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]


Inner nuclear membrane protein

Inner nuclear membrane (INM) proteins are proteins that are embedded in or associated with the inner membrane of the nuclear envelope (NE). There are about 60 INM proteins, most of which are poorly characterized with respect to structure and function. Among the few well-characterized INM proteins are lamin B receptor (LBR), lamina-associated polypeptide 1 (LAP1), lamina-associated polypeptide-2 (LAP2), emerin and  MAN1.

Common structural features
Several integral nuclear membrane proteins of different size and structure have been identified. It is proposed that they share some structural features with respect to nucleoplasmic domain(s) and lipid-soluble domain(s). Some INM proteins contain common protein domain structures, and can thus be categorised into known protein domain families. These include the LEM-, SUN-, and KASH-domain families. Members of the LEM-domain family play a part in chromatin organisation. SUN- and KASH-domains participate in linking the cytoskeleton and nucleoskeleton through the LINC complex.

Function
Lamins and chromatin found at the nuclear envelope are organised with the assistance of proteins embedded in the INM. INM proteins also aid in organization of nuclear pore complexes (NPCs). The protein mPom121 is targeted to the INM and is necessary for NPC formation. Proteins containing the LEM domain, such as emerin, LAP2β and MAN1, seem to have a number of roles. They interact with the barrier-to-autointegration factor (BAF). and help to repress gene expression, both by tethering specific genomic regions to the nuclear periphery, and by interaction with histone deacetylase (HDAC) 3.

Synthesis and translocation
There are several proteins associated with the inner nuclear membrane. It is likely that the majority of them are also associated with the nuclear lamina. Some may interact directly with the nuclear lamina, and some may be associated with it through scaffold proteins. All INM proteins are arranged such that their N-termini is facing the nucleoplasm and targeted by various kinases. They are synthesized in one of three places; in the cytoplasm, the cytoplasmic ER, or the outer nuclear membrane (ONM). All require localisation to the INM. Since the outer nuclear membrane is continuous with the endoplasmic reticulum it is possible that the inner nuclear membrane proteins are translated on the rough endoplasmic reticulum, whereby the proteins move into the nucleus by lateral diffusion through a nuclear pore. In this model, proteins diffuse freely from the ER to the inner nuclear membrane, where association with nuclear lamina or chromatin immobilizes them. A nuclear localisation signal (NLS) is not sufficient to target a protein to the INM, and the N-terminal domain of LBR cannot translocate into the nuclear lumen if its size is increased from 22 to approximately 70 kDa, supporting this view. Current opinion is that INM proteins synthesised in the cytoplasm are transported to the INM through nuclear pore complexes (NPC).

Potential role in cell differentiation
It has been proposed that chromatin-binding/modifying proteins embedded within the inner nuclear membrane may be central in determining the identity of newly differentiated cells. The nucleoplasmic domains of such proteins can interact with chromatin to create a scaffold and restrict the conformation of chromosomes within three dimensions. Such inner-nuclear-membrane proteins (INMs) may function simply by restricting the movement of bound chromatin, by recruiting chromatin-remodeling proteins, or through inherent enzyme activity. INM:chromatin interactions causes some segments of chromatin to be more exposed to the nucleoplasm than others.

Once INM:chromatin interactions have been established following formation of the nuclear envelope, soluble nuclear proteins may bind to exposed chromosomal segments. Such proteins could include enzymes that modify histones—such as methylases and acetylases—which act to alter the three-dimensional conformation of chromatin, as well as DNA binding proteins—such as helicases, gyrases, and transcription factors—that are involved in unwinding/looping DNA and/or recruiting RNAP holoenzyme. This will promote the transcription of some genes and down-regulate or prevent transcription of others. Thus, the nuclear scaffold places limits on what genes can and can not be expressed within a given cell and, hence, may serve a basis for cell identity.

Once all regulatory proteins, etc. have been synthesized and the scaffold has been established, the cell has attained its own specific expression profile.  This allows it to synthesize cell-specific enzymes and receptors characteristic of its particular function.  The nuclear scaffold is predicted to be relatively permanent for a given cell type, but induction of a signaling pathway—by ligand binding, cell:cell contact, or some other mechanism—can temporarily shift the expression profile. When such a signal changes expression of genes coding for INM or a chromatin-modifying enzymes, it can induce differentiation in to a different cell type. Thus, the Nuclear Scaffold Theory predicts that symmetric cell division occurs when a daughter cell contains the same complement of INMs as the parent cell. Conversely, asymmetric cell division is expected to result in parent and daughter cells with different INM profiles.

The INM profile of closely related cells (e.g., CD4+ TH1 and TH2 helper T-cells) is expected to be more similar than for cells that are more distantly related (e.g., T-cells and B-cells). The degree of INM complementarity is expected to be roughly proportional to the degree of relatedness (e.g., % complementarity to TH1 helper T-cells will be: TH2 > CD8+ > B-cell > Erythrocyte > cardiomyocyte). Some cells that are very closely related may have similar INMs, but transient changes in expression—e.g., in response to extracellular signals—could possibly lead to more permanent changes in expression profile by altering transcription rates for chromatin modifying enzymes, transcriptional modulators, or other regulatory proteins.

Examples
 Emerin
 Lamina-associated polypeptides 1 and 2 (LAP1, LAP2)
 Lamin B receptor (LBR)
 MAN1
 Nurim
 Dpy19L1 to L4

Posttranslational modifications
Posttranslational modifications of INM proteins play a critical role in their functional modulation. For example, lamin B receptor, lamina-associated polypeptide 1 and lamina-associated polypeptide 2 are targets for different protein kinases. Arginine and serine residues phosphorylation control LBR's interaction with other subunits of the LBR complex and was proposed to modulate the interaction with chromatin.

Disease

Laminopathies

The wide array of diseases involving lamins and their associated inner nuclear membrane proteins are collectively called laminopathies. Mutations in the gene EDM, encoding the INM protein emerin may be the cause of X-linked Emery–Dreifuss muscular dystrophy. As mutations in lamins cause the autosomal dominant form of Emery–Dreifuss muscular dystrophy, and lamins and emerin are known to interact, it has been hypothesised that muscle disease is caused by a structural defect in the NE brought on by dysfunction in one of these proteins. Mutations in the gene LBR, encoding lamin B receptor, causes Pelger-Hüet anomaly.

Cancer

Tumor cells often show an aberrant nuclear structure, which is used by pathologists in diagnostics. As changes in the nuclear envelope correspond to functional changes in the nucleus, morphological changes in the nucleus may be involved in carcinogenesis. The regulatory functions of inner nuclear membrane proteins strongly suggest this possibility.

See also
 Integral membrane protein
 Laminopathy
 Transmembrane protein

References

Category:Proteins