Georgia southern portal

Georgia Southern University

2010.03.09 19:41 jlovins Georgia Southern University


2019.10.28 15:29 bitchassslutasswhore WelcomeToPlathville

The nine flaxen-haired children in the Plath family have never had a soda, don't know who Spiderman or Tom Brady is and have never watched TV, living remotely in rural Georgia with their "follow their own rules" parents Kim and Barry Plath.

2008.09.09 07:02 The Internet's Tailgate

The home of college football on reddit.

2023.06.10 07:25 ZazyzzyO Is it to hot in Greece( athens and the islands) in July?

Haven't booked the trip yet but it's looking more like July or August.
My concern is i'm coming with people who are a older and i worry about them in the heat. When your on vacation your outside 90% of the day.In Athens i plan on taking day tours to see the main sites and walking around the main areas..... i know we would try to do most things in the early AM when its cooler and not as hot.
On the islands... i didn't make a plan yet for what to do. But, i gather we would take a few day tours as well. I just don't know how hot islands get.
I am use to southern California summers and east coast summers---- which are horrible and humid! I've gone to Savannah, Georgia and Charleston, SC in August and it was horrible! lol.
Also i googled past years temps in Athens, Paros, Santorini, and Crete for example. But, idk how hot it is when u take into account humidity or the breeze from the water. AS a side note we are not spend all day at the beach people or everyday.
submitted by ZazyzzyO to GreeceTravel [link] [comments]

2023.06.10 05:25 SupperTime [H] AAA Games [W] PAYPAL/EMT CDN

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Find games that add up to $30CAD / $22USD or more and I will provide the discounted price. Keep in mind I also get XP discounts which is another 10%.
Check my post history for other similar threads. I've sold many now. I have had ZERO issues with my orders.
Is this code available in my region? See below for eligible locations.
submitted by SupperTime to GameTrade [link] [comments]

2023.06.10 04:22 funeralbrood My Sister’s Vinyl Shelf

My Sister’s Vinyl Shelf submitted by funeralbrood to vinyljerk [link] [comments]

2023.06.10 03:57 BelleHades I was about to breathe my worldbuilding project's magic system into our IRL universe when it was cruelly interrupted by the symbol of everything I hate about my life

My recollection of the dream starts at some party, where I enter a bathroom occupied by a dozen guys, and as soon as a girl walks in, they all start sitting on the long counter. They start telling me she's a bad influence because she's a cheater. I didnt mind that so I left the party to get something I thought would help me with her, and ended up on the east coast of Florida, and there's a highway going down all along the coast, ending at a deity's sanctum on the southern tip. The highway to the sanctum is a recurring location in my dreams; the deity is usually a Goddess, sometimes a nature Goddess, sometimes Death herself. I went to the beach next to the highway and found a clear crystal, and I immediately wanted to do some magic, so I headed down to the sanctum. My mom happened to be in the area, so I met with her and told her about the sanctum, since Mom is a witch and I thought she would like it, so we headed down.
For some reason, the highway went through some large rooms hosting a fancy rich people event and dinner, so we went through there discreetly. I ended up disrupting it when I saw to my right a door that I thought also held a dimensional portal and tried to go through the portal, only find out it had been removed during the renovation for the party, and replaced with a garbage chute. I dropped the clear crystal I found into it and tried to retrieve it, but it was in wet sewage so I gave up, and exited back onto the highway to resume the trip to the Sanctum.
In this dream it was the nature goddess' abode, but it was also being visited by other people as if the dream was an online MMO. It was there that mom took it over and revealed she had been cheating on Dad and tried to kill me once I confronted her. When trying to get her to realize common sense turned futile, I evacuated and headed back up the highway heading north at first, but I split to the west following a boarded trail to find another dimensional portal. Eventually the terrain dropped and I realize I'm holding a leash to a small dog, so we ran down the board bridge, but hit a dead end when we saw it had been partially collapsed. We tried to balance on it but the dog fell into the water below and I went in after it to take it to safety. Mom was still looking for me so I teleported out west. (The fate of the dog is unknown). I ended up in another recurring dream location in Wyoming, where a highway turns south in a mountain town to head to Denver. The place was triggering me due to memories of visits in past dreams, and I saw no dimensional portals, but I knew there was one in Los Angeles, so I teleported there.
I ended up in a house somewhere, and there was a door to a basement. Opening it revealed a stairway down to a corridor with spiders and spider webs. The dimensional portal was at the end of it, in front of another door. I realize a couple guys are with me, and when I get to the bottom of the stairs, I see the spiders and realize my shorts were down, so I pulled them back up before a spider could crawl up there. We go through the portal into another universe and open the door, which leads to a furnace room and some stairs headind down. One set going to the right, with 5 steps, and then to the left some split level stairs. We followed them and the next door opened into an office room. A living skeleton was in the left corner on the other end of the room, with a few more guys, next to an archway leading to an arcade room. The living skeleton turned out to be a woman wearing a magic necro mask. It tended to corrupt the wearer with promises of power, so it couldn't be worn for long. Before the girl took it off, she breathed a dark flag into existence for keepsakes. Once she took it off, she reverted to her normal human self. I wanted to wear it next because I wanted to create something for myself.
I put it on, and I transformed into a necroid. At first I wanted to create a "plutonium fusion bomb," a magically enchanted thermonuclear device from my sci fi world building project that can create a star. Then I couldn't truly decide on what I wanted to do, and the people around me kept telling me I needed to take it off soon or it would permanently bind to me and corrupt me. I also kept trying to get comfortable with the gloves the mask made for me. At one point I considered dabbling in necromancy (what the mask was originally meant for by its unknown creators). At last I thought of something I really wanted to do: Come to the IRL universe and breathe a real magic system into our universe. The guys around me immediately disagreed, saying that it would be taken advantage of by the wrong people. I immediately began running out the office/arcade to head back up the stairs to the dimensional portal back to our universe, to breathe my sci fi universe's magic system into our universe, and the people started running after me to rip the mask off my head. I held my hand on my head to prevent them from taking it off, and I had just almost made it to the door when they succeeded.
I screamed "Damn you fcking dream characters!" I mouthed it in real life but it didnt wake me up. I ran after them and jumped over the ledge over the bottom stairs, catching them by surprise and I wrestled the mask away and put it back on. As I ran back up the split level stairs, I decided I had enough of these guys so I breathed a living skeletal marine with an AR-15 to gun down the other people so I could make it back to the IRL universe with the mask to give it the magic system I always wanted. The skeletal marine had fired several rounds and I was about to breathe a second one into existence when my phone began ringing and woke me up.
I am hard of hearing, but had to leave it on cuz I was expecting a call from my life coach but he never came. Instead the call was from my mentally disabled baby brother, a figure in my life who seems to represent everything I hate about my life. Because reasons. I rejected the call, took off my hearing aid, and tried to go back to sleep. But I was too infuriated by the turn of events to fall back asleep so now I'm posting here, mainly to vent.
Naturally it wouldnt have made our IRL universe magical IRL, but that would have been a great feeling/placebo to wake up to. But this turn of events only serves to reinforce my utter hopelessness ive developed lately. Which is funny, i guess, since feeling hopeless about reality and how shitty all my dreams have become the past few decades was on my mind when I fell asleep.
While succeeding in my crusade in my dream may have waken me up feeling hope and feeling good about it, I have been thinking lately that hope only serves to prolong suffering. Like that one scene from that one movie, where the guy says "Dont do that. Dont give me hope."
Sorry for rambling lol
submitted by BelleHades to Dreams [link] [comments]

2023.06.10 00:28 rrmdp 📢 GitLab is hiring a Strategic Account Executive - Alps (Switzerland and Austria)!

Company: GitLab
Location: Afghanistan Albania Algeria Andorra Angola Antarctica Armenia Austria Azerbaijan Bahrain Belarus Belgium Benin Bosnia and Herzegovina Botswana Bouvet Island Bulgaria Burkina Faso Burundi Cabo Verde Cameroon Central African Republic Chad Comoros Congo Congo, The Democratic Republic of the Cook Islands Croatia Curaçao Cyprus Czechia Côte d'Ivoire Denmark Djibouti Egypt Equatorial Guinea Eritrea Estonia Eswatini Ethiopia Faroe Islands Finland France French Guiana French Southern Territories Gabon Gambia Georgia Germany Ghana Gibraltar Greece Greenland Guadeloupe Guernsey Guinea Guinea-Bissau Heard Island and McDonald Islands Holy See (Vatican City State) Hungary Iceland Iran Iraq Ireland Isle of Man Israel Italy Jersey Jordan Kazakhstan Kenya Kuwait Kyrgyzstan Latvia Lebanon Lesotho Liberia Libya Liechtenstein Lithuania Luxembourg Madagascar Malawi Mali Malta Martinique Mauritania Mauritius Mayotte Moldova Monaco Montenegro Morocco Mozambique Namibia Netherlands Niger Nigeria North Macedonia Norway Oman Palestine, State of Poland Portugal Qatar Romania Russian Federation Rwanda Réunion Saint Barthélemy Saint Helena, Ascension and Tristan da Cunha Saint Martin (French part) Saint Pierre and Miquelon San Marino Sao Tome and Principe Saudi Arabia Senegal Serbia Seychelles Sierra Leone Sint Maarten (Dutch part) Slovakia Slovenia Somalia South Africa South Sudan Spain Sudan Svalbard and Jan Mayen Sweden Switzerland Syrian Arab Republic Tajikistan Tanzania Togo Tunisia Turkey Turkmenistan Uganda Ukraine United Arab Emirates United Kingdom Uzbekistan Western Sahara Yemen Zambia Zimbabwe Åland Islands 📍
Date Posted: June 09, 2023 📅
Apply & Description 👉
submitted by rrmdp to jobboardsearch [link] [comments]

2023.06.09 22:06 SnooAbbreviations52 The Komnenos Restoration, a Trezibond AAR

The Black Sea Villa saw much in its marble hallways that day.
War was coming to the Empire. Ionnas IV knew it. He will not falter, nor will his realm. The Pontic Eagle will stand once again.
A pivotal time in the history of the Byzantine Empire was marked by the establishment of the Komnenos Dynasty. The Dynasty of Manuel Erotikos Komnenos gave birth to some of the empire's most illustrious emperors. The Komnenos Dynasty would consolidate its authority and influence over several generations, having a significant impact on Byzantine history.
However, it was Isaac's son, Alexios I Komnenos, who truly propelled the Komnenos Dynasty to the forefront of Byzantine politics. Alexios came to power in 1081, during a tumultuous period marked by external threats and internal instability. The Byzantine Empire was facing encroachment from the Seljuk Turks, Norman invaders in Italy, and the First Crusade. Alexios faced the formidable task of restoring the empire's stability and preserving its territorial integrity.
Alexios I Komnenos proved to be a skilled statesman and military tactician. He implemented a series of reforms aimed at strengthening the empire's military forces and central administration. Alexios also sought to establish alliances and secure the support of Western powers, particularly the Crusaders. Through his diplomatic efforts, he successfully convinced the Crusaders to divert their attention to the Holy Land rather than further threatening Byzantine territories.
Under Alexios' rule, the Komnenos Dynasty achieved significant military successes. He pushed back the Seljuk Turks, recaptured lost territories, and secured the empire's borders. Alexios' reign also witnessed a cultural and intellectual revival known as the Komnenian Renaissance. The dynasty patronized scholars, artists, and theologians, leading to the flourishing of literature, art, and architecture.
Alexios was succeeded by his son John II Komnenos, who continued his father's policies and accomplishments. John II expanded Byzantine influence in the Balkans and undertook successful military campaigns against the Normans in southern Italy. He ruled for almost 25 years and left a stable and prosperous empire to his successors.The subsequent rulers of the Komnenos Dynasty, Manuel I Komnenos, and Alexios II Komnenos faced challenges but managed to maintain the dynasty's stability and prestige. Manuel, I pursued an ambitious foreign policy, seeking to reclaim territories lost to the Crusaders.
But, it was not to last.
By the time of Alexios II's reign, however, the dynasty's power began to decline. Internal conflicts and external pressures weakened the empire, leading to its eventual fragmentation and collapse in the late 12th century.But, that is only half the Story.The Grand Komnenos were a significant figure in the history and administration of the Trebizond Empire. Following the fall of Constantinople in 1204, when family members of the Komnenos sought safety in the Trebizond region, this branch of the Komnenos Dynasty began. From 1204 to now, the Grand Komnenos dominated the Trebizond Empire, reshaping its political, cultural, and military landscape.
The Grand Komnenos initially established their rule in Trebizond under the leadership of Alexios I, who became the first Emperor of Trebizond. Alexios I laid the foundations of the Empire of Trebizond and worked towards consolidating its territories and establishing its political institutions. He focused on fortifying the city of Trebizond and expanding the empire's influence in the surrounding regions.
Under the rule of the Grand Komnenos, the Empire of Trebizond flourished as an independent state. They successfully defended the empire against external threats, particularly from neighboring powers such as the Seljuk Turks and the Mongols. Through diplomatic maneuvers, military strategies, and alliances with other regional powers, the Grand Komnenos were able to maintain the independence and territorial integrity of the empire.
The Grand Komnenos were not only skilled military leaders but also patrons of culture, arts, and learning. They supported the development of literature, architecture, and the arts, fostering a cultural renaissance in Trebizond. They patronized scholars, poets, and artists, contributing to the intellectual and cultural vibrancy of the empire. The capital city of Trebizond became a center of artistic and scholarly activity, attracting renowned figures from the Byzantine and broader Eastern Mediterranean world.
The Grand Komnenos also played an important role in trade and commerce. Trebizond served as a significant port and gateway for commercial activities between the Black Sea region, the Middle East, and Europe. The empire benefited from its strategic location, engaging in trade with various Mediterranean powers and establishing economic ties with cities such as Genoa and Venice.
Throughout their rule, the Grand Komnenos faced numerous challenges, including conflicts with neighboring states, internal power struggles, and dynastic rivalries. However, they managed to maintain the stability and independence of the Empire of Trebizond for several centuries, preserving its distinct identity in the face of shifting geopolitical dynamics.

Ionnas IV, the Pont

As the Crusade of Varna failed, Ionnas could tell the writing on the wall. His spies in Europe, anticipating a potential homecoming, came back, many mutilated by the wars and Ottoman Units stationed in Greece. If Ionnas were to want his crown back, he would need more strength. The rise of Georgian pretenders in the east gave him something to work on, however. February 1446 was the date of the First Ponto-Georgian War. The Imereti dynastic Feud with the Kingdom of Georgia allowed Ionnas a diversion of which to claim the coastline of the Georgian Principality. Immediately, the emboldened Pontic Army crushed the weak militia the "King" of Immereti could muster, and the coastline was secured. What followed was the hunting of the Circassian Army, one that had failed to unsiege the capital of the Imereti King, who was under Pontic supervision, and secondarily, a mass uprising of Pontic brothers in this region, leading to the overall shift from war to reclaim land, to a war of Pontic Unity.
August 1449 would be the death of Ionnas IV's Older brother, and his full-blooded heir, Alexios. The babe was never well-liked by the Nobles, however, Alexios would be crucial in the Muskovite alliance of 1450.
1451 led to the death of Alexios "The Elder" and the birth of Alexios "The Younger". 4 years later, the Civil War would start. Hermes Komnenos, cousin to the King would rally Georgian-Circassian nobles, those who resist the pontification of the realm. During this, Alexios of Gothia, the Prince of the Goths would enter the side of Alexios "The Younger" in this conflict, due to the relations between the 2 rulers, Cousins. After the battle of Guria, the rebel army would scatter into the hills. It would take two years to find Hermes Komnenos and have him killed. Thus forward, Alexios II, the Warrior, would take the lead.

Alexios II, Sword of Pontus, the Warrior

To the south, the Turks shattered. A force, veterans of the Pontic Dynastic War would be dispatched to occupy the Armenian Highlands to the south. At this time, Manuel of Muskovy, brother to the Grand Knaz was declared heir by the Nobles. Being half-brother to Alexios II did not harm his claim, as Alexios at the age of 30 had only 1 heir, his daughter. But, the winds shifted. The Turks engaged with the Venetians, and 1464 was a state of war. Within the year, the fortresses of Ankara, Sinope, and Izmir to the Pontic Sword. Venitian efforts into the Balkans went increasingly better. The Ottoman army could not break the Pontic forts, Venitian Mercenaries from the Holy Roman Empire, or the defenders of their sieged capital. In the resulting peace, the sea until the province of Kocheli was given to us, Hellas being sold to the Venetians because of Ottoman War debts would come later. The peace was signed for the year 1466.
The state underwent a period of Renaissance development at this time, the filled treasuries from campaigns, and a growing need to see temples for the conversion of the new Turkish Citizens would mean that in most provinces, marketplaces, Temples, and workshops would be littered through the, which would lead to more and more money. June 1475 saw the purchase of Genoese land in the Black Sea. These lands would, with the exception of Azov, be ethnically pont, and orthodox. But then, the Crimeans attacked. Raiding our northern border, our men demobilized in Trezibond, had to pack north, before they would take our lands. The Crimeans fought hard, however, the battle for Azov was their doom, a joint Gothic-Pontic assault against the besieged fortress and sieging Crimean forces would see all of them taken prisoner, save for the 6,000 dead. Their lands would be integrated back into the Kingdom of Vospórou. Immediate efforts to integrate them would be taken. Our forces, on the upswing, would have a year to recover, however, Manuel of Moskow would die. Alexios III would be declared heir.
December of 1480 would be the second Ottoman Crusade. Pontic men hoisted Pikes, Arquibuses, and Crossbows, and the Turks would face a renewed tide. They fractured. City-states of Free Turkish men forming, and the Beileks saw a chance and took it. Most of Southern Anatolia erupted into a fire of battle, independence and revolt. The war took 5 long years, and saw the total death of the Ottoman Army, against Alexios II's hand. 1485 would mark the end, with most of Central Anatolia being taken, and the Ottomans forced to the Balkans. Alexios would die in 1504, in the following month, the Azeri Tribesmen would start their war.

Thats all she wrote folks! I'll start playing after my eu4 block goes up! I am still getting used to writing these, so I do hope it turns outwell.

submitted by SnooAbbreviations52 to eu4 [link] [comments]

2023.06.09 18:03 thinkingstranger June 8, 2023
This morning the Supreme Court handed down a decision in Allen v. Milligan, a case that challenged the Alabama legislature’s redistricting of the state after the 2020 census on the grounds that the new districts had been configured to pack the state’s growing numbers of Black voters into a single district and thus dilute their vote. Such discrimination based on race, plaintiffs charged, violated the 1965 Voting Rights Act (VRA).
District courts agreed with the plaintiffs and told the state it couldn’t use the new map, but in February 2022 the Supreme Court issued a stay of the injunction prohibiting that map. The Supreme Court ruling left the Alabama map intact for the 2022 election. Legal scholar Stephen Vladeck noted that the decision was part of the court’s recent use of the “shadow docket,” unsigned, unexplained orders issued without a hearing.
Today’s 5–4 decision upheld the verdicts of the lower courts, agreeing that the new Alabama map was, after all, illegal, because it violates Section 2 of the VRA, which prohibits the denial of the right to vote on account of race. This leaves intact the ability of plaintiffs to sue when states appear to discriminate against minority voters. Similar lawsuits are pending in ten different states.
But, as Vladeck notes, the Supreme Court’s February 2022 decision leaving the discriminatory map in Alabama, as well as similar maps in other states, in place for the November election, is likely responsible for the Republicans’ current majority in the House of Representatives. The Cook Political Report, which follows elections, immediately changed their ratings for the leanings of five House districts after news of the Supreme Court decision.
That House majority is currently at an impasse that makes it impossible to conduct business. The extremist House Freedom Caucus (HFC) has revolted against House speaker Kevin McCarthy (R-CA) because of the budget deal he cut with President Biden before he would agree to raise the debt ceiling. Members of the HFC are demanding deeper cuts than McCarthy agreed to. The revolt of the far right puts into danger crucial spending bills, raising fears of a government shutdown in the fall.
To placate the extremists, McCarthy has apparently agreed to take up two bills: one to kill a Biden-backed gun regulation and another to push even more strongly against abortion rights. This move, which flies in the face of popular opinion, has angered Republicans in battleground districts, who are revolting against measures that will hurt them at home. It also runs the risk of alienating Democrats McCarthy will need to pass spending measures if the far right refuses to vote for them.
The extremism of today’s Republican Party grew in large part from the work of televangelist Pat Robertson, who died today at age 93. The son of a segregationist southern Democratic senator, Baptist minister Robertson urged evangelical Christians to vote and made them a core constituency of the Republican Party. Paving the way for those today calling for an end to liberal democracy, Robertson blamed LGBTQ Americans and women for secularizing the United States, which he saw as a tragedy and frequently blamed for natural disasters.
That political ideology depended on creating a false picture of what was really going on in the country. The Republican Party has become so wedded to lying about reality that today we saw Florida governor and Republican candidate for president Ron DeSantis circulating fake images of rival candidate Donald Trump embracing right-wing nemesis Dr. Anthony Fauci as a way to discredit Trump.
Trump’s team cried foul at the fake images, but the former president himself relies on manipulating reality to garner political support. CNN national correspondent Kristen Holmes reported today that Trump’s people reached out this week to congressional allies to encourage them to flood the airwaves with a defense of Trump and attacks on special counsel Jack Smith before a possible indictment of the former president.
To that end, Trump’s supporters spent the week trying to gin up outrage over a document they claimed shows that President Biden had taken a bribe as vice president. The document in question appears to be an unverified report that came to the Department of Justice through Trump lawyer Rudy Giuliani, one that the Trump Department of Justice dropped after it determined that the allegation was not supported by facts. But the practice of influencing politics through sham investigations is one of the Republicans’ key tools, and Trump allies have flooded social media this week insisting that this document is a smoking gun.
They were, of course, trying to set up a defense for the former president’s possible indictment on charges related to his refusal to hand over national security documents he had taken when he left the White House.
This evening, news broke that Trump has, indeed, been indicted by a grand jury in South Florida in connection with the documents discovered at Mar-a-Lago. The indictment is sealed, but there are reports that it includes seven counts of lawbreaking, including at least one related to the Espionage Act. These charges are serious indeed.
Trump is now the first former U.S. president in history to face federal criminal charges (his first indictment, on March 30, was at the state level). As The Guardian’s David Smith puts it, “he really might be going to jail.” Smith—who is a keen observer of American politics—notes that it is hard to figure out what is important and what is not in the general drama around the former president, but this indictment is “genuinely monumental.”
According to Trump’s outraged posts on social media, he has been summoned to appear at the Federal Courthouse in Miami next Tuesday.
Trump’s team asked his allies to jump to his defense, and they did. Trump loyalists implied that the “sham indictment” was destined to distract from the blockbuster story they had invented about Biden. House speaker McCarthy implied that Biden, who has had nothing to do with the Department of Justice investigation, special counsel in charge of the investigation Jack Smith, or the grand jury deliberations, was responsible for launching a political attack on a rival. The third Republican in House leadership, New York representative Elise Stefanik, also defended Trump…in a fundraising email that assured donors their money would go to the “OFFICIAL TRUMP DEFENSE FUND” though, in fact, most of it would be diverted to Stefanik’s operations. Trump, too, lost no time in fundraising off the indictment.
Significantly, though, all Republicans who do not identify with the far right have remained steadfastly silent in the face of the day’s news. The exception has been long-shot presidential candidate Asa Hutchinson, who has called for Trump to end his campaign.
New York Times reporter Maggie Haberman, who communicates with the Trump camp, says he holed up tonight not with his legal team but with political advisors. CBS News correspondent Robert Costa reports tonight that the camps of Republican rivals think that this news will actually help Trump in the short term, as his base rallies to him, but that the news of what is at stake in the theft of national security documents might well lose him support over time. If another indictment comes from Georgia concerning his attempts to overturn the results of the 2020 election there, rival camps say he might “bleed out.”

Twitter links:
submitted by thinkingstranger to HeatherCoxRichardson [link] [comments]

2023.06.09 15:07 subredditsummarybot Your weekly /r/AltCountry roundup for the week of June 02 - June 08

Friday, June 02 - Thursday, June 08

Top 10 Posts

score comments title & link mirrors
57 4 comments The Allman Brothers Band Columbia High School Junior Prom, Decatur, Georgia, May 23, 1970
26 3 comments Joshua Ray Walker - Cuz I Love You (Lizzo cover) [Sp] [AM] [Dzr] [SC]
24 2 comments Mike and the Moonpies - Rainy Day (Mike Harmeier acoustic)
22 14 comments Dooley's Farm- Molly Tuttle and The Golden Highway -totally awesome opening for Dierks Bentley last night
17 5 comments Cowboy Junkies’ Margo Timmins on Loss, Nature, and the Sharon sessions
12 4 comments Something Less Than Something More To You - Caitlin Cary (Whiskeytown) & Thad Cockrell [Sp] [AM]
11 1 comments Keep It Clean - Willie Watson & Dave Rawlings Machine (Live BU)
10 5 comments The Rolling Stones - Country Honk [Sp] [AM] [Dzr] [SC]
9 1 comments Mike Ness - Big Iron
7 5 comments 4 Tyler Childers tickets for the KCMO show 6/15

Top 5 Most Commented

score comments title & link mirrors
1 4 comments Lucero - Bright Stars on Lonesome Nights
3 4 comments [Music Promotion] Tuesday Music Promotion Thread
3 3 comments Save the World - Jason Isbell
4 2 comments The Wild Palominos - Long Way Home [Sp] [AM] [BC] [Dzr]
0 2 comments Hot take: What separates Americana from Country has a lot to do with wether there’s a southern accent or not.
submitted by subredditsummarybot to altcountry [link] [comments]

2023.06.09 14:46 Vykeying Monster 8 meter+ (26ft) waves between South Georgia Island and Falkland Island in the Southern Ocean. Seeking out the colossal squid 🦑

Monster 8 meter+ (26ft) waves between South Georgia Island and Falkland Island in the Southern Ocean. Seeking out the colossal squid 🦑 submitted by Vykeying to u/Vykeying [link] [comments]

2023.06.09 11:45 TheKiweGuye Project Americas: DLC/Update Maps

Project Americas: DLC/Update Maps
Note that this is just for fun, and I know that it will probably not be added, but just bear with me.
Since the name of GTA 6's development name was Project Americas, and that the development had to be shortened to just include Florida and the Caribbean (as far as we know), I believe that Rockstar has a golden opportunity in expanding upon this either in both singleplayer and in Online. By adding new areas around Florida and in the Caribbean. However, this is a stretch as not only as it is unlikely for this to happen (since most cut content is usually just abandoned), but it would take a shit ton of work. However, if Rockstar wants to, I think these places might be an interesting place to see it happen.
The Appalachian Mountains
A fictional parody of Atlanta (albeit not the size of Atlanta, as that would require too many resources for a map expansion).
Since Florida (and Vice City by extension) will be relatively flat compared to the rest of the US (and with older maps, except for Liberty City), so I believe that a parody of Georgia and the Appalachian mountains might be a great way to expand upon the map of GTA 6 (if Rockstar expands it at all lmao).
Not only is it another city (probably like 1/4 the size of Vice City), but there are tons of rural towns and farms that might allow the player (especially in Online) to build drug labs and export methamphetamine in the forests and plains of Georgia. Meanwhile, the mountains make it a beautiful way to expand the wildlife of GTA 6, as it is teeming with flora and fauna that can't be found in Florida, as well as having more of the woodland animals like black bears and deer compared to its Southern counterpart.
Georgian Countryside
Georgia would have a large amount of redneck and militia like factions within the countryside, while popular musicians and artists originate within the parody of Atlanta (known for its music business).
Brazil/Southern America
The Amazon River of Brazil, Peru and Colombia
A parody of a South American city like Medellin or Rio de Janeiro (both infamous for its crime) would tie the South American map expansion together
In order to further expand the drug trading operations that can occur in both singleplayer and Online, a map expansion into South America might be the most logical map expansion since it was originally intended to be added in the game (at least that we know of).
South America is not only incredibly humid, hot, and wet, it is also great for opening cocaine labs and maintaining a large international criminal organization, and would be a good place for both story reasons and for Online players to expand their criminal organizations. The parody of Medellin/Rio de Janeiro would be the same size of the parody of Atlanta, but there would also be tons of other towns and villages spread through out the jungles.
A small town in Brazil, and note the smaller homes and more elevated terrain, as well as an abundance of fauna.
Cartel members, gangsters, and paramilitary groups would be rampant in South America, as the climate and environment is a breeding ground for them.
and finally: Caribbean Islands
A beach in Cuba
A parody of Havana, Cuba would be a small addition to the biggest island in the Caribbean map expansion.
A satellite map of the real life Caribbean (not the real shape, more like an idea of how many islands).
While I expect there to be at least one or two Caribbean islands in GTA 6's release, I believe a further expansion into it would be a much appreciated addition to GTA 6's map.
There would be a ton of islands (both small and big) that feature wildlife, flora, and privacy for players on Online to ship their gunrunning businesses to the mainland or to South America, as well as a good story reason for the map expansion. Boats, airfields, and other infrastructure would allow for smuggling and gunrunning to become lucrative.
A Caribbean archipelago with a bunch of islands off in the distance.
Smugglers, paramilitary groups, and dictators would be the largest factions in the Caribbean.

In conclusion, I don't expect any of this to be added, but I believe this can make GTA 6 even better (better than it already is, which is god tier). Thank you for reading this, and I can't wait to see your opinions about this post.
submitted by TheKiweGuye to GTA6 [link] [comments]

2023.06.09 11:44 Tigrannes On this day in History, June 9

On this day in History, June 9
Ancient World
411 BC – The Athenian coup succeeds, forming a short-lived oligarchy.
53 – The Roman emperor Nero marries Claudia Octavia.
68 – Nero dies by suicide after quoting Vergil's Aeneid, thus ending the Julio-Claudian dynasty and starting the civil war known as the Year of the Four Emperors.
Middle Ages
721 – Odo of Aquitaine defeats the Moors in the Battle of Toulouse.
747 – Abbasid Revolution: Abu Muslim Khorasani begins an open revolt against Umayyad rule, which is carried out under the sign of the Black Standard.
1311 – Duccio's Maestà, a seminal artwork of the early Italian Renaissance, is unveiled and installed in Siena Cathedral in Siena, Italy.
Early Modern World
1523 – The Parisian Faculty of Theology fines Simon de Colines for publishing the Biblical commentary Commentarii initiatorii in quatuor Evangelia by Jacques Lefèvre d'Étaples.
1534 – Jacques Cartier is the first European to describe and map the Saint Lawrence River.
1732 – James Oglethorpe is granted a royal charter for the colony of the future U.S. state of Georgia.
1772 – The British schooner Gaspee is burned in Narragansett Bay, Rhode Island.
Revolutionary Age
1798 – Irish Rebellion of 1798: Battles of Arklow and Saintfield.
1815 – End of the Congress of Vienna: The new European political situation is set.
1856 – Five hundred Mormons leave Iowa City, Iowa for the Mormon Trail.
1862 – American Civil War: Stonewall Jackson concludes his successful Shenandoah Valley Campaign with a victory in the Battle of Port Republic; his tactics during the campaign are now studied by militaries around the world.
1863 – American Civil War: The Battle of Brandy Station in Virginia, the largest cavalry battle on American soil, ends Confederate cavalry dominance in the eastern theater.
1885 – Treaty of Tientsin is signed to end the Sino-French War, with China eventually giving up Tonkin and Annam – most of present-day Vietnam – to France.
1900 – Indian nationalist Birsa Munda dies of cholera in a British prison.
World Wars
1915 – William Jennings Bryan resigns as Woodrow Wilson's Secretary of State over a disagreement regarding the United States' handling of the sinking of the RMS Lusitania.
1922 – Åland's Regional Assembly convened for its first plenary session in Mariehamn, Åland;[1] today, the day is celebrated as Self-Government Day of Åland.
1923 – Bulgaria's military takes over the government in a coup.
1928 – Charles Kingsford Smith completes the first trans-Pacific flight in a Fokker Trimotor monoplane, the Southern Cross.
1930 – A Chicago Tribune reporter, Jake Lingle, is killed during rush hour at the Illinois Central train station by Leo Vincent Brothers, allegedly over a $100,000 gambling debt owed to Al Capone.
1944 – World War II: Ninety-nine civilians are hanged from lampposts and balconies by German troops in Tulle, France, in reprisal for maquisards attacks.
1944 – World War II: The Soviet Union invades East Karelia and the previously Finnish part of Karelia, occupied by Finland since 1941.
Cold War
1948 – Foundation of the International Council on Archives under the auspices of the UNESCO.
1953 – The Flint–Worcester tornado outbreak sequence kills 94 people in Massachusetts.
1954 – Joseph N. Welch, special counsel for the United States Army, lashes out at Senator Joseph McCarthy during the Army–McCarthy hearings, giving McCarthy the famous rebuke, "You've done enough. Have you no sense of decency, sir, at long last? Have you left no sense of decency?"
1957 – First ascent of Broad Peak by Fritz Wintersteller, Marcus Schmuck, Kurt Diemberger, and Hermann Buhl.
1959 – The USS George Washington is launched. It is the first nuclear-powered ballistic missile submarine.
1965 – The civilian Prime Minister of South Vietnam, Phan Huy Quát, resigns after being unable to work with a junta led by Nguyễn Cao Kỳ.
1965 – Vietnam War: The Viet Cong commences combat with the Army of the Republic of Vietnam in the Battle of Đồng Xoài, one of the largest battles in the war.
1967 – Six-Day War: Israel captures the Golan Heights from Syria.
1968 – U.S. President Lyndon B. Johnson declares a national day of mourning following the assassination of Senator Robert F. Kennedy.
1972 – Severe rainfall causes a dam in the Black Hills of South Dakota to burst, creating a flood that kills 238 people and causes $160 million in damage.
1973 – In horse racing, Secretariat wins the U.S. Triple Crown.
1978 – The Church of Jesus Christ of Latter-day Saints opens its priesthood to "all worthy men", ending a 148-year-old policy of excluding black men.
1979 – The Ghost Train fire at Luna Park Sydney, Australia, kills seven.
Modern World
1995 – Ansett New Zealand Flight 703 crashes into the Tararua Range during approach to Palmerston North Airport on the North Island of New Zealand, killing four.
1999 – Kosovo War: The Federal Republic of Yugoslavia and NATO sign a peace treaty.
2008 – Two bombs explode at a train station near Algiers, Algeria, killing at least 13 people.
2009 – An explosion kills 17 people and injures at least 46 at a hotel in Peshawar, Pakistan.
68: Roman Emperor Nero dies by suicide, leading to the end of the Julio-Claudian dynasty and the Year of the Four Emperors in Ancient Rome.
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2023.06.09 05:24 rrmdp 📢 omnipresent is hiring a Accounts Receivable Analyst - Fully Remote - Work from anywhere!!

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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!
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2023.06.09 03:40 BikerJedi The Origin of Video Games.

A yarn incoming, be warned. :) But I hope a fun one. I really hope you enjoy it, I love this story.
I'm 53, which means I was around when the internet became a thing. I was online before AOL was a company. That means although 53 isn't chronologically old, but it is old as fuck in terms of the Internet's lifespan.
So, when I was still in middle school, my friend Danny and I played a lot of Dungeons and Dragons. There were video games then on the Amigas and such that you could (if you had a lot of money) or the Atari systems if you didn't have enough money for a computer, but he and I envisioned MMO type play. Dozens, hundreds, or even thousands of users playing together at once. We didn't have the knowledge or skills to make it happen, maybe only a few people on Earth did back then. Back then it was games on huge floppy disks and talking to folks on BBS's.
Fast forward more than 10 years. Danny and I are both out of the Army, and we reunite with another high school friend, Richard. Our love of D&D in high school comes up, and Richard mentions that his brother runs a MUD. It seems his Dad had a T1 line dropped into his home and is running a private internet provider and hosting this MUD. I hadn't heard of a MUD.
MUD: Multi-User Dungeon. A 100% text based game for potentially hundreds of people at once. No graphics. Example:
You are in a room. In front of you is a pool of clear water. It seems to call you. To the left, you see an exit from this area, leading to an unknown fate.
At this point, you might type, "drink water" and get ambushed by a monster or "exit left" and something else scripted would happen. You can run entire dungeons that way, leveling up, collecting equipment and unlocking abilities. They all had different rules. Some only allowed you to kill monsters (PvE or Player vs Enemies) and others let you kill both (PvP or Player vs Players, which also includes enemies like monsters hostile.) The MUD that Richard's brother ran was the Wild Wild West - No rules at all besides not hacking the MUD itself. There were specific areas where you could not be killed, but almost anywhere else you could be.
When I made an account and logged in over my 56k dial up modem for the first time, it was amazing. There were safe areas inside the cities and where you couldn't be attacked. One step outside the city, and another player would kill you and loot your corpse before you could log back in. It was BRUTAL. If you couldn't read fast, you were dead. If you couldn't type AT LEAST 80 wpm and memorize a shit ton of keyboard shortcuts, you were dead. Players would kill you just for the joy of it, even if they didn't need your gear. Life was harsh.
I would get up in the morning, hit a couple of classes at the college, maybe play Magic the Gathering in the smoking lounge, do a few hours in the computer lab on internship, then head home to eat, chain smoke and fight. (I am so glad I gave up smokes - seriously. Fuck tobacco.)
The worst part was that on this particular MUD, there were clans. The largest and most powerful was The Toadies. They were a group of students at Georgia Technical University who where absolute fascist assholes as far as the MUD was concerned. Only a few other clans that existed since the MUD started were allowed to exist. Independent players were fair game, and new clans that formed were hunted and destroyed by The Toadies. They went so far as to not allow players weren't in The Toadies to kill certain bosses and get certain gear. They would hunt you, kill you, and loot that equipment from you if they learned you had it. And because they had been there forever and were so large, they could do it. A group of four or five of The Toadies would log in, hunt you down, and kill you in seconds.
One of the tactics they used: There was an Inn that was a safe area on the second floor, but if you went to ground level, the innkeeper would kill you. You had to type incredibly fast to get out of there safely, either going upstairs to the safe area or leaving that safe area to the safe outside though the dangerous open room. So The Toadies would wait until someone was lost. That person would broadcast something like "Hey, I need a teleport back to town." Then the Toadie would quickly run upstairs, teleport that person back to town, then wait. The person would read the room, see the exit down, then leave. They would get killed by the inkeeper if they didn't exit fast enough. The Toadie would run down, type "Loot all" and run back upstairs or out of the Inn.
Then one day, it all changed. I met Erabus when he joined the MUD.
Erabus was an older adult in college like I was. We had similar schedules. We partied up on the MUD together often. We both hated The Toadies. So we said, "Fuck it, we are making a new clan and fighting. These assholes don't get to make the rules" It also pissed us off that the admins (like Richard's brother) who ran it didn't care that a small group of players was fucking with everyone else. He loved the chaos and drama.
Because we are poor white trash, we called our new clan The Dukes of Hazard and changed our flair. We quickly recruited 10-15 others to join us after we convinced them we had a plan, and set about leveling them up. The first few hours we hung around in the main area, people saw our flair and were talking about it. "OOOOOOoooohhhh - The Toadies are going to kill you." We gave no fucks. We were tired of being pushed around. We set about leveling up our new comrades and getting them equipment and spells to compete. Start by getting everyone the special falchion. Then the armor they need. Get that mage his staff. Oops - that staff is embargoed by The Toadies and they took it from my clan mate. Time to get him another one.
What resulted was four months of spectacular warfare. We grouped up during hours they weren't online and made runs to gear us up with the best weapons and armor. We stayed in safe areas when The Toadies were on. After a bit, we were leveled up and equipped enough we could fight quickly.
It started out by scouting. The really cool thing about this MUD was you could be logged in twice, so you could run two different characters. So imagine, I have two different text windows open and I'm switching back and forth between characters. We could find a Toadie out by themselves and jump them, loot them, then rush back to safe zones. We got the first four or so before we lost one. This tit for tat went on until we were strong enough to go 1v1. It became a months long hate fest.
One day I logged in and didn't see a Toadie on, so I took out my Mage and Ranger. My mage was the one who did the damage. My Ranger fought the enemies and kept the Mage safe. While they were following each other, I get a message that a portal opens in front of me and steps out in front of me. (I don't remember his name.)
My heart rate spiked. The adrenaline that hit me was almost nauseating. I cast several spells in quick succession between switching back to my ranger and beating the shit out of him with my mace. Then I fucked up. I didn't know it, but I had managed to beat this leader of The Toadies to about 10% health. He had done enough damage to my two characters that I panicked and noped out of there. So he survived that encounter, but we got him a few days later.
In the end, the Dukes of Hazard won. The Toadies either quit or mostly graduated GTU and gave up on the MUD after months of fighting. I lost a few, I won a few. By time I graduated and quit playing, I was typing over 100 words per minute just to stay alive. Lol. I can't type nearly that fast any more, but I still do a respectable amount.
That is how video games started. Reading INCREDIBLY fast and typing even faster to stay alive. Good times.
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2023.06.09 02:56 ShibaInu-229 Yet another reason why its State Not Southern

Yet another reason why its State Not Southern
Go Panthers lol
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2023.06.08 23:48 CashForEarth Monster 8 meter+ (26ft) waves between South Georgia Island and Falkland Island in the Southern Ocean. Seeking out the colossal squid 🦑

submitted by CashForEarth to oceans [link] [comments]

2023.06.08 22:41 SnarfsParf DPEs for IR and Advice

Hey everyone, I’m getting towards the end of my instrument rating and I’m starting to shop around for DPEs in the Northwest Georgia/Northeast Alabama/Southern Tennessee(KCHA) area. If anyone has any particularly good experiences, horror stories or just a straight up gouges, it is much appreciated!
Also, I still feel like I have a decent amount of holes in my knowledge, so any advice on efficient studying to fill those in would be great as well. I’m definitely working with my CFII on these, but it doesn’t hurt to hear some other points of view. Thanks!
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2023.06.08 22:02 CashForEarth Monster 8 meter+ (26ft) waves between South Georgia Island and Falkland Island in the Southern Ocean. Seeking out the colossal squid 🦑

Monster 8 meter+ (26ft) waves between South Georgia Island and Falkland Island in the Southern Ocean. Seeking out the colossal squid 🦑
Wait for the third whomp, it’s a doozy. Happy World Oceans Day. 🌊
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2023.06.08 21:59 OdysseyK My DNA Results + Selfie for Comparison

My DNA Results + Selfie for Comparison submitted by OdysseyK to AncestryDNA [link] [comments]

2023.06.08 21:42 G_Daddy2014 If you live in North Georgia, SE Tennessee, or Southern North Carolina I highly suggest checking out Blairsville, Georgia for a round or 5.

If you live in North Georgia, SE Tennessee, or Southern North Carolina I highly suggest checking out Blairsville, Georgia for a round or 5. submitted by G_Daddy2014 to golf [link] [comments]

2023.06.08 21:00 Anxious-Peach-3869 OSLG Cashier TEMPERATURES?! How hot is too hot?!

Hey y’all new employee here, how hot is too hot for the garden center to be open? It’s southern Georgia and it’s getting SOOOO hot. I was just wondering when hot is too hot and they shut it down. I had 2 fans blowing on me yesterday and ice water all day and still was miserable!! I had asked a manager and they said they have never shut down the garden center for it being too hot that they are aware of. Anyone else ever wonder these things?? Lol
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2023.06.08 20:30 SirSignificant6576 I just binged Season One. Lots of ups and downs. Mostly ups, but still.

I had never heard of OGOA until yesterday, when I saw a Reddit link to the prologue of S1. I was immediately hooked, of course. I grew up in Alabama, descended from hillbillies from North Carolina, Virginia, and Georgia. I live in north Georgia, in the shadow of the Blue Ridge. I've long thought about writing a series of stories based around Southern horror - our history is absolutely savage and soaked in gore - mixed with cosmic horror elements, so I was attracted to OGOA immediately. The Alabama version of cosmic horror would look somewhat different to this in my mind, but given my roots in the deep hollers of the Appalachians, how could I not jump all over this with both feet? So while my wife and kids were out of town last night, and I was getting some other work done, I binged Season 1 like a fiend.
Impressions and thoughts, if you're interested...
1) The narrator's accent took some getting used to. It was, at times, really broad and over the top. It may sound natural and authentically Appalachian to someone not from the region, but to my ears, it came off as hokey and a bit too on-the-nose and stereotypical. At the end of some episodes, when he turned the accent off and made podcast announcements, I actually enjoyed his voice more. But I'm very aware it was all part of the expected atmosphere and set-up, so ultimately it was a pretty minor gripe. I recognize that I tend to be sensitive about it! See also, Timothy Olyphant in "Justified." His awful accent griped at me for so long. It was Walton Goggins, who actually is Southern, who ultimately made me watch the entire series.
2) I very much enjoyed the implications of the deep lore - that the land itself (in this alternate Appalachia) is corrupted by the presence of the Old Gods, and that those who make their living off the land also make a devil's bargain - the paycheck in return for your soul and ultimately your life. It's such a good metaphor for the awfulness that those mining towns and families are still enduring. But also:
3) I have to be a bit of a geography/geology wonk here. This podcast (well, season 1, at least) is not set in the Appalachian Mountains. It's set in the Interior Plateaus to the west of the Appalachians. The Appalachian Mountains themselves do not have any significant coal-bearing strata. The two regions are even physically separated by a huge, wide valley known, appropriately, as the Great Valley. I guess I was expecting something more along the lines of high-Appalachian North Carolina mythology and folk magic, which is related to, but distinct from, coal country mythology. Again, that was a personal thing though, and ultimately did not damage my appreciation for the work. I recognize that orogeny and culture are complicated. I'm certainly not arguing that the cultures of the two regions are unrelated, or that it's "not Appalachian," or at least not derived from the same source.
4) Linguistic wonkery - I was very glad that "Appalachia" is pronounced properly. I'd expect nothing less from creators who are actually from the region, but I've been disappointed before. If it had been pronounced "App uh lay chuh" in the prologue, I likely would have turned it off and never listened again.
5) I really loved the corruption of Pastor Cletus. The fact that he was flawed and his church was ultimately corrupted into a straight up Cult of the Outer Gods, complete with blood sacrifice, without anyone realizing it, was very well done.
6) I really like my cosmic horror to be bleak, cold, and hopeless lol. I like Lovecraft's model of "the best we can hope to do is survive an encounter with the Old Gods with our sanity sort of intact." I thought season one of "True Detective" did this extremely well. The degenerate Louisiana cult was defeatable, but they were horrifically inhuman and nihilistic, and their defeat didn't really do anything to change the nebulous, reality-shattering experience of encountering Hastur's avatar in the heart of the cult's compound.
OGOA's approach of having witch bottles be effective at blocking Horned Head, and then Daughter Dooley being able to defeat it with a simple trick of blood magic, feels...not right, somehow. Confusing, I guess. It makes me wonder if there are multiple Old Gods of varying potency at play here. There's Horned Head, who seems to be an avatar of something terrible, yes, but bound by laws. Lawful Evil, if you will. Whereas there may be something else out there, exemplified by the raucous disorder of the possessed miners, the awful violence of the school house, what happened to Carol Anne and her house. Something Chaotic Evil I guess. I might be reading way too much into that.
But the ability of Horned Head to be bargained with, restrained, and ultimately defeated reminds me of a very humanistic Neil Gaiman-esque style of mythology. I guess I just like my Lovecraftian horrors to be even worse lol.
7) None of the above thoughts or critiques will stop me from listening to the rest of the podcast. And none of them should be taken seriously by anyone at all, ever. They most DEFINITELY should not stop you from listening, if you're just looking for input before you start. The story is overall superb, and it's completely unique as far as I can tell. It is well worth the time spent listening, and I want lots more.
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