![]() ![]() All Cell Painting data and processing scripts are available at. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.ĭata Availability: All scripts and computational environments to download and process data, train all VAEs, and reproduce all results and figures in this paper can be found at. Received: NovemAccepted: FebruPublished: February 25, 2022Ĭopyright: © 2022 Chow et al. Haugh, North Carolina State University, UNITED STATES Our benchmark and publicly available software will enable future VAE modeling improvements, and our drug polypharmacology predictions demonstrate that we can model potential off-target effects in drugs, which is an important step in drug discovery pipelines.Ĭitation: Chow YL, Singh S, Carpenter AE, Way GP (2022) Predicting drug polypharmacology from cell morphology readouts using variational autoencoder latent space arithmetic. We discover that modeling cell morphology requires vastly different VAE parameters and architectures, and, importantly, that the data types are complementary they predict polypharmacology of different compounds. Gene expression and cell morphology are the two most common types of data for modeling cells. Importantly, we train other VAEs using a gene expression assay known as L1000 and compare performance to cell morphology VAEs. In a comprehensive evaluation, we learn that an approach called latent space arithmetic (LSA) can predict cell states of compounds that interact with multiple targets and mechanisms, a well-known phenomenon known as drug polypharmacology. ![]() We train and systematically evaluate three different kinds of VAEs, each that learn different patterns, and we document performance and interpretability tradeoffs. Known as variational autoencoders (VAE), these algorithms are unsupervised, meaning that they do not require any additional information other than the input data to learn. We train machine learning algorithms to identify patterns of drug activity from cell morphology readouts. Inferring cell state for specific drug mechanisms could aid researchers in developing and identifying targeted therapeutics and categorizing off-target effects in the future. We reliably simulated morphology and gene expression readouts from certain compounds thereby predicting cell states perturbed with compounds of known polypharmacology. We found that the β-VAE and MMD-VAE disentangle morphology signals and reveal a more interpretable latent space. To test the generalizability of the strategy, we also trained these VAEs using gene expression data of the same compound perturbations and found that gene expression provides complementary information. We trained and evaluated these three VAE variants-Vanilla VAE, β-VAE, and MMD-VAE-on cell morphology readouts and explored the generative capacity of each model to predict compound polypharmacology (the interactions of a drug with more than one target) using an approach called latent space arithmetic (LSA). In this project, we evaluated the ability of VAEs to learn cell morphology characteristics derived from cell images. However, standard vanilla VAEs suffer from entangled and uninformative latent spaces, which can be mitigated using other types of VAEs such as β-VAE and MMD-VAE. These representations have been generated from various biomedical data types and can be used to produce realistic-looking simulated data. A variational autoencoder (VAE) is a machine learning algorithm, useful for generating a compressed and interpretable latent space. ![]()
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Trademarks, design patents and copyrights are used with the approval of the owner AUDI AG. property under design, trademark and trade dress regulations. The body designs of the Ferrari cars are protected as Ferrari S.p.A. ![]() The name FERRARI, the PRANCING HORSE device, all associated logos and distinctive designs are property of Ferrari Spa. ![]() Manufacturers, cars, names, brands and associated imagery featured in this game in some cases include trademarks and/or copyrighted materials of their respective owners. FMOD Studio, copyright Firelight Technologies Pty, Ltd., 2012-2016. The Assetto Corsa’s logo is a registered trademark of KUNOS Simulazioni Srl. All other trademarks are property of their respective Owners. ![]() ![]() ![]() This can be especially true for power tools, which can present a hazard when they have electrical faults or unstable guard protectors. Tradespeople may use the same equipment daily, so it's a priority to inspect tools regularly to ensure they remain in a safe and sturdy condition. Related: What Does a Scaffolder Do? (And How to Become One) Inspect equipment They arrange it so that the tradesperson can access any required tools or fittings as they perform the repair work. With this information, an assistant often knows what equipment to gather for the task. ![]() For example, before arriving at a worksite, a plumber might tell their assistant that their job is to fix a leaking shower head. Tradespeople typically require a lot of tools to complete various tasks, so assistants are usually responsible for knowing what's needed for specific jobs. A scaffolder's assistant may help erect scaffolding polls by using a magnetic level and a scaffold hammer. For example, a carpenter's assistant might use a circular saw to cut pieces of timber or use a level, caulking gun and cordless drill to assist with the installation of window frames. Because of this, assistant tradespeople are routinely required to use various hand and power tools, such as cordless drills, nail guns, wrenches and hammered tools, to help tradespeople complete manual tasks. Hand and power tools are essential to the daily duties of a tradesperson. Here are some responsibilities you might perform as an assistant tradesperson: Use hand and power tools to perform tasks Related: 23 In-Demand Jobs in Trade (With Average Salary Figures) Responsibilities of an assistant tradespersonĪssistant tradespeople undertake a variety of tasks depending on their particular field and industry. A tradesperson often requires a variety of hard and soft skills, including knowledge of occupational health and safety (OHS) procedures, an ability to operate various hand and power tools and excellent customer service, problem-solving, physical fitness and time management abilities. They can work in a range of fields within construction, agriculture and mining industries, such as carpentry, plumbing, farming, telecommunications, painting, heavy plant repairs, manufacturing and refrigeration and electrical professions. Related: How to Get Into an Apprenticeship (With Steps and Benefits) What's a trade assistant?Ī trade assistant is an entry-level professional who's responsible for providing assistance to a qualified tradesperson. In this article, we explain what a trade assistant is, outline some of their responsibilities and provide answers to commonly asked questions about an assistant tradesperson's role. Learning about the responsibilities of an assistant tradesperson can help you decide if this is a career that's right for you. Pursuing work as an assistant tradesperson can offer you attractive salary expectations, help you develop a variety of transferable skills and provide you with opportunities for career advancement. If you're someone who's mechanically talented and enjoys performing a range of different manual tasks, then an assistant tradesperson job might interest you. ![]() ![]() ![]() Levels= 5 (each has two numbers as stated right under this) or more, thats 100% of the original speed btw.so basicly from the document whats important to notise is: Ive made the parts i've edited bold so you can see what part of each section you will have to concentrate on, Why i only changed the last numbers on that ability is baicly cuz i had gotten the 5th engine speed ability, so no need to "fix" the lower ones, tho i could have ,made em all 100\200. NameDisplayable=Ability-Engines-Speed-Increase-Nameĭescription=Ability-Engines-Speed-Increase-Description, Ability-Engines-Speed-Increase-Description, Ability-Engines-Speed-Increase-Description, Ability-Engines-Speed-Increase-Description, Ability-Engines-Speed-Increase-DescriptionĪbilityType=SurfaceSpeed, SubmergedSpeed increases engine speed (in percents)ĪbilityValue= 5, 5, 10, 10, 15, 15, 20, 20, 100, 100ĪbilityInternalValue= 18.5, 17.25, 37, 34.5, 55.5, 51.75, 74, 69, 200, 200 factor1: 3.7, factor2: 3.45ĪbilityRequirements= 0, 1, Ability-Engines-Speed-Increase, 1, 1, Ability-Engines-Speed-Increase, 2, 1, Ability-Engines-Speed-Increase, 3, 1, Ability-Engines-Speed-Increase, 4 upc (like those other files in same directory) REMEMBER MAKE A BACKUP OF ORIGINAL BEFORE EDITING ANYTHINGĪND AFTER EDITING RENAME FILE BACK TO. Open it and half way down the document you see the important stuff. To edit the file, rename it to SpecialAbilities.cfg or.txt \Ubisoft\Silent Hunter 5\data\ UPCDataGE\UPCCrewData If you wanna give it a try urself, its not hard, just gotta know basic editing with a cfg document. I can aslo edit the damage % a torpedo does, how fast it is and so on, basicly everything that an ability mods, can be modded. got about 14 now to use Active abilities on, also modded the chef to fill 75% each 2 hours. Ive tried some modding on my game, but all i seem to be able to mod is the Special abilities, wich in my case i edited things like, more Morale Points total. ![]() ![]() ![]() RETURNS ARE NOT ACCEPTED, but if there are any problems, please contact us. Choose from Same Day Delivery, Drive Up or Order Pickup plus free shipping. 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PLEASE MESSAGE US WITH ANY CUSTOM LENGTH YOU WOULD LIKE. ![]() ![]() ![]() Our show is so specific and layered and complicated that it’s interesting for me to see how the clothes can be adapted.īenjamin Kirchhoff: It’s nice when you see all these girls and boys walking around Dalston doing DIY looks. I have the girl pictured in my head that I present on the runway and then beyond that I want to leave it up to whoever works on the pieces and whatever way they want to wear them. It’s much more important to us.Įdward Meadham: We use models for the show but everyday reality is not about those girls. We have no problem with celebrities in theory – it’s just that so far we haven’t hadĭ&C: Would you rather see your clothes on real girls?īenjamin Kirchhoff: Yeah. ![]() You really don’t want celebrities wearingĮdward Meadham: There are almost no celebrities in this day and age who actually express any point of view or personal style. I wanted it to be about girls being happy about being girls, without there being the threat of a male gaze.īenjamin Kirchhoff: We’ve been quite obsessed lately with something that Leith Clark said to coincide with the launch of her magazine, that she was terrified that every shoot and every representation of women in fashion always had this invisible male presence.ĭ&C: Recently you’ve been more controlling about who wears Meadham Kirchhoff. The whole idea was more celebratory than confrontational.Įdward Meadham: I wanted to feel like nothing bad was going to happen, in terms of the moods and the colours.ĭ&C: But perhaps confrontational in a very light way?Įdward Meadham: Well, it being so light is sort of confrontational. We didn’t want to have an undercurrent of anything. The idea of the wolf was as a confrontational and aggressive thing masquerading as something sweet and innocent.īenjamin Kirchhoff: We tried to really not have a dark side. There was going to be another section actually, but that didn’t really work out.ĭ&C: Why did you title the collection ‘A Wolf in Lamb’s Clothing’?Įdward Meadham: It comes from the idea of ‘mutton dressed as lamb’ and ‘a wolf in sheep’s clothing’. I knew I wanted to have a block of Courtney Loves powdering themselves and a giant cake, and the ballerinas. How did you come up with the concept?Įdward Meadham: I tend to work backwards – I see the show, styling and everything way before I actually know what the clothes are going to be. Splattered princesses sit happily alongside the fluffy candies from Louis Vuitton’s Carousel show or Prada’s 50s heroines – whether they like it or not.ĭazed & Confused : This season’s show was a particularly big performance. ![]() Meadham Kirchhoff’s fearlessness has paid off, and its cotton-candy, ice-cream. At a time when fashion has recoiled from fun, and performance is in fear of going under, it’s refreshing to see such courage and gusto from a young brand. The spectacle began with a procession of Courtney Loves and ended with a whirlwind of Sylvia Young ballerinas sandwiched between these catwalk theatrics was a brilliant collection of 25 sickeningly sweet looks. This season the catwalk was transformed into a tween girl’s’ saccharine birthday party, decorated with a pastel palette fit for My Little Ponies and Care Bears. I knew I wanted to have a block of Courtney Loves powdering themselves and a giant cake, and the ballerinas I tend to work backwards – I see the show, styling and everything way before I actually know what the clothes are going to be. The designers have gone from strength to strength ever since, sometimes slotting boys into their womenswear show but concentrating mostly on womenswear, for now. In 2007 they embarked on their first womenswear collection, showing within London’s Fashion East line-up. ![]() The pair met in 2002 while studying fashion at Central Saint Martins, and even though the British-born Meadham was on the womenswear course and French-born Kirchhoff was doing menswear, they joined forces after graduation with the menswear label Meadham Kirchhoff. Edward Meadham and Benjamin Kirchhoff created yet another new world for their spring/summer 2012 show, a candy and ice-cream-coloured universe where the soft and fluffy forces of good prevailed. ![]() ![]() This section needs additional citations for verification. Instant messaging remains very popular today IM apps are the most widely used smartphone apps: in 2018 there were over 50 million Signal users, 980 million monthly active users of WeChat and 1.3 billion monthly users of WhatsApp Messenger. BBM was for instance the most used mobile messaging app in the United Kingdom and Indonesia. Beginning with its first introduction in 2005, BlackBerry Messenger, which initially had been available only on BlackBerry smartphones, soon became one of the most popular mobile instant messaging apps worldwide. Later in the 1990s, ICQ was among the first closed and commercialized instant messengers, and several rival services appeared afterwards as it became a popular use of the Internet. Instant messaging was pioneered in the early Internet era the IRC protocol was the earliest to achieve wide adoption. Instant messaging applications can store messages with either local-based device storage (e.g WhatsApp, Viber, Line, WeChat, Signal etc.) or cloud-based server storage (e.g Telegram, Skype, Facebook Messenger, Google Meet/ Chat, Discord, Slack etc.). It is usually distinguished from text messaging which is typically simpler and normally uses cellular phone networks. Depending on the IM protocol, the technical architecture can be peer-to-peer (direct point-to-point transmission) or client–server (an IM service center retransmits messages from the sender to the communication device). IM can also consist of conversations in " chat rooms". a wider social media platform, or a website where it can for instance be used for conversational commerce. Instant messaging systems tend to facilitate connections between specified known users (often using a contact list also known as a "buddy list" or "friend list"), and can be standalone applications or integrated into e.g. Most modern IM applications (sometimes called "social messengers", "messaging apps" or "chat apps") use push technology and also add other features such as emojis (or graphical smileys), file transfer, chatbots, voice over IP, or video chat capabilities. ![]() It differs from email in that conversations over instant messaging happen in real-time (hence "instant"). Messages are typically transmitted between two or more parties, when each user inputs text and triggers a transmission to the recipient(s), who are all connected on a common network. Instant messaging ( IM) technology is a type of online chat allowing real-time text transmission over the Internet or another computer network. A classic example of instant messaging on a desktop computer: the left window of this software showing a list of contacts (" buddy list") and the right window an active IM conversation ![]() ![]() ![]() ![]() ![]() So how can you watch Jury Duty online? Read more below to find out. So in the course of four weeks, we’re serving jury duty in an abandoned courthouse that he thinks fully is an operational courthouse.” He continued saying that it wasn’t functioned to be a prank show, “There’s no dialogue that is scripted but there are circumstances are scripted that we push beats along the way and make a hero’s journey for this guy to unify a ragtag group of weirdos by the end and get to the finish line with him and it worked.” There’s a complete cast of characters playing all different kinds of characters and one guy who doesn’t know that this whole thing is fake. There’s me playing a heightened and entitled Hollywood version of myself. The backdrop of the three or four weeks is all of these characters having to serve on this jury for this case. “I would describe this as basically, The Truman Show serving jury duty. In an interview with E! News he talked about his role and the TV show as a whole. James Marsden, the actor who you’d know from Westworld and Dead to Me, plays an exaggerated version of himself who was summoned to go to jury duty and uses his Hollywood star fame to try to get out of scenarios, but the actors do not know who he is. Everyone except him is an actor, and everything that happens is carefully planned.” The show was created by The Office’s Gene Stupnitsky and Lee Eisenberg. The official synopsis describes the show as “it follows the workings of an American jury trial through the eyes of Ronald Gladden, a juror who is unaware the entire case is fake. The FreeVee show is now available to stream, but where can you watch it? If you’ve been seeing ads about a reality show that takes place in a courtroom (and James Marsden is just…there), you might be wondering how to watch Jury Duty. ![]() ![]() ![]() So, while this figure’s sculpt certainly has an impressive amount of detail, it’s far from movie accurate. Topher Grace’s Venom wasn’t anywhere near as big as the comics version, but all the SM3 Venoms seemed to go with a more comics-inspired sizing. It’s a rather sizeable sculpt to be sure, though it’s more than a little off from the movie Venom. Of the eight figures in the series, Venom was one of the four to get a new sculpt. Venom stands just over 7 inches tall and has 30 points of articulation. The series was released at roughly the same time as the Fantastic Four-themed “Ronan Series,” which was between Series 2 and 3 of the main line (The SM3 and FF series served to discontinue attempts at referring to Hasbro Legends by numbered series from there on). Venom was released in the “Sandman Series” of Hasbro’s first go at Marvel Legends. Most of the heavy hitters from the films were covered, including the third film’s (somewhat maligned) version of Venom, whose figure I’ll be looking at today. Fortunately, Hasbro recognized the frustration, and put together a series of Marvel Legends based on the Spider-Man trilogy. The end result was a large number of fans boycotting the smaller line (I didn’t boycott it I just happened to not get many of the figures). It was a really odd move, and it wasn’t helped by the fact that the overall quality of the toys fell pretty steeply too. Despite the prior two Spider-Man films (and pretty much everything else Marvel-related from the early 2000s on) having been pretty much exclusively 6-inch scale, Hasbro opted to release the Spider-Man 3 figures in 5-inch scale. Spider-Man 3 came out in 2007, which was the year that Marvel toys switched from Toy Biz to Hasbro. I actually don’t own a ton of toys from Spider-Man 3, though (apart from the Minimates), because of some general weirdness surrounding the tie-in figures. It still entertains me, and that’s really all I can ask. Honestly, it’s probably aged the worst of the three Raimi films, and even Sam Raimi’s said he feels it could have been better. Spider-Man 3 is a movie that a lot of people don’t care for. ![]() ![]() Or, if you are in a campaign with plenty of humanoid opponents, a disarm attack is devastating to most enemies, especially if your companions get wise, and pick up the weapon. Get Maneuver Mastery, then trip stuff or kill stuff depending on your whim (not everything can be tripped). Get a Scorpion Whip (same proficiency), and you won't have to think about dealing non-lethal damage. Probably trip, but it depends on the campaign. I'd go with full Dex Magus then, get weapon finesse ASAP, and focus on one of either Disarm or Trip combat manoeuvres. Besides, the Magus is a strong enough class that you can optimize your way out of such little things. Roleplaying/Minds eye concepts beats optimization any day of the week. ![]() If you like the sound of it, it is worth it. Is it worth investing a feat into using a whip? Watch the morale of your enemies plummet! Plus, cursing someone with a whip strike is awesome. Trait2: Magical Lineage (shocking grasp), for 10d6 dmg shocking grasp at higher levels, with only a 1st level spell slotĭo take the Hexcrafter archetype and deliver touch spells from 15 ft away, while you Cackle to keep your Evil Eye hex active. Trait1: Heirloom weapon (whip), gives free proficiency with whip The image of cracking your whip at the barbarian, it bouncing off his head (no dmg) and suddenly he doubles in size as Enlarge person takes effect, is delightful. With this setup, you can easily use a buckler, use touch attacks to deliver your spells at range and even use your whip to deliver buff spells to your allies (+1 AC or +3 natural AC takes no damage from the whip). Allows for your Spell Combat to be used effectively, leave you able to strike when AoO appears and keeps you out of the front line most of the time. ![]() Do you want to be able to deliver touch spells from 15ft away? My favorite low-level magus combination is spiked guantlet + whip. ![]() |
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