![]() The post was published on Tuesday 6th December following Morocco’s penalty shootout victory over Spain in the round of 16. Morocco’s goalkeeper Bono is the subject of the fourth most popular World Cup tweet. “ LIONEL MESSI” generated a total of 305,641 reactions, including 272,000 likes, 3,341 replies, and 30,300 re-tweets. The third most engaged post is the tweet from Argentina’s opening goal against Croatia in the semi-final on December 13, and simply names the scorer of the penalty. The minimalist post generated an impressive 267,335 likes, 42,600 retweets and the most replies of any tweet in the list – 4,156. The tweet with the second most total engagement from FIFA’s official account is from the opening day of the competition, Sunday 20 November, and says one single word “Today”, without any image or video attached. The tweet simply, “WOW #FIFAWorldCup | #Qatar2022”. ![]() So far at this year’s showpiece, a photo of Richarlison’s spectacular overhead volley against Serbia in the group stage is the tweet that has generated the most engagements, racking up 285,000 likes, 44,600 re-tweets and 1,896 replies. Richarlison’s goal is definitely one of the best this World Cup has seen, so it’s a worthy winner, while there were plenty of upsets, shocks and great performances to fill up the top ten. The study by sports betting site Nostrabet analyzed tweets from the official Twitter account to discover which of its football-related posts since the opening day of the tournament have had the most combined likes, re-tweets and replies.Ĭommenting on the study, a spokesperson for Nostrabet said: “The World Cup is reaching a climax and soon fans will start feeling nostalgic about the action at the tournament, so it’s fascinating to take a look back and see which moments made the biggest impact at the time. Richarlison scored a sensational goal for Brazil against SerbiaĪccording to a new research, Richarlison’s stunning acrobatic goal against Serbia is the biggest social media moment of the World Cup so far. Qatar 2022: New study reveals top 10 social media moments of the tournament so far These moments amongst others have lit up social media globally triggering reactions and opinions from fans and lovers of the beautiful game as well. Neither could we forget about Japan’s epic comeback against the 2014 champions Germany. Who could forget Saudi Arabia’s remarkable opening group stage upset against Argentina? However, we’ve seen some incredibly mind-blowing moments so far at football’s greatest showpiece. Qatar’s showpiece has actually turned out to be far better than most had anticipated following the controversies surrounding this year’s venue as well as the host nation’s bid. ![]() The FIFA World Cup 2022 has no doubt offered fans around the world more than a fair share of premium drama.
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![]() People whose job is to build conversational interfaces are called conversation designers, conversational UI designers, or voice UX designers. And either one is a conversational interface. So, Google Assistant in a Google Home smart speaker is an example of voice UI (or VUI), while Google Assistant in a smartphone that understands both text-based and voice-based commands is conversational UI (CUI). At the same time, Voice User Interfaces (VUI) are part of the CUI concept, which implies voice-only interaction with devices. There are two types of conversational interfaces: Conversational User Interfaces (CUI), which comprise both text- and voice-based interfaces where users communicate in natural language. Be it playing voice games, using in-car voice controls or voice search, messaging to virtual assistants, anything can be part of the dialog here - voice-based and text-based information input/output, dialog boxes, pop-up windows - you name it. Thus, Conversational UX, is how users communicate with other people and conversational interfaces, aka Conversational UI, that include chatbots and virtual assistants. As one might guess, UI - or user interface - is the point of that very interaction. What is UX? As the name suggests, UX - short for user experience - is the way users experience services, systems and products and interact with them. So, if you’re already familiar with the basics, feel free to move to a more advanced level. We’ll explain how to make conversational services user-friendly and create smooth bot flows, starting from the simplest and gradually moving to the more complex. Here we’ve put together the most important insights gathered over the years of designing voice assistants and chatbots. Many businesses rely on conversational technology to promptly address user queries, grow direct sales, and increase customer loyalty. A 2021 study by Voicebot.ai discovered that 60% of marketing experts surveyed thought voice assistants would make a great marketing channel. Conversational agents like chatbots and virtual assistants are becoming an integral part of our lives on many different levels. ![]() Experiment with different styles, such as abstract, realistic, or cartoonish. Thirdly, practice sketching the different shapes and angles of the eyes. ![]() The highlights and shadows can also create a 3D effect, making the eyes look more prominent. For instance, the light source can reflect on the iris, creating a brighter and contrasting effect. Secondly, observe the light source, shadows, and highlights to make the eyes look more realistic. You can use different shades of dark and light colors to create depth and highlight the reflection in the eyes. Pay close attention to the size and shape of the iris and pupil, which can convey the mood and emotion of your subject. Here are some tips and techniques that will help you to add life to your portraits.įirst, it is essential to understand the anatomy of the human eye, which includes the iris, pupil, sclera, and eyelashes. However, will make this task much easier. ![]() Unlocking the Secrets of Human Eye Drawingĭrawing the human eye is a challenging task for many artists. So always approach your shots with intention and sensitivity, and let the eyes speak for themselves. ![]() By capturing the gaze and expression of your subject, you are communicating something profound about their personality and emotions. Keep in mind that the human eye is not just a physical feature, but also a window to the soul. By establishing trust and rapport, you can bring out their true essence and capture a gaze that is both authentic and captivating. Capturing the human eye also requires a certain level of connection and empathy with your subject. It’s not just about technical skills, though. Use natural light or artificial lighting to create a catch light in the eyes, which adds sparkle and depth. Lighting: Proper lighting can make all the difference in highlighting the eyes.An intense or fleeting gaze can add depth and emotion to your image. Timing: Wait for the perfect moment to capture the person’s gaze.Framing: Make sure the eyes are your focal point and use framing techniques, such as the rule of thirds or leading lines, to draw the eye to the subject’s gaze.Whether you’re shooting portraits, landscapes, or street scenes, getting the viewer’s attention through the eyes is crucial. When it comes to photography, capturing the human eye is an essential element in creating an impactful and memorable image. Whether you are a beginner or a seasoned artist, this article will offer valuable insights and tips to help you master the art of drawing the human eye. In this article, we will delve into the world of human eye drawing, exploring its history, anatomy, and the techniques used to create stunning eye drawings. However, with the right knowledge, skills and technique, it is possible to create a realistic and striking eye drawing that captures the essence of this mesmerizing feature. The eye is a complex structure that requires a deep understanding of its anatomy, proportion and texture. It is a complex and captivating feature, with its unique shape and vibrant colors, which has inspired artists to explore its beauty and intricacies in various forms of art.ĭrawing the human eye can be a challenging task, even for the most experienced artists. From ancient Egyptian hieroglyphics to modern day portraits, the human eye has been the key focus for artists all around the world. And that's it.The human eye has been the subject of artistic expression for centuries. Then choose the Pencil Tool and draw 2 different points. Choose the Elliptical Marquee Tool and make a round selection (holding Shift) in the center. Apply Image > Adjustments > Hue/Saturation with the following settings: Hue-> 31, Saturation-> 93, Lightness-> -35 and set the Blending Mode to " Overlay".Ĭreate a new layer (Layer 4). Apply Filter > Noise > Add Noise with the following settings: Amount-> 400%, Distribution> Uniform, Monochromatic-> OFF.Ĭhoose the Smudge Tool ( Diameter-> 21px) and spread the noise from the center to the border. Choose the Radial Gradient Tool and fill the selection from the center to the border.Ĭreate a new layer (Layer 3) and fill it by the white colour. Press " D" to reset colours and then press " X". Choose the Elliptical Marquee Tool and make a round selection (holding Shift) in the "eye" center. Then apply Select > Deselect.Īpply Layer > Layer Style > Drop Shadow and use the following settings:Ĭreate a new layer (Layer 2). Create a new layer (Layer 1) and fill it by the white colour (apply Edit > Fill. Choose the Elliptical Marquee Tool and make a round selection (holding Shift). Create a new 400X400 pixels document with the white background. ![]() This will give the gluten time to relax and help the batter thicken up a bit, resulting in a crispier waffle. Let the batter rest: Allow the batter to rest for a few minutes before using it to make waffles. Mix the batter just until the dry ingredients are incorporated, and then stop. Sorry.ĭon't overmix the batter: Over mixing the batter can cause the gluten in the flour to develop, resulting in tough, chewy waffles. Neither of those will do the job of cooking spray. Releasing the waffles from both sides of the waffle iron is so important I am willing to use cooking spray.not oil, not butter. Use a cooking spray: this is my least favourite tip of the day, but it is pretty vital. Go with a longer heat up time than recommended by the appliance. This will also help to prevent the waffles from sticking to the iron. Use a high temperature: Set your waffle iron to a high heat to ensure that the waffles cook quickly and the exterior crisps up nicely. ![]() My top tips for crispy waffles are as follows We love these, they were very hard to stop eating, even though we had had a taste and approved, we managed to polish off quite a few. Pandan leaves themselves, can be used to add a subtle sweetness and aroma to savory dishes such as curries and stews. ![]() The smell is quite distinctive in a good way (as opposed to the distinctive fragrance of durian). It also pairs well with vanilla, chocolate, and caramel in Western-style desserts and of course often appears in baked goods in Asian countries. Pandan is commonly paired with coconut, mango sticky rice, and other tropical fruits in Southeast Asian cuisine. Well we made the Pandan Extract, so we thought we better use if for something specific. ![]() This guest column was written by Luke Wilhoit, Managing Editor, CarPartPlanet.Hey everyone I'm working on final assembly of my 34 Ford Pickup with a GM 350/357 crate engine and an NV3500 transmission. While attention to detail is not something many want to deal with in today’s age of instant gratification, it is often these small details that are the difference between failure and success, boom and bust. A resourceful mechanic could create compatible, working transmissions across multiple models for much cheaper than others. Another advantage of the NV3500 is that it is easier to find scrap parts for other manual transmissions thanks to its close relation to so many other models. What may seem at first glance like an unnecessary frustration, can actually help us when proper knowledge is applied. Being able to use the same transmission (with only a few slight modifications) across several different makes, models, and engines, is an advantage that few transmissions can claim, even in modern manufacturing. The interchangeability of the NV 3500 transmission should not be overlooked. With just a little due diligence however, we can turn what seems to be disadvantage, to advantage. Many subtle changes exist inside these transfer cases, much to the chagrin of mechanics and diyers everywhere. As a result, you have a period of time when it seems many transmissions are the same, but this is only external appearance. There were many small changes made in rapid succession that led up to big differences in outcomes. It is important to note that some of these require adaptations, which can be done with conversion kits, or through manual modification if the mechanic is knowledgeable enough.īefore and leading up to when the NV3500 hit the market, there was a lot of progress and innovation being made in the transmission space. With some modification, the NV3500 can be adapted to the Jeep Amc 4.0 L I6 engine as well.The NV3500 is also compatible with a number of different engines, including: Because the NV3500 and the NP231 both have a 23 spline outer shaft, they are interchangeable. The Jeep NV3500 was made to have the same transfer cases as the NP231 and the NP241OR. While transmission similarities can be a source of confusion, it also has the added benefit of making different models more compatible. The outer shaft has 23 splines, and is flush with the adapter flange’s rear transfer case. Some of the later NV3500 models that came out in 2004 Jeeps feature a surprising and impressive 19 splines per 1″ input shafts. The spline count for the input shaft is 10 splines per 1 and 1/8″ diameter, there are some exceptions to that rule however. The specifications for the transmission are as follows: All gears except reverse are synchronized and helically cut in the NV3500. The 4th gear is directly driven, while the 5th one is overdriven. The NV3500 is a five speed manual transmission that features top shifting, and is longitudinally loaded. 2004 was the last year that the NV3500 was put in Jeep vehicles, after this point it was replaced by the NSG370 model, a 6 speed manual. This transmission was also present in several light-duty Dodge pick-up trucks. This manual transmission was meant to be an upgrade from the AX15 model. The Jeep NV3500 transmission was released by New Venture Gear in the year 2000 for the Jeep TJ Wrangler and the XJ Cherokee. These distinct features differ from GM, making the two incompatible. Dodge utilizes unique specs for their input shafts, pilot diameter, and even spline count. This is because the bellhousing and case of the transmission are both one piece, and they have different bolt patterns that are specific to each engine. It is also important to note that transmissions of both Dodge and GM are not interchangeable. The master went from 11/16 to 18mm, while the slave went from 13/16 to 20mm. Both changed their bore measurements to metric from standard after the 1990s. Another key difference is the master and slave cylinders. This is because the C/Ks have a shorter tail shaft length than GM’s own S models. A “drop-in” change out between a GM S and C/K trucks requires a modification to the length of the driveshaft, as well as altering the crossmember placement. ![]() ![]() Thursday morning the Incident Management Team reported that the fire had burned 678,000 acres. The blaze is still very active in Wilcox Valley and on the west side of the 2019 Walker Fire. Approximately five miles of the eastern side of the fire is now alongside Highway 395 west of Honey Lake between Janesville and Milford. It crossed the highway in at least two places but firefighters were able to limit the spread east of the roadway. The spot fire that started five miles east of the Dixie Fire near Highway 395 has grown to about 20,000 acres. The brown areas had extreme heat when the fire was mapped Wednesday evening. The white line was the perimeter at 8:55 p.m. The red areas represent heat detected by a satellite at 3:26 a.m. Satellite photo, Western Fires at 6:26 p.m. Next, is the satellite photo showing smoke from fires in Washington, Oregon, and California. The fire on the north side of Beckwourth Genesee Road is currently backing down the middle slopes and crews continue to construct lines to mitigate impacts to structures in the Genesee Valley.”īelow is the map showing the boundary between the two zones, revised August 16. After aerial retardant application, the spot fire remains at approximately the same footprint of 30 to 40 acres and firefighters are constructing and reinforcing contingency lines to the south. In an additional priority area, rotary aircraft supported crews in the Genesee Valley this morning when they were able to fly. Fire line was constructed on the south end from Highway 395 to the Walker fire scar. Along Honey Lake, the northern edge near fruit grower’s road has remained in its current footprint due to the continued northeasterly winds. “ Dixie Fire East Zone: West Zone and East Zone crews, equipment, and aircraft have maintained aggressive engagement on the portion of the fire near Janesville. Please see below for information affecting your area.” Damage assessment is ongoing, and the number of damaged and destroyed structures may change as teams are able to access the fire area safely. This process includes guaranteeing roads are safe for travel and basic utilities to infrastructure is secured. A methodical, multi-pronged process of inspection and evaluation must be conducted to ensure the health, safety and welfare of all the residents affected. There are many considerations before allowing an area to be repopulated. Fuel moistures are historically low which is contributing to the critical fire behavior. Smoke from other fires nearby did limit activity in some places, but not enough to prevent additional growth. Fire remained active under northeast winds, with spotting and torching contributing to fire growth. “Dixie Fire West Zone: Firefighters continue to build and bolster containment lines on the Dixie Fire. Below are their updates from today at 7 p.m. After closely reading them for a week, it became obvious that they are written by two different people with different views on what information should be included. ![]() In CAL FIRE’s twice daily updates the “Current Situation” section is broken down into the West and East Zones. The fire is being managed by two Incident Management Teams, one on the west side and the other on the east side. ![]() (To see all articles on Wildfire Today about the Dixie Fire, including the most recent, click HERE.) The acreage figure was about 22,000 higher than the number from 12 hours earlier, and now stands at 699,666 acres.Īt least 659 residences have been documented as destroyed and 137 commercial buildings. local time CAL FIRE released an update on the Dixie Fire. ![]() Higher dosage of nicotine making it perfect for pod open system device and for mouth to lung vaping. Try this e-liquid with starter kits and pods kits for best results.ĭinner Lady 50/50 e-liquids are popular thanks to their wide range of flavours with fruit, candy, menthol and tobacco available, as well as the range of nicotine strengths allowing them to support different vaping styles. Bubble Gum by Dinner Lady tastes like classic bubblegum. Shop Bubble Mint by Dinner Lady Ice Moments 60ml The classic flavor of sweet gum from the pilgrimage, which is gently complemented by the menthol end. When vaped you'll experience discreet vapour production and improved flavour clarity. ![]() This means it's easy to find a blend that delivers both your ideal nicotine concentration and level of throat hit.Ĭreated for use with mouth to lung vape kits, this is a 50% VG e-liquid. A sweet bubblegum flavour which is consistent throughout delivers a simple yet bold vape.īubblegum 10ml e-liquid is available in either a 3mg, 6mg or 12mg nicotine strength. Over 18s Only You must be over 18 to purchase from this website, all customers will be age verified.īubblegum e-liquid by Dinner Lady is a candy blend with a sugary taste. Dinner Lady Ejuice prides itself in providing high quality eliquid vape juice through research, development, rigorous testing and innovation. Tuck Shop – Bubble Trouble ICE by vape dinner lay e-liquid is a vapable reiteration of bubble gum and menthol, capturing the sweet and upliftingly chill scent, translating into a delicious flavor that will have 4/5 vapers agree that this is it.38 Reviews In Stock Order by 7:00PM for same day dispatch & tracked next day UK delivery.* FREE when you spend over £20! Price Match Guarantee We will never be beaten on price! Terms & conditions apply. Dinner Lady 39 products Dinner Lady Eliquid is an Ultra Premium European Ejuice company that specializes in the creation of gourmet vape juice. Tuck Shop – Bubble Trouble ICE by Vape Dinner Lady E-Liquid is a vapable reiteration of bubble gum and menthol, capturing the sweet and upliftingly chill scent, translating into a delicious flavor that will have 4/5 vapers agree that this is it. ![]()
Now we will add the rest of the keys (highlighted green) as XPUBs in Sparrow. In this example, keys with fingerprints 7b71b9cb and 6a7bed37 (highlighted red) were already imported. Note the fingerprints of the keys you already imported. ![]() To get the XPUBs, open the wallet configuration file. Next, you will fill in the other keys in the wallet by putting in their extended public keys (XPUBs). In this example, the second key we are importing was created in COLDCARD, so its path is m/48h/0h/0h/2h (if unsure, review the wallet configuration file).Īlso take note of the master fingerprint of the key. Then click “Create Keystore”.Īgain you will be prompted to enter the derivation path for the key. If there was a passphrase, you must enter that as well. Under “Mnemonic Words (BIP39)”, choose either the 24-word or 12-word option, depending on the length of your seed phrase. To restore a key using a seed phrase: Switch to an unused Keystore tab, click “New or Imported Software Wallet”. Take note of the master fingerprint of the key. M/48h/0h/0h can also be written as m/48’/0’/0’ (the characters h and ‘ are interchangeable), as shown in the image here. In this example, the first key we are importing is a TAPSIGNER, so its path is m/48h/0h/0h (if unsure, review the wallet configuration file). You will be prompted to enter the derivation path for the key. ![]() To restore a key using a master private key: Navigate to Settings, under one of the unused Keystore tabs, click “New or Imported Software Wallet” -> “Master Private Key (BIP32)” -> “Enter Private Key”, then paste in the master private key and click “Import”. Now you can start restoring the keys one-by-one by using either the seeds, the master private keys, or the extended public keys (XPUBs). Switch to Multi-Signature and adjust the M and N parameters on the Cosigners slider, so that they match your wallet configuration. Once you have a copy of the wallet configuration file, proceed to download and install Sparrow Wallet on your computer.Ĭreate a new wallet in Sparrow and name it “Recovered wallet”. In this example, we will be recovering a 2-of-4 multisig wallet (a Honey Badger wallet). The file should look similar to the one on the right of the image below. Once downloaded, open the file using any text editor. You will be prompted to save a text file. Select “Export wallet to COLDCARD” and choose the file option. To get the configuration in the COLDCARD format, navigate to your wallet in Nunchuk, tap on “View wallet config”, then tap on the 3-dot menu (top right of the screen). For this guide however, we will use the COLDCARD format, which is compatible with Sparrow and is human-readable. Nunchuk supports multiple wallet configuration formats and natively uses BSMS, which is based on BIP129. It is a good idea to back up the wallet configuration in another place besides Nunchuk, such as in a password-protected cloud storage, your personal drive or email. You can export your wallet's configuration at any time from inside the Nunchuk app. Restore keys using seeds or master private keys.To do so, under Sparrow's wallet settings, select either “Connected Hardware Wallet” or “Airgapped Hardware Wallet”, depending on your device type. (d) An alternative to importing seed phrases is to add the original signing devices that were initialized with those seed phrases to Sparrow (if you still have access to the devices). For example, if you had created a multisig wallet by adding keys A -> B -> C -> D sequentially, during recovery you can import them as B -> D -> A -> C, or any other order, and it will still be able to reconstruct the same wallet. This means during recovery you can import keys in any order. (c) Both Nunchuk and Sparrow sort keys automatically. If you are unsure, you can always get the path information for your keys from the wallet configuration file. For keys created in Nunchuk, including the TAPSIGNER: m/48h/0h/0h.For keys created in common hardware signing devices: m/48h/0h/0h/2h.Nunchuk defaults to using Native SegWit multisig wallets which typically use these paths: (b) Importing a key during wallet recovery requires knowing the key's BIP32 derivation path. (a) If you have a TAPSIGNER in your setup, you can learn how to extract its master private key here. For example, for a 2-of-4 multisig wallet, you will need either 2 seeds, 2 master private keys, or 1 seed and 1 master private key. ![]()
We suggest being an active member of reddit before submitting links to your own site. Self Promotion - The community has spoken: If you only submit links to your own content, your links will be removed as spam. Message the moderators, and we will free it for you (assuming it is not actually spam.) If your submission does not appear in the new tab, and you don't think that it counts as spam - then it may have been caught by the spam filter. No computer-generated responses.ĥ - Don't be a jerk. We use the reddit FAQ guidelines for spam when removing spam posts.Ġ - No bots of any sort. No complaints.READ FIRST For LIVE CHAT regarding cycling please visit #bicycling on Snoonet Is there anything you don’t like about Vanyar? ![]() What do you like the most about this bike? Left Gossamer custom 100mm crank with Assioma pedalĪs of January 2022, I have done 280 watts for an hour during a solo ride. Having such a short crank makes it much harder to produce torque at low speeds, so gear selection is very important for acceleration. How do the short cranks affect your pedaling style? What is your average RPM? It does an excellent job with road vibrations. How comfortable is it on a scale from 1 to 10? Does it absorb road vibrations? Does the riding comfort change on a rough tarmac? This is how it feels when riding the Elves Vanyar. To understand this effect, imagine when you are riding and shifting your weight back, you notice the steering becomes lighter, almost like a floating feeling. It descends well, but you can feel that the front end is much lighter. So, how are the riders on flats and rolling terrain? Can you keep up with your friends in a draft?Įven though this is considered a lightweight climb bike, it’s very fast on the flat. I didn’t have much chance to ride it on climbs in Florida, but I recently took this bike to North Carolina, and the bike climbs like a goat. Thanks to its low weight, I guess it accelerates quickly and is super responsive, which is ideal for attacks and steep climbs, right?Ĭorrect. My weight is 165 lbs, and the frame feels stiff. The Elves Vanyar is a very lightweight frame. Elves Vanyar unopened box Elves Vanyar headset spacers Elves Vanyar seatpost markings Elves Vanyar handlebar cable routing detail Elves Vanyar complete buildĭayan’s Riding Experience with Elves Vanyar ![]() In the future, I plan on upgrading to 30mm extra light wheels to lower the weight even more. ![]() The goal was to build a lightweight bike on a budget. eeBrakes weight EEbrakes rear break EEbrakes front break I replaced the Ultegra brakes with the EEbrakes dupe from AliExpress at 189g a pair. Omni Racer QR weight Front Omni Racer titanium quick release skewer Rear Omni Racer titanium quick release skewer Elves Vanyar seatpostĭuring the build, I upgraded to Omni Racer QRs at 42g a pair and used an Easy 90 carbon saddle that weighs 120g. ![]() Bottom bracket, bike computer mount, and other partsĪ neat part of the build was the lower portion of the seatpost, which came with a permanent rough surface coating that doesn’t require carbon paste. The pressed BB86 was a breeze to install, with no hiccups and zero creaks. Elves Vanyar frame Elves Vanyar fork Elves Vanyar handlebar Elves Vanyar frameset with handlebar The frameset and handlebars both included internal housing for cable routing. You find out why Dayan decided to go for Elves Vanyar, if he encountered any issues when building its new machine, and much more.īecause of its great price point and low weight.ĭid you (or the mechanic) experience any issues, for example, with the bottom bracket area? In this section, we dive deeper into Dayan’s build.
In preclinical studies, CT-05 has demonstrated attractive features that differentiate CT-05 from inhibitors that failed in clinical trials due to side effects: The potential of the PKCӨ protein pathway is underpinned by BMS’s latest in-licensing of Exscientia’s PKCӨ inhibitor EXC4318 The IL-17 pathway is a clinically validated pathway in autoimmune diseases such as psoriasis with established modulators2 The PKCӨ protein acts via the CD3/CD28 – IL-2/IL-17 pathway. Importantly, the approach behind CT-05 is partially de-risked thanks to: PKCӨ is a high-value target with opportunities in certain autoimmune diseases, such as allergy, psoriasis, and inflammatory bowel disease, as well as certain malignancies, such as breast and gastrointestinal cancer. It is therefore expected that degrading the PKCӨ protein would lead to an increased T cell suppressive function. Indeed, PKCӨ plays an important role in the modulation of T cells by limiting the suppressive function of T cells. Optimised compounds with good pharmacokinetics in animals have been developedĬompounds with the ability to cross the blood-brain-barrier have been identified and provide opportunity for further development in the area of neurodegenerationĬT-05 targeting (new disclosure) PKCӨ (PKC theta)ĬT-05 targets the PKCӨ protein, a protein highly relevant in both autoimmune diseases and cancer. Pre-clinical studies have revealed the following benefits of CT-02:Įffective NEK7 degradation at low concentrations in vitro (high potency) and ex vivoĭegradation of NEK7 is correlated with the desired in-vitro biological effects on the inflammatory response It is therefore expected that selective degradation of NEK7 would also remove the NEK7 scaffolding function leading to potent inflammatory inhibition. Importantly, it is established that NEK7 pro-inflammatory activity is largely driven by its scaffolding function, and because of that, classical inhibition of NEK7’s kinase function doesn’t provide therapeutic benefit. Captor believes that selective NEK7 degraders have the potential to overcome the limitations shown in the past of NLRP3 inhibitor drugs related to increased susceptibility to infection. Such NEK7 degradation allows the modulation of the inflammasome, a complex that plays a critical role in the regulation of the inflammatory response. In addition to the potential benefits of NEK7 degradation combined with the degradation of GSPT1 and SALL4 in cancer, as mentioned above for the CT- 01 Project, the selective degradation of NEK7 alone in the CT-02 Project has many potential benefits as a treatment of several autoimmune diseases. Moreover, CPT-6281 is particularly well suited for liver, lung, and neuroendocrine tumors since it is a prodrug1 activated by an enzyme present in high concentration in the liver, the lungs, and some gastrointestinal tumors. GSPT1 is a protein involved in the termination of translation, SALL4 is a transcription factor often over-expressed in HCC patients and correlating with poor prognosis, and NEK7 is a protein in which degradation leads to a reduction in IL-1b production, a well-known pro-carcinogenic factor. CPT-6281 is a first-in-class degrader of GSPT1, SALL4, and NEK7. The first indication will be in Hepatocellular Carcinoma (HCC). ![]() CT-01 / CPT-6281 targeting GSPT1, SALL4 and (new disclosure) NEK7ĬT-01 / CPT-6281 is currently undergoing IND/CTA-enabling studies with the first clinical trial expected to start at the end of 2023. Webcast invitation to discuss scientific rational and market potential of new targetsĭate: March 30th 2023 at 4pm CET / 10 am ET Dr Michal Walczak, Chief Scientific Officer and Co-founder of Captor, will present the scientific rational for these targets as well as the market potential of each of Captor’s lead programs and will answer questions during a webcast on March 30th 2023. (“Captor”) (WSE:CTX), a leader in the development of Targeted Protein Degradation (TPD)-based drugs, today discloses the identity of the drug targets as well as associated supporting data, and provides an update on the progress in the research and development of its pipeline lead programs CT-01, CT-02 and CT-05. WROCŁAW, Poland, Ma(GLOBE NEWSWIRE) - Captor Therapeutics S.A. Webcast to take place on Thursday 30th March at 4 pm CET / 10 am ET – Registration link below Strong preclinical data generated with CT-02 against NEK7ĬT-05 potential best-in-class profile in high potential / partially de-risked PKCӨ protein pathway Captor Therapeutics Discloses Molecular Targets of Pipeline’s Lead Assets and Invites Stakeholders to Webcast |
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