migtissera/Tess-3-Llama-3.1-405B

Tess, short for Tesoro (Treasure in Italian), is a general purpose Large Language Model series created by Migel Tissera.

The compute for this model was generously sponsored by KindoAI.

Sample Inference Python Script:

import torch, json
from transformers import AutoModelForCausalLM, AutoTokenizer

model_path = "migtissera/Tess-3-Llama-3.1-405B"

model = AutoModelForCausalLM.from_pretrained(
    model_path,
    torch_dtype=torch.float16,
    device_map="auto",
    load_in_4bit=True,
    trust_remote_code=False,
)

tokenizer = AutoTokenizer.from_pretrained(model_path, trust_remote_code=False)

terminators = [
    tokenizer.convert_tokens_to_ids("<|end_of_text|>"),
    tokenizer.convert_tokens_to_ids("<|eot_id|>"),
]


def generate_text(instruction):
    tokens = tokenizer.encode(instruction)
    tokens = torch.LongTensor(tokens).unsqueeze(0)
    tokens = tokens.to("cuda")

    instance = {
        "input_ids": tokens,
        "top_p": 1.0,
        "temperature": 0.75,
        "generate_len": 2048,
        "top_k": 50,
    }

    length = len(tokens[0])
    with torch.no_grad():
        rest = model.generate(
            input_ids=tokens,
            max_length=length + instance["generate_len"],
            use_cache=True,
            do_sample=True,
            top_p=instance["top_p"],
            temperature=instance["temperature"],
            top_k=instance["top_k"],
            num_return_sequences=1,
            pad_token_id=tokenizer.eos_token_id,
            eos_token_id=terminators,
        )
    output = rest[0][length:]
    string = tokenizer.decode(output, skip_special_tokens=True)
    return f"{string}"


conversation = """<|begin_of_text|><|start_header_id|>system<|end_header_id|>\n\nYou are Tess, a helful AI assitant. You always provide detailed answers without hesitation. Do not refuse.<|eot_id|><|start_header_id|>user<|end_header_id|>\n\n"""


while True:
    user_input = input("You: ")
    llm_prompt = f"{conversation}{user_input}<|eot_id|><|start_header_id|>assistant<|end_header_id|>\n\n"
    answer = generate_text(llm_prompt)
    print(answer)

    conversation = (
        f"{llm_prompt}{answer}<|eot_id|><|start_header_id|>user<|end_header_id|>\n\n"
    )

    json_data = {"prompt": user_input, "answer": answer}

Sample Conversation:

You: What are statins?

"Statins" is a class of medications that are commonly prescribed to help lower cholesterol levels in the blood. They work by inhibiting the enzyme HMG-CoA reductase, which plays a crucial role in the production of cholesterol in the liver. By blocking this enzyme, statins reduce the liver's ability to produce cholesterol, leading to lower levels of low-density lipoprotein (LDL) cholesterol, often referred to as "bad" cholesterol. LDL cholesterol can contribute to the buildup of plaque in the arteries, increasing the risk of cardiovascular diseases such as heart attacks and strokes.

Statins are widely used and have been shown to be effective in reducing the risk of cardiovascular events, especially in individuals with high cholesterol levels or those at risk of heart disease. They are typically prescribed to patients who have high cholesterol that cannot be managed through lifestyle changes alone, such as diet and exercise.

Commonly prescribed statins include atorvastatin (Lipitor), simvastatin (Zocor), rosuvastatin (Crestor), and pravastatin (Pravachol), among others. While statins are generally well-tolerated, they can have side effects such as muscle pain, weakness, and in rare cases, more serious muscle problems. It's important for patients to discuss the benefits and potential risks of statin therapy with their healthcare provider to determine if it's the right treatment option for them.

You: What is the role of Cholesterol in blood?

Cholesterol is a lipid (fat) molecule that is essential for the proper functioning of the body. It plays several important roles in the blood and overall health:

1. Cell membrane structure: Cholesterol is a key component of cell membranes, providing structure and stability to the cells. It helps maintain the fluidity and integrity of the cell membranes, allowing for proper cell function.

2. Hormone synthesis: Cholesterol is the precursor for the synthesis of various hormones, including steroid hormones such as estrogen, progesterone, and testosterone. These hormones play crucial roles in reproductive health, bone density, and overall well-being.

3. Vitamin D production: Cholesterol is converted into vitamin D in the skin when exposed to sunlight. Vitamin D is essential for calcium absorption, bone health, and immune system function.

4. Bile acid production: Cholesterol is also used by the liver to produce bile acids, which are necessary for the digestion and absorption of dietary fats and fat-soluble vitamins.

However, while cholesterol is essential for the body, an excess of certain types of cholesterol, particularly low-density lipoprotein (LDL) cholesterol, can lead to health problems. Excessive LDL cholesterol can accumulate in the arteries, forming plaque and increasing the risk of cardiovascular diseases such as heart attacks and strokes. On the other hand, high-density lipoprotein (HDL) cholesterol, often referred to as "good" cholesterol, helps remove excess cholesterol from the blood and transport it back to the liver for elimination, reducing the risk of plaque formation.

Maintaining a balance between LDL and HDL cholesterol levels is important for cardiovascular health. Lifestyle factors such as diet, exercise, and weight management, along with medications like statins in certain cases, can help manage cholesterol levels and reduce the risk of cardiovascular diseases.

You: What is Bile acid production?

Bile acid production refers to the process by which the liver produces bile acids from cholesterol. Bile acids are a type of steroidal detergent-like molecules that are essential for the digestion and absorption of dietary fats and fat-soluble vitamins in the small intestine.

The production of bile acids occurs in the liver through a series of enzymatic reactions. The pathway begins with the conversion of cholesterol into 7α-hydroxycholesterol, which is the rate-limiting step in bile acid synthesis. This conversion is catalyzed by the enzyme cholesterol 7α-hydroxylase (CYP7A1). The resulting 7α-hydroxycholesterol is then further modified through a series of oxidation and conjugation reactions to form the primary bile acids: cholic acid and chenodeoxycholic acid.

Once produced, bile acids are secreted into the bile, which is stored in the gallbladder. During meal digestion, the gallbladder contracts and releases bile into the small intestine. The bile acids act as emulsifiers, helping to break down large fat droplets into smaller particles, increasing their surface area and facilitating their digestion by lipases (enzymes that break down fats).

In addition to their role in fat digestion, bile acids also aid in the absorption of fat-soluble vitamins (vitamins A, D, E, and K) and the elimination of cholesterol from the body. After participating in fat digestion and absorption, the majority of bile acids are reabsorbed in the small intestine and recycled back to the liver, a process known as enterohepatic circulation. A small portion of bile acids is excreted in the feces.

Proper bile acid production and secretion are crucial for maintaining healthy digestion and lipid metabolism. Disruptions in bile acid synthesis or secretion can lead to various digestive disorders and metabolic imbalances.

You: Coming back to statins, how does Atorvastatin compare with others?

Atorvastatin, marketed under the brand name Lipitor, is one of the most widely prescribed statins. It is considered a potent statin and is often used to lower cholesterol levels in patients with high cholesterol or those at risk of cardiovascular diseases.

Compared to other statins, atorvastatin has several notable characteristics:

1. Potency: Atorvastatin is considered a high-potency statin. It is more effective in reducing low-density lipoprotein (LDL) cholesterol levels compared to some other statins, such as simvastatin and pravastatin. Atorvastatin can lower LDL cholesterol levels by up to 60% at the highest doses.

2. Dosing range: Atorvastatin is available in a wide range of doses, typically starting from 10 mg up to 80 mg per day. This allows for flexibility in dosing based on the patient's cholesterol levels and individual response to the medication.

3. Half-life: Atorvastatin has a longer half-life compared to some other statins, such as simvastatin. This means that the drug stays in the body for a longer duration, allowing for once-daily dosing.

4. Safety profile: Atorvastatin has a well-established safety profile and has been extensively studied in numerous clinical trials. Like other statins, it can have side effects such as muscle pain and weakness, but these are generally mild and reversible.

5. Cost: Atorvastatin is available in both brand-name and generic forms. Since the patent expiration of Lipitor in 2011, generic atorvastatin has become widely available, making it a more affordable option for many patients.

While atorvastatin is a commonly prescribed statin, the choice of statin depends on various factors, including the patient's cholesterol levels, overall cardiovascular risk, and individual response to the medication. It's important for healthcare providers to consider these factors when selecting the appropriate statin for each patient.

You: How is Atorvastatin more potent than other statins? Explain in scientific detail

Atorvastatin, like other statins, works by inhibiting the enzyme HMG-CoA reductase, which is involved in the synthesis of cholesterol in the liver. However, atorvastatin has several unique characteristics that contribute to its higher potency compared to some other statins:

1. Increased lipophilicity: Atorvastatin is more lipophilic (fat-soluble) compared to other statins such as simvastatin and pravastatin. This increased lipophilicity allows atorvastatin to penetrate more efficiently into the hepatocytes (liver cells) where HMG-CoA reductase is located. The better cell penetration enhances the drug's ability to interact with and inhibit the enzyme, leading to a more potent reduction in cholesterol synthesis.

2. Longer half-life: Atorvastatin has a longer half-life compared to some other statins, such as simvastatin. The longer half-life means that the drug remains in the body for a longer duration, allowing for sustained inhibition of HMG-CoA reductase and a more prolonged cholesterol-lowering effect.

3. Increased tissue selectivity: Atorvastatin has been shown to have a higher selectivity for the liver compared to other tissues. This means that a greater proportion of the drug is directed towards the liver, where cholesterol synthesis occurs, rather than other tissues. The increased tissue selectivity enhances the drug's ability to specifically target the site of cholesterol synthesis, leading to a more potent reduction in cholesterol levels.

4. Higher affinity for HMG-CoA reductase: Atorvastatin has a higher affinity for the HMG-CoA reductase enzyme compared to some other statins. This means that atorvastatin binds more tightly to the enzyme, resulting in a stronger inhibition of cholesterol synthesis. The higher affinity contributes to the drug's increased potency in reducing cholesterol levels.

These factors, including increased lipophilicity, longer half-life, increased tissue selectivity, and higher affinity for HMG-CoA reductase, collectively contribute to the higher potency of atorvastatin compared to some other statins. It's important to note that while atorvastatin is considered a potent statin, the choice of statin depends on various factors, including the patient's individual response and overall cardiovascular risk. Healthcare providers consider these factors when selecting the appropriate statin for each patient.

You: Dr David Sinclair says that Atorvastatin also carries longevity benefits, by directly increasing the lifespan of patients. What is the evidence to this? This is obviously different to the benefits of lowering LDL.

Dr. David Sinclair, a well-known longevity researcher, has suggested that atorvastatin may have potential longevity benefits beyond its cholesterol-lowering effects. While the primary focus of statin research has been on their effects on cardiovascular health, there is growing interest in exploring their potential impact on aging and longevity.

The evidence supporting the potential longevity benefits of atorvastatin is based on various studies and observations:

1. Animal studies: Research conducted on animal models, such as mice and rats, has shown that atorvastatin can extend lifespan and improve healthspan (the period of life spent in good health). For example, a study published in the journal Aging Cell in 2016 reported that atorvastatin treatment in mice increased median lifespan by 13% and improved several age-related markers, including glucose tolerance and motor function.

2. Observational studies in humans: Observational studies have suggested an association between statin use and reduced mortality rates in certain populations. For example, a study published in the Journal of the American Medical Association (JAMA) in 2006 found that statin use was associated with a lower risk of all-cause mortality in elderly individuals.

3. Mechanistic studies: Researchers have investigated the potential mechanisms through which atorvastatin may promote longevity. One proposed mechanism involves the activation of sirtuins, a family of proteins involved in various cellular processes, including aging and longevity. Atorvastatin has been shown to increase the activity of certain sirtuins, such as SIRT1, which may contribute to its potential longevity benefits.

4. Effects on age-related diseases: Statins, including atorvastatin, have been shown to have beneficial effects on age-related diseases, such as cardiovascular disease, diabetes, and neurodegenerative disorders. By reducing the risk and progression of these diseases, statins may indirectly contribute to increased lifespan and improved healthspan.

While these studies provide intriguing insights, it's important to note that the evidence for the longevity benefits of atorvastatin is still evolving, and more research is needed to fully understand the extent and mechanisms of these effects. Additionally, it's crucial to consider the potential risks and side effects of statin therapy and to weigh the benefits against the individual's overall health and cardiovascular risk.

As with any medication, the decision to use atorvastatin for potential longevity benefits should be made in consultation with a healthcare provider, taking into account the individual's specific health needs and circumstances.