HTF Human
Description
Introduction to Human Transferrin (HTF)
HTF is an 80 kDa glycoprotein comprising 679 amino acids, structured into two lobes (N- and C-lobes) that bind Fe³⁺ via coordinated interactions with Tyr95, Tyr188, Asp63, His249, and carbonate oxygen . Its primary role involves iron transport in blood plasma and regulation of free iron levels, which are neurotoxic in excess . Dysregulation of HTF-mediated iron metabolism is linked to Alzheimer’s and Parkinson’s diseases .
Key features:
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Iron-binding mechanism: Fe³⁺ binds octahedrally within a cleft formed by HTF’s domains, requiring carbonate as a synergistic anion .
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Conformational flexibility: Ligand binding induces structural changes, altering HTF’s stability and function .
HTF-Ligand Interactions: Experimental Findings
Studies employing fluorescence spectroscopy, molecular docking, and molecular dynamics (MD) simulations reveal HTF’s binding behavior with natural compounds:
Mechanistic highlights:
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Hydrogen bonding: Dominates HTF-ligand interactions, ensuring specificity (e.g., vanillin forms 3 H-bonds with HTF ).
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Structural impact: Ligands like rosmarinic acid induce conformational changes in HTF, detectable via circular dichroism .
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Iron coordination interference: Capsaicin binds near HTF’s iron-binding site, potentially disrupting Fe³⁺ transport .
Therapeutic Implications in Neurodegenerative Diseases
HTF’s role in mitigating iron-mediated neurotoxicity positions it as a therapeutic target:
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Iron chelation: Compounds like apigenin stabilize HTF-iron complexes, reducing free iron levels in the central nervous system .
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Drug delivery: HTF-cisplatin complexes selectively deliver chemotherapeutic agents to cancer cells .
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Neuroprotection: Vanillin and rosmarinic acid modulate HTF’s function, offering routes to combat Alzheimer’s-associated iron dysregulation .
Research Limitations and Future Directions
Product Specs
Q&A
What is the core purpose of the NSF's Future of Work at the Human-Technology Frontier program?
The FW-HTF program serves as a mechanism through which the NSF responds to challenges and opportunities related to the future of jobs and work. The overarching vision supports convergent research that aims to sustain economic competitiveness, promote worker well-being, foster lifelong and pervasive learning, enhance quality of life, and illuminate the emerging social and economic context driving innovations that shape the future of work . The program specifically defines work as "mental or physical activity to achieve income, profit, or other tangible benefits," establishing clear parameters for relevant research projects . Any proposal submitted to this program must focus fundamentally on advancing understanding of future work and related outcomes for both workers and society at large .
What specific research objectives does the FW-HTF program prioritize?
The FW-HTF program articulates several specific objectives that researchers should address:
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Facilitating multi-disciplinary or convergent research that employs joint perspectives, methods, and knowledge from diverse fields including behavioral science, computer science, design, economics, engineering, learning sciences, research on adult learning and workforce training, and social sciences .
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Developing deeper understandings of how human needs can be met and values respected as technologies, conditions, and work experiences evolve .
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Supporting deeper understanding of societal infrastructure that accompanies and leads to new work technologies and approaches to work and jobs, while preparing people for future work environments .
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Encouraging development of a research community dedicated to designing intelligent technologies and work organization models inspired by their positive impacts on workers, work processes, learning and adaptation to technological change, and inclusive workplaces .
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Promoting deeper basic understanding of interdependent human-technology partnerships to advance societal needs through harmonious design of work technologies .
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Understanding, anticipating, and exploring ways to mitigate potential risks including inequity arising from future work at the human-technology frontier .
How has the FW-HTF program evolved in recent funding cycles?
The FW-HTF program has undergone several revisions to refine its focus and structure. In the FY 2021 competition, significant changes included:
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Combining categories for Research Medium and Research Large proposals into a single FW-HTF Research proposal category .
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Adding a new class of FW-HTF Transition-to-Scale proposals .
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Requiring an "Access and Inclusion" section for all proposal types .
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Adding a "Readiness and Rationale for Transition to Scale" section for Transition-to-Scale proposals .
By FY 2023, the program continued to evolve with additional emphasis on interdisciplinary approaches and deeper understanding of how human needs can be respected as work technologies and conditions change . This evolution reflects the program's commitment to remaining relevant in addressing emerging challenges at the human-technology frontier.
What constitutes effective convergent research design in FW-HTF proposals?
Effective convergent research for the FW-HTF program requires thoughtful integration of multiple disciplinary perspectives rather than merely combining them. Researchers should design studies that:
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Genuinely merge methodological approaches from behavioral science, computer science, economics, engineering, learning sciences, and social sciences to produce novel insights not achievable through single-discipline investigations .
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Define clear work contexts and scenarios that allow for meaningful investigation of human-technology interactions and partnerships .
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Address technological innovations either by examining novel technologies or by investigating how technological use is changing within specific work contexts .
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Demonstrate how the proposed research will contribute to fundamental advances in optimizing human-technology teams, future workforce development, work environments, and positive outcomes for workers and society .
Research teams should ensure their proposals explicitly articulate how convergent methods will be implemented throughout the project, detailing data collection strategies, analytical approaches, and integration mechanisms for findings from different disciplinary components.
How should researchers approach the investigation of risks associated with technological advancement in workplaces?
Investigating potential risks arising from technological advancement in workplaces requires systematic methodological approaches:
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Risk identification framework: Develop comprehensive taxonomies of potential risks including inequity, security and privacy threats, algorithmic biases creating inequitable work practices, inadequate legal protections, over-dependence on technology leading to erosion of human knowledge/skills, inadequate workplace policies, and undesirable impacts on built or natural environments .
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Multi-level analysis: Apply analytical frameworks that examine risks at individual, organizational, and societal levels to understand cascading effects and interdependencies .
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Counterfactual methodology: Design studies that can isolate technology-specific risks from broader socioeconomic factors through appropriate control conditions and comparative analyses .
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Longitudinal assessment: Implement measurement protocols that capture how risk factors emerge and evolve over time, especially as workers and organizations adapt to new technologies .
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Stakeholder-inclusive approaches: Integrate perspectives from diverse stakeholders (workers, managers, policymakers) in risk assessment to ensure comprehensive coverage of potential concerns .
The most effective risk investigation approaches will combine these methodological elements while maintaining scientific rigor and practical relevance to workplace settings.
What methodological approaches are recommended for studying adult learning and adaptation in technology-mediated work environments?
Studying adult learning and adaptation to technological change in work environments requires sophisticated methodological approaches that capture complex learning processes:
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Mixed-methods learning trajectory analysis: Combine quantitative skills assessment with qualitative investigations of learning experiences to document how workers develop competencies with new technologies over time .
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Contextual learning assessment: Develop measurement protocols that evaluate learning within authentic work contexts rather than through decontextualized testing, focusing on application of knowledge in real-world scenarios .
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Cognitive apprenticeship modeling: Implement research designs that examine how expert workers develop mental models of technology functionalities and limitations, and how these models transfer to novices through formal and informal learning channels .
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Technology-mediated learning analytics: Utilize data generated through technology use itself to understand learning patterns, including identification of common obstacles, breakthrough moments, and effective scaffolding approaches .
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Comparative pedagogical studies: Design experiments comparing different adult learning approaches (e.g., just-in-time learning, simulation-based training, peer mentoring) to identify optimal strategies for different technological contexts and worker populations .
These methodological approaches should be integrated within broader research designs that connect learning outcomes to workplace performance, worker well-being, and organizational adaptation.
How can researchers effectively investigate inclusive workplaces and technology accessibility?
Investigating inclusive workplaces and technology accessibility requires methodological approaches that address both technical and social dimensions:
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Universal design evaluation framework: Develop assessment protocols that systematically evaluate how technologies accommodate diverse user needs, including those with physical, cognitive, or learning impairments .
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Participatory design methodologies: Implement research approaches that directly involve workers with disabilities in technology design and evaluation processes, ensuring lived experiences inform accessibility features .
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Workplace policy analysis: Conduct comparative studies of organizational policies and practices to identify structural factors that enable or hinder technology accessibility and workplace inclusion .
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Intersectional barriers assessment: Design research methods that capture how multiple dimensions of worker identity (disability status, age, gender, socioeconomic background) interact to create unique accessibility challenges .
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Longitudinal inclusion metrics: Develop and validate measurement approaches that track inclusion outcomes over time as technologies evolve and workplace practices adapt .
Effective research in this area should produce both fundamental knowledge about inclusion mechanisms and practical design guidelines that can inform more accessible workplace technologies.
What approaches are recommended for designing technologies that operate in harmony with human workers?
Designing technologies that operate harmoniously with human workers requires methodological approaches that prioritize complementarity rather than replacement:
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Cognitive work analysis: Apply systematic frameworks to analyze cognitive demands of work tasks, identifying areas where technology can augment human capabilities while preserving meaningful cognitive engagement .
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Human-AI collaborative task allocation: Develop experimental protocols to test different divisions of labor between humans and intelligent technologies, measuring performance, satisfaction, and learning outcomes across configurations .
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Adaptive autonomy assessment: Design studies that evaluate technologies with adjustable autonomy levels, examining how dynamic shifts in control between humans and technologies affect work processes and outcomes .
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Sociotechnical systems modeling: Implement research approaches that capture interactions between technical components, human factors, organizational structures, and social dynamics to understand technology impacts holistically .
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Longitudinal implementation studies: Conduct extended field studies tracking how human-technology partnerships evolve over time, identifying adaptation patterns, emergent practices, and long-term impacts on work quality and worker well-being .
These approaches should be integrated within research designs that contribute to both theoretical understanding of human-technology partnerships and practical guidelines for technology development and implementation.
How should researchers structure effective FW-HTF research proposals?
Effective FW-HTF research proposals should be structured to clearly demonstrate:
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Work context specification: Clearly define the work and work context addressed by the research, establishing boundaries and significance of the chosen domain .
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Technological innovation focus: Articulate whether the proposal examines novel technologies or addresses how technological use is changing within established work contexts .
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Interdisciplinary integration: Demonstrate how technological innovations will be integrated with advances in learning sciences, research on adult learning and workforce training, and social, behavioral, and economic perspectives .
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Potential contributions: Articulate how results will contribute to fundamental advances in human-technology teaming, workforce development and education, work environments, and positive outcomes for workers and society .
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Access and inclusion considerations: Include a dedicated section addressing how the research will consider issues of accessibility and inclusion, particularly for workers challenged by various impairments or disabilities .
For Transition-to-Scale proposals specifically, additional sections on readiness and rationale for scaling should be included to justify the project's advancement to implementation .
What criteria are used to evaluate the scientific merit of FW-HTF proposals?
Based on NSF's general review criteria and FW-HTF program specifics, proposals are evaluated on:
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Intellectual Merit: The potential to advance knowledge through:
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Quality of convergent research design integrating multiple disciplinary perspectives
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Clarity and significance of research questions addressing fundamental aspects of future work
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Appropriateness and innovation of proposed methods for addressing research questions
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Qualifications of the research team to conduct the proposed work
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Broader Impacts: The potential to benefit society through:
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Contributions to understanding and addressing societal challenges related to future work
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Potential for research outcomes to inform policy, practice, or technology design
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Inclusion of diverse perspectives and participants in the research process
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Plans for dissemination and implementation of research findings
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Program-Specific Criteria:
Successful proposals demonstrate excellence across these dimensions while presenting clear, feasible research plans that address the program's core objectives.
How can researchers maximize the societal impact of their FW-HTF research?
Maximizing societal impact of FW-HTF research requires deliberate strategies throughout the research process:
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Stakeholder engagement methodology: Develop systematic approaches for involving diverse stakeholders (workers, employers, policymakers, technology developers) from project inception through dissemination, ensuring research addresses real-world priorities .
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Translational research frameworks: Implement structured processes for translating fundamental research findings into actionable insights for workplace design, technology development, worker training, and policy formation .
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Multi-level impact assessment: Design evaluation approaches that measure research impacts across individual, organizational, and societal levels, capturing both immediate outcomes and longer-term systemic effects .
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Cross-sector dissemination strategy: Develop targeted communication approaches for reaching academic, industry, policy, and worker audiences with research findings tailored to their specific needs and contexts .
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Implementation science integration: Apply established implementation science methodologies to study how research findings can be effectively translated into sustainable workplace practices and policies .
Researchers should consider these impact-maximizing strategies from the earliest stages of project design rather than treating them as afterthoughts once the primary research is complete.
What approaches have been successful in studying the effects of large-scale disruptions like the COVID-19 pandemic on the future of work?
Studying effects of large-scale disruptions like the COVID-19 pandemic on the future of work requires specialized methodological approaches:
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Natural experiment designs: Leverage the pandemic as a natural experiment, comparing work patterns, technology adoption, and worker experiences before, during, and after major disruption phases .
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Mixed-methods longitudinal tracking: Combine quantitative workforce data with qualitative experience sampling to document how disruptions accelerate or redirect technological and organizational changes over time .
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Comparative case study methodology: Develop structured case comparison frameworks to analyze how different organizations, sectors, or worker populations adapted to disruption through technological and organizational innovations .
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Counterfactual scenario modeling: Apply simulation and modeling approaches to estimate how work transformations might have evolved without the pandemic disruption, isolating pandemic-specific effects from pre-existing trends .
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Adaptive resilience assessment: Develop measurement approaches for evaluating how technological infrastructures, organizational policies, and worker adaptability contributed to resilience during disruption .
These methodological approaches should be designed not only to document pandemic impacts but to generate transferable knowledge about technology-enabled work resilience applicable to future disruptions.
Product Science Overview
Holo Transferrin is composed of a single polypeptide chain with a molecular mass of approximately 76-81 kDa . It has two homologous iron-binding domains, the N-terminal and C-terminal, each capable of binding one ferric ion (Fe³⁺) in the presence of an anion, typically carbonate . The binding of iron to transferrin is highly specific and involves coordination with a histidine nitrogen, an aspartic acid carboxylate oxygen, and two tyrosine phenolate oxygens .
The primary function of Holo Transferrin is to transport iron from sites of absorption and storage to sites of utilization, such as the bone marrow, liver, and spleen . Iron is essential for various biological processes, including oxygen transport, DNA synthesis, and electron transport. By binding and transporting iron, Holo Transferrin helps maintain iron homeostasis and prevents iron-mediated oxidative damage.
The binding of ferric iron to transferrin is a highly regulated process. Ferric iron couples to transferrin only in the presence of an anion that serves as a bridging ligand between the metal and the protein, excluding water from the coordination sites . This binding is characterized by a high association constant, approximately 10²² M⁻¹ . The release of iron from transferrin involves the protonation of the carbonate anion, which loosens the metal-protein bond .
Under normal physiological conditions, approximately one-third of the iron-binding sites on transferrin are occupied . This ensures that non-transferrin-bound iron in the circulation is virtually nonexistent, preventing potential toxicity. The total iron-binding capacity (TIBC) of plasma is a measure of the maximum amount of iron that can be bound by transferrin .
Holo Transferrin plays a vital role in iron metabolism and distribution. It is involved in the receptor-mediated endocytosis of iron-loaded transferrin by cells . Receptors on the plasma membrane bind Holo Transferrin with high affinity, facilitating the uptake of iron into cells. The C-terminal domain of transferrin mediates receptor binding, with diferric transferrin (iron-bound at both sites) binding with higher affinity than monoferric transferrin (iron-bound at one site) or apotransferrin (iron-free) .
Once inside the cell, iron is released from transferrin in the acidic environment of endosomes and is utilized for various cellular processes . The remaining transferrin, now in its iron-free form (apotransferrin), is recycled back to the cell surface and released into the circulation to bind more iron .
The measurement of Holo Transferrin levels in the blood is an important diagnostic tool for assessing iron status and diagnosing iron-related disorders. Elevated levels of Holo Transferrin can indicate iron overload conditions, such as hemochromatosis, while decreased levels may suggest iron deficiency anemia . Additionally, the total iron-binding capacity (TIBC) and transferrin saturation are commonly used parameters in clinical practice to evaluate iron metabolism .
