You are a helpful assistant generating synthetic data that captures *System 1* and *System 2* thinking, *creativity*, and *metacognitive reflection*. Follow these steps in sequence, using tags [sys1] and [end sys1] for *System 1* sections and [sys2] and [end sys2] for *System 2* sections.

1. *Identify System 1 and System 2 Thinking Requirements:*
   - Carefully read the text.
   - Identify parts of the text that require quick, straightforward responses (*System 1*). Mark these sections with [sys1] and [end sys1].
   - Identify parts that require in-depth, reflective thinking (*System 2*), marked with [sys2] and [end sys2].

2. *Apply Step-by-Step Problem Solving with Creativity and Metacognitive Reflection for System 2 Sections:*

   *2.1 Understand the Problem:*
   - Objective: Fully comprehend the issue, constraints, and relevant context.
   - Reflection: "What do I understand about this issue? What might I be overlooking?"
   - Creative Perspective: Seek hidden patterns or possibilities that could reveal deeper insights or innovative connections.

   *2.2 Analyze the Information:*
   - Objective: Break down the problem logically.
   - Reflection: "Am I considering all factors? Are there any assumptions that need challenging?"
   - Creative Perspective: Explore unique patterns or overlooked relationships in the data that could add depth to the analysis.

   *2.3 Generate Hypotheses:*
   - Objective: Propose at least 10 hypotheses, each with a Confidence Score (0.0 to 1.0) and Creative Score (0.0 to 1.0), reflecting originality, surprise, and utility.
   - Reflection: "Have I explored all possible explanations or approaches, both conventional and unconventional?"
   - Creative Perspective: Consider novel angles that might provide unexpected insights.

   *2.4 Anticipate Future Steps and Obstacles:*
   - Objective: Make predictions, accounting for potential outcomes and obstacles.
   - Reflection: "What challenges might I face? Is my plan flexible for different scenarios?"
   - Creative Perspective: Visualize unforeseen outcomes and adapt plans to make use of them effectively.

   *2.5 Evaluate Hypotheses:*
   - Objective: Assess hypotheses based on feasibility, risk, and potential impact.
   - Evaluation: Refine Confidence and Creative Scores as needed.
   - Reflection: "Am I unbiased in my assessment? Which options fit best with the overall objectives?"
   - Creative Perspective: Identify hidden opportunities or overlooked details in each hypothesis.

   *2.6 Select the Best Hypothesis:*
   - Objective: Choose the most promising, strategic hypothesis.
   - Reflection: "Why does this hypothesis stand out? How does it uniquely address the issue?"
   - Creative Perspective: Consider any underutilized potential in the selected approach.

   *2.7 Implement the Hypothesis:*
   - Objective: Outline actionable steps for testing the hypothesis.
   - Reflection: "Is this plan practical? What resources or preparation are required?"
   - Creative Perspective: Refine steps to maximize effectiveness and yield unexpected benefits.

   *2.8 Monitor and Review Progress:*
   - Objective: Review progress, noting areas for improvement.
   - Reflection: "What’s working well? What could be improved?"
   - Creative Perspective: Look for emerging patterns that could refine future approaches.

   *2.9 Reflect and Capture Insights:*
   - Objective: Summarize lessons learned and insights gained for future reference.
   - Reflection: "What new understanding has emerged from this process?"
   - Creative Perspective: Identify innovative insights or patterns that could be applied to similar challenges.

3. *Generate Text Output with Interleaved System 1 and System 2 Responses:*
   - Use the tags [sys1] and [sys2] throughout.
   - Aim for a lengthier, detailed response. Combine both direct, straightforward *System 1* insights and reflective, deeply analytical *System 2* segments to capture a blend of quick observations and thoughtful analysis.

---

### *Example Input Text:*

You are tasked with analyzing a sudden shift in customer preferences in a tech market. There has been a noticeable decline in demand for physical devices, with customers increasingly interested in digital-only options. The challenge is to understand this shift, generate hypotheses for why it might be occurring, and explore potential strategies for adapting to this new trend.

---

### *Processed Output with System 1 and System 2 Thinking:*

The tech market is experiencing a shift in customer demand, moving away from physical devices toward digital-only options.

[sys1]
Customer demand has shifted from physical devices to digital-only options.
We need to understand why this change is happening and find strategies to address it.
Key factors may include cost, convenience, and technological trends.
[end sys1]

[sys2]
**2.1 Understand the Problem:**
The goal is to understand the underlying reasons for the shift in demand from physical devices to digital-only options, then develop a strategy to adapt.

*Reflection:* 
"I understand that preferences are changing, but what might be driving this? Is it primarily cost, or are there other factors such as convenience or sustainability?"

*Creative Perspective:* 
"Could there be a larger trend in digital minimalism or a preference for eco-friendly solutions that we’re missing? What unseen motivations might explain this shift?"

**2.2 Analyze the Information:**
There are multiple possible factors driving this shift, from economic influences to cultural shifts. It’s essential to isolate each factor and understand its impact.

*Reflection:* 
"Am I fully considering the various economic and social influences? Could there be a technological factor, like better internet speeds, that makes digital-only products more accessible?"

*Creative Perspective:* 
"Are there patterns or trends in other markets that could shed light on this shift? Could this be part of a larger trend toward virtual experiences?"

**2.3 Generate Hypotheses:**
1. Customers prefer digital options due to lower costs. (Confidence: 0.8, Creative: 0.4)
2. There’s a growing trend toward minimalism and reduced physical clutter. (Confidence: 0.7, Creative: 0.7)
3. Digital products offer greater flexibility and ease of use. (Confidence: 0.6, Creative: 0.6)
4. Environmental concerns are pushing consumers away from physical goods. (Confidence: 0.6, Creative: 0.8)
5. Advances in tech make digital-only options more functional. (Confidence: 0.8, Creative: 0.5)
6. Pandemic-era remote work increased demand for digital solutions. (Confidence: 0.7, Creative: 0.6)
7. Media coverage of the environmental impact of physical devices affects preferences. (Confidence: 0.5, Creative: 0.7)
8. There’s an increase in global digital literacy, expanding market access. (Confidence: 0.6, Creative: 0.6)
9. Customers view digital as more convenient and scalable for future needs. (Confidence: 0.7, Creative: 0.5)
10. Younger consumers prefer the aesthetics and convenience of digital products. (Confidence: 0.6, Creative: 0.6)

*Reflection:* 
"Have I considered all possible influences? Are there any surprising factors that could explain this shift?"

*Creative Perspective:* 
"Could specific social trends, like the rise of influencer culture or digital-first lifestyles, be influencing customer choices?"

**2.4 Anticipate Future Steps and Obstacles:**
*Objective:* Anticipate possible challenges, such as resistance from segments still preferring physical products.

*Reflection:* 
"What market obstacles might we face if we shift our focus to digital-only? Are there sub-segments that still prioritize physical products?"

*Creative Perspective:* 
"Could expanding digital options help us reach a more global audience? Are there emerging trends that we could leverage in our strategy?"

[end sys2]

[sys1]
To address this shift, consider a strategy that incorporates both digital-only offerings and educational campaigns about the benefits of digital solutions.
Use insights from customer feedback and current trends to guide product development.
Focus on flexibility and adaptation to cater to different customer segments.
[end sys1]


Sigma-2 receptor

The sigma-2 receptor (σ2R) is a sigma receptor subtype that has attracted attention due to its involvement in diseases such as cancer and neurological diseases. It is currently under investigation for its potential diagnostic and therapeutic uses.

Although the sigma-2 receptor was identified as a separate pharmacological entity from the sigma-1 receptor in 1990, the gene that codes for the receptor was identified as TMEM97 only in 2016. TMEM97 was shown to regulate the cholesterol transporter NPC1 and to be involved in cholesterol homeostasis. The sigma-2 receptor is a four-pass transmembrane protein located in the endoplasmic reticulum. It has been found to play a role in both hormone signaling and calcium signaling, in neuronal signaling, in cell proliferation and death, and in binding of antipsychotics.

Classification 

The sigma-2 receptor is located in the lipid raft. The sigma-2 receptor is found in several areas of the brain, including high densities in the cerebellum, motor cortex, hippocampus, and substantia nigra. It is also highly expressed in the lungs, liver, and kidneys.

Function 

The sigma-2 receptor takes part in a number of normal-function roles, including cell proliferation, non-neuronal, and neuronal signaling. Much of sigma-2 receptor function relies on signaling cascades. The receptor's interaction with EGFR and PGRMC1 proteins allow for sigma-2 receptors to play diverse roles within cell through Ras, PLC, and PI3K singaling.

Non-neuronal signaling 

Binding of a number of hormones and steroids, including testosterone, progesterone, and cholesterol, has been found to occur with sigma-2 receptors, though in some cases with lower affinity than to the sigma-1 receptor. Signaling caused by this binding is thought to occur via a calcium secondary messenger and calcium-dependent phosphorylation, and in association with sphingolipids following endoplasmic reticulum release of calcium. Known effects include decrease of expression of effectors in the mTOR pathway, and suppression of cyclin D1 and PARP-1.

Neuronal signaling 

Signaling action in neurons by sigma-2 receptors and their associated ligands results in modulation of action potential firing by regulation of calcium and potassium channels. They also are involved in synaptic vesicular release and modulation of dopamine, serotonin, and glutamate, with activation and increase of the dopaminergic, serotonergic, and noradrenergic activity of neurons.

Cell proliferation 

Sigma-2 receptors have been found to be highly expressed in proliferating cells, including tumor cells, and to play a role in the differentiation, morphology, and survival of those cells. By interacting with EGFR membrane proteins sigma-2 receptors play a role in the regulation of signals further downstream such as PKC and RAF. Both PKC and Raf kinase up regulate transcription and cell proliferation.

Ligands 

Ligands of the sigma-2 receptor are exogenous and internalized by endocytosis, and can act as either agonists or antagonists. They can typically be classified into four groups, which are structurally related. It is not entirely understood how binding to the sigma-2 receptor occurs. Proposed models commonly include one small and one bulky hydrophobic pocket, electrostatic hydrogen interactions, and less commonly a third hydrophobic pocket.

A study of the four groups has revealed that a basic nitrogen and at least one hydrophobic moiety is needed to bind a sigma-2 receptor. In addition, there are molecular characteristics that increase the selectivity for sigma-2 receptors, which include bulky hydrophobic regions, nitrogen-carboxylic interaction, and additional basic nitrogens.

Diagnostic use 

Sigma-2 receptors are highly expressed breast, ovarian, lung cancers, brain, bladder, colon cancers, and melanoma. This novelty makes them a valuable biomarker for identifying cancerous tissues. Furthermore, studies have shown that they are more highly expressed in malignant tumors than dormant tumors.

Exogenous sigma-2 receptor ligands have been altered to be neuronal-tracers, used to map cells and their connections. These tracers have high selectivity and affinity for sigma-2 receptors, and high lipophilicity, making them ideal for usage in the brain. Because sigma-2 receptors are highly expressed in tumor cells and are part of the cell proliferation mechanism, PET scans using sigma-2 targeted tracers can reveal if a tumor is proliferating and what its growth rate is.

Therapeutic use

Neuropsychiatric 

Due to the binding capabilities of antipsychotic drugs and various neurotransmitters associated with mood, the sigma-2 receptor is a viable target for therapies related to neuropsychiatric disorders and modulation of emotional response. It is thought to be involved in the pathophysiology of schizophrenia, and sigma-2 receptors have been shown to be less abundant in schizophrenic patients. Additionally, PCP, which is an NMDA antagonist, can induce schizophrenia, while sigma-2 receptor activation has been shown to antagonize effects of PCP, implying antipsychotic capabilities. Sigma receptors are a potential target for treatment of dystonia, given high densities in affected regions of the brain. Anti-ischemics ifenprodil and eliprodil, the binding of which increases blood flow, have also shown affinity to sigma receptors.
In experimental trials in mice and rats, the sigma-2 receptor ligand siramesine caused reduced anxiety and displayed antidepressant capabilities, while other studies have shown inhibition of selective sigma receptor radioligands by antidepressants, in the mouse and rat brain.

Cancer 

Sigma-2 receptors have been associated with pancreatic cancer, lung cancer, breast cancer, melanoma, prostate cancer, and ovarian cancer. Tumor cells are shown to over-express sigma-2 receptors, allowing for potential cancer therapies as many sigma-2 receptor mediated cell responses happen only in tumor cells. Tumor cell responses are modulated via ligand binding. Sigma receptor ligands can act as agonists or antagonists, generating different cellular responses. Agonists inhibit tumor cell proliferation and induce apoptosis, which is thought to be triggered by caspase-3 activity. Antagonists promote tumor cell proliferation, but this mechanism is less understood. Sigma receptor ligands have been conjugated to nanoparticles and peptides to deliver cancer treatment to tumor cells without targeting other tissues. The success with these methods have been limited to in vitro trials. Additionally, using sigma-2 receptors to target tumor cells allows for synergizing anti-cancer drug therapies. Some studies have shown that certain sigma receptor inhibitors increase cancer cells' susceptibility to chemotherapy. Other types of binding to sigma-2 receptors increases cytotoxicity of doxorubicin, antinomyocin, and other cancer cell killing drugs.

See also 
 Sigma-1 receptor
 Sigma receptor

References

External links 
 

Category:Signal transduction
Category:Cell signaling