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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)
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.submitted by Bubzoluck to SAR_Med_Chem [link] [comments]
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:
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.
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.
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.
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2023.06.08 19:02 Joadzilla China to establish spy facility in Cuba off southeastern US -WSJ
WASHINGTON, June 8 (Reuters) - China has reached a secret deal with Cuba to establish an electronic eavesdropping facility on the island roughly 100 miles (160 km) from Florida, the Wall Street Journal reported on Thursday, citing U.S. officials familiar with classified intelligence.
Such a spy installation would allow Beijing to gather electronic communications from the southeastern U.S., which houses many U.S. military bases, as well as monitor ship traffic, the newspaper reported.
The U.S. Central Command headquarters is based in Tampa. Fort Liberty, formerly Fort Bragg, the largest U.S. military base, is based in North Carolina.
The countries have reached an agreement in principle, the officials said, with China to pay Cuba "several billion dollars" to allow the eavesdropping station, according to the Journal.
“I cannot speak to this specific report, but we are well aware of – and have spoken many times to – the People’s Republic of China’s efforts to invest in infrastructure around the world that may have military purposes, including in this hemisphere," John Kirby, spokesperson for the White House National Security Council, said in a statement.
"We monitor it closely, take steps to counter it, and remain confident that we are able to meet all our security commitments at home, in the region, and around the world," he said.
A spokesperson for the Chinese Embassy in Washington said: "We are not aware of the case and as a result we can't give a comment right now."
The Cuban government did not respond to a request for comment. But veteran Cuban diplomat Jose Cabanas, former ambassador to the U.S., wrote in a tweet that Washington was “trying to demonize Cuba again." He did not elaborate.
The agreement between the two U.S. rivals, both ruled by communist governments, has caused alarm in President Joe Biden's administration, the newspaper said, posing a new threat close to America's shores. The Journal said U.S. officials declined to provide more details about the proposed location of the listening station or whether construction had begun. I
The reported deal comes as Washington and Beijing are taking tentative steps to soothe tensions that spiked after a suspected Chinese high-altitude spy balloon crossed the United States before the U.S. military shot it down off the East Coast in February.
It could also raise questions about a trip to China that U.S. officials say Secretary of State Antony Blinken is planning in coming weeks. Washington's top diplomat had earlier scrapped the visit over the spy balloon incident.
Ties have deteriorated over disputes ranging from military activity in the South China Sea and near Taiwan, Beijing's human rights record, and technology competition.
U.S. Senator Bob Menendez, Democratic chairman of the Senate Foreign Relations Committee and a Cuba hawk, said if the report is true, it would be “a direct assault upon the United States.”
“So I hope the administration will think about how they'll react, if it’s true," he told reporters.
A former U.S. intelligence official said on condition of anonymity that a Chinese listening post would be a “big deal,” marking an expansion of Beijing's spying capabilities and giving it access to signals intelligence as far north as Washington.
If such a facility is built, the Chinese will use Cuba "as a beachhead for collection against the United States," said
Daniel Hoffman, a former senior CIA undercover officer.
However, the U.S. has a long history of spying on China in its own neighborhood. It is widely reported to have used Taiwan as a listening post for the mainland and regularly flies spy planes in the South China Sea, angering Beijing.
The head of Taiwan’s National Security Bureau told the island’s parliament in April that Taiwan was conducting real-time encrypted intelligence sharing with Five Eyes partners, which includes the U.S.
A cash infusion would likely be welcomed in Cuba, where the economy is sputtering and inflation, fuel shortages, plunging farm production and a cash crunch continue to fan discontent.
Relations between Washington and Havana remain strained. The Biden administration last year partially rolled back some Trump-era restrictions on remittances and travel to the island, but Cuban officials called the steps insufficient.
The intelligence on the agreement was gathered in recent weeks and was convincing, the Journal reported. The officials said it would allow China to conduct signals intelligence, including emails, phone calls and satellite transmission.
Cuba, an old Cold War foe of the United States, has long been a hotbed of espionage and spy games.
The Cuban missile crisis in 1962 began after Moscow began placing Soviet nuclear weapons on the island. It backed down and removed the missiles, but it is widely regarded as the moment when the United States and the Soviet Union came closest to a nuclear confrontation.
The Soviets installed a spy base on the island at Lourdes, just south of Havana, in the mid-1960s, with parabolic antennas aimed at Cuba´s northern neighbor. Russian President Vladimir Putin closed the facility in the early 2000s.
2023.06.08 12:59 texchange07 How the Invention of Cotton Gin Changed the World for Textile Companies
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2023.06.08 02:19 stankdiggy Matthew Furlong - Contract and severance package details...
åItem 5.02 Departure of Directors or Certain Officers; Election of Directors; Appointment of Certain Officers; Compensatory Arrangements of Certain Officers.So I highlighted a few sections and dates of note. Matt did not quite make 2 full years (out of 48 months which is 4 years (edit: I am an idiot who cant do maths so I fixed thanks to comments.)) but it looks like he was close enough that the section "iii" and "iv" above still grants him his payments and shares. this also seems to be verified by the 10.1 offer letter:
Appointment of President and Chief Executive Officer
On June 9, 2021, the GameStop Corp. (the “Company”) announced the appointment of Matthew Furlong, age 42, as the Company’s President and Chief Executive Officer, effective on or about June 21, 2021. Prior to joining the Company, Mr. Furlong served as Country Leader, Australia for Amazon.com, Inc. (“Amazon”) since September 2019 and in various other roles at Amazon since October 2012, including as Director, Technical Advisor, Amazon North America. Prior to joining Amazon, Mr. Furlong served in various roles at The Procter & Gamble Company focused on brand, marketing and sales strategies.
In connection with his appointment as the Company’s President and Chief Executive Officer, the Company entered into a letter agreement with Mr. Furlong on June 9, 2021 describing the basic terms of his employment (the “Furlong Letter Agreement”). The Furlong Letter Agreement provides that Mr. Furlong’s starting annualized base salary will be $200,000 and that he will also be eligible to earn a total of $4,700,000 in sign-on bonuses, paid in 24 monthly installments, subject to his continuous employment with the Company through the payment date of the applicable installment unless he is terminated by the Company without Cause (as defined in the Furlong Letter Agreement). In each of the first 12 months of his employment with the Company, Mr. Furlong will receive a sign-on bonus installment of $229,167. In each of months 13 through 24 of his employment with the Company, Mr. Furlong will receive a sign-on bonus installment of $162,500. Mr. Furlong is also entitled to a relocation bonus in the amount of $250,000 to assist with the costs of his relocation to the Dallas/Fort Worth area. The Furlong Letter Agreement also provides that, on the first business day of the first calendar quarter that commences after the effective date of his employment, Mr. Furlong will be entitled to a grant of a number of restricted stock units or restricted shares of the Company’s Class A common stock determined by dividing $16,500,000 by the average closing price of the Company’s Class A common stock for the 30 trading days immediately preceding the grant date (the “Initial Equity Award”). This equity award will vest as follows: 5% on the first anniversary of the grant date, 15% on the second anniversary of the grant date, and 20% on each of the dates that are 30, 36, 42 and 48 months following the grant date, subject in each case to his continuous service to the Company through the applicable vesting date. Finally, the Furlong Letter Agreement provides that Mr. Furlong’s employment is conditioned on his execution of a non-competition, non-solicitation and confidentiality agreement.
Under the Furlong Letter Agreement, if Mr. Furlong’s employment is terminated by the Company without Cause (as defined in the Furlong Letter Agreement), he will be entitled to receive the following severance benefits: (i) an amount equal to six months of his base salary, (ii) an amount equal to six months of COBRA premiums for Mr. Furlong and his eligible dependents, (iii) any sign-on bonus installments which then remain unpaid and (iv) the vesting of that portion of the Initial Equity Grant, if any, that was otherwise scheduled to vest in the ordinary course during the six month period immediately following his termination date. Mr. Furlong’s eligibility for these severance benefits is subject to his execution of a release of claims against the Company and his compliance with any applicable post-employment covenants.
The foregoing description of the Furlong Letter Agreement is not complete and is qualified in its entirety by the full text of the Furlong Letter Agreement, a copy of which is filed herewith as Exhibit 10.1 and incorporated herein by reference.
There are no other arrangements or understandings between Mr. Furlong and any other persons pursuant to which Mr. Furlong was named President and Chief Executive Officer. Mr. Furlong does not have any family relationship with any of the Company’s directors or executive officers or any persons nominated or chosen by the Company to be a director or executive officer. Mr. Furlong does not have any direct or indirect interest in any transaction or proposed transaction required to be reported under Item 404(a) of Regulation S-K.
June 9, 2021Soooo... He seems to get all payments and seems to be leaving on good terms. It may be a nothing-burger, but it is certainly interesting that he left almost exactly 2 years from the start as though it was part of the plan all along.
Congratulations! I am pleased to offer you employment with GameStop Texas, Ltd. and as the President and Chief Executive Officer GameStop Corp. (the “Company”). You will report to the Board of Directors of the Company (the “Board”). You will be subject to all policies of the Company and GameStop Texas, Ltd. in effect from time to time, including the Company’s Anti-Hedging Policy, Clawback Policy, Insider Trading Policy and Code of Ethics.
We would like you to start on a mutually agreed upon date no later than June 21, 2021. Your starting annualized base salary will be $200,000, less applicable taxes.
You will also be eligible to earn a total of $4,700,000 in sign-on bonuses. These bonuses will be paid in 24 monthly installments, as follows: In each of the first 12 months of your employment with us, you receive a sign-on bonus installment of $229,167, less applicable taxes. In each of months 13 through 24 of your employment with us, you will receive a sign-on bonus installment of $162,500, less applicable taxes. Your right to receive each installment is conditioned on your continuous employment with us through the payment date of that installment*.* Except as otherwise provided below in connection with a termination by the Company without Cause, if your employment with us ceases for any reason, no additional installments will be paid.
On the first business day of the first calendar quarter that commences after your start date, and subject to your active employment with us on that date, you will be granted a number of restricted stock units or restricted shares of the Company’s Class A common stock (“Common Stock”) determined by dividing $16,500,000 by the average closing price of Common Stock for the 30 trading days immediately preceding the grant date (the “Initial Equity Award”). The Initial Equity Award will vest as follows: 5% on the first anniversary of the grant date, 15% on the second anniversary of the grant date, and 20% on each of the dates that are 30, 36, 42 and 48 months following the grant date, subject in each case to your continuous service through the applicable vesting date. The above-described equity award will be documented in a separate award agreement; that agreement will contain additional terms and conditions (not inconsistent with this letter) and be delivered to you following the applicable grant date.
The Company’s agreement to grant equity to you and to pay you signing bonus installments does not guarantee your employment for any period or otherwise limit our ability to terminate your employment at any time, for any reason, even if your opportunity to receive or vest in such equity or receive such signing bonus installments would be forfeited as a result of such termination. We will periodically review your performance and compensation levels and may, beginning in 2022, make adjustments consistent with our executive compensation program, all as determined in the sole discretion of the Compensation Committee of our Board; provided, however, that such adjustments will not include a material adverse alteration of the above-described sign-on bonus installments or the Initial Equity Award without your consent.
You are eligible for 3 weeks of vacation per year. On the 61st day from your start date, you will be eligible to participate in the Company’s health (including dental and vision) benefits program, as well as be automatically covered in the Company’s company-paid life insurance program and, after 90 days, the long-term disability program. You will be eligible to participate in the 401(k) plan on the first day of the month following or coinciding with 60 days of service. You will be eligible for the company match commencing with the first of the month after or coinciding with your first year of service. The company match is funded on an annual frequency. Please feel free to contact our Benefits Team at (817) 722-7501 or 1-866-637-4387 with any specific benefit questions you may have.
Your position requires you to permanently relocate to Dallas/Ft Worth,TX. You are not eligible for benefits under our relocation policy. Instead, we will pay you a relocation bonus in the first pay period after your start date in the gross amount of $250,000 to assist you with your relocation costs.
Consistent with all roles in the organization, your employment will be on an at-will basis, having no specified term, and may be terminated at the will of either party on notice to the other. However, if we terminate your employment without Cause (as defined on Exhibit A***), you will receive the following severance benefits***, subject to the conditions noted below: (i) we will pay you an amount equal to six months of your base salary, (ii) if you are participating in our group health plans immediately prior to your termination, we will pay you an amount equal to the applicable premium for COBRA continuation coverage for you and your eligible dependents for six months, (iii) we will pay you any sign-on bonus installments which have not by then already been paid; and (iv) that portion of the Initial Equity Award (if any) that was otherwise scheduled to vest in the ordinary course during the six month period immediately following your termination date will become vested. To be eligible for these benefits you must (x) sign a release of claims on such form as we supply (which form will be substantially consistent with that used for other terminating senior executives) and that release must become irrevocable within 60 days after your termination date, and (y) comply with any applicable post-employment covenants under any other written agreement with us. The amounts described in clauses (i), (ii) and (iii) will be paid in a single cash lump sum (less required tax withholdings) as soon as practicable after the release becomes effective, and in no event later than 70 days after the termination date. The shares described in clause (iv) will be issued (if not already outstanding) and released from transfer restrictions as soon as practicable after the release becomes effective, and in no event later than 70 days after the termination date.
You will have rights (i) to indemnification in accordance with, and subject to the terms and conditions of, and limitations in, our Amended and Restated Certificate of Incorporation and Amended and Restated Bylaws and (ii) under any applicable directors and officers insurance under which you are covered.
2023.06.08 01:38 Thump4 💲 G M E 💵 Earnings Debrief, now-CEO Ryan Cohen, and Related Developments
submitted by Thump4 to DeepFuckingValue [link] [comments]
Earnings Debrief - Developments - Acquisition Target
Q1 Earnings Debrief
The Teddy trademark has been assigned, its review prior to publication completed, and will be published on July 4th, 2023, (the United States of America's Independence Day). If Matt Furlong wasn't let go due to capital-consolidation prior to a major acquisition, then perhaps Ryan Cohen needed a trustworthy leader to run either this ship, the Gmerica ship, or both
Now 76.6 Million shares have been Directly Registered (DRS'd)
The amount of shares directly registered with computershare is now higher than the publicly-reported shares on loan. Based on GameStop's $26.11 closing price, this equates to about $2 Billion of 💲 G M E shares lent out for short-borrowing. This is a giant liability for the associated borrowers, and is only what has been publicly reported with Ortex, and by institutions who 'self-police' themselves.
Regarding the idiosyncratic risk of this stock to short-selling firms, the SEC just voted 'yes' (meeting and agenda) to stop fraud and manipulation on swaps, which have long been used by funds as a technique to hide underwater-short positions (i.e. Archegos' position that then blew up Credit Suisse). Thus, the higher, more-accurate short liability could soon be revealed.
Related DevelopmentsThere is the big GameStop annual shareholder meeting Thursday of next week (June 15th), which is after both Bed Bath and Beyond's Stalking Horse Bidder deadline and subsequent court hearing on June 14th. Mysteriously, GameStop decided not to host an earnings call today, which under Merger and Acquisition policy would make sense if an acquisition target is pending a court hearing on the matter prior to public disclosure.
Investors are generally pleased with the company's direction:
Big investors appear to be very happy that Cohen is running acquisitions
GameStop has been selling droves of Diablo IV for both PS4, PS5, Xbox X/One
GameStop's Diablo IV sales continue to pour in for PS4. PS5, Xbox One, and Xbox Series X. GameStop's Zelda tears of the kingdom sales continue to pour in for Nintendo switch.
In web 3.0 developments, GameStop is building its web 3.0 GameStop video-game launcher with Telos. Further, GameStop's affiliate Loopring is working with Taiko, now deploying the alpha TestNet of the Layer 3.
GameStop's new 'Illuvium' is set for Monday, June 12th release
On the digital asset side of the house, GameStop's NFT marketplace transaction fees/revenues continue to pour in. And Monday, June 12th is the Release for the collectable Illuvitars (illuminated digital works of art with a capped-supply of 20,000), and the competitive game to follow.
Ryan Cohen - Running Merger(s) and Acquisition(s)
Executive Chairman Ryan Cohen will now be evaluating acquisitions
$BBBYQ's Buy Buy Baby arm has long been the only publicly-disclosed buyout target for Ryan Cohen, via his close networking with Bed Bath and Beyond leadership. Could Ryan Cohen be targeting this company's assets during the active court proceedings?
TLDR:Earnings: GameStop saw a Very Positive +$107.4 Million Delta (in operations) versus 2022's Q1. (GameStop performed $107.4 Million better as a company than it did in the same quarter of last year). $106.5 Million expense reduction vs previous Q1, now $1.31 Billion cash on hand, and still essentially debt-free.
Leadership: Ryan Cohen is now executive-chairman of GameStop and will be in charge of acquisition targets, likely due to Matt Furlong's 2 year contract being satisfied, [if not his profit-generating services being needed elsewhere for either TEDDY or GMERICA (July 4th publication)]
Misc: Diablo IV and Zelda Tears of the Kingdom sales continue to pour in. In Web 3.0, GameStop is building its Web 3.0 video game launcher with Telos, and affiliate LoopRing is running an alpha testnet for Eth Layer 3. And Monday, June 12th is the release for the digital 'Illuvitars' collectibles.
Annual Shareholder Meeting: Thursday, June 15th (next week)
2023.06.08 00:43 JeliPuff Felix Vail: The Pedophile Serial Killer Caught After 54 Years (PART 2)