Ohm20 posted:
"a-SMA [-], a1-antitrypsin [+],ADA2 (CCL5 migration to site of injury) [-], AKT [-], AMPK [+], arachidonic acid (upregulated by CCL2, CCL3, CCL4, CCL5, CCL7 [-],CCL8)[-}, ARG1 [-], ASC proteins (via NLRP3 downreg)[-], b-arrestin [-], BACH2 (via decrease of inflammatory TREG reaponse) [+], Bcl-2 [-], BDNF [+], bradykinin[-], beta- catenin (via downreg CCL5/CCL2) [-], bFGF (-), BTK (via SYK) [-], caspase-1 (via NLRP3/ASC downreg) [-], capase-3 [-], capase 9 [-], C5a, CA-2+[-], Calcineurin (via downreg CA-2+[-], cAMP (via CD38)[-], CCL2 (MCP-1)[-], CCL3 (MIP-1a)[-], CCL4 (MIP-1β)[-], CCL5 (RANTES)[-], CCL7 (MCP-3)[-], CCL8 (MCP-2)[-], CCL11(Eotaxin)[-], CCL13 (MCP-4)[-], CCL14 (HCC-1)[-], CCL16 (HCC-4)[-], CCL20 (LARC MIP3A)(not a CCR5 ligand) (via NF-kB, downreg)[-], CCR1 (via TNF-a and IL-4) [-], CDK2 (via CCL5 downreg) [-], CDK4 (via CCL5 downreg) [-], CDK6 (via CCL5 downreg) [-], collagen[-], CREB [+], CTLA-4, CX3CL1 (fractalkine) (NF-kB /TNF-a downregulation)[-], CXCL1 [-], CXCR4 (via downreg IL-17a, IL-5, TFN-y, TGF-b) [-], cyclin D1 (via CCL5 downreg) [-], cyclin E (via CCL5 downreg) [-],cytochrome c (via CCL5 downreg)[-], ECM [-], EGF (in cancer via downreg fibroblasts) [-], eIF2a (via PKR downreg) [-], eIF4E [-], Erk 1 and 2[-], FAK (via CCL5) [-], FLNa, FOXP3 (downregulation of PKB/Akt pathway)[+}, GLP-1 [+], GLUT-1 (via CCL5 downreg) [-], GM-CSF (CSF2)[-], GPR75 (increased binding of CCL5 to GPR75 due to CCR5 blockade) [effect is downreg CA2+],Gsdmd [-] , inositol monophosphate (IP-1) IP-1 implicated in bi-polar disorder)), HbA1c (correlated with CCL5), HDL (high density lipoprotein) [+], HGF, IFN-g [+], HIF-1a [-], IFNy (BACH2 upregulation)[-], IL-1b (via caspase-1 downreg)[-], IL-1Ra [+], IL-2 [-], IL-4, IL-6 (via CCL5) [-], IL-8, IL-10 [-], IL-13 [-], IL-16 [-], IL-17a [-], IL-18 (via caspase-1 downreg)[-], IL-33, IL-36 (via TNF-a and ILF downreg)[-], Jak 1, 2 and 3[-], LDL (low density lipoprotein).macrophage polarization M2 to M1 shift, MapK (p38 MAPK)[-], MCP-1 [-], MCP-2, MDSC (via downreg CCL5) [-], MEK [-], MMP-1, MMP-2 (via CCL3 downreg)[-], MMP-3, MMP-9 (CCL5/PLC pathway) [-], MMP-12 [-], MMP-13, mTORc1[-],N-GSDMD [-], NETosis[-], neuropilin-1[-], NF-kb (via PI3K/AKT downreg) [-], NFAT (via CA2+ downreg) [-], NLRP1 [-] NLRP3 (via IL-36, ATP, ROS downreg) [-], Nox1 (via CCL5) [-], p27 (tumor suppressor) [+], PCNA [-], p-CREB [+], PI3k[-], PDK1 (via PI3K)[-] PD-L1(via downreg Nf-kb/MapK/JAK2) [-], PDGF-B (upreg from ADA2) [-], PKA-Ca [+], PKB/AT (CCL3,CCL5 blockade)[-], PKC (-), PKR (via TNF-a downreg) -[-], PLC (CCL5 blockade)[-], PPARy [+], Prostaglandin D2 (formed from arachidonic acid) [-], Pyk2 (via RAFTK) [-], RAFTK (downreg of bradykinin, CCL5) [-], RAS (via downreg Src) [-], ROS (via CCL5)[-], sFas (via Nf-kB)[-], SHP1[-], SHP2[-], SOCS3 [-], SORT1 (neurotensin receptor-3) (MAP and PI3K dependent) [-], SREBP-1a [-], SREBP-2 [-], Src (via downregulation of Pyk2) [-], STAT3 [-], STAT5 [-], SYK (via CCL4) [-], TGF-b [-], TIMP-1 [-], TIMP-2 [-], TIMP-3 [-], TNF-a (via IL-10, MEK downreg)[-], TNFSF14, TRPM4 (via CA-2+ downreg) [-], VCAM-1 (via TNF-a, IL-1 downreg) [-], VEGF [-], ZAP70 (via CCL5) [-]"
Most people see this list of letters and symbols and get confused immediately. I can understand that. Not everyone knows HTML, like I do. It's not gibberish, I assure you.
It's HTML code that's supposed to result in a picture, except (by my trained analysis) there's a missing parentheses in there, otherwise we wouldn't see the code at all. Instead we'd see the picture this code is supposed to represent.
I did a little forensic analysis and adjustment to the code and realized it's supposed to be a photo of Craig at a local coffee shop trying to tell the barista that making real coffee requires coffee beans, and they're clearly not using coffee beans to make this coffee, and that all he's trying to do is make them aware of the problems with the flavored water they're serving that is clearly not coffee. And he should know, because he's an expert on all matters surrounding coffee. Hell, he's a long time purchaser of their coffee, only it's not coffee and people shouldn't be buying it. He has a cup of their coffee in his hand as he berates the 18yo behind the counter, who looks confused as she stands next to a machine that not only says "COFFEE BEAN GRINDER" on the front of it, but also has a large clear chute full of coffee beans leading into the device and ultimately out of the spout that poured the coffee in his hand.
Oh, and I almost forgot to mention that I've been reading all the posts about the call and just when you think there's no more room for the goal posts to move, they move again in new and "exciting" ways. Hell, even Cyrus seemed to chuckle in an almost absurd bemusement sort of way when announcing there was even more information to submit. It was a laugh that said, "I can't believe I'm saying this, but they've asked for even more information".
It seems purposeful by the FDA, because I don't think it's possible that Cyrus keeps submitting bad information. This isn't someone asking Craig to define quid pro quo and Craig responds with "that's when you buy something that's not what they say it was and they won't let you return it because they claim you've been banned from the store due to weirding out the other customers too many times".
Then they give him one more chance to define it correctly, even leading him most of the way there by saying, "We're going to give you a second chance because that first response was so bad we're concerned you may have a brain bleed. So let's try again. Quid pro quo is a favor or advantage granted or expected in return for..."
and Craig confidently jumps in with...
"in return for THIS GOLD QUARTER WITH THE PRESIDENT'S HEAD ON IT THAT I PAID $75 DOLLARS FOR BUT YET WHEN I WAS AT THE AS SEEN ON TV STORE TRYING TO BUY A SLAP CHOP THEY'RE TELLING ME IT'S ONLY WORTH TWENTY FIVE CENTS I'M NOT CRAZY YOU'RE CRAZY I HAVE A RECEIPT FOR WHAT I PAID FOR THIS COMMEMORATIVE TREASURE AND TELL YOU WHAT IF YOU TAKE IT BACK I WILL SPEAK TO YOUR MANAGER ABOUT PROMOTING YOU BECAUSE HE'S A CLOSE PERSONAL FRIEND!"
And then they point out that he actually somehow ended up giving a perfect example of quid pro quo during his perplexing response and he says, "EXACTLY! Like I said it's when something is defective and a store won't take it back."
At any rate, it seems Cyrus is catching up to the rest of us with his confusion over why this is taking so long. But he remains confident it'll be taken care of soon. I doubt soon means a week or two. They have to build a new protocol and I'm sure that'll take some time. I feel like this will take longer than we all want again (it already has on multiple occasions), but once this hurdle is complete we will have a very strong platform built from which we can launch trials with confidence that all of the safety and regulatory needs are already met or exceeded. It'll just come down to efficacy at that point, where, if I'm being honest here, I like our chances. A lot.
"a-SMA [-], a1-antitrypsin [+],ADA2 (CCL5 migration to site of injury) [-], AKT [-], AMPK [+], arachidonic acid (upregulated by CCL2, CCL3, CCL4, CCL5, CCL7 [-],CCL8)[-}, ARG1 [-], ASC proteins (via NLRP3 downreg)[-], b-arrestin [-], BACH2 (via decrease of inflammatory TREG reaponse) [+], Bcl-2 [-], BDNF [+], bradykinin[-], beta- catenin (via downreg CCL5/CCL2) [-], bFGF (-), BTK (via SYK) [-], caspase-1 (via NLRP3/ASC downreg) [-], capase-3 [-], capase 9 [-], C5a, CA-2+[-], Calcineurin (via downreg CA-2+[-], cAMP (via CD38)[-], CCL2 (MCP-1)[-], CCL3 (MIP-1a)[-], CCL4 (MIP-1β)[-], CCL5 (RANTES)[-], CCL7 (MCP-3)[-], CCL8 (MCP-2)[-], CCL11(Eotaxin)[-], CCL13 (MCP-4)[-], CCL14 (HCC-1)[-], CCL16 (HCC-4)[-], CCL20 (LARC MIP3A)(not a CCR5 ligand) (via NF-kB, downreg)[-], CCR1 (via TNF-a and IL-4) [-], CDK2 (via CCL5 downreg) [-], CDK4 (via CCL5 downreg) [-], CDK6 (via CCL5 downreg) [-], collagen[-], CREB [+], CTLA-4, CX3CL1 (fractalkine) (NF-kB /TNF-a downregulation)[-], CXCL1 [-], CXCR4 (via downreg IL-17a, IL-5, TFN-y, TGF-b) [-], cyclin D1 (via CCL5 downreg) [-], cyclin E (via CCL5 downreg) [-],cytochrome c (via CCL5 downreg)[-], ECM [-], EGF (in cancer via downreg fibroblasts) [-], eIF2a (via PKR downreg) [-], eIF4E [-], Erk 1 and 2[-], FAK (via CCL5) [-], FLNa, FOXP3 (downregulation of PKB/Akt pathway)[+}, GLP-1 [+], GLUT-1 (via CCL5 downreg) [-], GM-CSF (CSF2)[-], GPR75 (increased binding of CCL5 to GPR75 due to CCR5 blockade) [effect is downreg CA2+],Gsdmd [-] , inositol monophosphate (IP-1) IP-1 implicated in bi-polar disorder)), HbA1c (correlated with CCL5), HDL (high density lipoprotein) [+], HGF, IFN-g [+], HIF-1a [-], IFNy (BACH2 upregulation)[-], IL-1b (via caspase-1 downreg)[-], IL-1Ra [+], IL-2 [-], IL-4, IL-6 (via CCL5) [-], IL-8, IL-10 [-], IL-13 [-], IL-16 [-], IL-17a [-], IL-18 (via caspase-1 downreg)[-], IL-33, IL-36 (via TNF-a and ILF downreg)[-], Jak 1, 2 and 3[-], LDL (low density lipoprotein).macrophage polarization M2 to M1 shift, MapK (p38 MAPK)[-], MCP-1 [-], MCP-2, MDSC (via downreg CCL5) [-], MEK [-], MMP-1, MMP-2 (via CCL3 downreg)[-], MMP-3, MMP-9 (CCL5/PLC pathway) [-], MMP-12 [-], MMP-13, mTORc1[-],N-GSDMD [-], NETosis[-], neuropilin-1[-], NF-kb (via PI3K/AKT downreg) [-], NFAT (via CA2+ downreg) [-], NLRP1 [-] NLRP3 (via IL-36, ATP, ROS downreg) [-], Nox1 (via CCL5) [-], p27 (tumor suppressor) [+], PCNA [-], p-CREB [+], PI3k[-], PDK1 (via PI3K)[-] PD-L1(via downreg Nf-kb/MapK/JAK2) [-], PDGF-B (upreg from ADA2) [-], PKA-Ca [+], PKB/AT (CCL3,CCL5 blockade)[-], PKC (-), PKR (via TNF-a downreg) -[-], PLC (CCL5 blockade)[-], PPARy [+], Prostaglandin D2 (formed from arachidonic acid) [-], Pyk2 (via RAFTK) [-], RAFTK (downreg of bradykinin, CCL5) [-], RAS (via downreg Src) [-], ROS (via CCL5)[-], sFas (via Nf-kB)[-], SHP1[-], SHP2[-], SOCS3 [-], SORT1 (neurotensin receptor-3) (MAP and PI3K dependent) [-], SREBP-1a [-], SREBP-2 [-], Src (via downregulation of Pyk2) [-], STAT3 [-], STAT5 [-], SYK (via CCL4) [-], TGF-b [-], TIMP-1 [-], TIMP-2 [-], TIMP-3 [-], TNF-a (via IL-10, MEK downreg)[-], TNFSF14, TRPM4 (via CA-2+ downreg) [-], VCAM-1 (via TNF-a, IL-1 downreg) [-], VEGF [-], ZAP70 (via CCL5) [-]"
Most people see this list of letters and symbols and get confused immediately. I can understand that. Not everyone knows HTML, like I do. It's not gibberish, I assure you.
It's HTML code that's supposed to result in a picture, except (by my trained analysis) there's a missing parentheses in there, otherwise we wouldn't see the code at all. Instead we'd see the picture this code is supposed to represent.
I did a little forensic analysis and adjustment to the code and realized it's supposed to be a photo of Craig at a local coffee shop trying to tell the barista that making real coffee requires coffee beans, and they're clearly not using coffee beans to make this coffee, and that all he's trying to do is make them aware of the problems with the flavored water they're serving that is clearly not coffee. And he should know, because he's an expert on all matters surrounding coffee. Hell, he's a long time purchaser of their coffee, only it's not coffee and people shouldn't be buying it. He has a cup of their coffee in his hand as he berates the 18yo behind the counter, who looks confused as she stands next to a machine that not only says "COFFEE BEAN GRINDER" on the front of it, but also has a large clear chute full of coffee beans leading into the device and ultimately out of the spout that poured the coffee in his hand.
Oh, and I almost forgot to mention that I've been reading all the posts about the call and just when you think there's no more room for the goal posts to move, they move again in new and "exciting" ways. Hell, even Cyrus seemed to chuckle in an almost absurd bemusement sort of way when announcing there was even more information to submit. It was a laugh that said, "I can't believe I'm saying this, but they've asked for even more information".
It seems purposeful by the FDA, because I don't think it's possible that Cyrus keeps submitting bad information. This isn't someone asking Craig to define quid pro quo and Craig responds with "that's when you buy something that's not what they say it was and they won't let you return it because they claim you've been banned from the store due to weirding out the other customers too many times".
Then they give him one more chance to define it correctly, even leading him most of the way there by saying, "We're going to give you a second chance because that first response was so bad we're concerned you may have a brain bleed. So let's try again. Quid pro quo is a favor or advantage granted or expected in return for..."
and Craig confidently jumps in with...
"in return for THIS GOLD QUARTER WITH THE PRESIDENT'S HEAD ON IT THAT I PAID $75 DOLLARS FOR BUT YET WHEN I WAS AT THE AS SEEN ON TV STORE TRYING TO BUY A SLAP CHOP THEY'RE TELLING ME IT'S ONLY WORTH TWENTY FIVE CENTS I'M NOT CRAZY YOU'RE CRAZY I HAVE A RECEIPT FOR WHAT I PAID FOR THIS COMMEMORATIVE TREASURE AND TELL YOU WHAT IF YOU TAKE IT BACK I WILL SPEAK TO YOUR MANAGER ABOUT PROMOTING YOU BECAUSE HE'S A CLOSE PERSONAL FRIEND!"
And then they point out that he actually somehow ended up giving a perfect example of quid pro quo during his perplexing response and he says, "EXACTLY! Like I said it's when something is defective and a store won't take it back."
At any rate, it seems Cyrus is catching up to the rest of us with his confusion over why this is taking so long. But he remains confident it'll be taken care of soon. I doubt soon means a week or two. They have to build a new protocol and I'm sure that'll take some time. I feel like this will take longer than we all want again (it already has on multiple occasions), but once this hurdle is complete we will have a very strong platform built from which we can launch trials with confidence that all of the safety and regulatory needs are already met or exceeded. It'll just come down to efficacy at that point, where, if I'm being honest here, I like our chances. A lot.
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