Cellular sales fleming island

Xbox YoY sales in Europe down 16%

2023.06.09 17:25 Gamesby29 Xbox YoY sales in Europe down 16%

Xbox YoY sales in Europe down 16% submitted by Gamesby29 to XboxSeriesX [link] [comments]

2023.06.09 16:49 AdamLikesBeer Weekend Rundown June 9th - 11th

Around Town:





I have had suggestions for a patreon or something of the sort in the past. I do this because I like to provide whatever tiny help I can to the community. BUT I also like to raise money for Gillette's Children Hospital every year. So if you have some virtual loose change you can help me help dem kids here: https://www.extra-life.org/participant/482633


Be da real MVP and add anything I missed below.
submitted by AdamLikesBeer to TwinCities [link] [comments]

2023.06.09 16:48 AdamLikesBeer Weekend Roundup 6/9-11

Around Town:





I have had suggestions for a patreon or something of the sort in the past. I do this because I like to provide whatever tiny help I can to the community. BUT I also like to raise money for Gillette's Children Hospital every year. So if you have some virtual loose change you can help me help dem kids here: https://www.extra-life.org/participant/482633


Be da real MVP and add anything I missed below.
submitted by AdamLikesBeer to Minneapolis [link] [comments]

2023.06.09 16:46 No_Competition4897 [HIRING] 25 Jobs in NY Hiring Now!

Company Name Title City
HelioHire Sr. DevOps Engineer New York
Tata Consultancy Services Limited Analyst Hempstead
Wells College Campus Safety Officer Auburn
Wells College Campus Safety Officer Aurora
Wells College College Security Officer Aurora
Dollar Tree Family Dollar Store Support Manager Barneveld
STG Logistics Owner Operator Wanted - Home Nightly Bronx
Epic Cardiovascular Staffing Perfusionist Elmira
STV Inc Assistant Superintendent Forest Hills
Global Partners Sous Chef Fort Edward
Global Partners Guest Service Supervisor Germantown
Konica Minolta Business Solutions Senior Account Executive Hempstead
Konica Minolta Business Solutions Senior Account Executive - Government & Education Specialist Latham
STV Inc Superintendent Long Island City
Konica Minolta Business Solutions Sales Account Executive Melville
Konica Minolta Business Solutions Senior Account Executive Melville
Konica Minolta Business Solutions Sr. Account Executive Melville
Konica Minolta Business Solutions Field Support Engineer Plattsburgh
Epic Travel Staffing Travel Imaging Tech (Medical Imaging Technician) CT (Computed Tomography) Riverhead
Travel Nurse Across America Intensive Care Unit - ICU RN - TravelNurse Rochester
Lowe's Companies, Inc. Store Worker Rosedale
Lowe's Companies, Inc. Shop Hand Rosedale
Competition Auto Group Mercedes-Benz Technician--Top Technicians Needed All Apply Saint James
Soapbox Strategists Social Media Strategy Intern Yonkers
Albany Medical Center Clinical Nurse IV Albany
Hey guys, here are some recent job openings , feel free to comment here if you have any questions, I'm at the community's disposal! If you encounter any problems with any of these job openings please let me know that I will modify the table accordingly. Thanks!
submitted by No_Competition4897 to NewYorkJobsforAll [link] [comments]

2023.06.09 15:47 PeacefulProtest69 My (23M) GF (23F) wants to move farther west to make super commuting easier for an airline. I'm already far from my family out east. Is there a fair way to work this out?

Some background: We've been dating now for around 2 years. I graduated college at 22 and moved from State A to State B (11 hour drive, no family there for either of us). I got a job there to pair with her job as a flight attendant at that city's major airline hub. She grew homesick and wanted to move closer to family after about a year, so I spoke with my boss and was able to work out a remote work arrangement for the same office - I've been with that company since May 2022 and working remote since April, upon which time we moved in with her parents back in the same metro we grew up. Note that while her family is right here on the west side, my family and friends are all 1 hr+ away on the east side (60-70 miles) so it's been difficult to see them aside from weekends. I've already missed out on a lot I would have typically done with my friends.
Now, 2 people on my team of 5 either "resigned" or were outright terminated. While I don't think my job is in jeopardy and my managers have corroborated as such, I'm trying to keep my options open. One of those ways I want to keep my options open is to stay relatively close to the major city in our region. Well, with her airline's policy on commuting, long story short it's made more sense for her to drive to the next major city (currently around 2:05 drive away) instead of flying standby out of our airport to get to work (35 min drive + airport + flight time).With lower seniority in this base as compared to the old one in State B, super commuting has made her super cranky and she takes it out on me. She admits as such but instead of apologizing, she simply excuses it as normal. The solution, in her view, is to not only move closer to that airport but to BUY A HOUSE closer to that airport. One town she mentioned is still 1:53 away. Now, I'd possibly be willing to rent there, but I don't want to live my whole life in a place so far away from my friends and family. Where we are living currently is bad enough - an amicable compromise to both of us in that regard would be to live a little farther east so that we're 35-45 mins from both of our families and friends. To boot, I'd be closer to the city in the event should I need to commute to a new job's office, up to 5 days a week - I would not have the same luxury in the town she spoke about. I work in a sales-driven, high turnover industry to begin with.
Last night I finally lashed out on her a bit but I was finding her nitpicking about every little thing and taking things out on me I didn't deserve and frankly I let it go on too long. I know for a fact I communicated my boundaries politely several times, but she kept pushing. After moving to and from State B, one of the selling points that finally got me on board for the return trip was that we could be closer to family. Well, I can't if she wants to move. And I have no interest in being marooned on an island with someone who - even when she's only at home ~50% of the week - has a pattern of treating me this way when work is stressful or she woke up on the wrong side of the bed. My hope is that she gains seniority to aid in scheduling favorable trips, or the airline changes their policy to guarantee commuters a seat on a flight (which was the policy up until this year - it could realistically revert to what it was). Until either of those things ease up, I'd entertain the idea of RENTING closer to where she wants but I absolutely do not want to be there long term.I feel like I've sacrificed a ton already in the couple years we've been dating, but it feels like she just keeps taking.
tl;dr: Gf wants to move farther west to be closer to super commute, my family is way east. Moved to and from State B (11 hr drive one way) on her whims in the time we've been dating, and the major reason we came back is to be closer to friends & family. Currently working remote but there's been a lot of turnover there and the majority of job opportunities will be farther east toward the city center, not west. Looking for advice for the fairest compromise or anything else that can be offered. Thanks!
submitted by PeacefulProtest69 to Advice [link] [comments]

2023.06.09 14:38 ItsShorsey Bought that Live Free Kava/Kratom drink and it comes with this info card. Post lawsuit damage control maybe?

Bought that Live Free Kava/Kratom drink and it comes with this info card. Post lawsuit damage control maybe? submitted by ItsShorsey to JoeRogan [link] [comments]

2023.06.09 13:17 TemporaryTight1658 Pirate tribe

Pirate tribe
Inspired by the pirate kikoo skin : a tribe on island-type terrain generation. Even more water friendly than kikoo.

Start with 10 starts and the saling tech.
submitted by TemporaryTight1658 to Polytopia [link] [comments]

2023.06.09 10:24 mikesfamous Used motorcycles for sale Rhode Island

Used motorcycles for sale Rhode Island
Welcome to Mike's Famous, your premier destination for used motorcycles for sale Rhode Island! We pride ourselves on offering a wide selection of high-quality, reliable bikes that cater to all riding styles and budgets. Discover your perfect ride today and hit the road with confidence and style.

submitted by mikesfamous to u/mikesfamous [link] [comments]

2023.06.09 09:57 Okal99 GUARDIAN & THE NNN ECOSYSTEM

THE BEST WAY TO BECOME A SECURITY MAXIMALIST In the beginning, there was The GuardiaNNN.ai. It was an idea for a simple token listing - a list of projects. And it was the beginning of an idea for our team. At that time, we were still working full-time at an agency and only had time for occasional purchases of low-cap projects. It was then that we first encountered far more scams on the market than genuine efforts to build something. The more scams we encountered on our journey, the clearer it became that we had to do something about it.
So the idea for Smart Check with AI was born - a tool that would detect hidden threats and backdoors. As the bull market transformed and fraudulent practices increased, new features and ideas were packed into it to combat fake projects and to protect users from losing considerable money and trust in crypto.
With this concept, the core team quit their agency jobs and threw themselves 100% into developing the entire NNN ecosystem.
It is now growing into an emerging platform which combines a launchpad for creating new projects, an NFT marketplace free of malicious bots, a DEX hub for shopping on the famous DEXs, and a news centre that collects quality content from projects and crypto bloggers. It’s similar to Medium, but done in a decentralized way.
WE OFFER PROTECTION TO INVESTORS, BUT WE DON'T RESTRICT THEM GuardiaNNN.ai addresses how people make their investment decisions. It offers cold-blooded analysis without emotion. Facts in black and white. We have yet to determine how many people it has already saved. The check alone has been used over 3,000 times. Some users would say this tool has protected them from fraud and made research easier. And that's exactly what GuardiaNNN.ai is all about. It doesn't decide whether a project is a scam or a new gem. Instead, it provides the basis for a good, in-depth analysis of the technical aspects of projects.
Many people are just learning about the crypto world and need help understanding how to buy in. That’s why GuardiaNNN.ai will be followed later on by an academic library which will guide users through the world of cryptocurrencies. We are building a community of people around us - both experts and enthusiasts - who can and want to help newcomers.
MORE THAN 80% OF PROJECTS ARE NOT LEGIT OR TRANSPARENT The world of cryptocurrencies is a world of molten lava. Even the most significant and valuable projects can’t claim to be finished products. Every now and then, a new island surfaces and everyone jumps on it, hoping to make a quick buck. And many speculators exploit this. But it shouldn’t be said that a project has a bad intention coded into it from the get go. Sometimes it may just be an experiment that didn't work out. We can talk endlessly about the whys and hows of failures. Sometimes conspiracies arise, and shocking revelations surface. But no-one can see into the future. And that’s when GuardiaNNN.ai comes into play. It’s there, ready, willing and able to help and respond to what is happening in projects right now – in real-time.
Many people buy into the hype that comes with social trends. A typical example is meme tokens which the crazy crowd don’t do their research on. Things can then not turn out well. There are thousands of examples. Remember the Squidgame token? It was a showcase scam that succeeded precisely because the average user lacked the tools to help them analyze the project and keep their money out of it. Good risk management is essential for any type of investment - even the most seemingly stable ones. You can't rely on luck alone.
GuardiaNNN.ai IS THE SPINE OF THE NNN ECOSYSTEM GuardiaNNN.ai is a pilot project being developed at NNN. Its primary purpose is to eliminate scammers from the crypto world. Everyone can use it for free, but NNN token holders can also access advanced tools to make trading easier. And they also get more detailed analysis and special offers. This living ecosystem is growing and thriving thanks to the community's activity.
NNNNNFT MARKETPLACE IS ONE-OF-A-KIND The market is flooded with NFTs that have no value and no meaning. They are artificially maintained and often full of bots. Our concept is built on the idea of not giving bots a chance to join in and negatively influence projects.
We prioritize the community and our reward system, which we call Karma. 1.5% of all NFT sales on the marketplace flow into our Karma system, which in turn rewards people with incentives, so they’re more active in supporting and helping each other. This further develops the community and benefits the ecosystem so it can grow organically.
LET THERE BE DEX HUB and LAUNCHPAD! All good things come to those who wait, so DEX HUB will be added to the ecosystem. We want to develop GuardiaNNN.ai as a hub, which will let you choose the most suitable decentralized exchange based on your preferences or preferred exchange rates. And the list of exchanges will continue to grow.
We also plan to add Launchpad for new, ambitious projects which meet quality standards. But it all depends on how fast the community develops because we prefer to grow organically and sustainably.
The goal is to build a diverse and robust portfolio of comprehensive products and services on the blockchain. And so, the NNN Community can help the project - by setting up tailor-made contracts and taking care of auditing, promoting and moderating the project.
Another of the ecosystem’s unique elements is the news aggregator. This collects news from the crypto world and enables content creators and members of specific communities to present their aims and intentions and whatever it is that they’re passionate about. Every project can have a profile and create its own content. That means every community can create its own news hub in the ecosystem and spread its content to the world more efficiently than before.
WHAT MAKES US TICK We love exploring and evaluating how projects work. And we love exploring how others engage the community, how they evolve technically, and where their strengths and weaknesses are. The never-ending collection of data and information allows us to raise the bar higher. Our ambition is vast because we see in NNN a way to connect the very best of what works with the most useful things a person preoccupied with the crypto world needs for their comfort and safety.
For many years we have worked in teams that have helped others realize their dreams and visions. Two senior full-stack developers, Zdeno and Pato, are at the forefront of development. Lukáš works as our project and marketing manager. We have worked with corporates and agencies, and that’s why we know what the pitfalls of complex work on projects are. That’s also why we dare to create what no one else so far has done. And that’s why we love our work!
HOW DOES GuardiaNNN.ai AI WORK? This is top secret. Sometimes you shouldn’t blurt out things to the world because competition lurks everywhere. The bottom line is that it works. The main thing that makes us stand out from the competition is that GuardiaNNN.ai is dynamic. It can identify hidden threats with high accuracy.
This helps ordinary users and crypto fans avoid scams, and protect their assets from bad or emotionally-driven decisions. The universal adoption of cryptocurrencies into mainstream life will only happen when people have the tools to help them avoid scams. And it will all only be possible when there’s quality and reliable analysis, sufficient information, transparent communication, and a trusted community.
Only some crypto markets currently offer a comprehensive tool like GuardiaNNN.ai. At the moment, you still have to click through several pages of various checks. And the best quality tools are paid for yet still not sufficient. But we've found a way to give everyone a free security option.
Thanks to GuardiaNNN.ai, project creators can voluntarily arm their potential fans with a tool that strengthens their credibility. By having high traffic on the platform, they can more easily present themselves to new people. Through our innovation hub, they can gain reinforcements for their team and grow their community. And Launchpad will open the way for them to raise new capital for development. The listing has Trending Top Projects embedded in it, secured by an honest vote using a crypto wallet. Polls won't simply be bought. Instead, projects must earn their rightful place in them by being active, approachable, and engaging.
submitted by Okal99 to Moonshotcoins [link] [comments]

2023.06.09 09:41 Gattusso02 Monster Hunter Rise: Sunbreak

Monster Hunter Rise: Sunbreak

Monster Hunter Rise: Sunbreak
Time: 200 hrs +
100% Clear: 400 hrs +
Difficulty: 7.5/10
The Monster Hunter franchise returns with the previously Nintendo exclusive finally getting its release on PlayStation. Prepare for one long, grindy and fulfilling ride collecting monster crowns all over again. This guide will now include the massive Sunbreak DLC complete with new monsters and better end game gear to make your platinum or 100% completion more efficient.
Trophy Guide
Powerpyx Trophy Guide for Monster Hunter Rise
Powerpyx Trophy Guide for Monster Hunter Rise: Sunbreak
Full credit to Powerpyx for the guides.
Wiki Guides
Credit to Game8 and Fextralife for the excellent wikis. Game8 has the more comprehensive guide complete with locations on where to farm certain items, along with equipment builds and other very useful information. Best to choose one of those builds as your base and swap out armors and skills along the way to find the build perfect for you. Fextralife has a more tabulated approach on the info that helps you get a quick glance on what you are looking for with lesser clicks but may have only concise information compared to Game8. For example, If you are looking for an item drop from a small monster, Fextralife will show you drop rates and which map to visit for your hunt. Game8 will give you a little more and show you the areas in the map where these small monsters are located.
If you're a beginner to the game or the series in general, the beginning sections and tutorials will naturally be quite overwhelming. Take things one step at a time, find a weapon that fits your play style best and enjoy the ride until you get a decent amount of monster hunts in to familiarize yourself with the game.
There will be tons of things to tweak and learn about on this game and no single article can give justice to the complexities of how to fully optimize your experience so additional research is recommended. Treat this article as a supplementary guide.
Efficiency Tips
Enjoy the story and progress through the main quest line as soon and as often as you can. The reason for this is as you progress through the story and your hunter rank increases, more equipment upgrades will be available to you along with the ability to upgrade the base defense of your gear further which unlocks incrementally as you increase in rank. The more defense you have means the more hits you can take and less healing items you consume which you can spend learning the monsters moves and hitting it.
Work on the 🏆 Beat-up Construction Kit as soon as possible and unlock all camp site locations on each map so you can fast travel conveniently closer to your target's location.
Materials List and Locations can be found here on Game8 to search for your gear and quest requirements. Browse it or simply drop the item you are looking for on the search bar.
Blights and Status Ailments Explained and their Cures is explained best in GadgetGabe's Top Voted answer from this GameFAQs forum. Use this wisely to cure yourself ASAP and stay at tip top shape for your fight. You can eventually customize your item load outs when hunting particular monsters.
Register an inventory and radial menu layout that is best for your hunt and tweak it accordingly if you are working on a solo hunt or are in a group. You can set up your action bar (the bar that uses the left and right d-pad) too.
Learn about monster elemental and ailment weaknesses, weak points and parts that you can sever to improve your success rate in a fight. E.g. Flash bombs work well on monsters in flight. Severing a Pukei-pukei's tail makes the monster incapable of it's wide poison gas attack.
Monster Elemental and Ailment Weaknesses and Immunities credit to Pro Game Guides. Monster Hunter Rise explains monster elemental weaknesses well but does not give too much of a description of what elements the monster utilizes against you. To learn that and build the right resistances, refer to the Fextralife MHR Wiki.
As you progress through your hunts, make sure to pick up any hunting helpers and golden/gilded spiribugs along the way. You will need 500 and 1000 respectively for the trophies 🏆 Hunting Helpers Plate and 🏆 Golden Spiribug Plate. If you want to farm Spiribugs exclusively, this video shows an excellent route while displaying some skills on speedy map traversal.
When you are in town, there will be times when you will be prompted that a sale is ongoing from the two merchants. Always take action on this prompt and participate in the lottery that is only available during this sale to progress towards the 12 room decorations you need to win as part of the 🏆 Sturdy Padlock. If the grand prize of the lottery is a room decoration, you have to roll a Jackpot (different from a Bingo) to win it. Even if the grand prize is not a room decoration, you are given a required room decoration for winning 100 items in the lottery.
🏆 Extravagant Cashbox
Awarded for earning 1,000,000 Zenny. The fastest method to earn zenny is by participating in the 2 Star Low Rank Event Quest - Gotta Hoard Fast!. It can be done with a group in 1 minute and rewards you with a Golden Egg which you can sell to the merchant for 20,000z. Use whenever you are short on money. This is also the best quest to use if you want to trigger merchant sales quickly and roll on the lottery.
Using your silk bind/aerial moves to deliver mount damage (indicated by a blue cloud background on the damage inflicted) is a good tactic to learn and master. Arekkz Gaming's Monster Riding Tutorial video explains this well. You can also scout the area where you mount the monster and bump him into special areas on the map that will deal extra damage.
High Rank Quests
An Armorcharm and Powercharm will now be available to purchase from the two item merchants. These work as permanent stat increases as long as you have them in your Item Pouch. When you reach HR7, you will eventually be able to upgrade these charms into Armortalon and Powertalon. These stack and you may repurchase Armorcharm and Powercharm and hold all four items in your Item Pouch.
Decorations will unlock from the Smithy and the Melding Pot will unlock from the item merchants. This would be a good time to study the skills you have available in conjunction with your armor skills and start creating defensive/offensive load outs based on what you are up against.
For talisman crafting via the Melding Pot, craft out the desired skill you need and use accordingly. Once you have your talisman of choice, always roll with Melding - Wisp of Mystery and Melding - Rebirth (unlocks last on a higher HR). They will cost more materials to craft, but will also have better chances of a Rarity 7 Talisman with more skills and better decoration slots.
Prepare status resistances/immunities depending on the monsters you are up against and build up defense, elemental defense and even add elemental attack against them as well. Take note that elemental attack increases on skills only increases an existing element on weapons (or elemental ammo for bowguns) and can not create an element from a non-elemental weapon source.
For more on elemental damage and elemental resistances, see Fextralife's articles linked accordingly.
Armorskin and Demondrug and their corresponding Mega version are items consumed once and will last until you faint or complete the quest. Invest in them as soon as you have the zenny to afford them. You will need to farm Pale Extract from the monster Khezu or purchased as a rare find in the Argosy to craft the mega drugs. You may also choose to deploy the meowcenaries to fight a Khezu to increase your item farm.
Master Rank Quests and Sunbreak Content
With Sunbreak comes a whole new base map and two new locations to explore. Like the base game, there are a number of trophies that involve you interacting with the townsfolk and the goods and services they have to offer. Refer to this video guide for a checklist of what you need to be doing after every quest to cover the trophies 🏆 Snowy Cohoot Minipouch, 🏆 Secret Honey Jar, 🏆 Unbreakable Bag, 🏆 Solid Padlock, 🏆Polychrome Acorn and 🏆 Sojourn Necklace.
🏆 Solid Padlock requires another set of items you need to win in the lottery but take note that the Gargolda Statue only starts appearing after you take a picture of it. Take a daytime expedition for a photo of the creature. Gamer Guru's video shows you how to do it.
Refer to Game8's Eurekacorn article for more ways on farming Eurekacorns for your Polychrome Acorn trophy. Efficiency Tip: Target an expedition with a Herb Node in the Frost Islands together with a Khezu Node for both Eurekacorns and Pale Extracts.
For efficient map traversal, unlock the alternative camp sites on the two new Sunbreak areas along with the new buddy recon points. You will have to unlock 2 recon points per map, for a total of 12 for 🏆 Buddy Whistle. Darcblade has an excellent video guide to cover this.
Crown Hunting
🏆 Mini Crown Plaque and 🏆 Gold Crown Plaque will most likely be the last trophies you will get in the game as these are very grindy to obtain. These entail slaying or capturing the smallest and largest versions of each monster, awarding you a gold crown on your Hunter's Notes. An alternative grouped view of all your crowns can be found in OPT -> Multiplayer -> Guild Cards -> View -> L1 for Hunting Log. Unlike MH World, Rise does not include a crown notification in the points reward section after a hunt. You will have to check your Hunter Notes manually. You do get a prompt of "Monster Size Updated" right after the kill or capture though as your best indicator of a possible crown.
Crown Hunting Tips and Drop Rates explained by Luke Albigés of TrueAchievements
Efficient Strategy
You will want to clear out all the crowns you can possibly obtain from the quests with the 100% chance or boosted crown rate quests. For everything else, learn how to crown snipe to save time and not waste too much time on normal sized targets. If your are sure that your target monster is not a crown size, abort your quest and start a new one. Take note that you need to capture/kill 10 monsters of each type for their respective monster scroll to progress on your 🏆 Sturdy Padlock so anything close to a perceived small or large crown would be worth the kill. The Sunbreak Expansion and Master Rank buffs up the crown monsters appearance rate to as high as 10% for large and 6% for minis. You are best saving the crown hunt for last as you have to tackle Anomaly Investigations for the Sunbreak 🏆 Bahari's Hand Wound Birdie, which entails you earning and spending 3000 Investigation Coins as rewards for these type of quests along with clearing out every single Master Rank quest for the 🏆 Record of Utmost Valor - Master and clearing out 1-4 star anomaly quests for the 🏆 Painting - Crimson Nightmare. There are a total of 7 1-star anomaly quests to unlock and 8 quests for 2-4 stars. There is a good chance that you will be earning majority of these crowns along your progression towards these three trophies with minimal crown cleanup.
Videos for Monster Measurements
As of this writing, there seems to be a lack of content on Large and Mini Gold Crowns for MH Rise. Below is video clips to give some clues on how these monster sizes will look when you encounter them. Monster sizes with 100% chance drop quests will be excluded from this segment.
Kiranico has an excellent large monster guide which also displays the recommended quest to participate in with corresponding crown percentages.
Anomaly Investigation quest monsters have fixed sizes and will never yield any crowns. The normal Anomaly Quests will share the same 6% small and 10% large crown chance as the MR quests.
Base Game Crowns
Anjanath Mini Gold Crown
Barioth Large Gold Crown
Barioth Mini Gold Crown
Barroth Mini Gold Crown
Chameleos Large Gold Crown
Chameleos Mini Gold Crown
Great Izuchi Large Gold Crown
Great Izuchi Mini Gold Crown
Ku-Lu-Yaku Large Gold Crown
Ku-Lu-Yaku Mini Gold Crown
Kushala Daora Mini Gold Crown
Lagombi Large Gold Crown
Rakna-Kadaki Large Gold Crown
Rathalos Mini Gold Crown
Royal Ludroth Large Gold Crown
Teostra Large Gold Crown
Teostra Mini Gold Crown
Sunbreak Crowns
There are only 16 additional monsters tied up to the crown trophies for Sunbreak which are the monsters that were available at the original release of the game. You will need these 16 monsters along with all the base game crowns for the 🏆 Miniature Crown Shield and 🏆 Gold Crown Shield to unlock. Refer to the Gold Crown Shield segment of Powerpyx's guide for the full list.
Astalos Large Gold Crown
Aurora Somnacanth Mini Gold Crown
Gore Magala Large Gold Crown
Malzeno Large Gold Crown
Pyre Rakna-Kadaki Large Gold Crown
Scorned Magnamalo Large Gold Crown
Miscellaneous Grind
🏆 Antique Bookmark
Achieved by collecting all 60 Relics scattered over the 5 available maps. Powerpyx's guide for all Relic Locations shows these well. There is a correction to the linked article however, as it is mentioned there that the Rampage Relics unlock after collecting all 10 other Relics per map but is incorrect (unsure what triggers rampage Relic availability but I had access to them at 5 star quest availability on Village and Hub quests). To track the relics you have collected already, go to OPT -> Info -> Hunter Notes -> Notebook.
Gaming with Abyss has good Monster Hunter trophy content and shows locations of each relic per map clearly on his videos.
Shrine Ruins
Frost Islands
Flooded Forest
Sandy Plains
Lava Caverns

Other Useful Information
Affinity vs Raw Damage is discussed well on this steamcommunity forum.
The difference between KO/Stun and Trip is explained will in this article. Note that KO and Stun status are the same (in game and articles call it one or the other so this can be confusing) but Trip status is different.
Critical Boost at level 1 raises damage dealt by critical hits by 5%. Your critical hits are already at a base amplified damage of 25% (not mentioned in-game). This could be deceiving due to the in-game skill definition.
Palamutes and Palicos you bring on the hunt increase your ease and efficiency and are best slotted with the best gear for your playstyle. Game8 has an excellent buddy guide that discusses end game builds.
Use the Basic behavior if you are running a melee focused buddy and Follow if you are using a ranged buddy. This is discussed thoroughly by CheaterMcCheat.
On solo hunts, don't let the common combo of 1 Palico and 1 Palamute mold you to run with that as there are several builds that utilize 2 Palicos or 2 Palamutes in one hunt. For example, you may want to use a double Palamute with C Jelly Travel Bag X weapon on the Best Equipment For Sunbreak (Ranged)segment. Accompanied with the Palamute Silkbinder, this build can provide excellent monster control.
Ordering Motley Mixes in the canteen nets you dango tickets as a reward. Claim it from the chef after some orders and use the tickets with hopping skewers on your harder hunts.
Latent Power skill is triggered by an internal timer upon monster encounter and attack animations and is explained here on Fextralife's wiki.
Auto-shoutouts are useful for your party and even yourself. You can program these auto shoutouts via OPT -> Multiplayer -> Chat Menu -> Triangle and click on the field under Text to program what you want to shout-out, choose the box under speech timing to choose the condition. These conditions aren't fixed and you have more to choose from. The most useful ones are the auto shoutouts for "When you set a trap" and "When a monster is limping" where the monster enters the blue icon state and is capturable if it is not an elder, apex or afflicted monster.
Weapon Specific Notes
Light Bowgun
Light Bowgun Basic Moves and Ammo Types credit to Phemeto
Pay attention to the color of your reticle. An orange reticle tells you that your ammo type is in its ideal range and will deal its intended damage. A yellow reticle means your shots will hit, but will be significantly weaker.
The Fanning Vault Silkbind skill is best used with your Wyvernblast special ammo. Press circle while you are directly under the monster to plant a bomb directly on it. You will be replacing this with the Switch Skill Fanning Maneuver for end game builds.
Ammo Details can be found by going to Items and Equipment (opt button) -> Equipment Info -> Ammo Details (square)
You will normally run out of your full magazine of your most desired ammo. To minimize returning to camp, bring the materials you need to craft that ammo and set it on your radial menu. Also, avoid bringing the ammo type you never use to keep your ammo menu as decluttered as possible for efficient ammo switching. It is encouraged to bind the ammo you use and their craft commands in your radial menu as well.
Recoil is the delay between firing shots (different from Reload delay). Lower recoil = Faster Attack Speed
Deviation is the drift of the bullets when you fire. If you have a weapon with deviation, it will travel center for a medium distance then swerve to the L or R depending on the strength of the deviation. Targeting "No deviation" is ideal.
Decorations can be crafted to reduce Reload, Recoil and Deviation.
Light Bowgun Weapon & Armor Skills
Bombardier skill does not work with any ammos, including sticky, cluster, or wyvernblast.
Normal/Rapid Up skill improves Normal Ammo damage by 5%/10%/20% and stacks with the skill
Rapid Fire Up which enhances rapid fire damage also by 5%/10%/20%
Great Sword
Recommended Switch Skills are Tackle, Rage Slash (RS), and Adamant Charged Slash (ACS). All three can tank monster attacks (no knockbacks) and negates roar effects. Tackle is the bread and butter during roars and quick monster attacks since its easy to trigger, You can use Adamant Charged Slash for positioning, and Rage Slash to land your last charged attack on your desired direction, which True Charged Slash Skill cant do.
How to Unlock:
Adamant Charged Slash - Unlocked by crafting/upgrading 8 different Greatswords, no duplicates. Replaces the Hunting Edge skill.
Rage Slash - Unlocked by completing the quest "Grasp the Greatsword" (HR5 Quest). Replaces the True Charged Slash skill.
Low Rank Entry GS - Crit Eye Build
Low Rank GS - Crit Draw Build - 80% Affinity on Overhead and Charged Slash
High Rank GS Build - 90% Affinity on Weakpoints + Focus 3
Several members of the PSTHPH team contributed to the making of this guide.
There is an ongoing issue with this article preventing further edits. Please check the comments for more.
submitted by Gattusso02 to PSTrophyHuntersPH [link] [comments]

2023.06.09 05:36 GamingHearts1 Yoshi’s Island- Does it deserve to be remastered in 2D-HD?

Yoshi’s Island- Does it deserve to be remastered in 2D-HD?

The Yoshi’s Island game from 1995 is considered to be a classic for the Super Nintendo Entertainment System. Despite, not being quite as popular as Super Mario World from 1990 Yoshi’s Island stood out because of its childlike art style along with the fact that players controlled the green dinosaur opposed to Mario. In Yoshi’s Island Mario was an infant and Yoshi had to protect him throughout the game from adversaries like the Shy Guys throughout at least eight different levels before fighting Bowser in the end. Yoshi’s Island was officially known as Super Mario World 2 and managed to reach over four million copies in worldwide sales on the SNES console back in the mid 90’s. At this point Yoshi’s Island is almost 30 years old and Nintendo has nothing really special with the game since the early 2000’s when it was ported for the Game Boy Advance. Super Mario World 2 is arguably the best entry within the Yoshi series and its a game definitely deserves a 2D-HD remake for a current generation console like the Nintendo Switch. Unfortunately, Nintendo is not too big on remastering or remaking old games from the 90’s with exception of Zelda: Link’s Awakening. Yoshi’s Island is an absolute gem from the 16-bit era and many believe that something special should be done with the game during its 30th anniversary which is coming up in 2025.
submitted by GamingHearts1 to u/GamingHearts1 [link] [comments]

2023.06.09 05:35 GamingHearts1 Yoshi’s Island- Does it deserve to be remastered in 2D-HD?

Yoshi’s Island- Does it deserve to be remastered in 2D-HD?

The Yoshi’s Island game from 1995 is considered to be a classic for the Super Nintendo Entertainment System. Despite, not being quite as popular as Super Mario World from 1990 Yoshi’s Island stood out because of its childlike art style along with the fact that players controlled the green dinosaur opposed to Mario. In Yoshi’s Island Mario was an infant and Yoshi had to protect him throughout the game from adversaries like the Shy Guys throughout at least eight different levels before fighting Bowser in the end. Yoshi’s Island was officially known as Super Mario World 2 and managed to reach over four million copies in worldwide sales on the SNES console back in the mid 90’s. At this point Yoshi’s Island is almost 30 years old and Nintendo has nothing really special with the game since the early 2000’s when it was ported for the Game Boy Advance. Super Mario World 2 is arguably the best entry within the Yoshi series and its a game definitely deserves a 2D-HD remake for a current generation console like the Nintendo Switch. Unfortunately, Nintendo is not too big on remastering or remaking old games from the 90’s with exception of Zelda: Link’s Awakening. Yoshi’s Island is an absolute gem from the 16-bit era and many believe that something special should be done with the game during its 30th anniversary which is coming up in 2025.
submitted by GamingHearts1 to hotgamingtopics [link] [comments]

2023.06.09 04:44 Chonker73 Should I sell some of my monsters to get a wubbox?

Although yes the wubbox is on sale, I have yet to make any real coin farm apart from completing islands, and I spent some of my gold to upgrade castles. And I’m thinking of selling some of my more valuable monsters to afford the wubbox.
submitted by Chonker73 to MySingingMonsters [link] [comments]

2023.06.09 04:29 Bubzoluck [30 min read] The Opioid Epidemic before the Opioid Epidemic - Exploring Morphine Derivatives and the First Opium War (Part 1)

[30 min read] The Opioid Epidemic before the Opioid Epidemic - Exploring Morphine Derivatives and the First Opium War (Part 1)
Hello and welcome back to SAR! I have written and rewritten this post a few times now and I think I have landed on a format I am happy with. When we talk about the impact of medicine on history its important to get the context right, and I think I have found a way to talk about our topic. So what is it? No chemical is more important to the world of medicine than Opium, okay maybe Penicillin, but today we will say its Opium. Principally an analgesic (anti-pain), the Opium Poppy allowed for humans to take away pain in great degrees and further development on the natural chemicals has opened up surgery and post-op recovery. While we tend to look at the recent Opioid Epidemic as the only issue regarding Opiates, history reveals to us a very similar precursor. Also please head over to u/jtjdp post about morphine derivatives here! She does an amazing job explaining the higher level concepts of medicinal chemistry that I just wouldn’t do justice. Alright, enough quibbling, let’s get to the good stuff.
Disclaimer: this post is not designed to be medical advice. It is merely a look at the chemistry of medications and their general effect on the body. Each person responds differently to therapy. Please talk to your doctor about starting, stopping, or changing medical treatment.

How Much do you Know About Pain?

To be alive is to feel pain, and emo sentiments aside, this is one of the biggest biological properties of the central nervous system. When you think about it, how does the body take external stimuli and allow you to recognize it? The answer is the sensory nervous system which is responsible for sensing many different types of stimuli: temperature, pressure, pain, and chemicals. These sensory neurons carry the information from the extremities and transmit it up the spinal cord into the brain for processing. From there the brain alerts you to the issue allowing you to correct whatever problem is causing the pain. Let’s take a look:

  • We call these receptors Nociceptors and activation of these neurons in the periphery leads to a signal being sent towards the spinal cord. Those peripheral nerves eventually complex with the Dorsal Horn of the spinal cord and interface with the central nervous system to transfer the pain signal. This signal is then sent Ascending to the Thalamus where the pain signal is recognized and initiates a response (such as pulling your hand away from the hot stove). But that’s not the full story, the brain also sends signals back down Descending to modify the incoming signal and dampen it. Its this modifying that makes pain fade over time when you aren’t focusing on it—otherwise the brain would be overwhelmed by the repetitive signal and continuously think injury is still happening. Now let’s divide this process into its two parts, first up the Ascending pathway.

  • As the Action Potential travels from the periphery towards the Spine it causes the influx of Calcium into the Presynaptic Neuron. This neuron is what carries the original signal to then transfer into the Spine for further traveling. Eventually we reach the Synapse where the finger-nerve and spine meet and we get the transfer of information via Neurotransmitters. In this case, two chemicals are released: Glutamate and Substance P (which literally stands for Substance Pain). Glutamate will activate two receptors (AMPA and NMDA) which are Excitatory and stimulate the continuation of the pain signal up to the brain. Substance P activates the NK1 receptor which enhances the frequency of the pain signal (the throbbing) and the intensity of the pain burst. So to simplify, Glutamate allows the signal to be passed up to the brain but depending on the strength of the original pain signal more or less Substance P is released which modulates the strength and attention-grabbing nature of it. Okay great, we sent the pain pathway up and it will get processed in multiple different parts of the brain. But the brain can’t have that signal stinging it so it must send information back down to dampen that pain signal. This is where that aforementioned Descending pathway comes in. Above you can see how the blue line reaches down out of the brain and back into the spine to turn ‘off’ the signal. This is the basis of Analgesia or pain relief.

  • Okay so now we have to divide the action of the Descending pathway which acts to dampen and modulate the original signal coming into the brain. Now, normally at rest this Descending neuron is inhibited so any fresh incoming signal is not inhibited from the get go but once that pain signal does come in, we get the good stuff! In response to pain the brain releases substances called Endorphins which activate the mu Opioid Receptor (MOR) located on the Descending pathway. Now MOR are inhibitory in nature so they are inhibiting the inhibitory resting state of neurons, or in other words, are allowing the Descending neuron to activate. And this is an important fact to recognize, Opiates do not inhibit pain, they inhibit the physiology of the nervous system that prevents modulation of the pain signal.
    • Once the inhibition is inhibited, the Descending neuron is free to release two neurotransmitters onto the nerve that was carrying the original pain signal. Both Norepinephrine and Serotonin are released to activate their respective receptors which inhibit the release of Substance P and Glutamate thus decreasing the incoming pain signal. Likewise MOR receptors are found directly on the incoming nerve and further prevent the release of Glutamate and Substance P as well as being found on the Ascending neuron preventing the activation of the NMDA/AMPA and NK1 receptors. The result: dampened incoming signal and decreased pain sense being sent to the brain.

The Stars Align in the Shape of a Poppy

To start our story about Opiates we need to turn to the great precursor—Opium. Opium itself is not a chemical but rather a really thick liquor (called latex) that contains a high concentration of Morphine (and some Codeine). There are 38 species of Poppy plants but only two produce Opium is great enough supply that it is worth farming them and humans have been cultivating these varieties for as long as we have known about the plants. When humans settled into Mesopotamia (near modern day Iraq), Poppies were one of the few plants grown in plots as large grain or vegetable fields (meaning that they were thought of as valuable as food). Throughout the Greek age of medicine (pre-500 BCE) through the Islamic medicinal revolution (500 BC-1500 AD), Opium was a major component of treatment, assisted suicide, and poison. In fact its through the rise of the Muslim Caliphates that we see the export of Opium to other parts of the world, especially through the Mediterranean Sea once the Crusaders return. Opium trading to the East via the silk roads was an almost continuous affair since time immemorial and Pakistan was a major growing area for the Eastern Poppy trade.
  • By the time after the Crusades (11-13th centuries), we start to see the West’s fixation on Opium. For many reasons Europe didn’t develop many psychoactive plants to the same degree as more humid/hot climates like Africa, the Middle East, and India. This is why the importation of Opium (and also Marijuana) was such a trade commodity and staple in the development of Western medicine. During the Renaissance and the revival of Greek philosophy we start to see the re-fascination with Opium and by the 1600s we see merchants importing Laudanum into Europe for recreational and medicinal use. The standard use of Tincture of Opium (which is Opium dissolved in ethanol, a DEADLY combination) was a particularly favorite preparation which was prescribed to the lowest day-worker all the way up to kings.
    • The importation and use of Opium exploded in the late 1700s once the British conquered a major Poppy growing region of India. This region (western India and most of Pakistan) was originally slated to grow cotton like the American colonies but the region wasn’t wet enough to sustain the plant—it could however grow copious fields of Poppy plants to create Opium. Throughout the 18th century the British Raj became the largest exporter of Opium to Europe and after the discovery that Mercury and Arsenic may not be safe, Opium took over their duties. By 1780 almost all major remedies incorporated the use of Opium in some capacity and with the huge supply, it was incredibly cheap.

  • Poppy wasn’t only important to the British for its medicinal properties but also to bolster the huge amount of loss they were incurring in global trade to one trade partner—China. After she made contact with China in the mid-1500s, Britain starting to import HUGE amounts of tea as the Brits became literally addicted to the substance. By 1800 a full 15% of the ENTIRE British Empire’s revenue was being spent on importing tea, that’s 30 million pounds per YEAR, leading to a massive trade deficit. This means that more money was being sent to China literally enriching a foreign country while the British public was getting their fix on the black stuff. Oh and just in case you think things haven’t changed, Britain still accounts for 42.6% of the world’s tea consumption—seriously Brits, ever heard of coffee? Anyways, all this money leaving the British economy to be spent on non-Empire sustaining commodities was a major national security risk for the British. It would be different if they were importing gunpowder like the Dutch were or Silver as the Spanish had but literally they were consuming the riches they were spending the money on.
    • Remember too that the British were not in the best position by the turn of the 19th century—they had just lost their colonies in the Americas, involvement in the Napoleonic Wars killed a generation of men, and the push to develop industries over public health led to a focus on fast growth rather than smart growth. One of the results of the Napoleonic Wars was the British occupation of the Island of Java which developed a very potent Opium which was traded with Chinese merchants regularly. Soon British merchants realized they could rebalance the trade deficit by selling Javanese Opium into China but the small island was unable to produce enough Poppies to meet the demand. So Britain turned to another one of its colonies, India.

  • India by the end of the 1700s was a bit of a challenge. The British hold on the subcontinent was firm but they couldn’t grow the cash crops they wanted. Indian cotton was nothing compared to Egyptian or Southern American (i.e. Virginia/North Carolina/Georgia) cotton and the Indian tobacco was known for being bitter. But by the 1770s the British government realized that Poppy was an easy crop to grow and the demand across the border with China was an easy market; British traders brought their cargo to small islands off the coast of China where it was sold for silver. Initially the Chinese didn’t mind the sale of Opium in their territory—when the British traders collected the silver from the sale they would almost immediately use it to buy Chinese goods, thus driving tax revenue for the Chinese government.

  • But if you buy Opium, people are going to use that Opium. By the 1810s all trade with foreigners was restricted to just one port, Canton, and slowly the city started to develop a habit for the drug. The use of mind altering substances was curtailed pretty quickly for hundreds of years in China—the Ming Dynasty banned tobacco in 1640 and the Qing banned Madak (a powdered Opium containing tobacco) was similarly banned in 1729. But by 1790 more and more Chinese citizens were becoming addicted to the substance; what started as a recreational drug slowly became a crippling addiction that took hold over Canton. For a rigid society, the crippling Opiate addiction was a moral corruption for the Qing government and forced them to curtail Opium importation in 1780 and then an outright ban in 1796.

  • Knowing just how devastating the Opium was having on the inhabitants of Canton, as well as how it spread further inland, British merchants kept peddling their drug. Older ships with larger hulls were converted into floating warehouses and parked just outside of navigable waters. Once set up, Opium smugglers would pull up, purchase the Opium and avoid any oversight by the Chinese government to prevent the sale of the drug. Following their mother country, American merchants started to sell Turkish Opium, an inferior variety, at a much cheaper rate leading to drug peddling competition with more and more tons of Opium being sent into China. This drove down the price of Opium considerably which ultimately increased the demand.
    • This demand eventually led to reversal of trade, meaning that more silver was leaving China to pay for Opium than the British were using to pay for Chinese goods. American and European traders could show up in Canton with holds full of Opium, sell it off for a profit, and then make a tidy silver profit to bring back to Europe. Likewise the importation of cheap machine-made cotton, furs, clocks, and steel into China driving down domestic profits.

Let’s Look at the Drugs a Bit

Stepping away from the history a bit, let’s introduce the Family. Okay so we understand how pain is sent to the brain and how it modulates but there is so much more to the mu Opioid Receptor and that’s not the only kind of Opioid receptor that we have. The two most clinically useful receptors are the Mu and Kappa Opioid Receptors (KOR) because they result in analgesia but there is a Delta Opioid Receptor (DOR) that is worth mentioning. The majority of the Opiates that we know and love are Mu agonists but there are some very interesting Kappa agonists that are worth mentioning as well.

  • Above is a chart that shows the binding affinities of select Opiates to the Mu receptor. The smaller the number is, the more tightly they bond. Now affinity is different than potency—potency is a measure of how much drug (in g) is required to produce the same effect. So even though morphine has a higher affinity than fentanyl, fentanyl has a MUCH more potent effect (which is why it can be so dangerous, you only need a little). Now many of the opiates cause the same effect so I want to spend more time on what makes them all so different:
  • First up we have the 5-Ring Morphinians which are derived from the natural product Morphine. These structures have 5 component parts: an aromatic benzene ring (A), a completely saturated bridge ring (B), a partially unsaturated ring with an alcohol attachment (C), a piperidine heterocycle above the rest of the structure (D) and finally a ether linkage between the top and bottom of the structure to keep it fairly rigid (E). Truthfully we are only going to focus on two locations—firstly the top alcohol (red circle) can be methylated to form Codeine, a natural Prodrug of Morphine. A Prodrug is one that is biologically inactive but goes through an initial metabolism once ingested that makes it active.

  • In fact it’s this initial metabolism of Codeine that makes it very interesting. In order for Codeine to exert any pain relief it needs to be converted to Morphine which actually exerts the desirable properties. This is done by the liver enzyme CYP2D6 which is a pretty minor pathway for Codeine—only about 10% of the Codeine is actually converted to Morphine to have some action. Because of this 2D6 dependent pathway we have to be careful about administering drugs that might inhibit the 2D6 pathway because that would mean we are preventing codeine from being active. Drugs like Fluoxetine (Prozac) and Paroxetine (Paxil) are strong 2D6 inhibitors and so if we administered Codeine to someone taking this drug they’d never get any benefit from the Codeine. In addition there are genetic/ethnic differences that pharmacists can account for such as 2D6 activity. If you are someone with very little 2D6 activity then you would also not convert Codeine to Morphine and thus get no action from the drug—this may be a reason why some people say Codeine doesn’t work for them. Another reason could be that they are Rapid Metabolizers and quickly convert the Codeine to Morphine and thus get a massive hit quickly after ingestion—in that cause you’d need a much smaller dose than another person for the same effect.

  • A different drug that is the opposite of Codeine is Hydromorphone (Dilaudid) which has a Ketone on ring C. This ketone and the lack of the double bond on this ring increases the lipophilicity of the drug and increases its ability to penetrate into the brain and thus have a greater effect. In fact Hydromorphone is 5-10x more potent than Morphine due to its greater ability to penetrate into the brain and increased receptor affinity for the mu receptor. Because the A ring OH is not capped with a methyl group, we don’t need to rely on 2D6 to metabolize Hydromorphone into an active drug form which again increases the activity of this drug compared to Codeine.
  • So combine these two structural changes—the capped OH on ring A as seen in Codeine and the increased affinity found with the ketone in Hydromorphone and we get Hydrocodone (Norco, Lorcet). Well in this case you’d get a drug that has very good affinity for the mu receptor (better than codeine) BUT is still reliant on the small 2D6 pathway for activation (worse than morphine). In this regard only about 10% of Hydrocodone is active at a time. We can see this effect in the relative doses for equivalent effect: to match the effect of 30mg of Morphine, we’d need only 7.5mg of Hydromorphone (more active) but need 200mg of Codeine (less active).

  • This brings us to our last drug of this class, Oxycodone which has a special OH group found on Ring B. What you’ll notice is that Oxycodone has that capped OH on ring A so it requires metabolism through 2D6 just like Codeine and Hydrocodone. When it is uncapped it becomes Oxymorphone which has 3 times as much effect as Morphine BUT that extra OH makes Oxycodone an exclusive Mu receptor agonist. Unlike the other drugs which may go to other receptors causing side effects (more on this later).

  • Next up I want to look at some Mu opioid receptor Antagonists or those than inhibit the function of the opioid receptor. Looking at the first two drugs, Naloxone and Naltrexone, we can see that they have the structure similar to Hydromorphone so they would have incredible brain penetration and affinity for opioid receptors BUT they contain that funky Nitrogen tail. Now normally there is a short methyl tail that is required for the function of Morphine but by adding a bulkier tail the drug is able to fit inside the receptor but prevent activation. What’s most important about these two drugs is that they have much more affinity for the receptor than other opiates. We can see this effect in the graph above: when no Naloxone is present, Fentanyl occupies the opiate receptor about 75% of the time. But as soon as Naloxone is administered that number drops swiftly (within minutes)--this is because Naloxone has a higher affinity for sitting in the receptor than Fentanyl. Think of it like the bully Naloxone coming up and pushing the poor defenseless Fentanyl off the swings so the bully can play on it (except in this instance Fentanyl is causing an overdose and we need to save someone’s life).

  • Buprenorphine is similar but it is a Partial Agonist instead of being a full antagonist. Buprenorphine is not a 5-ring Morphinian byt a 6-ring Oripavine that has a few different modifications. The biggest additions is that it has the bulky Nitrogen tail found in full Antagonists but it has this funky C ring tail which fights the antagonism. The result is a tug of war between the antagonism of the Nitrogen tail and the agonism of this new C-ring tail resulting in Partial agonism—so if you took Buprenorphine you’d notice a markedly decreased pain relieving ability but importantly there is a ceiling effect, its much harder to overdose on Buprenorphine than other full agonists. In addition in the second graph we can see that Buprenorphine has the greatest affinity for the receptor than our other agonists which prevents someone from taking a more potent opiate while taking Buprenorphine. In this case the bully is already sitting on the swing and scaring away the other kids thus preventing them from having a turn (and potentially causing an overdose). This does mean that if someone was taking a more potent drug (like Fentanyl) and then took Buprenorphine, it would cause withdrawal just like Naloxone or Naltrexone.

  • Speaking of withdrawal, let’s take a look at how that happens. Remember that the pain signal is caused by the activation of AMPA and NMDA receptors from the peripheral nerve. AMPA is a type of receptor called a G-Protein Coupled Receptor or GPCR which in this case is linked to an Excitatory G-protein which leads to the activation of the nerve. When AMPA is activated, the G-protein (Ga) activates an enzyme called Adenylate Cyclase (AC) which increases the production of pro-activity cAMP—or in simpler terms—when AMPA is activated, it leads to an increase in levels of pro-pain molecule cAMP. The Opioid receptor is also a GPCR but it is linked to an inhibitory G-protein which prevents the action of Adenylate Cyclase and thus leads to a decrease in cAMP levels. So Opiates prevent pro-pain cAMP signaling from continuing.
    • In the second graph we can see how tolerance forms. Initially (A), Adenylate Cyclase and cAMP levels are not affected by having opiates even though their ability to push along the pain signal is blocked. After a few hours, the leftover cAMP is degraded and cAMP levels start to drop significantly (B). In response to these levels going down, the activity of Adenylate Cyclase starts to increase and increase (C) which raises the level of cAMP. This rise in Adenylate Cyclase activity opposes the action of the opiate which necessitates the need for increased doses of Opiates and is why tolerance forms. As sustained inhibition of Adenylate Cyclase continues, the body upregulates Adenylate Cyclase activity to create more cAMP and to combat this we increase the dose.
    • Now what if after years of taking an Opiate we suddenly administer Naloxone, an Opiate antagonist. Well after weeks to months of taking an Opiate, the level of Adenylate Cyclase activity is WAY above baseline. When you administer the antagonist, suddenly Adenylate Cyclase is able to produce a TON of cAMP that normally is blocked which leads to a MASSIVE amount of downstream signaling. The result is intense nausea and vomiting, stomach cramps, fever, anxiety, insomnia, and cravings. Thankfully the withdrawal process ends after about 72 hours but is one of the worst experiences someone can go through which is why proper down-tapering of Opiates is extremely important.

A Change in Trade Policy

Oh, you’re still here. Neat! So by the 1820s the Qing dynasty was running into many problems regarding Opium. Firstly they needed the Opium taxes to fund their efforts to put down the White Lotus Rebellion and retain power. But after almost 30 years of trade the effects on Chinese communities could not be ignored along with local officials operating under the imperial trade department, the Hong, profiting from bribes to allow Opium. Regardless of initial efforts things were getting out of hand for the Qing government. In 1800, about 4000 chests of Opium or 560,000 pounds entered the country but by 1830 that number exploded to 20,000 chests or about 3 million pounds. But more than the amount of Opium actually entering the country was the incessant rudeness of the British government to open trade.
  • One of the “problems” for the British traders was how clamped down trade was with China. By 1800 all trade was limited to just Canton and the Hong was a strict master of trade. Foreigners were not allowed to appeal decisions made by the Hong and only Chinese traders could sell goods further inland than Canton. Traders chafed against this extreme oversight and sent hundreds of letters to the Hong requesting special dispensations which were summarily denied. Things changed significantly in 1834 when the Chinese trade was de-monopolized away from the East India Company allowing any private trader to get involved in the Eastern trade.

  • In August of 1834, the British sent Lord William John Napier to Macau as superintendent of Chinese trade with the explicit order to follow all Chinese regulations. Thinking he knows best, Napier decided that the restrictive Chinese trade system was too restrictive and sent a letter to the Viceroy of Canton. This was unheard of—NO foreign traders were allowed to speak directly with Chinese officials and the Viceroy refused to accept it. So why not double down by ordering two British ships to BOMBARD two Pearl River forts as a show of force? Luckily Napier died of Typhus almost directly after else it would have resulted in a full blown war.
  • In 1839 the Qing government appointed Lin Zexu as the Opium czar to completely eradicate the Opium trade from China. Lin banned the sale of Opium in China completely, set up rehabilitation centers for those affected by the drug, and put addicts to work to distract them while detoxing. Lin demanded that all Opium supplies must be surrendered to Qing authorities and any Chinese citizen disobeying the order would be punishable by death. He even went as far as closing the Pearl River Channel, trapping British traders in Canton and seizing their Opium warehouse stockpiles.
  • The replacement for Napier was Admiral Sir Charles Elliot who protested the seizure of the Opium stockpile but knew that they could do nothing. He ordered all Opium ships to flee and prepare for battle which caused Lin Zexu to beseige a group of traders inside a Canton warehouse. Elliot convinced the traders to cooperate with the Chinese government and surrender their stock, saying that the British government would compensate for the lost Opium (which he had no authority to do). During April and May 1839 the British (and American) traders to surrender 20,000 chests of Opium which was burned for three days outside Canton. Following the burning, trade resumed to normal except no more Opium was allowed. Like many other instances of the government removing legitimate sale of a drug, the black market increased markedly.
  • In July 1839 a new scandal rocked the British-Chinese trade system; two British sailors became drunk and beat a man death outside of his village. In response, Superintendent Elliot arrested the two men and paid compensation to the villager’s family for the loss of the man but Elliot refused to hand over the sailors to the Qing government. Lin Zexu saw this as a blatant disregard for Chinese law—afterall traders needed to understand that they can’t just come to China and violate Chinese law as they saw fit. Elliot offered to hold a trial on a British ship in front of Chinese officials to show that the men would not get off free. This incident would start the smoldering.
    • On September 4th, Elliot sent two ships to Kowloon to buy food and provisions from Chinese peasants. While approaching the harbor, three Chinese war junks gave permission to the two British ships to trade but that permission was rescinded by the commander of Kowloon fort. Elliot fumed against the slight and said that if the British were not allowed to trade by 3pm, he would fire on the fort. 3pm passed and the British opened fire on the fort causing the Chinese junks to return fire. The fighting continued for 7 hours until nightfall and Elliot had to prevent the British officers from pressing the attack, thus ending the Battle of Kowloon. Having driven off the Chinese ships, the British purchased the supplies they needed while the Kowloon commander claimed that both ships were sunk and 50 British sailors killed.
    • The reaction in Britain was about as much as you expect. Prime Minister Palmerston sent out letters to the Governor General of India to prepare marines to invade China and another letter to the Chinese Emperor telling him that Britain would send a military force. He sent a letter to Superintendent Elliot to set up a blockade on the Pearl River and capture Chusan Island. He also instructed Elliot to accomplish the following objectives:
      • Demand the respect as a British envoy from the Qing Government.
      • Secure the right for British law to be doled out on British subjects
      • Get recompense for destroyed British property, especially the illegal drugs that they destroyed
      • And most important, End the Canton System thus opening up China to free trade for the first time, ever.
Alright this is where we will leave things off for now, on the brink of war with China. Stay tuned!
submitted by Bubzoluck to SAR_Med_Chem [link] [comments]

2023.06.09 03:53 AutoNewspaperAdmin [Local] - St. John’s University puts Staten Island campus up for sale — with no plans to house migrants NY Post

[Local] - St. John’s University puts Staten Island campus up for sale — with no plans to house migrants NY Post submitted by AutoNewspaperAdmin to AutoNewspaper [link] [comments]

2023.06.09 03:43 SonOfJesus1 Own a piece of history

Own a piece of history submitted by SonOfJesus1 to Tiki [link] [comments]

2023.06.09 03:38 AutoNewsAdmin [Local] - St. John’s University puts Staten Island campus up for sale — with no plans to house migrants

[Local] - St. John’s University puts Staten Island campus up for sale — with no plans to house migrants submitted by AutoNewsAdmin to NYPOSTauto [link] [comments]

2023.06.09 03:17 AnchorChained 38 (M4F) Mass / New England - seeking lucky lady for travel and chasing waterfalls

38 (M4F) Mass / New England - seeking lucky lady for travel and chasing waterfalls
38/m straight, Massachusetts. I have a great job as a city mail carrier for USPS. Great benefits, government work and great coworkers. I love the career I chose or well - it chose me at 30 after several interesting attempts at a career - lifeguarding for more than a decade, retail work, and sales. In my spare time - I love to read, travel, and enjoy the outdoors. Did I mention l love to cook? I almost went to school for cooking. I also do research for several true crime podcasts. I went to school for history - didn’t end up finishing my degree for various reasons - but I love to research and find out facts about our world, human nature and what makes us all tick. One of the most daring things I ever did was get up on stage in Boston and tell jokes naked. So yeah - definitely crazy. I’m also very comfortable with how I look - and while I’m working on getting back into shape, I’m not insecure about my body. It was pretty liberating to be up there in the buff telling some jokes. I wish we could all be like that - I mean we were born naked after all. No one popped out wearing designer clothes or perfect everything. Do you think you could get up on a stage with strangers watching and tell jokes naked? I am a lifelong Eagle Scout - I felt confident enough in my skills to apply for Naked and Afraid and other survival shows - but sadly - I wasn’t picked. Maybe I wasn’t dramatic enough for them! I have several tattoos that I designed myself and have deep meaning to me. I have more planned - finances permitting. I had a dog Snickers whom I adore - I lost custody of him during my divorce. Worst case scenario is that I get another dog but I would be heartbroken. What do I want to do? So much to do. If we have the freedom to not have kids - then there is a whole world worth of travel / experiences for us to enjoy. One of the places I definitely want to go to is Easter Island with all those giant stone heads. An interesting place for sure. I’ve traveled to Canada, Mexico, Turks and Caicos, Dominican Republic, England, France and Spain. I have a two week trip planned in the fall to Portugal.
One thing I have done for fun this year is visiting waterfalls all over New England. It’s quite a bit of fun.
Let me leave you with a quote from one of my favorite movies “Safety Not Guaranteed”: [last lines] Kenneth: To go it alone, or to go with a partner. When you choose a partner, you have to have compromises and sacrifices, but it’s the price you pay. Do I want to follow my every whim and desire as I make my way through time and space? Absolutely. But at the end of the day, do I need someone when I’m doubting myself and I’m insecure, and my heart’s failing me? Do I need someone who, when the heat gets hot, has my back? Darius: So, do you? Kenneth: I do. **** Even if you’re not interested after my “novel” of a post - I wish you the best of luck in finding someone - we all deserve that special someone.
submitted by AnchorChained to cf4cf [link] [comments]

2023.06.09 03:01 Mean_Honeydew8561 LAGOON

LAGOON submitted by Mean_Honeydew8561 to namesoundalikes [link] [comments]

2023.06.09 02:02 Mean_Honeydew8561 lagoon

lagoon submitted by Mean_Honeydew8561 to namesoundalikes [link] [comments]

2023.06.09 00:15 Exact-Wafer-4500 Saints Row (2023) updated sales figures?

Would there happen to be any updates on SRR sales figures? I know it was mentioned from Embracer CEO that the game had to hit 2 million to breakeven. I’m assuming that was taking into account the game being full price.
I’m only bringing this up because Dead Island 2 announced it had hit over 2 million in sales.
submitted by Exact-Wafer-4500 to SaintsRow [link] [comments]

2023.06.08 23:30 KingsBanx Worst Three Years!

Worst Three Years!
I aged up and went bankrupt so I closed the game and decided to see how broke I could be!
submitted by KingsBanx to BitLifeApp [link] [comments]