![]() I bet you that they won't, and I'm willing to make a video on it. If they really had X-Ray vision, as soon as they pass or get near your building, they would open fire. If you really want to test this so-called "X-Ray" vision AI have, sit in a building in a town, and have a squad of opposing AI walk down the street right next to your building, not alert, just doing a patrol - don't use "Search and Destroy". The louder you are, the more likely you're going to get spotted and shot. Or, if you know AI are in the area and go to hide in a building, they won't magically start shooting at your position until you shoot first. How would this be possible if they hsve xray vision and detect everyyhing in a radius as you say?I can confirm a bit of this, as while playing MP with roaming AI, if you go AFK for a while (~10 minutes?) and AI spawn in, they can enter the same room as you, but will not shoot you, acting as though you're just part of the terrain until you start shooting. ![]() I can sneak into a town of AI and none of them respond until i become unsteatlthy or fire. They detect you if you move in a certain way ie stealthy movment will hide you. Originally posted by NathaN:But they dont see within a radius. ![]() How would this be possible if they hsve xray vision and detect everyyhing in a radius as you say? And I dont care if you are behind something or not! They can detect through the entire map and all objects! Like I say X-Ray Vision! But they dont see within a radius. As it is right now the AI can detect any unit within a set radius (distance) from the AI. It is not about magic it is about the only way to block (Vision) of the AI is to put up a barrier that BLOCKS the AI detection ability. A Search and destroy command only tells the AI to SEARCH (because they should not know where the troops are EXACTLEY) and once they FIND (SPOT) the enemy then they should engauge. Yeah but I didnt tell the AI that I was in the building and where EXACTLEY in the building. You told the AI what building you were in and then told then to destroy you and then complain that you get shot. Maybe because you are giving them a search and destroy command on a building thats why they are firing on the building. They wont shoot through the walls untill they have seen you through a window or whatever. I can stand inside of a building in ANY map and send a squad and give them a search and destroy command and they WILL shoot through the walls (on ANY MAP). If you run in like rambo you will get destroyed even at 600m or so. You need to be slow and dont move much and you can move without the ai seeing you. If you are in plain sight they will notice you. If you hold shift the ai will notice you. The bullets can even ricochet off rocks and the dirt. ![]() They will keep firing at your position to suppress you if they see you, Which can lead to you being shot through bushes, trees and walls if they are using high powered rifles. The exception are non arma 3 maps like cherno and lingor. Originally posted by NathaN:The ai cannot see through terrain or folliage. ![]()
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![]() ![]() Social media increases the opportunity for such harmful interactions. While teen males tend to express aggression physically, females do so relationally by excluding others and sharing hurtful comments. The earlier teens start using social media, the greater impact the platforms have on mental health. Researchers know the connection between the mind and the gut can turn anxiety and depression into nausea, headaches, muscle tension, and tremors. Social media use can affect users’ physical health even more directly. When people look online and see they’re excluded from an activity, it can affect thoughts and feelings, and can affect them physically.Ī 2018 British study tied social media use to decreased, disrupted, and delayed sleep, which is associated with depression, memory loss, and poor academic performance. Missing experiences can create anxiety and depression. If everyone else is using social media sites, and if someone doesn’t join in, there’s concern that they’ll miss jokes, connections, or invitations. When reviewing others’ social activity, people tend to make comparisons such as, “Did I get as many likes as someone else?,” or “Why didn’t this person like my post, but this other person did?” They’re searching for validation on the internet that serves as a replacement for meaningful connection they might otherwise make in real life.įOMO-fear of missing out-also plays a role. Couple that content with the structure of potential future reward, and you get a recipe for constantly checking platforms. To boost self-esteem and feel a sense of belonging in their social circles, people post content with the hope of receiving positive feedback. The unknown outcome and the possibility of a desired outcome can keep users engaged with the sites.” One does not know how many likes a picture will get, who will ‘like’ the picture, and when the picture will receive likes. “The idea of a potential future reward keeps the machines in use. Think of a slot machine: if game players knew they never were going to get money by playing the game, then they never would play,” Sperling says. “When the outcome is unpredictable, the behavior is more likely to repeat. ![]() This puts a large amount of the population at an increased risk of feeling anxious, depressed, or ill over their social media use.īut what makes users come back for more even when it can literally make them feel sick? The platforms are designed to be addictive and are associated with anxiety, depression, and even physical ailments.Īccording to the Pew Research Center, 69% of adults and 81% of teens in the U.S. Using it activates the brain’s reward center by releasing dopamine, a “feel-good chemical” linked to pleasurable activities such as sex, food, and social interaction. Tips for healthy social media use in adults and teens.The impact of social media on our mental health. ![]() ![]() I used this note-taking app for two years. This note-taking app is so simple and feature-rich that your writing and note-taking become quicker and easier. This simple app was made for only one purpose, Fast note-taking and writing. Typora is a Markdown-powered simple note-taking app. Typora: A Destruction Free Writer And Note-Taking App: So, you can switch to Notejoy easily as your main Markdown notes. Notejoy has same user interface and features of Evernote, at a competitive price. I found, Notejoy’s Markdown Editor is strong enough to handle all of your notes. If you are a lawyer and become a slave of the traditional note-taking app, then choose this note-taking app. ![]() Markdown Editor (No Support For Creating Tables).Bi-directional Linking Note-Taking Made Easy.Maybe, Notejoy can full-fill all of your needs as a note-taking app Evernote Markdown alternative, if you are handy with Markdown syntax. This is the proper time to find a good Markdown-powered note-taking app for your notes. If you are a lawyer like me, then you may face many problems With other note-taking apps in recent days. Notejoy’s Markdown editor is powerful enough that you can do anything with the editor. There are many reasons to use Notejoy as a Markdown note. Notejoy provide you every Evernote, and some modern features too. The best feature of this app is a clean Markdown Editor note. I used this app for one month, and this app is very good at note-taking. This app fantastically looks and feels like Evernote. Notejoy is an Evernote-like note-taking app. Nimbus note is a true Markdown note-taking app in every way. One of its beat features is a good Markdown Editor. This note-taking app has more tools than many note-taking apps. Good Table Creation And Editing Features.Īs a lawyer, I always recommend Nimbus note to every lawyer.Nimbus Web For Access Your Notes From Anywhere.Offline Note-Taking And Editing (No Need A Pro Plan).This Is A Evernote Alternative Web Clipper. There are many reasons to choose Nimbus note. It has all features of Evernote, and some unique features of modern-day note-taking. Nimbus Note: The Best Evernote Like Note-Taking Apps: I strongly recommend this fantastic note-taking app who love Markdown note. Free Version Only Work With Roam Research Desktop App And No Sync To Cloud.Ĭan I consider Roam Research as a primary Markdown note-taking app? Yes, this note-taking app is one of the best Markdown note-taking app for researchers, programmers, etc.Insert PDF, Image,Videos Without Hassle.Bi-directional Note-Taking System Make Your Effort More Useful To You.Taking Notes Is So Easy With Bullet Journal Note-Taking.Till now, this amazing note-taking app earns respect and love from many users around the world. This note-taking app is gained popularity from mind 2020. Roam Research is popular among researchers around the world. ![]() This app has the most features Obsidian has. Roam Research is an Obsidian Style note-taking app. Roam Research: The Idea Connector Note-Taking App: Learn this app and enjoy the freedom of taking notes using Markdown editor and feel the power of Obsidian. If you want to learn something new and better, then Obsidian is the right choice for you. You can replace your traditional writing app like MS Word, LibreOffice, etc.All articles on this site I have ever posted have been written in Obsidian. Obsidian is so powerful that you can do anything with this note-taking app. As a result, what you need to take your notes, Obsidian will provide you. Obsidian provides all the modern features with extra features. Modern-day note-taking apps have provided so many features. ![]() Obsidian is one of the best Markdown note-taking app in the world. This app will be your second brain with your notes. Obsidian is not an old note-taking app like Evernote but like Roam Research. Here Are Some Best Markdown Note-Taking App: There are many features that are common with all the Markdown notes in this list. What Features I Considered While Making This List? The most important reason is that we are not seeing any other good markdown-based note-taking app till now in 2022. In 2022 the list of the best markdown note-taking apps is remaining the same. As a result, all the notes app Markdown has been tested by me personally. I have personally tested that Markdown app for at least two months. In this list I am giving you the best Markdown notes app. But, I have totally shifted to Obsidian, Nimbus Note, and Notion. Now, I use Google Keep for some less important jobs. Once upon a time, I was a big fan of Evernote, OneNote, and Google Keep. Many people use Markdown note instead of normal or traditional note-taking apps. ![]() ![]() Since its release in 1984, the Scorpions’ "‘Rock You Like a Hurricane" has become ubiquitous. The story might be slightly turbulent, but the music certainly jams.ĩ8: Scorpions, "Rock You Like a Hurricane" Livgren’s engaging storyline of a man embattled with the voices and visions in his head is driven forward by guitar riffing, organ swells and solos from nearly every member in the band. Next to some of the proggier moments on Leftoverture, "Carry On Wayward Son" feels comparatively restrained and compact, even though it stretches out across nearly five and a half minutes. ![]() Once the members heard the initial idea for "Carry On Wayward Son," they knew the songwriting gold that they had on hand and went straight into the recording studio without even pausing to rehearse the track. Luckily, guitarist Kerry Livgren was overflowing creatively with ideas and he still had one song that he hadn’t shared with the band. ![]() Taking a short breather to record what would become their fourth album, 1976's Leftoverture, frontman Steve Walsh ran into writer’s block. Like many groups in the time period, Kansas toured and recorded relentlessly, supporting three albums that sold modestly despite their growing live following. The now-familiar a capella intro for "Carry On Wayward Son" was the sonic hook that would help Kansas score their first major hit, a feat that was a long time coming for the band. We're guessing record sales from this song have paid for that ticket many times over by now. "I Can't Drive 55," as Hagar has explained many times, was inspired by a real-life incident that found him pulled over for doing 62 late at night on an empty highway in upstate New York. This new level of fame also paved the way for him to join Van Halen in 1985. We're not saying Hagar was directly responsible for the late-'80s national law changes that allowed states to once again set speed limits higher than 55, but it certainly couldn't have hurt. Nearly a decade of constant touring and increasing record sales – remember "Your Love Is Driving Me Crazy?" – had already established Hagar as a rock star prior to the release of his 1984 VOA album.īut the Red Rocker really hit a nerve with the message of the record's first single, which – aided by a truly entertaining video – quickly made him a household name and bona-fide arena headliner. His 2005 multi-platinum album Time Well Spent features everything you’d want: Dali-inspired cover art, cameos by Dolly Parton and William Shatner and an ode to white-people dance moves, “Alcohol.” ( Here’s the Joseph Gordon-Levitt cover of that song that you never knew you needed.Who better to get our Top 100 Classic Rock Songs list off to a fast start than Sammy Hagar and his anti-speed limit anthem, "I Can't Drive 55?" With 48 million albums sold, Kenny and that smooth, smooth sax have ensured we’ll never have to endure an awkward elevator silence again.Ĭountry singer, Grand Ole Opry member and active Freemason Brad Paisley was born and raised in Glen Dale. He’d form Dave Matthews Band in Charlottesville in 1991-inspiring generations of bros to slap a DMB poster onto their dorm room wall-and go on to sell millions of (multi-disc live compilation) albums.įor a state that prides itself as the birthplace of grunge, it’s only fitting that the highest-selling artist to emerge from Washington (in the early ’90s no less) is none other than Kenny G. While Dave Matthews himself was born in Johannesburg, South Africa, as a Quaker, he left the country to avoid conscription at 18. The band is embarking on their 50th anniversary tour this year. With nearly 47 million albums sold in the U.S., Alabama is the highest-selling country act in history, as well as out of anybody from their home state, Connecticut (kidding, kidding). ![]() As for streaming data - well, that’s another article for another time, sheerly for our sanity here at Paste. ![]() And we’re defining origin by state of birth or state where a band was formed. We’re looking at U.S.-only totals (for a global look, here are the best-selling albums of all-time). Gold records are equivalent to half a million albums, while platinum ones equate to a million albums. Curious to learn who’s the most popular band from your home state? From Idaho? From Puerto Rico and Guam? (Google those last two-we’re not heroes.) This list (updated in part from information organized by one dedicated Reddit user in 2017) ranks the highest-selling musical acts from each state according to statistics provided by the Recording Industry Association of America in terms of total units sold. ![]() ![]() You do need to calculate the amount of wattage that is running on the lights being dimmed. This reverses the electrical method of how the dimmer naturally works. The best solution is buying an ELV dimmer (electronic low voltage dimmer) instead. You might try several before finding the right one. Not every dimmer will be compatible with your LED light. If the buzzing still persists, then you have to move to the next step of replacing the light switch or dimmer switch. If this buzzing is annoying, then you can change the bulb with another brand. LED lights all have different levels of natural buzz or hum depending on the manufacturer. Perhaps your lights aren’t on the right circuit dimmer for the amount of wattage that it’s supposed to dim. These common problems can be fixed by changing the bulbs by brand name or by light switch brands. It’s mainly a problem with dimming bulbs that aren’t compatible with your dimmer switch. If these switches aren’t compatible, there will be humming or buzzing sounds. ![]() ![]() It can be due to the type of light switch or dimmer switch. It’s not so common with better-made LEDs but can also happen. The first common issue is a low-quality LED light that’s made poorly. Any light that you are close to that has a buzzing sound can be fixed if you start to look at a couple of key issues. If you aren’t near the light and it doesn’t bother you more than 2 or 3 feet away, then this common problem shouldn’t be an issue. When you install LED lights regardless if they dim or not, have an audible humming or buzzing to them. Otherwise, have an electrician friend do it for you. With too many appliances on the same circuit then switch the electrical lines to another source if possible.īad capacitors and drivers will need replacing likewise if you can do it yourself. Make sure the socket is dry and screw back the bulb, so it’s snug. Turn-off power to that location and clean the socket with a wire brush or a dry scrubbing sponge. Some bulbs that are screwed in can flicker because your electrical socket has corrosion inside it. It may also be necessary to change the capacitor or LED driver parts. Even the fluctuations that happen between electrical appliances that continue will cause your LED to malfunction forever. Any part of your LED light that isn’t getting enough electricity needs to be rerouted. If these common issues aren’t fixed, it can lead to the LED parts to stop working completely. It can also be a bad capacitor or even a bad driver. It can also be a light bulb that’s not screwed in properly. Appliances such as washers, dryers, air conditioners connected to the same circuit can cause flickering. It can be because the light is connected to another appliance that takes up too much wattage. There are several reasons why an LED is flickering. Is it a sign that the LED is already starting to die or is it something else? It can flicker randomly just like Morse code or be a constant flicker leading you to wonder what’s happening. ![]() It’s not constant and can be intermittent. You get a brand-new LED light and it starts to flicker at some point. Top 20 Common problems with LED lighting 1. Corn bulb protrudes outward outside the lampshade Using LED light at an extra-high wattage/current Using LED light in an incandescent light fixture LED recessed light turns off after a few seconds Top 20 Common problems with LED lighting. ![]() ![]() ![]() Recognize when your child is trying to push your buttons and try not to get pulled in. Work hard not to indulge that part of your child. If your child spews a lot of negativity at home, the trick for you is not to get pulled into it because that’s what will give them the feeling that they’re in control, the feeling that they’ve got you, and you’re paying attention to them. And you and your child’s siblings probably bear the brunt of it because home is that safe place where they can let out the absolute worst part of themselves. ![]() In these cases, they’re not necessarily trying to make everyone upset.īut other times, they use negativity intending to make everybody else feel as miserable as they do. Sometimes they respond automatically without thinking. Understand that kids who exhibit oppositional or defiant behavior often use negativity to get everyone around them worked up, including you. Understanding why it upsets you so much is half the battle knowing why it pushes your buttons will help you find more calm, effective ways of dealing with it.ĭo you tend to be negative and critical yourself? Our kids’ behavior can often put a mirror in front of us, and it’s not always what we want to see.ĭo you feel responsible as a parent to fix your child, shape them up, and make them happy? Do you futurize and get anxious and ask yourself if this is the life your child is destined to lead? If you don’t react to it from your own anxiety, your child will eventually move on.Īfter you determine what’s triggering your child’s negativity, consider why you get so stirred up by it. When your child complains, they feel better because they’re expressing themselves and venting their worries and fears. Yes, this is unpleasant, but remember, don’t take it personally-this could be a coping skill your child is employing.Īs strange as it sounds, negativity and complaining are ways your child manages their anxiety. They may not tell you about their awful day at school, but they will complain that the food you cooked tastes awful. Pushing you out is the name of the game.Īnd let’s not forget that home is the safe haven where all stresses of childhood can land. Sharing their inner feelings means opening themselves up to you-and that is probably the opposite of what they want to do at this point in their life. I love it!”īut, once adolescence arrives, enthusiasm becomes uncool, especially around parents. You’d hear them say, “Mom, look at this! Wow, it’s so cool. When your kids were young, they might have been enthusiastic about everything. ![]() So, where does all this complaining come from? If your child is in their teen years, adolescence may be the culprit. Futurizing is the tendency to expect the worst outcome for your child, and it’s one of the most potentially destructive things that parents can do. What’s worse, your mind starts futurizing, and you start thinking that their negative attitude will be a problem for your child down the road. Your child may be loving, funny, and sweet, but the negative attitude stands out because it’s such an energy drainer. When your child is a constant complainer, it can be emotionally exhausting. Some kids’ versions of, “Hi, how are you this morning?” come out as, “These eggs are disgusting!” While this is the way your child might want to connect with you, it doesn’t mean you have to enjoy it or listen to it endlessly. They may simply want contact with you, albeit negative contact. Kids thrive on the connection they have with you, and if a child is always negative, they will usually get a reaction from their parents.Īs odd as it sounds, sometimes the negativity spewing from your child’s lips is not meant to sound as bad as it does. ![]() ![]() ![]() It is only recommended to use liquid fertilizers when the growth is slow, and this is not normally needed. If using a granular fertilizer, we recommend organic formulations, apply an all purpose formula in early spring annually. A drought tolerant perennial when established.įertilizer: If using compost apply an 1" at planting time and side dress annually in late fall or early spring. Deer and rabbits seem to leave them alone. Loved by butterflies, bees, and those hummers. We are loving how quickly it grows in the greenhouse so we know it will be a win in the landscape. Water deeply but infrequently once established. Use in the perennial garden, native or pollinator garden or front of the border. Raised beds or containers are best in areas with clay soil. Wet winter feet will decrease cold hardiness. A strong performer in the garden and in the pot. This plant needs low-fertility sandy or loam well-drained soils in full sun. The tubular blooms are up to 2" long and borne abundantly on large flowering heads. The scent is a mild licorice smell and only noticeable when brushed. Agastache KUDOS Series Silver Blue has clear light blue. This series is extremely hardy and has excellent resistance to downy mildew, which can plague other varities. This selection of Agastache aurantiaca parentage has the smaller blue-green leaves that have a slight silver look. The KUDOS Series of Agastache are really exciting They are a dwarf variety, that is well branched, produces lots of beautiful flowers, and emits a wonderful fragrance. Agastache Kudos Mandarin (Hummingbird Mint) is a compact and bushy, upright herbaceous perennial forming a low tight mound of aromatic, dark green, oval to lance-shaped leaves. Bred to be the hardiest of orange flowering agastache, Kudos Mandarines plumes just bloom and bloom while the foliage maintains a neat appearance, making it a great selection for the sunny garden. Colors range from white to blue and shades of red and purple. They are showy, fragrant, long-blooming perennials with spikes of flowers that bloom most of the summer. 'Kudos Red' fixes that problem and is an exciting win for the hummingbirds. Agastache Kudos Mandarin Dwarf Hummingbird Mint. Giant Hyssop is an herbaceous perennial in the mint family of which most are native to North America and many from the southwest. Adapted well to growing in areas that have hot, humid summer weather.Missing from the agastache lineup has always been a really great red. Agastache, commonly called giant hyssop, is a genus containing about 30 species of upright herbaceous perennials, most of which are native to North America.Improved cold hardiness over a wider range of the US (especially wetter parts of the country). Dwarf Hummingbird Mint: USDA Zone: 6-9: Plant number: 1.024.A range of bright and unusual flower colors. Tribute to a Star: Actress Lee Remick, ill with cancer, walked slowly with the aid of a cane as her star was unveiled Monday on the Hollywood Walk of Fame.From early summer until fall, it boasts plump spikes of soft, clear light blue flowers. A compact and bushy form - much more compact than other Agastache Agastache Kudos Mandarin (Hummingbird Mint) is a compact and bushy, upright herbaceous perennial forming a low tight mound of aromatic, dark green. Agastache Kudos Silver Blue (Hummingbird Mint) is a compact and bushy, upright herbaceous perennial forming a low mound of aromatic, deep green, oval to lance-shaped leaves.So we decided to add some more of their hybrids to the High Country Gardens line-up, the Kudos™ series. The Terra Nova breeders had several primary goals on which they focused to breed the Kudos™ series. The nectar-rich tubular-shaped flowers are highly attractive to hummingbirds. Dan Heims, owner of Terra Nova Nursery in Portland, OR has been a visionary breeder of perennial plants, and is renowned for his groundbreaking breeding work with Heuchera (Coral Bells) and Tiarella (Foamflower).Ībout a decade ago, he became enamored with Agastache, and with his team of plant breeders, began work on the creation of new garden worthy hybrids. I’ve been very impressed with Terra Nova’s ‘Blue Boa’, a, tall, long-blooming lavender-purple flowered hybrid that we’ve offered through High Country Gardens since 2017. Agastache Kudos Gold (Hummingbird Mint or Hyssop) is compact-growing and extremely long-blooming with golden-yellow flowers on short, tidy flower spikes from late spring to September. Agastache Kudos Mandarin is a diminutive plant that maintains a tidy, upright habit while producing clear, eye-catching orange blossoms over a long season. ![]() ![]() Make sure you’ve done event 4.8, then take a ride in the elevator in the Watch Tower, and you’ll pop up in the Underground Maze. It’s in a red chest on the Old Tree Hill.ĭefeat the Evil Pig in the Familiar Mansion. Smack that Evil Pig in Masakari Jungle, and the spell on Baccus Village will be lifted. I think you just have to finish the “We Need Power” event. Go inside the Rusty Door and use the switch. Speak to the man at the left of the Lumber Factory, then find the bomb on top of one of the tall trees in the Jungle. Give Charles the monkey his banana juice and he’ll teach you the art of swimming. You must jump into the water to meet him.įind the bananas, go to the Clock Tower, give the miner his hat, and then the miner will make you some banana juice. He’s located at the far right of the Masakari Jungle. Give/feed the Bunk Flowers to the Pheonix.įind Charles, who’s a monkey. Go up to a smiling door, and open it by laughing (eat a “laughing” mushroom).ĭefeat the Pig at the Haunted Mansion to save the caves.ĭefeat the Pig at the Lava Caves to save the mansion.Ĭollect five Bunk Flowers from the Lava Caves. In the chest, next to the mouse at the start of the Lava Caves. Inside the large key room, in Pheonix Mountain. Talk to the man outside the Lava Caves, once you’ve rescued the 1000 Year Old Man. Inside the large key room in the Haunted Mansion. It’s in the Haunted Mansion, inside a chest. Get a key off the mice at the Haunted Mansion, and use it on the small keyhole.īreak every egg in the Haunted Mansion, then break the glowing egg. Search the room with a moving platform, the room with the smiling door, the room with a blue chest, and a gap in the middle, the room with a fountain and the room with a chest and some water.Īfter doing 2.8, either open the door in the Haunted Mansion or Pheonix Mountain. Then turn it on, and speak with the mouse at the Town Hall.įind him in the Haunted Mansion (enter the really big door).įind all five fragments of the key in the Haunted Mansion. Put the pipe that you found on the dock into the machine on your right. Save the baby mouse, then go to the bridge in Baccus, and the mouse will take you to a lake. Talk to the mouse, then talk to the mouse in the Town Hall. Read the board in Baccus Billage, then enter the bar on the left hand side. Same as 2.1, but eat a “crying” mushroom. Rescue everyone and then you may speak to the old fart.Īfter you speak to the Dwarf Elder, you will recieve this.įind a “laughing” mushroom, swallow it and laugh at the Dwarf who is guarding the way to Pheonix Mountain. ![]() Head to the left of it and find the child. In the Watch Tower, find the L-shaped platform. Seven Dwarves…sound familiar? Two are under the spores on the cactuses (cacti?) near the Dwarf Village, two under the spores in the Watch Tower, one under the spore at Wobbly Wharf, and two in the spores at the start of the 100 Year Old Forest. Jump on all the dwarfs in the forest, and one in the Elder’s place to learn Dwarf language. ![]() Open all of the four eggs (they’re coloured red, blue and white), jump on the chicks, then take them to the 100 Year Old Man. To finish this, you must defeat all of the eight pigs and finish the game.Ĭlear the fog blocking access to the Forest, using the tornado found in the letterbox at the start. A great game, though some may say the graphics are childish, it’s a great game…for anyone!!! ![]() ![]() ![]() This article reviews our research on supramolecular metalloproteins.Ĭomputational Protein Design has the potential to contribute to major advances in enzyme technology, vaccine design, receptor-ligand engineering, biomaterials, nanosensors, and synthetic biology. Protein oligomer formation was controlled for the 3D-DS dimer of a dimer-monomer transition protein. We have also utilized 3D-DS to construct heterodimers with different active sites, a protein nanocage encapsulating a Zn-SO4 cluster in the internal cavity, and a tetrahedron with a designed building block protein. Cytochrome c forms cyclic oligomers and polymers by 3D-DS, whereas other metalloproteins, such as various c-type cytochromes and azurin form small oligomers and myoglobin forms a compact dimer. We have been studying the mechanism of 3D-DS and utilizing 3D-DS to construct supramolecular metalloproteins. In nature, proteins have been shown to form oligomers by 3D domain swapping (3D-DS), a phenomenon in which a structural region is exchanged between molecules of the same protein. Several methods, including disulfide bond, metal coordination, and surface-surface interaction, have been utilized to construct supramolecular proteins. thus, the number of studies on the regulation of supramolecular proteins is increasing year by year. The design and creation of supramolecular proteins will lead to development of new enzymes, functional biomaterials, drug delivery systems, etc. Supramolecules have evolved into molecular machines in the field of chemistry, and various supramolecular proteins are responsible for life activities in the field of biology. Supramolecules, which are formed by assembling multiple molecules by noncovalent intermolecular interactions instead of covalent bonds, often show additional properties that cannot be exhibited by a single molecule. This review provides an overview of significant progress and prospects in accurate protein design for solubility and stability. The findings and opportunities for Cryo-EM are presented. Computational methodologies behind these endeavors, including structure prediction programs, machine learning algorithms, and specialty software dedicated to the evaluation of protein solubility and aggregation, are discussed. The designs of stable protein complexes and high-order assemblies are covered. Traditional strategies to enhance protein solubility and structural stability are introduced. After introducing fundamental design rules, we discuss the transmembrane protein solubilization and de novo transmembrane protein design. In this review, we summarize recent advances in the protein design field with respect to water solubility and structural stability. The continuous developments in protein science, increasing computing power, new algorithms, and characterization techniques provide sophisticated toolkits for solubility design beyond guess work. Emulated designer proteins with well-defined properties both fuel the knowledge-base for more precise computational design models and are used in various biomedical and nanotechnological applications. Their manipulation represents important aspects of the protein design field that relies on the accurate placement of amino acids and molecular interactions, guided by underlying physiochemical principles. Water solubility and structural stability are key merits for proteins defined by the primary sequence and 3D-conformation. By eschewing use of fragments from existing protein structures, SCUBA-driven structure design facilitates far-reaching exploration of the designable backbone space, thus extending the novelty and diversity of the proteins amenable to de novo design. We report the crystal structures of nine de novo proteins whose backbones were designed to high precision using SCUBA, four of which have novel, non-natural overall architectures. These terms are learned with a two-step approach that comprises kernel density estimation followed by neural network training and can analytically represent multidimensional, high-order correlations in known protein structures. ![]() Here we show that this goal is met by a statistical model named SCUBA (for Side Chain-Unknown Backbone Arrangement) that uses neural network-form energy terms. However, a sufficiently comprehensive and precise energy function has yet to be established for this purpose. It has been suggested that the designability of backbones is governed mainly by side chain-independent or side chain type-insensitive molecular interactions3–5, indicating an approach for designing new backbones (ready for amino acid selection) based on continuous sampling and optimization of the backbone-centred energy surface. A protein backbone structure is designable if a substantial number of amino acid sequences exist that autonomously fold into it1,2. ![]() ![]() ![]() ![]() Do you provide tools such as “kill switches” if a connection drops and DNS/IPv6 leak protection? Do you support Dual Stack IPv4/IPv6 functionality?ġ1. What is the most secure VPN connection and encryption algorithm you would recommend to your users?ġ0. Which payment systems/providers do you use? Do you take any measures to ensure that payment details can’t be linked to account usage or IP-assignments?ĩ. Is BitTorrent and other file-sharing traffic allowed on all servers? If not, why? Do you provide port forwarding services? Are any ports blocked?Ĩ. What steps would be taken in the event a court orders your company to identify an active or former user of your service? How would your company respond to a court order that requires you to log activity for a user going forward? Have these scenarios ever played out in the past?ħ. In the event you receive a DMCA takedown notice or a non-US equivalent, how are these handled?Ħ. Google Apps), analytics, or support tools ( e.g Live support, Zendesk) that hold information provided by users?ĥ. Do you use any external email providers (e.g. What tools are used to monitor and mitigate abuse of your service, including limits on concurrent connections if these are enforced?Ĥ. What is the name under which your company is incorporated (+ parent companies, if applicable) and under which jurisdiction does your company operate?ģ. Do you keep (or share with third parties) ANY data that would allow you to match an IP-address and a timestamp to a current or former user of your service? If so, exactly what information do you hold/share and for how long?Ģ. The order of the providers is arbitrary and doesn’t carry any value.ġ. We have included all VPNs we contacted that don’t keep extensive logs or block lawful torrent traffic on all of their servers. This year’s questions and answers are listed below. ![]() This article is not a recommendation of any kind. Also, we advise people to properly research the company behind the VPN service. However, we stress that users themselves should always make sure that their VPN setup is secure, working correctly, and not leaking. We hope that this helps users to make an informed choice. Many of these questions relate to privacy and security, and the various companies answer them in their own words. Instead, we aim to provide an unranked overview of VPN providers, asking them questions we believe are important. Vulnerabilities are always lurking around the corner and even with the most secure VPN, you still have to trust the VPN company with your data. When it comes to privacy and anonymity, an outsider can’t offer any guarantees. Some VPN companies, such as Kape, even own review sites.Īt TF we don’t want to make any recommendations. Just do a random search for “ best VPN service” or “ VPN review” and you’ll see dozens of sites filled with recommendations and preferred picks. The VPN review business is also flourishing as well. All claim to be the best, but some are more privacy-conscious than others. The VPN industry is booming and prospective users have hundreds of options to pick from. ![]() |
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