue building your tree by adding additional individual family members. Prepares 15 types of beverages, including ristretto, 2 x ristretto, espresso, 2 x espresso, coffee, 2 x coffees. Itll make a lovey decoration for the home. Call your local Sur La Table for availability. You may contact the owner of a family tree to get in. The accuracy and completeness of the data cannot be guaranteed. Its handy to be aware of family illnesses. Family trees are dynamic and constantly change as the users add more data and update them.The information about individuals in family trees varies greatly based on what users know and wish to document about their family. It improves conversation, research, communication, fine motor and concentration skills. Once you enter this information, MyHeritage will start suggesting additional information about ancestors and relatives using Smart Matching™ technology to automatically create your family tree. It helps them realise theyre part of something bigger. When you begin a family tree at MyHeritage, you will be prompted to add your gender, name, email address, year of birth, and the names of your parents and grandparents. You can also begin building a family tree online with a free Basic subscription at MyHeritage. You can add photos, historical records, and DNA test results. This program is used by millions of people worldwide and it helps you to do the research to build a family tree. MyHeritage has a free desktop genealogy program called Family Tree Builder. ![]() ![]() ![]() Farewell to Minecraft Steve’s meat, wherever you are. A comparison of Minecraft Steves Meat in his victory pose which was removed in the latest update 9.0.1 in Super Smash Bros Ultimate for the Nintendo Switch. If youve played Minecraft, youll know that characters will do. Now, our parents Nintendo have stepped in. After Steve was victorious, one of his victory screens had him chomping down on a piece of meat. All you fans have gone and sullied Minecraft Steve and Alex for far too long. The player's hunger value is shown on the heads-up display in the form of a hunger bar (or food bar), which is similar to the health bar (located above the hotbar), located opposite to it and represented by. Where did it go? GameXplain’s Twitter is one of the many to detail the changes, which we’ve added for you below. Hunger is a player-specific feature of Minecraft that regulates certain abilities (health regeneration and the ability to sprint), the value of which is managed by the player's activity. ![]() You can purchase the pass to have access to all six characters once they eventually release, or. Gone is now the meat in Steve and Alex’s victory screen. Minecraft Steve is the second DLC fighter to be released as part of the Fighter’s Pass Vol. Ultimate update emphasises that yes, this is a children’s game. You can see the changes below as detailed by GameXplain. We’re not quite sure where it’s gone but it’s no longer sitting where no meat should ever be seen in a Nintendo game. The Realistic Minecraft family are having a fun time with fake friends when they realise the friends are fake Nitro gives them some special milk to ease th. Did no one at Nintendo stop to think of how it looked? Well, fast forward to update 9.0.1 and Steve’s meat is no longer. The same was also able to be witnessed with Alex. ![]() As seen below, the blocky hero wielded a piece of meat (traditionally an item for use in level) in quite the unfortunate location on his body. It wasn’t long then, until the victory screen for when Steve wins became a meme. Fast forward to last week and the duo made their debut. Some weeks ago, Minecraft’s Steve and Alex were announced to be the latest two fighters to join Super Smash Bros. added their newest character, Steve from Minecraft, to the game, they didnt realize that one little animation they made for him happened to look like Steve holding his erect penis. That is to say at least in their victory screen. It’d be one thing if the Nintendo Overlords never allowed Steve to bring his meat from the Minecraft universe into the Super Smash Bros Universe to begin with, but to allow him to travel through the multiverse with his meat only to then severe him from it, leaving him hungry and alone in a strange land, where he must fight for his life against mustached-Italians, various princesses, and Pac-Man from sunrise to sunset just seems cruel to me.I don’t know how else to say this: Minecraft Steve’s meat in Super Smash Bros. Curiously, however, the official patch notes make no mention of any changes related to Steve’s meat. Many of these changes are related to the blocky fighter’s previously wonky minecart move. Unfortunately, the angle and placement of the object made. Chickens that die while on fire drop cooked chicken instead. When Steve won a round, he'd be holding onto a slab of meat, the same kind that he regularly munches on both in Minecraft and Smash Bros. The maximum is increased by 1 per level of Looting, for a maximum of 1-4 with Looting III. Upon death, an adult chicken drops 1 raw chicken. It can be cooked in a furnace, smoker, or a campfire to make cooked chicken. Get Minecraft: Java Edition and Bedrock Edition as a package deal for Windows With Minecraft: Java & Bedrock Edition, you. Version 9.0.1, which is available for download now, has a variety of Steve-related bug fixes. Raw chicken is a food item that can be eaten by the player. How tf was this approved man /rHUqPOgfrDįans soon discovered that Steven’s end-of-match win screen had him holding a piece of meat which, if paused at exactly the right moment, seemed like an NSFW pose. Minecraft Steve holding his meat in smash bros. ![]() ![]() With just a few clicks, you will have a visually stunning QR code perfect for your unique brand identity. Whether you are an entrepreneur, blogger, freelancer, or creative professional, Adobe Express QR code generator saves you precious time and resources when you need to create a QR code. ![]() Want your QR code to contain your brand logo? Go for it! Use the drag-and-drop editor to upload your brand logo and create a QR code that stands out. ![]() Use the online editor to generate a color palate for your QR code or add custom frames to make your design visually appealing and instantly recognizable. 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Adobe Express QR code creator helps you create a QR code for your website, social media, business cards, and even product sales. ZIP file containing these.Easily create custom QR codes for different content. The generated QR codes are free to use, will always work and will never contain advertisements in any way. Therefore, when you download the OBJ file, you will receive a. GenQRCode is a free QR code generator for creating high quality print format SVG, EPS, TIFF, PNG, GIF, WEBP and JPEG QR codes, but also 3D formats such as STL, 3MF and OBJ QR codes. The MTL file and the texture (PNG in our case). Once your account is activated, select Create QR. ![]() We do support full color on the OBJ files, but it requires 2 additional files. How to create a QR Code for video Sign up to QR Code Generator PRO and get started with a 14-day free trial. While our current support is limited to black and white, we have plans to include additional color options in the future. 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Which 3D formats do you provide support for, and what is the difference? ![]() ![]() ![]() However, since a simple mistake at the front can easily cause chaos at the back, the goalkeeper needs to be a person who can read the game through their vision of the pitch and pass commands effectively. Having 4 players at the back plus a defensive midfielder essentially means that the goalkeeper is heavily protected from the flanks and front. But since this strategy requires creating the play from the back, the goalie needs to have excellent ball skills to be able to support the first phase of the attack. The keeper's primary role when playing the 433 soccer formation remains that of protecting the goal with his life. 4 3 3 Formation Numbers, Roles, and Type of Players Goalkeeper So, let's see each players' role when coaching the 433 system. However, despite its proven success when playing counter-attacking, playing 4 3 3 requires specific players to make the most out of it. This system positions the players in 3 lines a back four, three central midfielders, and three forward players.Īlthough this soccer formation has evolved a lot since its inception in the 1920s and 30s, its goal remains the same: occupy every inch of space in the midfield while making it a cinch to pass the ball to the front. The 4 3 3 is more attack-oriented than other popular soccer strategies, including the 4-2-3-1 formation, 4-5-1, and the like. ![]() In this 4 3 3 formation guide, we give you a closeup look at soccer position numbers in 4 3 3, how to employ this strategy, and its key strengths and weaknesses. Fast forward in the modern game, PSG, Liverpool, and Man City's winning streaks using 4 3 3 formation tactics are excellent examples of how lethal this soccer strategy can be. Louis Van Gaal heavily relied on it to build his successful tenure at Ajax in the '90s, and so did Pep Guardiola's all-conquering Barcelona squad in 2009. This style of play heavily depends on the 4 3 3 formation and has dramatically changed the world's perception of how soccer should be played.Ĥ 3 3 formation tactics have been widely used by most of the greatest clubs in soccer history. While they didn't actually invent it, the Dutch are the original creators of Total Football. This ball-hungry system is commonly associated with Dutch coaches and teams to an extent where they are thought to be its inventors. ![]() Remarkable wing-backs are Marcelo, Dani Alves, Dani Carvajal and David Alaba.The 4 3 3 soccer formation has been one of the most used strategies in the last 2-3 decades. Also, if you have five defenders (three center-backs and two wing-backs), this allows more liberty for the wing-backs to venture attacking. For example, if you have a defensive line of four defenders (two center-backs and two full-backs) and your team is in need of a goal, you will want the full-backs to behave more like wing-backs and attack. If, on the contrary, you are clinging to a narrow advantage, you will want your wing-backs to play more defensively. Many full-backs have played as wing-backs and wing-backs have played as full-backs.Ī wing-back's role depends on the team formation and specific moments of the game. The main difference is that wing-backs have much more attacking responsibility than full-backs do. The wing-back position is similar to the full-back in that wing-backs play close and along the sidelines of the field. ![]() Traditionally Assigned Soccer Position Numbers: 2, 3 & 6 Let’s take a look at the role of each soccer position and the iconic players who illustrate each role. Here, we provide an overview of how numbers were traditionally assigned by position. In the modern game, jersey numbers vary greatly depending on formation as well as a player's personal preference. Historically, these numbers were used to indicate position, with the players on the field designated as #1 - 11. Below, we outline the traditional numbers for each soccer position. A common question is how numbers get assigned to positions. Second Forward / Second Striker / Support or Withdrawn Striker (CF or S)Īs you can see, there are plenty soccer positions and not all of them can play at once. Center-back / Center Full-back / Central Defender (CB) Names And Abbreviations For Key Soccer Positions Have you ever wondered how soccer positions work, how soccer position numbers are traditionally assigned or how the roles and responsibilities of each position are defined? Ever considered the difference between a full-back and a wing-back? Well, you are in luck: The18 introduces you to the ultimate guide to understanding soccer positions.įirst things first: let’s take a look at where the most common positions play on the field. ![]() ![]() ![]() ![]() Features and devices may vary by OEM, device manufacturer, and country. Subscription, purchase, or download may be required for viewing. Hulu + Live TV is best for those who want a huge live TV channel selection. To access Google TV and its features, a Google account, internet connection and a compatible streaming device, smart TV, or smartphone is required. As a bonus, you can instantly access popular streaming service (with a subscription) right from the Dish interface, including Netflix, Prime Video, and YouTube. Subject to availabilityĥ Access to the Google TV kids section requires that your child have either a Google account or profile managed with Family Link.Ħ To see personal photos, Google Photos is required.ħ Casting optimized for selected services only.Ĩ Compatible smart device(s) and an internet connection is required to access smart home features.ĩ Virtual remote is available through the Google TV app for Android and iOS. Popular examples of streaming services include Netflix, Spotify, and YouTube. Setup may be required.Ĥ Some apps and/or content may not be available in all countries. Watch NEW movies and shows plus on demand. ![]() A&E, The HISTORY Channel, MeTV, Hallmark Channel, INSP, Lifetime, Great American Family, The Weather Channel, & more. Subscription(s) required to access certain live TV content.ģ Google TV has the most free TV channels in one electronic programming guide (EPG). The most affordable LIVE TV streaming service 40+ channels starting at 6.99/mo. 1 To access or edit your watchlist you must be signed into your Google Account.Ģ Live TV recommendations available in the US only. FuboTV is an excellent streaming service for sports fans that also features many appealing news and entertainment channels for mainstream audiences. GET PARAMOUNT+ WITH SHOWTIME Watch hit originals, movies and docs, all in one place and ad free (except live TV and a few shows), for just 11.99/month when you sign up for the Paramount+ with SHOWTIME plan. ![]() |
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