GPT2 Human, Active

Glutamic-Pyruvate Transaminase 2 Human Recombinant, Active
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Description

Biochemical Properties and Production

GPT2 Human, Active is engineered as a single polypeptide chain fused with a 23-amino acid His-tag for purification. Key specifications include:

PropertyDescription
Molecular Weight60.3 kDa
Amino Acid Sequence546 amino acids (residues 1–523) with an N-terminal His-tag
Purity>90% (confirmed via SDS-PAGE)
Formulation0.5 mg/mL in 20 mM Tris-HCl (pH 7.5), 30% glycerol, 0.2 M NaCl, 2 mM DTT
ActivityConfirmed via transamination assays under standardized conditions

The enzyme is expressed in E. coli and purified using chromatographic techniques, ensuring high stability and activity retention .

Metabolic Functions

  • Amino Acid Metabolism: Facilitates the interconversion of alanine and 2-oxoglutarate, linking carbohydrate and nitrogen metabolism .

  • Neurotransmitter Regulation: Modulates glutamate levels, impacting excitatory neurotransmission and brain development .

  • TCA Cycle Support: Generates pyruvate and α-ketoglutarate, critical intermediates for mitochondrial energy production .

Disease Associations

  • Cancer:

    • Overexpression in breast cancer correlates with tumorigenesis and stemness by stabilizing HIF-1α and activating Shh signaling .

    • Hypoxia-induced GPT2 in glioblastoma promotes cell migration via integrin signaling .

  • Neurological Disorders:

    • Homozygous mutations (e.g., G96R) impair enzyme activity, leading to developmental encephalopathy and intellectual disability .

    • Mouse models show GPT2 loss causes motor deficits and premature death, highlighting its role in neuronal growth .

Key Studies

  1. Breast Cancer Mechanisms (2017):

    • GPT2 overexpression increased colony formation in MDA-MB-231 cells by 3.5-fold, while knockdown reduced it by 70% .

    • Mechanistic link: GPT2 depletion lowered α-ketoglutarate levels, destabilizing HIF-1α and inhibiting Shh signaling .

  2. Glioblastoma Hypoxia Response (2022):

    • Hypoxia (1% O₂) upregulated GPT2 mRNA by 4.2-fold in U251MG cells via HIF-2α binding to a hypoxia-response element .

    • GPT2 knockout reduced cell migration by 60% under low oxygen .

  3. Neurodevelopmental Defects (2019–2022):

    • GPT2 mutations reduced intracellular glutamate by 40% in patient-derived neurons, impairing synaptic function .

    • Conditional GPT2 deletion in mice caused spastic paraplegia-like motor deficits and disrupted TCA cycle metabolites .

Clinical and Therapeutic Implications

  • Biomarker Potential: Elevated serum GPT2 correlates with metabolic syndrome and liver dysfunction .

  • Therapeutic Targets:

    • Inhibiting GPT2 in cancer models reduced tumor growth by 80% in xenografts .

    • Small-molecule activators of α-ketoglutarate could mitigate GPT2-related neurological deficits .

Product Specs

Introduction
Alanine aminotransferase 2 (GPT2) is an enzyme that facilitates the reversible transamination between alanine and 2-oxoglutarate, resulting in the production of pyruvate and glutamate. GPT2 is primarily found in muscle, fat, and kidney tissues and plays a role in the metabolism of glucose and amino acids. There are multiple transcript variants of GPT2, which encode different isoforms of the enzyme.
Description
Recombinant human GPT2, produced in E. coli, is a single polypeptide chain with a molecular weight of 60.3 kDa. It consists of 546 amino acids, including a 23 amino acid His-tag at the N-terminus (amino acids 1-523). The protein is purified using proprietary chromatographic techniques.
Physical Appearance
A clear, colorless solution that has been sterilized by filtration.
Formulation
The GPT2 solution has a concentration of 0.5 mg/ml and is supplied in a buffer containing 20mM Tris-HCl (pH 7.5), 30% glycerol, 2mM DTT, and 0.2M NaCl.
Stability
For short-term storage (up to 2-4 weeks), the product can be stored at 4°C. For long-term storage, it is recommended to store the product frozen at -20°C. The addition of a carrier protein (0.1% HSA or BSA) is recommended for long-term storage. Avoid repeated freeze-thaw cycles.
Purity
The purity of the protein is greater than 90% as determined by SDS-PAGE analysis.
Biological Activity
The specific activity of the enzyme is greater than 100 units/mg. One unit of activity is defined as the amount of enzyme required to catalyze the conversion of 1 μmole of L-Alanine to L-Glutamate per minute at a pH of 7.5 and a temperature of 37°C.
Synonyms
ALT2, AAT2, Alanine aminotransferase 2, Glutamate pyruvate transaminase 2, Glutamic--alanine transaminase 2, Glutamic--pyruvic transaminase 2.
Source
E.coli.
Amino Acid Sequence
MGSSHHHHHH SSGLVPRGSH MGSMQRAAAL VRRGCGPRTP SSWGRSQSSA AAEASAVLKV RPERSRRERI LTLESMNPQV KAVEYAVRGP IVLKAGEIEL ELQRGIKKPF TEVIRANIGD AQAMGQQPIT FLRQVMALCT YPNLLDSPSF PEDAKKRARR ILQACGGNSL GSYSASQGVN CIREDVAAYI TRRDGGVPAD PDNIYLTTGA SDGISTILKI LVSGGGKSRT GVMIPIPQYP LYSAVISELD AIQVNYYLDE ENCWALNVNE LRRAVQEAKD HCDPKVLCII NPGNPTGQVQ SRKCIEDVIH FAWEEKLFLL ADEVYQDNVY SPDCRFHSFK KVLYEMGPEY SSNVELASFH STSKGYMGEC GYRGGYMEVI NLHPEIKGQL VKLLSVRLCP PVSGQAAMDI VVNPPVAGEE SFEQFSREKE SVLGNLAKKA KLTEDLFNQV PGIHCNPLQG AMYAFPRIFI PAKAVEAAQA HQMAPDMFYC MKLLEETGIC VVPGSGFGQR EGTYHFRMTI LPPVEKLKTV LQKVKDFHIN FLEKYA.

Q&A

Basic Research Questions

  • What is GPT2 and how does it function in natural language processing contexts?

GPT2 is an unsupervised deep learning transformer-based language model developed by OpenAI in February 2019, designed specifically for predicting the next word(s) in a text sequence. The model functions through a generative pre-trained transformer architecture that processes natural language by analyzing patterns in vast quantities of unlabeled text data .

GPT2 operates by generating text either through zero-shot generation (using the model "out of the box") or after fine-tuning on specific datasets to produce particular styles of text. The model can process and generate human-like text across multiple domains due to its diverse training data, enabling it to perform various language tasks such as reading comprehension, summarization, and translation without domain-specific training .

The transformer architecture utilizes self-attention mechanisms that weigh the importance of different words in the input sequence, allowing it to capture long-range dependencies and contextual relationships in text. This ability to maintain context over extended sequences distinguishes it from earlier language models and contributes to its more coherent and contextually appropriate text generation capabilities.

  • What are the core parameters and training methodologies behind GPT2?

GPT2 was trained on over 1.5 billion parameters using a diverse dataset of internet text. OpenAI developed several versions with increasing parameter sizes: 124 million, 355 million, 774 million, and 1.5 billion parameters . This staged approach to model development allowed researchers to study how performance scales with model size.

The training methodology employed unsupervised learning on a dataset called WebText, which contains approximately 8 million documents (40GB of text) from web pages with high-quality content. The training process involved predicting the next word in a sentence given all previous words, optimizing the model through backpropagation.

GPT2 VersionParameter SizeRelease Timeline
Small124 millionFebruary 2019
Medium355 millionMay 2019
Large774 millionAugust 2019
Extra Large1.5 billionDelayed release

This architecture enables GPT2 to process text and maintain coherence over longer passages, making it particularly effective for human-like text generation tasks .

  • What detection methods exist for identifying GPT2-generated text?

Several approaches have been developed for detecting text generated by GPT2. These detection methodologies range from statistical analysis to machine learning classifiers and human evaluation protocols. Research acknowledges the importance of reliable detection as a safeguard against potential misuse.

Statistical detection methods analyze linguistic patterns that distinguish machine-generated text from human writing, examining:

  • Distribution of word frequencies

  • Sentence structure variability

  • Use of rare or uncommon phrases

  • Consistency of style throughout a document

Machine learning approaches train classifiers on datasets containing both human and GPT2-generated text. The University of Texas at Austin conducted research on the statistical detectability of GPT2 outputs, particularly examining how detection effectiveness transfers across different language models .

Human detection capabilities have been systematically studied, revealing that the quality of GPT2 outputs increases with model size up to at least the 774 million parameter version. Research suggests that humans can be deceived by carefully selected GPT2 outputs, highlighting the need for combined automated and human-based detection strategies .

Detection ApproachMethodologyEffectiveness
Statistical AnalysisPattern recognition in text featuresModerate
ML ClassificationTrained on human/AI text examplesHigh for known models
Human EvaluationExpert review with specific criteriaVariable by expertise
Combined MethodsIntegrated statistical and human reviewMost robust
  • What are the documented limitations of GPT2 in processing human language?

GPT2 exhibits several documented limitations in its processing and generation of human language, which researchers must consider when utilizing the model for experiments.

Fundamental limitations include generating repetitive text patterns, particularly when producing longer passages. The model can become trapped in loops, repeating phrases or concepts, which diminishes the naturalness of its outputs . This repetition tendency increases with the length of generated text.

Technical understanding represents another significant limitation. GPT2 demonstrates inconsistent comprehension of specialized and technical topics, often producing text that appears superficially coherent but contains factual inaccuracies or conceptual contradictions . This limitation becomes particularly evident in scientific or mathematical contexts.

Contextual understanding poses challenges for GPT2, especially with:

Contextual ChallengeDescriptionResearch Implication
Ambiguous ReferencesDifficulty resolving unclear pronounsRequires explicit experimental design
Figurative LanguageLimited processing of metaphorsMay misinterpret non-literal instructions
Implicit KnowledgeInability to access unstated informationNecessitates comprehensive prompting
Temporal ReasoningChallenges with time relationshipsAffects longitudinal experimental designs

Additionally, GPT2 exhibits biases present in its training data, potentially reproducing stereotypes found in internet text sources. This limitation raises ethical concerns regarding the model's use in research contexts where fairness is crucial .

  • How effective are fine-tuning techniques in adapting GPT2 for domain-specific research applications?

Fine-tuning GPT2 for domain-specific applications has proven to be an effective adaptation strategy, allowing researchers to tailor the model's capabilities to specialized contexts. The effectiveness varies by domain, dataset quality, and methodological approach.

Evidence from multiple applications demonstrates that fine-tuning can significantly enhance performance in targeted domains. GPT2 has been successfully fine-tuned for biomedical literature analysis, generating synthetic test data, and creating specialized reports in fields such as radiology and EEG analysis . These applications show meaningful improvements in domain relevance compared to the base model.

Software engineering represents a notable success area, with fine-tuned GPT2 models demonstrating effective code autocompletion capabilities. Deep TabNine, trained on approximately two million GitHub files, illustrates how fine-tuning can produce practical research tools that enhance developer workflows .

Research DomainFine-Tuning ApproachOutcome Assessment
Biomedical LiteratureDomain corpus trainingImproved term recognition and relationships
Medical DiagnosticsAnnotated report datasetsEnhanced report structure and terminology
Programming LanguagesGitHub code repositoriesAccurate syntax completion and documentation
Creative WritingLiterary corpus adaptationStyle-specific generation capabilities

Research indicates that smaller, well-targeted training datasets can achieve effective domain adaptation, making fine-tuning accessible to researchers with limited computational resources .

Advanced Research Questions

  • What methodologies have proven most effective for evaluating human perception of GPT2-generated content?

Evaluating human perception of GPT2-generated content requires rigorous methodological approaches that assess both objective detection capabilities and subjective quality judgments. Research has employed various experimental designs with different strengths and limitations.

Comparative evaluation protocols have demonstrated effectiveness in assessing perceived quality. These typically present human evaluators with pairs of texts (one human-authored, one GPT2-generated) and request judgments about which is machine-generated or which exhibits higher quality. Cornell University researchers employed this approach to study human susceptibility to digital disinformation generated by language models, finding that carefully selected GPT2 outputs could be perceived as credible by human evaluators .

Blind evaluation studies remove potential bias by presenting text without indicating its source. Researchers at the Middlebury Institute implemented this approach when studying potential extremist content generation, allowing for unbiased assessment of how convincing the generated content appeared .

Evaluation ProtocolExperimental DesignAssessment Metrics
A/B TestingDirect comparison of human/AI textsAccuracy of source identification
Likert Scale RatingsMulti-dimensional quality assessmentPerceived naturalness, coherence, fluency
Confidence MeasurementAttribution with certainty ratingsRelationship between accuracy and confidence
Time-based AssessmentLimited exposure duration studiesDetection accuracy under time constraints

Research findings consistently indicate that human detection ability decreases as model size increases, with the 774 million parameter GPT2 model producing text that humans find significantly more difficult to distinguish from human-authored content than smaller models .

  • How can researchers implement active learning protocols to improve GPT2's performance in specialized knowledge domains?

Implementing active learning protocols with GPT2 for specialized knowledge domains requires systematic approaches that strategically select training examples to maximize performance improvements while minimizing computational costs. Effective protocols combine model-driven sample selection with human domain expertise.

The core methodology involves an iterative process where the model identifies areas of uncertainty or knowledge gaps, and then receives targeted training examples to address these specific deficiencies. This approach differs from standard fine-tuning by prioritizing the most informative examples rather than processing the entire dataset.

A recommended active learning implementation framework includes:

  • Initial model evaluation on domain-specific validation sets to identify baseline performance

  • Uncertainty sampling to identify examples where the model has low confidence predictions

  • Diversity sampling to ensure broad coverage of the domain's conceptual space

  • Expert annotation and validation of selected training examples

  • Incremental fine-tuning on the curated examples

  • Repeated evaluation to measure improvement and identify next areas for focus

Active Learning StrategyImplementation MethodResearch Application
Uncertainty SamplingEntropy-based prediction analysisIdentifying knowledge boundaries
Diversity SelectionRepresentation-based clusteringEnsuring domain coverage
Committee ApproachesMultiple model variant consensusReducing individual model bias
Human-in-the-LoopExpert validation of critical examplesEnsuring factual accuracy

Research applications have successfully employed active learning to enhance GPT2's capabilities in specialized domains such as medical question-answering systems and grammatical error correction . These implementations demonstrate that targeted example selection can achieve comparable performance to full-dataset fine-tuning while using significantly fewer examples.

  • What approaches have shown promise in mitigating encoded biases in GPT2 outputs for research applications?

Mitigating encoded biases in GPT2 outputs represents a significant research challenge requiring multi-faceted approaches. Several promising methodologies have emerged from ongoing research efforts in this domain.

Systematic bias identification forms the foundation of effective mitigation strategies. The University of Oregon developed a series of "bias probes" to analyze bias within GPT2, creating structured evaluation frameworks to identify problematic patterns in model outputs . These probes provide researchers with tools to quantify and characterize various forms of bias, from gender and racial stereotypes to more subtle representational disparities.

Once biases are identified, several technical approaches show promise for mitigation:

Bias Mitigation ApproachMethodological ImplementationEffectiveness Assessment
Dataset AugmentationCounterfactual example generationReduces specific targeted biases
Controlled GenerationConstraint-based output filteringEffective for known bias patterns
Fine-tuning InterventionBalanced corpus retrainingMost comprehensive approach
Post-processingStatistical detection and modificationQuick implementation for known biases

Research indicates that combining multiple approaches yields more comprehensive bias mitigation than any single technique. Documented challenges include trade-offs between reducing bias and maintaining general performance, difficulty in addressing intersectional biases, and the risk of introducing new biases when correcting for known ones .

  • How do contextual factors influence human susceptibility to GPT2-generated disinformation in experimental settings?

Research into human susceptibility to GPT2-generated disinformation reveals complex interactions between contextual factors, content characteristics, and individual differences. Understanding these influences is crucial for developing effective experimental controls and educational interventions.

Cornell University's research partnership with OpenAI investigated how contextual presentation affects perception of GPT2-generated content. Their findings indicate that cherry-picked fake content from GPT2 can appear credible to human evaluators, particularly when presented within familiar information formats or authoritative contexts .

Several key contextual factors have been identified as particularly influential in experimental settings:

Contextual FactorInfluence MechanismExperimental Finding
Source AttributionAuthority of claimed authorAttribution to trusted sources increases acceptance
Presentation FormatVisual and structural elementsProfessional formatting enhances perceived credibility
Prior BeliefsAlignment with existing viewpointsContent confirming prior beliefs faces less scrutiny
Information EnvironmentSurrounding contentEmbedding within legitimate content increases acceptance

Individual differences also moderate susceptibility, with variations based on factors including domain expertise, media literacy, cognitive reflection tendencies, and familiarity with AI capabilities. Research indicates that individuals with higher domain knowledge demonstrate greater ability to detect factual inconsistencies in generated content .

Methodological approaches for studying these factors typically involve experimental designs that systematically vary contextual elements while controlling for content characteristics, providing crucial insights for developing experimental controls in GPT2 research.

  • What experimental designs best evaluate the intersection of GPT2 capabilities with human cognitive processes?

Designing experiments that effectively evaluate how GPT2 capabilities interact with human cognitive processes requires methodological rigor and interdisciplinary approaches. Several experimental paradigms have demonstrated particular effectiveness in this research domain.

Comparative judgment tasks offer insight into how humans process and evaluate GPT2-generated content relative to human-authored text. These experimental designs typically involve presenting participants with text samples from different sources and collecting judgments about quality, credibility, coherence, or source attribution. Key findings indicate that as model size increases, human ability to distinguish sources decreases significantly .

Interactive experimental paradigms examine how humans engage with GPT2 in collaborative contexts, revealing insights about trust development, reliance patterns, and complementary capabilities. These approaches are particularly valuable for understanding how GPT2 might function in research assistance or augmentation contexts.

Experimental ParadigmResearch FocusMeasurement Approach
Turing-style TestsSource attribution accuracyBinary classification with confidence
Think-aloud ProtocolsCognitive processing differencesQualitative analysis of reasoning
Eye-tracking StudiesAttention patterns during readingFixation duration on anomalous content
Collaborative Writing TasksHuman-AI interaction dynamicsProcess and outcome measures

When designing experiments at this intersection, researchers should consider potential confounding variables including prior AI exposure, domain expertise, cognitive style differences, and demand characteristics. Controlling for these factors requires careful participant selection, counterbalanced designs, and appropriate statistical analyses .

Longitudinal experimental designs have shown particular promise for examining how human-GPT2 interactions evolve over time, revealing adaptation patterns and learning effects that may not be visible in single-session studies. These approaches are especially relevant for understanding how human trust and reliance on GPT2 systems develop in research contexts.

Product Science Overview

Gene and Protein Structure

The GPT2 gene is located on chromosome 16 at the band 16q11.2 . The gene encodes a pyridoxal phosphate-dependent enzyme, which is essential for its catalytic activity . The enzyme is predominantly expressed in tissues such as skeletal muscle, kidney, and liver, where it contributes to various metabolic processes .

Function and Biological Role

GPT2 is involved in several key biological processes, including:

  • Amino Acid Metabolism: It facilitates the conversion of alanine to pyruvate, which can then enter the citric acid cycle for energy production .
  • Gluconeogenesis: By generating pyruvate, GPT2 supports the synthesis of glucose from non-carbohydrate sources, which is vital during periods of fasting or intense exercise .
  • Metabolic Stress Response: The expression of GPT2 is upregulated by activating transcription factor 4 (ATF4) under metabolic stress conditions, particularly in hepatocyte cell lines .
Clinical Significance

Mutations in the GPT2 gene have been associated with developmental encephalopathy, a condition characterized by impaired brain development . Additionally, GPT2 activity is often measured in clinical settings as an indicator of liver health, as elevated levels can signify liver damage or disease .

Recombinant GPT2

Recombinant human GPT2 is produced using genetic engineering techniques, where the GPT2 gene is inserted into a suitable expression system, such as bacteria or yeast, to produce the active enzyme. This recombinant enzyme is used in various research and diagnostic applications to study its function and role in metabolic processes.

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