Offshore
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Librarian Capital
"Two men charged with insider dealing in Britain" (Reuters)
FCA press release stated the two made a profit of £110k over 5 years (2016-20)
The two are in their 40s
Neither name appears on the FCA register
This is likely to be another case of ancillary staff doing small trades https://t.co/n1NsVPEv7F
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"Two men charged with insider dealing in Britain" (Reuters)
FCA press release stated the two made a profit of £110k over 5 years (2016-20)
The two are in their 40s
Neither name appears on the FCA register
This is likely to be another case of ancillary staff doing small trades https://t.co/n1NsVPEv7F
Two men charged with insider dealing in Britain https://t.co/u5pvZz0VSk https://t.co/oJe535bEzR tweet
Alex Bilzerian
I admire Glenn Shafer’s choice to leave his name & title off this PDF — a challenge to the reader to evaluate the work purely on its substance.
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I admire Glenn Shafer’s choice to leave his name & title off this PDF — a challenge to the reader to evaluate the work purely on its substance.
Betting scores as a replacement for p-values: https://t.co/FL0bwp82EV tweet
twitter.com
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Alex Bilzerian
Few people with fervent beliefs have a solid epistemic foundation to justify their level of certainty. There's often a disconnect between how sure they feel and how sure they ought to be if they followed sound reasoning.
When you look at who they're proxying their sense-making to, it becomes clear that they rarely defer to those who conducted the original research.
Even among those researchers, there’s often disagreement, potential funding influences, and the presence of epistemic biases.
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Few people with fervent beliefs have a solid epistemic foundation to justify their level of certainty. There's often a disconnect between how sure they feel and how sure they ought to be if they followed sound reasoning.
When you look at who they're proxying their sense-making to, it becomes clear that they rarely defer to those who conducted the original research.
Even among those researchers, there’s often disagreement, potential funding influences, and the presence of epistemic biases.
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Offshore
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Stock Analysis Compilation
Guinness GI on Advanced Drainage Systems $WMS US
Thesis: As a leader in recycled plastic stormwater solutions, ADS stands poised for growth amid rising infrastructure investment and increasing market share.
(Extract from their Q2 letter) https://t.co/eq8JDAHpVe
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Guinness GI on Advanced Drainage Systems $WMS US
Thesis: As a leader in recycled plastic stormwater solutions, ADS stands poised for growth amid rising infrastructure investment and increasing market share.
(Extract from their Q2 letter) https://t.co/eq8JDAHpVe
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Alex Bilzerian
RT @TenreiroDaniel: you never hear people describe technologies as 'disruptive' anymore, but it was once the adjective of choice
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RT @TenreiroDaniel: you never hear people describe technologies as 'disruptive' anymore, but it was once the adjective of choice
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Offshore
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Alex Bilzerian
RT @alexbilz: Luis Raúl Pericchi: "The language of science is the language of probability, and not of p-values.”
https://t.co/OSYIsfMTdg https://t.co/gXeu6nvqi9
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RT @alexbilz: Luis Raúl Pericchi: "The language of science is the language of probability, and not of p-values.”
https://t.co/OSYIsfMTdg https://t.co/gXeu6nvqi9
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Offshore
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Alex Bilzerian
RT @alexbilz: Taleb's note on p-hacking is worth a close read if you haven't already: https://t.co/xXhGz1QZRT https://t.co/jNONBKSpRr
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RT @alexbilz: Taleb's note on p-hacking is worth a close read if you haven't already: https://t.co/xXhGz1QZRT https://t.co/jNONBKSpRr
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Offshore
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Alex Bilzerian
'The Nobel Prize in Economic Sciences is a dubious thing at best.'
https://t.co/b1uRPlEt8d via @mises
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'The Nobel Prize in Economic Sciences is a dubious thing at best.'
https://t.co/b1uRPlEt8d via @mises
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Alex Bilzerian
RT @DeryaTR_: I absolutely love working with o1-preview! I haven’t felt this intellectually stimulated in a long time. Not only am I brainstorming ideas, but now I’m designing experiments with o1 and asking it to virtually run them, predict potential outcomes, and then refine and iterate.
Below is just one example. While this is a highly specific and complex topic that may be hard to grasp without a deep immunology background, I wanted to share the thought process. It might be useful for others to apply similar scenarios in their own fields.
The question below is about developing engineered cells to fight cancer, the idea was also from o1-preview with some guidance and brainstorming from me😀:
Prompt: "You have now completed all the experiments you proposed. Determine three potential outcomes for each experiment, whether they succeed or fail. Then, propose solutions or reflect on what you have learned, and ask new questions. Based on that, suggest what you would do next as an experiment. Be critical of your own approach."
Engineering CAR-T Cells with ‘Reserve Energy Packs’ via Metabolic Modulation
Experimental Approach:
1. Overexpression of Metabolic Enzymes:
• Target Genes: Enzymes involved in energy storage and release, such as glycogen synthase or creatine kinase.
• Vector Construction: Clone target genes into lentiviral vectors.
2. Transduction of T Cells:
• Activation: Isolate and activate CD8+ T cells.
• Transduction: Introduce metabolic enhancement constructs and CAR vector.
3. Metabolic Assessments:
• Energy Storage Measurement: Assess glycogen levels or creatine phosphate stores in CAR-T cells.
• Energy Utilization: Measure ATP levels and energy expenditure during activation.
4. Functional Assays:
• Exhaustion Induction: Subject cells to prolonged activation.
• Assessment: Evaluate cytotoxicity, cytokine production, proliferation, and survival.
Potential Outcomes of experiments:
Outcome 1: Enhanced Energy Reserves Improve CAR-T Cell Function
• Observations:
• Engineered CAR-T cells have increased energy stores.
• Display sustained function under prolonged activation.
• Reduced exhaustion markers compared to controls.
• Implications:
• Supports the idea that bolstering energy reserves can mitigate exhaustion.
• Provides a metabolic strategy to enhance CAR-T cell endurance.
• Next Steps:
• Optimize Energy Utilization:
• Ensure that enhanced energy stores are efficiently mobilized during activation.
• Combine with Other Metabolic Enhancements:
• Integrate with mitochondrial biogenesis or metabolic flexibility strategies.
• Long-Term Monitoring:
• Assess the stability of metabolic enhancements over time.
• Critical Reflection:
• Positive results suggest a viable approach. However, metabolic interventions require careful calibration.
Outcome 2: No Significant Impact on CAR-T Cell Function
• Observations:
• Despite increased energy stores, CAR-T cell function remains unchanged.
• Exhaustion markers and functional assays are similar to controls.
• Implications:
• Additional energy reserves may not be the limiting factor in exhaustion.
• Energy utilization pathways may not be effectively engaged.
• Next Steps:
• Enhance Mobilization Mechanisms:
• Overexpress enzymes involved in energy release during activation.
• Assess Metabolic Integration:
• Examine whether energy stores are accessible during high-demand periods.
• Explore Alternative Pathways:
• Focus on improving energy efficiency or reducing energy consumption.
• Critical Reflection:
• Suggests that simply increasing energy stores is insufficient. The entire metabolic network must be considered.
Outcome 3: Metabolic Modifications Cause Cellular Stress
• Observations:
• Altered energy metabolism l[...]
RT @DeryaTR_: I absolutely love working with o1-preview! I haven’t felt this intellectually stimulated in a long time. Not only am I brainstorming ideas, but now I’m designing experiments with o1 and asking it to virtually run them, predict potential outcomes, and then refine and iterate.
Below is just one example. While this is a highly specific and complex topic that may be hard to grasp without a deep immunology background, I wanted to share the thought process. It might be useful for others to apply similar scenarios in their own fields.
The question below is about developing engineered cells to fight cancer, the idea was also from o1-preview with some guidance and brainstorming from me😀:
Prompt: "You have now completed all the experiments you proposed. Determine three potential outcomes for each experiment, whether they succeed or fail. Then, propose solutions or reflect on what you have learned, and ask new questions. Based on that, suggest what you would do next as an experiment. Be critical of your own approach."
Engineering CAR-T Cells with ‘Reserve Energy Packs’ via Metabolic Modulation
Experimental Approach:
1. Overexpression of Metabolic Enzymes:
• Target Genes: Enzymes involved in energy storage and release, such as glycogen synthase or creatine kinase.
• Vector Construction: Clone target genes into lentiviral vectors.
2. Transduction of T Cells:
• Activation: Isolate and activate CD8+ T cells.
• Transduction: Introduce metabolic enhancement constructs and CAR vector.
3. Metabolic Assessments:
• Energy Storage Measurement: Assess glycogen levels or creatine phosphate stores in CAR-T cells.
• Energy Utilization: Measure ATP levels and energy expenditure during activation.
4. Functional Assays:
• Exhaustion Induction: Subject cells to prolonged activation.
• Assessment: Evaluate cytotoxicity, cytokine production, proliferation, and survival.
Potential Outcomes of experiments:
Outcome 1: Enhanced Energy Reserves Improve CAR-T Cell Function
• Observations:
• Engineered CAR-T cells have increased energy stores.
• Display sustained function under prolonged activation.
• Reduced exhaustion markers compared to controls.
• Implications:
• Supports the idea that bolstering energy reserves can mitigate exhaustion.
• Provides a metabolic strategy to enhance CAR-T cell endurance.
• Next Steps:
• Optimize Energy Utilization:
• Ensure that enhanced energy stores are efficiently mobilized during activation.
• Combine with Other Metabolic Enhancements:
• Integrate with mitochondrial biogenesis or metabolic flexibility strategies.
• Long-Term Monitoring:
• Assess the stability of metabolic enhancements over time.
• Critical Reflection:
• Positive results suggest a viable approach. However, metabolic interventions require careful calibration.
Outcome 2: No Significant Impact on CAR-T Cell Function
• Observations:
• Despite increased energy stores, CAR-T cell function remains unchanged.
• Exhaustion markers and functional assays are similar to controls.
• Implications:
• Additional energy reserves may not be the limiting factor in exhaustion.
• Energy utilization pathways may not be effectively engaged.
• Next Steps:
• Enhance Mobilization Mechanisms:
• Overexpress enzymes involved in energy release during activation.
• Assess Metabolic Integration:
• Examine whether energy stores are accessible during high-demand periods.
• Explore Alternative Pathways:
• Focus on improving energy efficiency or reducing energy consumption.
• Critical Reflection:
• Suggests that simply increasing energy stores is insufficient. The entire metabolic network must be considered.
Outcome 3: Metabolic Modifications Cause Cellular Stress
• Observations:
• Altered energy metabolism l[...]