12/31/2023 0 Comments Grafana annotations influxdb![]() I’ll likely just say for “Me and my friends” on the next prompt. Let’s setup discord (which unlike teams doesn’t require me to endlessly sign out and in again to swap orgs). ![]() More and more, I’m seeing my colleagues looking to Discord as the ‘new’ Slack. I’ll use an icon (which I’ll leave for you to grab here):īack in Grafana we can setup a Teams Notification Contact Type We can go to the Connectors for the Channel I can see similar (including the drop off of delivered metrics) in Cloudwatch (The drop at the end is because I just stopped the cluster in the last 5 minutes) I’m only sending out Kafka Metrics to Datadog and Cloudwatchīut we can see that in both cases, our Kafka cluster was fine While the error message would lead me to believe it was from Kafka, the Spike (since I aggregated all the metrics) was actually from Grafana itself (times are in Zulu/GMT) However as we can see above, 5 minutes later it was resolved. Had I set a proper description, I might have put in a link to wiki pages, or who to call, perhaps a runbook on remediation. Several days later I actually got a real alert I think only recently did they add “(work or school)” to the App name. The White tile, which Windows would always suggest when searching for teams is not going to let you sign into Orgs. One with Blue and one with a White “T” tile. There are two ( insert profane explicative) Teams apps. I’ve been stymied by this over and over for a long while. Quick Note on Teams: This has been plaguing me for a while - I can never sign in. We can create other contact points such as Teams and Pagerduty We can now create a Notification Policy that uses it Which brings me to a minor issue I have with Aiven - I don’t like seeing my passwords left visible plain text Which I can now see in the list (and revoke later) You need to follow these steps to generate an “App” password we can use for STMP ![]() I found using a real 2FA password won’t work. ini file used by Grafana to set the section.įor Aiven.io, we will do it in the Advanced Configuration area In an on-prem install, we would likely change the. However, this just informed me SMTP was not setup out of the box We can, for instance, define an email address to which we will send alerts. We can get there from Alerting/Contact Points, then selecting “New contact point” To send any kind of alert, we first need to define a “contact point” SELECT * FROM "_internal"."database" LIMIT 10 Within Grafana we now see InfluxDB listed in Data Sources In Grafana, we’ll then add a new IntegrationĪt which point we can choose the InfluxDB With InfluxDB now running, let’s add it to Kafka Metrics In a bit, we’ll see it has a proper cert and respondsīefore we can graph anything, we need to add a data sourceīesides setting it up in Grafana, we can setup Data sources from Aiven via the Integrations section "Comment": "CREATE awx fb.s CNAME record " $ aws route53 change-resource-record-sets -hosted-zone-id Z39E8QFU0F9PZP -change-batch file://r53-aiven-grafana.json "Comment": "CREATE awx fb.s CNAME record ", that domain has issues let’s use our primary I’ll create and wait on the new service to get past ‘Rebuilding’ Of the Options to gather metrics in Aiven, InfluxDB is one of the less expensive at US$60/mo for a startup size instance in US Central Once running, we can login with the credentials in the service page ![]() ![]() It’s one of the least expensive hosted services from Aiven.io starting (presently) as US$35/mo in GCP We first create the service from the Services page. Lastly, we’ll dig in to Grafana queries and dashboards and wrap by setting up Email, Teams and Discord integrations (including setting up a new Discord server) Grafana We’ll setup a hosted InfluxDB to collect metrics from Kafka and Redis, then show how to use native Aiven integrations to link InfluxDB to Grafana. Today we’ll wrap our series on Aiven.io by looking at setting up a hosted Grafana instance and tying a custom DNS name to it. We’ve covered using Datadog and other tools to monitor and display metrics. ![]()
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12/31/2023 0 Comments Boomerang for gmail troubleshoot![]() ![]() True beginners or those who don’t need software of this magnitude will be better off going with SendX or Constant Contact.Ĭonstant Contact is one of the most well-known tools for email marketing. HubSpot’s marketing and sales email tools are fairly easy to use but have a steeper learning curve than other platforms, partly due to the sheer size of the HubSpot ecosphere. You can use HubSpot’s email tools to create messages that look like mass emails or plain text personal messages to send company updates, announce new products and services, extend special offers, and reignite cold leads. Automatically send a welcome email and launch lead nurturing drip email campaigns to move prospects through your sales funnel.Ĭonnect your advertising accounts to see results and ad interactions, tie ad spend to sales, and re-engage contacts. ![]() Build landing pages to generate leads and automatically assign leads generated to specific sales agents for follow-up. You’ll get some pretty impressive lead generation tools included when you opt to use HubSpot’s free email tools. Plus, you can use the HubSpot email app to work on the go from anywhere. U.S.-based users also get access to Payments. When you’re ready to upgrade, the base tier includes up to 1,000 contacts, an email send limit of five times your number of contacts, form and email automation, and two user seats. Starting free can generate the revenue needed to offset paid plans. Teams that rely heavily on data to improve marketing and sales campaigns.Companies with large-scale email campaigns for sales and marketing.Sales-forward startups and small businesses needing free sales and marketing tools.As such, HubSpot’s sales and marketing email tools are best for: However, it offers free use of its marketing and sales email tools of up to 999 contacts, giving startups and small businesses a way to get started for free, along with low-cost base tier options. In higher-plan tiers, HubSpot’s world-class, industry-leading software for sales and marketing is admittedly expensive. ![]() 12/31/2023 0 Comments Gre math practice problems bestseller![]() ![]() Algebra: These questions include factoring and simplifying algebraic expressions relations between different expressions, functions, and equations solving simultaneous equations and inequalities and coordinate geometry and its principle concepts such as intercepts, slopes of lines, etc.Arithmetic: These questions include integers and their properties (divisibility, factorization, prime numbers, etc.), number line, exponents and roots, absolute value, percent, and ratios, etc.The GRE Quantitative Reasoning section’s questions are broadly divided into four subjects: Even though GRE Math does not ask questions about higher order Calculus, it still requires a lot of practice to earn a good score. The section comprises questions related to Algebra, Arithmetic, Geometry, and Data Analysis. And our Android/iPhone Prep App allows you to access that content on the go.The GRE’s Quantitative Reasoning section has a strong emphasis on Math Reasoning and Mathematical problems. You can also choose between a live cohorted class with an instructor (which includes all our lessons and practice questions) or access to the self-study option by itself. Magoosh GRE prep offers lesson videos and practice questions to help you learn to put these formulas to use. ![]() You’ll also need to practice so that you know when it’s appropriate to use each formula. ![]() Like we mentioned before, simply memorizing these GRE math formulas is not enough. (-8, 1) Show answer and video explanationĬonclusion: Is This All You Need for GRE Math? Which of the following points cannot lie on line k? In the xy-coordinate system, line k has slope and passes through point (0, 5). If the area of the triangular region enclosed by line k and the two axes is 30, what is the slope of line k?Ĩ. In the xy-coordinate system, line k has y-intercept 12 and an x-intercept greater than zero. If Pat weighs 126 pounds, what is Kim’s weight?ħ. Tuk weighs 60 percent more than Kim, Lee weighs 50 percent less than Tuk, and Pat weighs 25 percent more than Lee. If the percent increase from 2004 to 2005 was the same as the percent increase from 2005 to 2006, how much did Cindy have in this account in 2006?Ħ. In 2005, the amount in the same account was $5000. In 2004, Cindy had $4000 in a mutual fund account. If the average (arithmetic mean) score is 62, what is the value of x?ĥ. Ten students wrote a test, and the distribution of scores is shown on the frequency table. If the largest integer is 90, what is the least possible value of the smallest integer?Ĥ. The average (arithmetic mean) of 4 different integers is 75. If the circle with center O has area 9π, what is the area of equilateral triangle ABC?ģ. Given two other points B (4a, b) and C (2a, 5b), what is the area of triangle ABC in terms of a and b?Ĭlick here to view the video explanation.Ģ. Point A in the xy-coordinate system is shown below. Here are the most important GRE math formulas to know and practice before exam day! Geometry And you won’t get partial credit for showing your work, so picking the correct answer choice is very important! So study up the GRE math formulas cheat sheet and then practice using the formulas so you will know when they pertain to a question. Figuring out what each question is asking you to accomplish can be really tricky, whereas the math involved in solving them tends to be fairly straightforward. The thing that takes these concepts to the GRE level is their complexity. They DO INCLUDE things you’ve probably long forgotten like properties of shapes, integer properties, exponent rules, and word problems. These concepts DO NOT INCLUDE higher level math like trigonometry, calculus, or geometry proofs. The GRE Quantitative Reasoning section tests concepts that you likely learned during sophomore and/or junior year of high school. Knowing which math formulas to use, then using them quickly and correctly, can really help you do well on GRE quant. Memorizing this GRE math formula cheat sheet is just the first step to mastering GRE math. How to Use the GRE Math Formulas Cheat Sheet Conclusion: Is This All You Need for GRE Math?.How to Use the GRE Math Formulas Cheat Sheet. ![]() 12/31/2023 0 Comments Equinox hotel opening![]() There will also be a 75 foot indoor salt water pool, hot and cold plunge pools and an outdoor pool for more relaxed swimming. Hotel guests will have fitness club memberships during their stay with access to guidance on holistic approaches to high performance living, recovery and regeneration techniques, personal training, individual Pilates and other classes. The fitness club will, naturally, be a highlight: 60,000 square feet and highly designed by Hong Kong’s Joyce Wang whose past projects includes eye catching designs in Hong Kong’s Mott 32 and the Landmark Mandarin Oriental. But the idea is to create a high performance setting to boost a healthy lifestyle starting with optimum sleeping conditions: total soundproofing and total soundproofing, a rarity in New York as residents will attest, plus COCO-MAT natural fiber mattresses that adapt to individual body shapes and Scandinavian duvets that regulate body temperatures. Within Hudson Yards, the 25 billion dollar development taking a formerly meh corner of Chelsea to new heights, literally (note the Vessel structure, designed by Thomas Heatherwick, which seemed to take over Instagram as a latter day Eiffel Tower when it opened in 2019).The fitness ethos won’t extend as far as workout equipment in every one of the 212 rooms, of which 48 are suites. Restaurant & Bar- fresh, seasonal elevated American cuisine on the 24th-floor Location Deviled crab? Crispy polenta fries? A chocolate moon rock with honeycomb and goat’s milk ice cream? Wellness has never tasted so very insubordinate, and you’re living for it. Find Equinox Hotels Hudson Yards, Manhattan, New York City, New York, United States, ratings, photos, prices, expert advice, traveler reviews and tips. You weren’t particularly hungry when you settled into the 24th-floor perch at Electric Lemon, but then you got your first glance of the menu. Plus, with the bottomless fitness classes and 27,000-square-foot spa complete with cryotherapy and an infrared sauna on-site, this may be the first time you actually *lose* weight on a trip to New York. You’re devoted to the latest and greatest, and this is both. ![]() Ah, New York: the city that always sleeps. ![]() Still not sleeping well, despite the downy soft king sized bed swaddled in linen and goose down duvets? Just call the Equinox Sleep Coach. Tex., who worked for Altamarea Group and left to open Scampi in the Flatiron district, plans to feature a. made with herbs grown on-site soundproofing that includes the 10-foot floor to ceiling windows (a blessing in frenetic Midtown). Equinox Hotel, 33 Hudson Yards (11th Avenue and 33rd Street), 21. fitness center-a veritable temple to the gods of sleek physiques-the hotel's 212 rooms are tech-forward enough to wow an ultra-toned George Jetson, including an iPad that draws the blackout shades and more clinical-grade filtered air and water a triple head shower whose glass walls become private at the touch of a button bath products tailored to both a.m. ![]() The sleek and elite vibe extends to the brand’s first (of hopefully many) hotels, Equinox Hotel New York. Some of the world’s most devoted and driven people are members of Equinox ultra-luxe fitness clubs, and not solely because they’re places to see and be seen, from London to SoCal. The hotel has an 8,000-square-foot rooftop terrace that feels like it hovers alongside the Manhattan skyline (and adorned with a sculpture by Spanish artist Jaume Plensa, no less). ![]() The first hotel from the megawatt gym brand is a paean to wellness on every level-with a spa and on-site SoulCycle-in the newly iconic Hudson Yards. ![]() 12/31/2023 0 Comments World market explorer membership![]() ![]() ![]() "A weather window has just opened up and we are going to attempt a dive tomorrow. “Due to the worst winter in Newfoundland in 40 years, this mission is likely to be the first and only manned mission to the Titanic in 2023," Harding wrote in a Facebook post Saturday, the day before the Titan voyage, according to the New York Times. He had been looking forward to his Titan ride. He held three Guinness World Records related to his explorations by plane and into the deep ocean. Hamish Harding, 58, was chairman of Action Aviation, a global sales company in business aviation. Stockton Rush was married to Wendy Rush, the great-great granddaughter of Isador and Ida Straus, who were on board the sinking Titanic ship together.īritish billionaire explorer Hamish Harding Rush had familial ties to the Titanic, NPR reported. And that is he was ahead of the regulations.” And I liked where he was going,” Stone said.īut, he added, Rush “had the problem that a lot of frontier people have. Greg Stone, the former executive vice president and chief scientist for Conservation International as well as a friend of Rush, said there was a need for advances in research submersibles. He went on to oversee business ventures that included serving on the board of Seattle’s BlueView Technologies and as chairman of Remote Control Technology. There is no private access to the deep ocean, and yet there’s all this life to be discovered.”Īt the same conference, he also said submarine safety programs were “over the top in their rules and regulations.”īefore graduating from Princeton University with a degree in aerospace engineering in 1984 and obtaining a master’s degree in business administration from the University of California in 1989, Rush had obtained his captain’s rating at the United Airlines Jet Training Institute. Rush said at a conference in Seattle last year: “One of the reasons I started the business was because I didn’t understand why we were spending 1,000 times as much money to explore space as we were to explore … the oceans. He was also the co-founder of OceanGate Foundation, a non-profit organization "which aims to catalyze emerging marine technology to further discoveries in marine science, history, and archaeology," according to the company's website. Stockton Rush, 61, founded OceanGate in 2009. The passengers on the sub were: OceanGate's CEO Stockton Rush "This is an incredibly unforgiving environment down there on the seafloor," he said.įor live updates on this disaster, read USA TODAY’s live blog here. Coast Guard said during a press conference Thursday he did not know whether the Coast Guard would be able to recover the bodies. Our hearts are with these five souls and every member of their families during this tragic time," OceanGate said in a statement Thursday. "These men were true explorers who shared a distinct spirit of adventure, and a deep passion for exploring and protecting the world’s oceans. The Coast Guard said families of the men had been notified of their deaths. Each paid $250,000 to ride on the submersible. The passengers were well known for their devotion to extreme exploration, desire to collect artifacts from the Titanic or their exorbitant wealth. Coast Guard also announced Thursday that rescue teams had found debris from the ship on the ocean floor “consistent with catastrophic loss of the pressure chamber.” OceanGate, the company that hosted the mission on the Titan submersible to the Titanic, said Thursday that the entire crew – including its founder and CEO who was the pilot in the mission – were “lost at sea.” The U.S. Watch Video: Search for five in missing Titanic submersible comes to an endįive men, including one teenager, have been declared dead days after they left for a voyage in a 22-foot submersible to see the wreckage of the Titanic in the North Atlantic Ocean. ![]() 12/31/2023 0 Comments Weight watchers lemon tart recipe![]() ![]() You will need about 1/2 of a lemon to get 1 tablespoon fresh lemon juice. – Use fresh lemon juice! Not the bottled lemon juice. Save the leftovers, covered, in the fridge for up to 3 days. – The leftovers of this pie are amazing and get better and better each day. For best results, make this the night before and let it sit in the fridge overnight and into the next day until you’re ready to serve it. – This pie needs at least 8 hours of refrigeration time to allow the pie to thicken and set up. I highly recommend following the recipe as is.įresh Lemon Juice – It’s not very much but it makes a huge difference and provides a fresh lemon taste for this lemon pie. If wanted, you can replace the heavy whipping cream and powdered sugar with 8-12 oz of Cool Whip. Heavy Whipping Cream – Please whip your own cream! It only takes about 5 minutes and the taste is out of this world amazing. Whole Milk or Half & Half – You want a higher fat percentage of milk for this recipe to help the pudding set up nice and thick. Do not get sugar-free (I mean you could if you really want to, but it tastes much better with the regular pudding mix) and do not prepare the pudding according to the package directions. Instant Lemon Pudding Mix – You want two of the small boxes of lemon pudding. If I can find the shortbread one (not all stores have it) I will get it because it’s my favorite but normally I just use a graham cracker crust. You just want the regular (6 oz) sized crust. Do not get the ‘2 extra servings’ sized crust. Graham Cracker or Shortbread Crust – These are the store bought ones that you will find in the baking aisle. And the leftovers just get better and better! This no bake lemon pie literally takes 5 minutes to make and it’s the perfect thing to make the night before so it can refrigerate until ready to serve the next day. No bake lemon pudding pie has three fabulous layers of instant lemon pudding mix, fresh lemon juice, and freshly whipped cream! Layered in a no bake, store-bought graham cracker crust. So easy to make and it’s no bake ! Perfect for summer and only 5 ingredients needed. No Bake Lemon Pudding Pie has three layers of lemon pudding, fresh whipped cream, and fresh lemon juice. ![]() 12/30/2023 0 Comments Bissell proheat2x cleanshot![]() ![]() It also comes with an extra long cord and large wheels for easy maneuvering. This is a must have home cleaning tool.īut there’s much more, this powerhouse cleaning machine safely and effectively cleans tile, sealed hardwood and other hard floor surfaces. Deep down cleaning power, rug stain protection, and drying power, all in one machine. ![]() If this is not enough, the unit’s DryAire system blows heated air that helps dry the carpet as you clean. This prevents dirt and dirty water from seeping back into your carpet.Īnd, don’t worry about your delicate wool and oriental rugs - there is also a no-heat option. Clean water is put into the center tank, and the extracted dirty water conveniently goes into the surrounding bladder. Bissell took care of it – the unit has a ‘tank in tank’ feature. You may be wondering what happens to the dirt that is suctioned up into the machine. Just push the button for that extra concentrated spot cleaning. And, for the occasional tough stain, this powerful machine has a CleanShot feature. The unique dual DirtLifter brushes effectively, yet gently, lifts debris and stains (including red wine) that have soaked into the rug fibers. Working in unison with the Bissell Wash and Protect cleaner, it easily removes ground in dirt, stains, and particulate matter (allergens, smoke, pollutants, bacteria, and other) from your rug, while at the same time protecting it from future stains. Whether you need a simple light cleaning, a normal cleaning, or a heavy traffic, deep down cleaning, the 9500 Proheat has it under control with 4 custom settings. With a patented water heating system, extra hot water (25 degrees hotter than hot tap water) works in combination with 12 cleaning rows of dual DirtLifter brushes. This sturdy upright home deep cleaning machine offers the best in cleaning for all your rugs. Not to worry though, the Bissell 9500 Proheat 2X Deep Cleaner is the solution to your dirty, allergen laden rug problems. Bugs, allergens, pollution, and even viruses and bacteria make their way into your carpets. Well, even if you have amazingly avoided these situations, your rugs get dirty from you, your clothing and shoes, a pet’s dander, and the indoor air in your home. Or, maybe you have a pet that has the occasional accident. Surely, at one time or another, you or someone else has spilled a drink or food onto the carpet. The Bissell 9500 Proheat 2X Deep Cleaner is a must-have home rug and floor cleaning machine. ![]() 12/30/2023 0 Comments Best hotels near statue of unity![]() Maharaja Tent Resort is one of the adequate tented resorts under its classification. ![]() There is a swimming pool which is covered with a Garden so the tourists can attract. Maharaja Tent Resort is top-rated among tourists among all the budget hotels near Statue of Unity in Ekta Nagar. Maharaja Tent Resort is a sensible choice for tourists starting for a budget accommodation near Statue of Unity. Top Amenities: Swimming Pool, Restaurant, Room Service & Housekeeping, Parking, Musical System for Night. ![]() ![]() Unity Village Resort delivers a range of amenities and capacities to make your stay more than prosperous for your trip to the Statue of Unity. There is also a swimming pool which is covered with a garden area. Unity Village Resort at Ekta Nagar proposes 30 Well Equipped Beautiful developed Cottages encircled by Nature and peaks.
12/30/2023 0 Comments Uk models female![]() Her modeling commitments are with Range Media Partners, CAA, Emptage Hallet, Hansen Jacobson, Teller, Newman, Warren Richman, Rush, Kaller & Gellman. She bagged the prestigious BAFTA awards in 2018 as a Multiple Critics Choice Award.Īlso, she was listed among the 100 most influential people by Time magazine. She is also cited as one of the most beautiful Hollywood actresses in 2021. The 4 time Emmy nominee, Clarke sparked the screen for her performance in HBO’s global hit Game of Thrones. There are some people who do not just have a good-looking face, but also possess the best runway walks. Top 10 Most Beautiful Models in the World She appeared in the 2018 TV Movie Vows of Deceit. She also appeared in the 2016 short film Queen of Hearts. Kelly starred in the 2013 comedy film Awful Nice and the 2015 horror film Whispers. Also, ranked top on FHM’s “100 Sexiest Women In The World in. She was at #1 in Zoo’s Britain’s 10 Sexiest Models, in Zoo’s 100 Sexiest Bodies 2005, in The Sun’s Favourite Girls of All Time and in Zoo’s 100 Sexiest Bodies 2006. Keeley was the winner of The Sun’s Idol 2004. She has been on the cover of The Sun’s 20 calendars. She was regularly featured in Nuts and Zoo. And while she did land a few roles and continues to pursue her Hollywood dreams, Keeley returned to modeling with a 2012 FHM cover shoot. She actually gave up modeling in 2009 to pursue an acting career here in the States. The former Page Three girl, actress and glamour model, Keeley started her career at the age of 17. She’s blessed – she’s beautiful and she’s the only possible number one in this category. Kelly has been graced with a natural 34E size. She’s been featured on MovieHotties more frequently than other hotties who have appeared in more movies. And, also she was the cover star of FHM’s World Cup 2010 special issue. She topped the ‘FHM 100 Sexiest Women in the World’ list in 2005, and as of 2015 had appeared in every FHM 100 Sexiest countdown since 1998. She’s considered as to have the best British female body. ![]() Ever since then, Kelly’s taken over the Internet with her charming smile and hot curves. In 2010, she was cast alongside Parks & Recreation’s Adam Scott and Hollywood legend Richard Dreyfuss in the surprise hit, Piranha 3D. Over the past few years, she has infiltrated the United States in a big way. Kelly Brook’s modelling career began at 16 after winning a beauty competition. That is why, she is referred to be the most attractive, good-looking, popular, and desirable woman in the UK. So, you can see her cover photo in almost all the fashion magazines. Without any doubt, everyone gets attracted by her charm and beauty. In particular, she is a social activist too. ![]() Emma Watson is an English model cum actor. Emma WatsonĮmma Watson is on top of the list, as she is the all-time favorite actress of everyone. Daisy Lowe Who Are The Most Beautiful Female Models in the UK? 1. The List of 10 Most Beautiful Female Models in the UKġ0. The modeling world is made up of talent from all around the globe.Īlthough the United Kingdom may not be thought of as a home for hotties, some of the sexiest models in the world hail from the European island nation, with many of them going on to become huge stars in the industry. ![]() There are women from all types of countries and cultures currently strutting up and down catwalks, but many of the best models from the last few years have been British. Check out the beautiful British people below, and then vote up the women you find to be the most attractive.Most Beautiful Female Models in UK - Illustrated picture. ![]() You will also recognize British female celebrities who are famous for singing, like Cheryl Cole and Rachel Stevens. Many women on the list worked initially as models (including Elizabeth Hurley and Transformers: Dark of the Moon actress Rosie Huntington-Whiteley) before moving into an acting career in the United States. (She's probably most closely identified with the vampire Seline in the Underworld series.) Another of the pretty British girls Emma Watson of Harry Potter fame. Kate Beckinsale was primarily known in her native London for period dramas and romantic comedies until her later movies rocketed her to international fame. Though nearly all of the women on the list first garnered male attention in the UK, most of them have also gone on to international celebrity based both on their gorgeous good looks and, in some cases, impressive talent. Your votes determine who is the prettiest British girl in the world. Here is the list of the most beautiful celebrity women from Great Britain, including actresses, singers, reality tv personalities, models, and more. ![]() 12/30/2023 0 Comments Vaccine production companies![]() Lipids suppliers to BioNTech include Merck and Evonik Industries, according to the Wall Street Journal, while Dermapharm in Germany, Acuitas Therapeutics in Canada and Polymun Scientific Immunbiologische Forschung in Austria are involved in the formulation process. ‘The entire supply chain of components and materials that go into these vaccines is new,’ adds Kis, who notes that the supply of some specialised lipids is likely squeezed by intellectual property issues. ‘The manufacturing step is very unusual and tricky,’ Lowe warns. Other drug companies cannot easily chip in. Reports reveal ‘very exotic mixing technology’ to control the shape and composition of the lipid nanoparticles and mRNA, says Lowe. The two mRNA vaccines on the market use commercially available lipids but also ‘proprietary, bespoke lipids’, notes Lowe. This view is shared by Derek Lowe, a drug discovery chemist in the US, who has written about mRNA manufacture in his blog, In the pipeline. ‘Here is the bottleneck, the rate limiting step in the process,’ says Kis. Microfluidics must mix the mRNA and lipids in a controlled environment. Next the mRNA is encapsulated into lipid spheres. ‘The goal is to purify out the RNA to the highest possible degree, because you don’t want any impurities that could lead to side effects,’ explains Kis. This is separated out according to electrical charge or size, using tangential flow filtration or various chromatography methods. The mRNA synthesis takes two hours, while making the vaccine takes a couple of days.Įnzymes are added to degrade the DNA template, leaving behind an RNA molecule between 40 nucleotides long. ‘The reaction mix has a well-defined composition and relatively few components, with no living cells or cell excretions or cell debris,’ says Zoltán Kis, a chemical engineer at the Future Vaccine Manufacturing Hub at Imperial College London in the UK. Making the mRNA itself – which codes for the virus spike protein inside our cells – is uncomplicated. The entire supply chain of components and materials that go into these vaccines is new The nucleotides are made chemically,’ explains immunologist Drew Weissman at the University of Pennsylvania, who contributed to the technology licensed by Moderna and BioNTech. ‘All of the enzymes are made in bacteria. Moderna and BioNTech are reticent on manufacturing specifics, but in general a polymerase follows a DNA template to make the mRNA sequence by linking nucleotides together. Large-scale production of such a vaccine has never happened before. The Vaccines Manufacturing and Innovation Centre will be the UK’s first national vaccines manufacturing and innovation facility mRNA bottlenecksīioNTech–Pfizer’s vaccine is the first mRNA vaccine ever to be approved for people by the FDA. Source: © Richard Pohle/WPA Pool/Getty Images ![]() Vaccine developers are also adapting existing facilities and partnering with sometime rivals to take advantage of their manufacturing capacity and expertise. Last weekend the British government announced an additional £47.6 million to get the UK Vaccine Manufacturing and Innovation Centre being built at the Harwell Science and Innovation Campus, online even sooner. Building additional capacity is one way companies and governments are approaching the challenge. And as Matt Hancock, the UK’s health secretary, told the House of Commons on 18 March ‘the process of manufacturing vaccines is complicated, and subject to unpredictability’.Įach vaccine faces production issues the newer technologies are effectively starting from scratch. But those companies that have surmounted the challenges of development now face the next phase: manufacturing doses on an enormous scale. Hot on their heels are rivals based on adenovirus vectors from AstraZeneca and Johnson & Johnson, as well as Sputnik V from Russia.Įarly successes in developing vaccines by upstarts like Moderna and BioNTech papered over the struggles of vaccine heavyweights like Merck, GSK and Sanofi. ![]() By December 2020, these two had become the first vaccines to be approved by the US Food and Drug Administration (FDA). ![]() The mRNA candidate from BioNTech and Pfizer followed in April. The first Covid-19 vaccine candidate went into the arms of volunteers in Seattle in March 2020. ![]() |
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