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Nanomaterials: a review of synthesis methods, properties, recent progress, and challenges.

* Corresponding authors

a Center of Research Excellence in Desalination & Water Treatment, King Fahd University of Petroleum and Minerals, Dhahran 31261, Saudi Arabia E-mail: [email protected] , [email protected]

b Center for Environment and Water, King Fahd University of Petroleum and Minerals, Dhahran 31261, Saudi Arabia

c Interdisciplinary Research Center for Membranes and Water Security, King Fahd University of Petroleum and Minerals, Dhahran 31261, Saudi Arabia

d Department of Chemical & Biological Engineering, University of Alabama, Tuscaloosa, Alabama 35487-0203, USA E-mail: [email protected] , [email protected]

e Department of Mechanical Engineering, King Fahd University of Petroleum and Minerals, Dhahran 31261, Saudi Arabia

Nanomaterials have emerged as an amazing class of materials that consists of a broad spectrum of examples with at least one dimension in the range of 1 to 100 nm. Exceptionally high surface areas can be achieved through the rational design of nanomaterials. Nanomaterials can be produced with outstanding magnetic, electrical, optical, mechanical, and catalytic properties that are substantially different from their bulk counterparts. The nanomaterial properties can be tuned as desired via precisely controlling the size, shape, synthesis conditions, and appropriate functionalization. This review discusses a brief history of nanomaterials and their use throughout history to trigger advances in nanotechnology development. In particular, we describe and define various terms relating to nanomaterials. Various nanomaterial synthesis methods, including top-down and bottom-up approaches, are discussed. The unique features of nanomaterials are highlighted throughout the review. This review describes advances in nanomaterials, specifically fullerenes, carbon nanotubes, graphene, carbon quantum dots, nanodiamonds, carbon nanohorns, nanoporous materials, core–shell nanoparticles, silicene, antimonene, MXenes, 2D MOF nanosheets, boron nitride nanosheets, layered double hydroxides, and metal-based nanomaterials. Finally, we conclude by discussing challenges and future perspectives relating to nanomaterials.

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N. Baig, I. Kammakakam and W. Falath, Mater. Adv. , 2021,  2 , 1821 DOI: 10.1039/D0MA00807A

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International Conference on Medical and Biological Engineering

CMBEBIH 2021: CMBEBIH 2021 pp 690–702 Cite as

Artificial Intelligence in Nanotechnology: Recent Trends, Challenges and Future Perspectives

• Faris Hrvat 9 ,
• Amina Aleta 9 ,
• Amra Džuho 8 ,
• Osman Hasanić 8 &
• Lemana Spahić Bećirović 8  
• Conference paper
• First Online: 01 June 2021

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Part of the book series: IFMBE Proceedings ((IFMBE,volume 84))

Nanoscience and nanotechnology are two overlapping areas of human activity, that take into consideration characteristics and utilization of nanoscale materials, and thus have applications in majority of science fields. Nanoscience and nanotechnology can be used in conjunction with Artificial Intelligence, since they are present in various fields ranging from medical diagnostics to robotics. Advancements in precision of medicine were highly influenced by nanomaterials. This paper is a review of artificial intelligence in nanotechnology, and was done through a literature review of 10 papers. According to the available literature on different platforms, it can be concluded that the concern for artificial intelligence in nanotechnology has been highly increased in the past decade. The paper presents how this combination of sophisticated techniques can be used for different medical purposes, and with different methodologies of both, artificial intelligence and machine learning.

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Hrvat, F., Aleta, A., Džuho, A., Hasanić, O., Spahić Bećirović, L. (2021). Artificial Intelligence in Nanotechnology: Recent Trends, Challenges and Future Perspectives. In: Badnjevic, A., Gurbeta Pokvić, L. (eds) CMBEBIH 2021. CMBEBIH 2021. IFMBE Proceedings, vol 84. Springer, Cham. https://doi.org/10.1007/978-3-030-73909-6_79

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It may all come down to the mechanisms of nanoparticle delivery

A long-standing nanoparticle delivery paradigm in cancer, that is, the enhanced permeability and retention effect, has been challenged, shifting the focus to active delivery mechanisms, which may provide a new mechanistic foundation for nanoparticle design.

Ultrabright near-infrared light

• Andries Meijerink

The potential for academics to inspire the next generation

Programmes to inspire the next generation of researchers can have a huge impact, as Rachel Lou explains in the recounting of her own experience.

Landmark study links microplastics to serious health problems

People who had tiny plastic particles lodged in a key blood vessel were more likely to experience heart attack, stroke or death during a three-year study.

In vivo biomolecule corona and the transformation of a foe into an ally for nanomedicine

Nanoparticles (NPs) administered in the human body will undergo rapid surface modification upon contact with biological fluids driven by their interfacial interaction with a diverse range of biomolecules. Such spontaneous self-assembly and adsorption of proteins and other biomolecules onto the NP surface constitute what is commonly known as the protein or biomolecule corona. This surface biotransformation of the NPs modulates their biological interactions and impact on physiological systems and can influence their overall pharmacological profile. Here, we comment on how the initially considered ‘nuisance’ of the in vivo corona formation can now be considered a nanoparticle engineering tool for biomedical use, such as in endogenous tissue targeting, personalized biomarker discovery and immunomodulation.

• Marilena Hadjidemetriou
• Morteza Mahmoudi
• Kostas Kostarelos

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Top 50 Geography Research Topics [Revised]

Geography isn’t just about maps and memorizing capital cities; it’s a dynamic field that delves into everything from understanding our planet’s physical features to unraveling the complexities of human societies. In this blog, we’ll embark on a journey through fascinating geography research topics, ranging from climate change and urbanization to cultural dynamics and emerging trends. Whether you’re a curious student or simply someone intrigued by the world around you, join us as we explore the diverse realms of geography research.

What Are The Three Main Topics Of Geography?

Table of Contents

• Physical Geography
• Study of Earth’s physical features, processes, and phenomena.
• Example: Investigating the formation of mountains, erosion patterns in river systems, or the impact of climate change on ecosystems.
• Human Geography
• Examination of the interactions between human societies and their environments.
• Example: Analyzing urbanization trends, migration patterns, cultural landscapes, or economic activities within specific regions.
• Environmental Geography
• Focus on the relationship between humans and their natural surroundings, including the impact of human activities on the environment.
• Example: Researching pollution levels in urban areas, deforestation rates in tropical rainforests, or the conservation of endangered species and habitats.

50 Geography Research Topics: Category Wise

Physical geography research topics.

• Impact of climate change on polar ice caps.
• Patterns of desertification in arid regions.
• Formation and evolution of volcanic islands.
• Study of river meandering and channel migration.
• Factors influencing the distribution of biomes worldwide.

Human Geography Research Topics

• Urbanization dynamics in developing countries.
• Social and economic impacts of gentrification in urban neighborhoods.
• Migration patterns and trends in Europe.
• Cultural landscapes and identity politics in contested territories.
• Gender disparities in access to resources and opportunities in rural areas.

Environmental Geography Research Topics

• Analysis of air quality in megacities.
• Impacts of deforestation on local biodiversity in the Amazon rainforest.
• Water scarcity and management strategies in arid regions.
• Ecotourism and its role in sustainable development.
• Effects of marine pollution on coral reef ecosystems.

Geographical Techniques and Tools Research Topics

• Applications of Geographic Information Systems (GIS) in disaster management.
• Remote sensing techniques for monitoring agricultural productivity.
• Cartographic visualization of population density and distribution.
• Spatial analysis of crime patterns in urban areas.
• Geographical modeling of disease spread and containment strategies.

Regional Geography Research Topics

• Socioeconomic disparities between urban and rural regions in India.
• Geopolitical tensions in the South China Sea.
• Cultural diversity and integration in multicultural cities like London or New York.
• Environmental challenges facing the African Sahel region.
• Regional impacts of globalization on indigenous communities in South America.

Cultural Geography Research Topics

• Influence of religion on cultural landscapes in the Middle East.
• Cultural diffusion and globalization in the digital age.
• Preservation of intangible cultural heritage in UNESCO World Heritage sites.
• Impact of colonialism on indigenous cultures in Australia.
• Gender roles and cultural practices in traditional societies.

Economic Geography Research Topics

• Spatial distribution of industries in emerging economies.
• Trade patterns and economic integration in the European Union.
• Impact of globalization on labor markets in Southeast Asia.
• Role of transportation infrastructure in regional economic development.
• Economic consequences of natural disasters on local communities.

Political Geography Research Topics

• Border disputes and territorial conflicts in the Middle East.
• Secessionist movements and autonomy struggles in Europe.
• Role of international organizations in conflict resolution and peacebuilding.
• Geopolitical implications of Arctic resource extraction.
• Influence of soft power and cultural diplomacy in international relations.

Social Geography Research Topics

• Spatial patterns of poverty and social exclusion in urban areas.
• Dynamics of neighborhood segregation and integration in diverse cities.
• Impact of social media on community engagement and activism.
• Gender-based violence and spatial justice in urban environments.
• Cultural dimensions of health disparities in rural communities.

Historical Geography Research Topics

• Legacy of colonialism in shaping urban landscapes in former colonies.
• Evolution of trade routes and their impact on cultural diffusion.
• Archaeological landscape studies of ancient civilizations.
• Historical geography of migration and diaspora communities.
• Environmental history of industrialization and its long-term impacts on ecosystems.

How To Write A Geography Research Paper?

Writing a geography research paper involves several key steps to ensure a well-structured, coherent, and informative document. Here’s a step-by-step guide on how to write a geography research paper:

• Choose a Topic: Select a specific and focused research topic within the field of geography that interests you. Consider the scope of your paper, available resources, and the significance of the topic in the field.
• Conduct Research: Gather relevant sources of information such as scholarly articles, books, journals, government publications, and online databases. Use both primary and secondary sources to support your research and develop a comprehensive understanding of the topic.
• Develop a clear and short thesis statement that explains what your research paper is about. This statement should show the main idea or point you’re going to talk about in your paper.
• Organize your paper by making a plan or outline. Split it into different parts like the introduction, where you start talking about your topic and explain why it’s important. Then, include a literature review where you talk about what others have already studied about your topic. If you did any special methods in your research, talk about them in the methodology section. Then, show your findings or results, discuss them, and finally, conclude your paper. Make sure you outline all the important things you want to talk about in each section.
• Start your paper with an interesting introduction. Tell the reader some background information about your topic and why it’s important. Also, introduce your thesis statement here. Explain what you’ll be talking about in your research paper to help guide the reader through your paper.
• Conduct a Literature Review: Review existing literature and research related to your topic to contextualize your study and identify gaps or areas for further investigation. Summarize key findings, methodologies, and theories from previous studies to support your own research.
• Describe Your Methodology (If Applicable): If your research involves empirical data collection or analysis, describe the methodology and research design used in your study. Explain the research methods, data sources, sampling techniques, and analytical tools employed to gather and analyze data.
• Present Your Findings: Present the results of your research in a clear and systematic manner. Use tables, graphs, maps, and other visual aids to illustrate your findings and enhance comprehension. Provide descriptive and analytical interpretations of the data to support your arguments.
• Discuss Your Results: Analyze and interpret the significance of your research findings in relation to your thesis statement and research objectives. Discuss any patterns, trends, or relationships observed in the data and explore their implications for the broader field of geography.
• Draw Conclusions: Summarize the main findings of your research and reiterate the significance of your study. Discuss any limitations or constraints encountered during the research process and propose areas for future research or further investigation.
• Cite Your Sources: Ensure that you properly cite all sources of information used in your research paper according to the citation style specified by your instructor or academic institution. Use in-text citations and include a comprehensive bibliography or reference list at the end of your paper.
• Proofread and Revise: Review your research paper carefully for grammatical errors, typos, and inconsistencies. Revise and refine your writing to improve clarity, coherence, and overall quality. Consider seeking feedback from peers, mentors, or academic advisors to further enhance your paper.

Emerging Topics in Geography Research

As our world continues to evolve, new frontiers of geography research are constantly emerging. From the quest for sustainable development to the rise of smart cities and the challenges of climate resilience, researchers are grappling with complex issues that defy easy solutions.

One promising avenue of research is the integration of indigenous knowledge and perspectives into geographic studies. By recognizing the wisdom of traditional cultures and their deep connection to the land, researchers can develop more holistic approaches to environmental management and conservation.

In conclusion, geography research offers a rich tapestry of topics that span the natural and social sciences. Whether it’s unraveling the mysteries of climate change, exploring the dynamics of urbanization, or celebrating the diversity of cultural landscapes, there’s something for everyone in the world of geography research.

So, whether you’re a student embarking on geography research topics or simply a curious explorer seeking to understand the world around you, take heart in knowing that the adventure has only just begun. Happy exploring!

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Nanotechnology Research: Applications in Nutritional Sciences 1 , 2

Pothur r. srinivas.

3 Atherothrombosis and Coronary Artery Diseases Branch, Division of Cardiovascular Sciences, National Heart, Lung, and Blood Institute, 4 Division of Nutrition Research Coordination, 5 Office of Science Policy Analysis, Office of Science Policy, Office of the Director, 6 Office of Dietary Supplements, Office of the Director, and; 7 Nutritional Science Research Group, Division of Cancer Prevention, National Cancer Institute, NIH, Bethesda, MD 20892; 8 University of Michigan School of Public Health, Ann Arbor, MI 48109; 9 Oregon Health and Sciences University, Portland, OR 97239; 10 Rutgers University, New Brunswick, NJ 08901; 11 University of Illinois Urbana-Champaign Urbana, IL 61801; 12 National Institute for Food and Agriculture, USDA, Washington, DC 20024; 13 Telemedicine and Advanced Technology Research Center, U.S. Army Medical Research and Materiel Command, Fort Detrick, MD 21702; and 14 Jean Mayer Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111

Martin Philbert

Tania q. vu, qingrong huang, josef l. kokini, hongda chen, charles m. peterson, karl e. friedl, crystal mcdade-ngutter, van hubbard, pamela starke-reed, nancy miller, joseph m. betz, johanna dwyer, john milner, sharon a. ross.

The tantalizing potential of nanotechnology is to fabricate and combine nanoscale approaches and building blocks to make useful tools and, ultimately, interventions for medical science, including nutritional science, at the scale of ∼1–100 nm. In the past few years, tools and techniques that facilitate studies and interventions in the nanoscale range have become widely available and have drawn widespread attention. Recently, investigators in the food and nutrition sciences have been applying the tools of nanotechnology in their research. The Experimental Biology 2009 symposium entitled “Nanotechnology Research: Applications in Nutritional Sciences” was organized to highlight emerging applications of nanotechnology to the food and nutrition sciences, as well as to suggest ways for further integration of these emerging technologies into nutrition research. Speakers focused on topics that included the problems and possibilities of introducing nanoparticles in clinical or nutrition settings, nanotechnology applications for increasing bioavailability of bioactive food components in new food products, nanotechnology opportunities in food science, as well as emerging safety and regulatory issues in this area, and the basic research applications such as the use of quantum dots to visualize cellular processes and protein-protein interactions. The session highlighted several emerging areas of potential utility in nutrition research. Nutrition scientists are encouraged to leverage ongoing efforts in nanomedicine through collaborations. These efforts could facilitate exploration of previously inaccessible cellular compartments and intracellular pathways and thus uncover strategies for new prevention and therapeutic modalities.

Introduction

“Nanotechnology” is the creation of functional materials, devices, and systems through the manipulation of matter at a length scale of ∼1–100 nm. At such a scale, novel properties and functions occur because of size ( 1 ). This emerging field is becoming important in enabling breakthroughs of new and effective tools in the medical sciences (e.g. nanomedicine), because it offers the possibility of examining biological processes in ways that were not previously possible. The medical use of nanotechnology includes the development of nanoparticles for diagnostic and screening purposes (i.e. early detection of cancer), development of artificial cellular proteins such as receptors, DNA and protein sequencing using nanopores and nanosprays, the manufacture of unique drug (and nutrient) delivery systems, as well as gene therapy and tissue engineering applications ( 2 ). Nanotechnology offers a range of tools capable of monitoring individual cells at the level of individual molecules. It enables researchers to investigate and monitor cellular and molecular function and to alter systems that are deregulated in disease. It is conceivable that nanomachines with the ability to circulate through the bloodstream, kill microbes, supply oxygen to hypoxic organs, or undo tissue damage could one day be delivered to the human body through medicines or even foods. There are challenges with the emergence of nanomedicine that include issues related to toxicity and the environmental impact of nanoscale materials. The social, ethical, legal, and cultural implications of nanotechnology must also be considered.

In nutrition research, nanotechnology applications may assist with obtaining accurate spatial information about the location of a nutrient or bioactive food component in a tissue, cell, or cellular component. Ultrasensitive detection of nutrients and metabolites, as well as increasing an understanding of nutrient and biomolecular interactions in specific tissues, has become possible. In theory, such new technologies have the potential to improve nutritional assessment and measures of bioavailability. They may help to identify and characterize molecular targets of nutrient activity and biomarkers of effect, exposure, and susceptibility and therefore may also inform “personalized” nutrition. Specific applications of nanotechnology to date in food and nutrition include: modifying taste, color, and texture of foods; detection of food pathogens and spoilage microorganisms; enhancing nutrition quality of foods; and novel vehicles for nutrient delivery, as well as serving as a tool to enable further elucidation of nutrient metabolism and physiology ( 3 – 5 ). For example, one food technology application involves creating coatings for foods and food packaging that serve as barriers to bacteria or that contain additional nutrients ( 6 ).

Nutritional products claiming to use nanotechnology are currently available in the market. It is important to recognize that the potential toxicity of nutrients can be affected by a change in particle size [see ( 7 ) for current updates]. Furthermore, little is known about the absorption and excretion of nanoparticles by experimental animals or in humans. Thus, there are challenges with the application of nanoscale compared with microscale materials. These include higher exposure per unit mass; small size:large surface area ratio; different routes of exposure due to smaller size (i.e. dermal penetration); different distribution to tissues by virtue of their different size or surface coating, chemistry, or particle charge; and novel properties of a nanoscale material that may alter absorption, digestion, metabolism, or excretion in the body.

To highlight nanotechnology applications and challenges for nutrition research and to encourage collaboration between various disciplines with the aim of advancing food and nutrition research, a symposium was convened at Experimental Biology 2009 on the topic “Nanotechnology Research: Applications in Nutritional Sciences.” This session presented various nanotechnology approaches for use in food and nutrition research. It also identified several safety/regulatory issues in nanotechnology, foods, and health. Experts focused on topics that included “Nanotechnology approaches for medical and nutrition research,” presented by Martin A. Philbert, University of Michigan School of Public Health. He provided an overview to set the stage about the application of nanotechnology in research, particularly focusing on how nanotechnology will be used to guide new prevention and therapeutic strategies for nutrition scientists. “Quantum dot technologies for visualizing live cell dynamic signaling and ultra-sensitive protein detection” was presented by Tania Q. Vu, Oregon Health and Sciences University. She discussed the use of quantum dots (QD) 15 to visualize cellular processes. The 3rd presentation, focused on nanotechnology applications for increasing bioavailability of bioactive food components in new food products, was presented by Dr. Qingrong Huang, Rutgers University (entitled “Bioavailability and delivery of dietary factors using nanotechnology”). “Food, nutrition and nanotechnology research: challenges and promises” was presented by Jozef Kokini, University of Illinois. He provided a compendium of nanotechnology opportunities for food science as well as safety and regulatory issues. A panel comprised of individuals from various federal agencies discussed and emphasized research opportunities and challenges in nanotechnology, foods, and health. The sections that follow provide a synopsis of each of these topics as well as recommendations for future applications of nanotechnology research in the nutritional sciences.

Nanotechnology approaches for medical and nutrition research

Dr. Martin Philbert discussed the challenges and opportunities of nanotechnology applications in clinical and nutrition settings. The very properties of nanostructured materials that make them so attractive could potentially lead to unforeseen health or environmental hazards ( 8 ). Some of these properties include high aspect ratio, bio-persistence, reactive surfaces and points that are capable of producing reactive oxygen species, composition and solubility. Coating the nanoparticle with biocompatible materials, however, has been shown to significantly reduce toxicity in some applications. Dr. Philbert also encouraged the design of products and processes in nanotechnology that reduce or eliminate the use and generation of hazardous substances. The translation of much of the current research in nanotechnology into clinical practice will rely on solving challenges that relate to the toxicity of nanoparticles.

Examples from this presentation highlight both the promises/possibilities and problems of nanomedicine. Probes encapsulated by biologically localized embedding (PEBBLE) 15 are sub-micron optical sensors that have been designed for minimally invasive analyte monitoring in viable, single cells ( 8 ). PEBBLE nanosensors are composed of matrices of cross-linked polyacrylamide, cross-linked poly(decyl methacrylate), or sol-gel silica, which have been fabricated as sensors for H + , Ca 2+ , K + , Na + , Mg 2+ , Zn 2+ , Cu 2+ , Cl − , and some nonionic species ( 9 ). A number of techniques have been used to deliver PEBBLE nanosensors into mouse oocytes, rat alveolar macrophages, rat C6-glioma, and human neuroblastoma cells ( 9 ). Using gene gun injection as a delivery method, a sol gel-based PEBBLE nanosensor for reliable, real-time measurement of subcellular molecular oxygen was inserted into rat C6 glioma cells. The cells responded to differing oxygen concentrations and provided real-time intracellular oxygen analysis. The PEBBLE contained an oxygen-sensitive fluorescent indicator, Ru(II)-Tris(4,7-diphenyl-1,10-phenanthroline) chloride ([Ru(dpp) 3 ] 2+ ), and an oxygen-insensitive fluorescent dye, Oregon Green 488-dextran, as a reference for the purpose of ratiometric intensity measurements ( 10 ). The small size and inert matrix of these sensors allow them to be inserted into living cells with minimal physical and chemical perturbations to their biological functions. Compared with using free dyes for intracellular measurements, the PEBBLE matrix protects the fluorescent dyes from interference by proteins in cells, enabling reliable in vivo chemical analysis. The matrix significantly reduces the toxicity of the indicator and reference dyes to the cells so that a wide variety of dyes can be used in optimal fashion. Hence, the sol gel-based PEBBLE sensors are extremely useful for real-time intracellular measurements such as oxygen levels. It is conceivable that PEBBLE technology can be utilized to monitor nutrient metabolism, the effects of reactive oxygen species generation, and ion distributions.

A nanoimaging example highlights the current challenge of brain tumor surgery to achieve complete resection without damaging normal structures near the tumor. Achieving maximal resection currently relies on the neurosurgeon's ability to judge the presence of residual tumor during surgery ( 11 ). The use of fluorescent and visible dyes has been proposed as a means of visualizing tumor margins intraoperatively. Such investigations have been hampered by difficulties in achieving tumor specificity, achieving adequate visual contrast, and identifying a dye useful for a wide range of tumors. Dye-loaded nanoparticles may be able to meet these challenges ( 11 ). Nanoparticle-based magnetic resonance contrast agents have been demonstrated to be useful to visualize portions of tumor in the brain that would be unclear with conventional imaging techniques. Nanoparticle-based contrast agents with a core of iron oxide crystals with or without a shell of organic material, such as polyethylene glycol, have been designed for such purposes ( 11 ).

Challenges related to nanoparticle clearance and toxicity need to be overcome before nanoparticles can be used clinically. Also, a greater understanding of the relationship between toxicity and particle size, geometry, pharmacokinetics, and surface coating is required before nanoparticles should be used in clinical practice.

QD technologies for visualizing live cell dynamic signaling and ultra-sensitive protein detection

Dr. Tania Vu demonstrated how nanotechnology can offer new capabilities that allow investigators to probe the function of key molecules using multiple modalities at the scale of single molecules in live cells. QD allow investigators to examine activities that cannot normally be resolved under a microscope with conventional dyes and florescent labels. When excited by laser light, the QD nano crystals emit photons and shine more brightly and longer in duration than any conventional label. Dr. Vu presented 2 main QD-based technologies that her laboratory has developed to investigate cellular function: 1 ) QD imaging probes for imaging protein trafficking and endocytic events in live cells; and 2 ) ultrasensitive QD assays for studying protein expression and specific protein-protein interactions in limited cell samples. Dr. Vu described tracking a protein within rat cells that regulates the growth of nerve tissue with the use the peptide ligand β nerve growth factor (NGF) conjugated to QD surfaces ( 12 ). The βNGF-QD were found to retain bioactivity, activate tyrosine kinase A (TrkA) receptors, and initiated downstream cellular signaling cascades to promote neuronal differentiation in PC12 cells. This example of receptor-initiated activity of QD-immobilized ligands has wide-ranging implications for the development of molecular tools and therapeutics targeted at understanding and regulating cell function. It is possible that QD may soon be used to visualize drugs or nutrients as they move in cells and cellular compartments in living systems.

QD hybrid gel blotting, which allows the purification and analysis of the action of QD bioconjugate-protein complexes in live cells, was also discussed. This is an alternative approach to PAGE-based Western blotting and immunoprecipitation ( 13 ). Interestingly, the protein interactions that are identified can also be correlated with spatial location in cells. Dr. Vu initially employed this technique to investigate the association of ligand NGF with the TrkA receptor in PC12 cells ( 14 ). It was found that NGF-QD could be retrieved and separated from a mixture of cellular lysate, NGF-QD were colocalized with an anti-TrkA receptor antibody, indicating TrkA −NGF-QD ligation, and discrete NGF-QD were bound to TrkA receptor puncta on the cell membrane surface. This novel nano-based technique has several advantages as a method for: 1 ) identifying specific QD-protein interactions in cells; 2 ) correlating QD-protein interactions with their spatial location in live cells; 3 ) studying the size and composition of QD bioconjugate probes/complexes; and 4 ) directly isolating and visualizing proteins from complex mixtures, offering an improvement over traditional bead-based immunoprecipitation methods ( 13 ).

These QD-based technologies offer investigators a means to probe specific inter-molecular interactions with significantly improved sensitivity and to relate these interactions with high-resolution in real time in live cells at the scale of single molecules. Nutrition researchers can adopt these QD-based technologies to examine questions of interest in nutrient metabolism and physiology.

Bioavailability and delivery of dietary factors using nanotechnology

Dr. Qingrong Huang described how the disease prevention properties of dietary supplements such as polyphenols have attracted much attention in recent years. Their biological effects include antioxidative, anticancer, and other properties that may prevent chronic disease as suggested by evidence from in vitro, animal, and human studies. Sales of the dietary supplements are high and growing annually. Thus, the development of high quality, stable dietary supplements with good bioavailability could become important. Although the use of dietary supplements in capsules and tablets is abundant, their effect is frequently diminished or even lost, because many of these compounds present solubility challenges. The major challenges of dietary polyphenols include their poor water solubility and oral bioavailability. Thus, novel delivery systems are needed to address these problems.

Dr. Huang presented a series of experiments integrating food processing, formulation, and in vivo/in vitro test development for the design of novel polyphenol nanocapsules, specifically for the water insoluble compounds curcumin, extracted from the turmeric plant ( Curcuma longa ), and dibenzoylmethane, a β -diketone analogue of curcumin. For example, high-speed and high-pressure homogenized oil-in-water emulsions using medium-chain triacylglycerols as oil and Tween 20 as emulsifier, were successfully prepared to encapsulate curcumin ( 15 ). These curcumin nanoemulsions were evaluated for antiinflammatory activity using a mouse ear inflammation model. An enhanced antiinflammatory activity was demonstrated (43 and 85% inhibition effect of 12- O -tetradecanoylphorbol-13-acetate-induced edema of mouse ear for 618.6 and 79.5 nm 1% curcumin oil-in-water emulsions, respectively), but a negligible effect was found for 1% curcumin in 10% Tween 20 water solution ( 15 ). Dr. Huang highlighted other recent in vivo biological and pharmacological experiments, which included a skin carcinogenesis model, measures of a series of proinflammatory biomarkers, and products that have demonstrated greatly improved antiinflammation activity and oral bioavailability of nanoencapsulated curcumin and dibenzoylmethane.

A wide variety of encapsulation platforms, including nanostructured emulsions, water-in-oil-in-water or oil-in-water-in-oil double emulsions, solid lipid or biopolymer-based nanoparticles, and direct conjugation of phytochemicals to biopolymer side chains have been developed to encapsulate food constituents for enhanced delivery and bioavailability ( 6 , 16 ). With the aid of nanoencapsulation, in vivo absorption and circulation of bioactive food components appear to increase, which should assist in achieving the desired concentration and biological activity of these compounds. Although an increase in nutrient intake from an enhanced food supply may be beneficial, food and nutrition professionals may need to monitor overconsumption and potential signs of toxicity more closely. Additionally, micronutrient imbalances may become more prevalent and drug-nutrient interactions will also require careful observation ( 5 ). Thus, a greater understanding of the metabolic consequences of nutrients in novel food systems are required as nanotechnology applications expand in the food sciences.

Food, nutrition, and nanotechnology research: challenges and promises

Dr. Josef Kokini described the opportunities for nanotechnology applications to foods and agriculture, including nanomaterials in food packaging, food protein-based nanotubes to bind vitamins or enzymes, and rapid sampling of biological and chemical contaminants using nanocantilevers as detection tools for water and food safety. Nanotechnology has the potential to transform the entire food industry by changing the way food is produced, processed, packaged, transported, and consumed. Applications in food packaging are very promising, because they can improve the safety and quality of food products ( 17 ). The use of bionanocomposites for food packaging not only has the potential to protect the food and increase its shelf life but can also be considered more environmentally friendly, because such composites would reduce the requirement to use plastics as packaging materials, thus decreasing environmental pollution in addition to consuming less fossil fuel for their production ( 17 ). Zein, a prolamin and the major protein found in corn, has been an important material in science and industry because of its distinctive properties and molecular structure. Novel approaches are expected to yield new applications for zein in the foods and biodegradable plastics industry. After solvent treatment, zein can form a tubular structure meshwork that is inert and resistant to microbes ( 17 ). Zein nanoparticles have been synthesized and examined as edible carriers of flavor compounds, for nanoencapsulation of dietary supplements, as well as to improve the strength of plastic and bioactive food packaging. Importantly, controlling the uniformity and organization of zein films at the nanolevel is critical for its mechanical and tensile properties. Dr. Kokini et al. ( 18 ) tested different solvents and found that zein films that were generated in acetic acid were smoother and structurally more homogeneous than those produced using ethanol. Other investigators are examining the use of silicates to strengthen zein films.

Novel nanosensors are being tested to detect food pathogens. Array techniques with thousands of nanoparticles on a platform have been designed to fluoresce in different colors on contact with food pathogens. Furthermore, intelligent packaging with nanosensors is being considered that has the ability to react to the environment and perhaps interact with the food product with specific applications. One application might be to detect food spoilage.

The challenges for the application of nanotechnology in food and food science were also described. Because of their increased surface area, nanomaterials might have toxic effects in the body that are not apparent in bulk materials. Extensive use of nanoparticles in foods as additives is less likely in the near future because of possible safety concerns. Although nanomaterials from food packaging would not ordinarily be ingested or inhaled, the potential exists for unforeseen risk, such as release of airborne nanoparticles that might aggravate lung function or inadvertent consumption due to leakage of packaging materials into foods. The U.S. FDA requires that manufacturers demonstrate that food ingredients and food products are not harmful to health, but specific regulations about nanoparticles do not exist. Although there is a lack of regulation and knowledge of risk, still there are a number of food and nutrition products that claim to contain nanoscale additives, including iron in nutritional drink mixes, micelles that carry vitamins, minerals and phytochemicals in oil, and zinc oxide in breakfast cereals ( 17 , 19 ). Although more research is needed on the health consequences of nanoparticles, it is unclear what the full range of concerns are, because measurement of exposure to nanomaterials is neither well developed nor characterized. Therefore, an emerging challenge to benefiting from nanotechnology is having the foresight to develop and use it wisely. To this end, governmental agencies (via the National Nanotechnology Initiative) are working together to proactively research and evaluate the benefits and harms of nanotechnology.

Research opportunities and challenges in nanotechnology, foods, and health

A panel discussion entitled “Research Opportunities and Challenges in Nanotechnology, Foods and Health” followed the presentations and included federal government representatives from the Division of Nutrition Research Coordination, NIH (Dr. Crystal McDade-Ngutter), Telemedicine and Advanced Technology Research Center, U.S. Army Medical Research and Materiel Command (Dr. Charles Peterson), and the National Institute for Food and Agriculture (NIFA; formerly Cooperative State Research, Education, and Extension Service), USDA (Dr. Etta Saltos). Each panelist provided information about research opportunities in nanotechnology from their agencies that would be of interest to nutrition scientists as well as a perspective on the challenges of nanotechnology, foods, and health. The NIH has supported many initiatives on the topic of nanotechnology, such as the NIH Nanomedicine Roadmap Initiative ( 20 ) and the NCI Alliance for Nanotechnology in Cancer ( 21 ), but none that have been specifically targeted for nutrition research. More opportunities for nutrition scientists to interact and collaborate with nanotechnology experts were emphasized as a way forward for such NIH applications. Similarly, Telemedicine and Advanced Technology Research Center, U.S. Army Medical Research and Materiel Command supports a Nanotechnology and Biomaterials Portfolio that is focused on identifying novel developments in materials science and biomaterials that can improve drugs and devices for diagnosis and therapy of a broad range of medical conditions ( 22 ). NIFA, USDA in collaboration with food and agricultural scientists from land grant universities and the National Nanotechnology Initiative agencies developed the first strategic roadmap titled “Nanoscale Science and Engineering for Agriculture and Food Systems” ( 23 ). The resulting NIFA, USDA initiative “Nanoscale Science and Engineering for Agriculture and Food Systems” has been offered every other year with next cycle of new applications to be announced in fiscal year 2010 ( 24 ). The goal of this program is to provide knowledge, expertise, and highly qualified research and development in nanotechnology for food and agricultural systems. Examples of 2008 priorities included novel nanoscale processes, materials and systems with improved delivery efficacy, controlled release, modification of sensory attributes, and protection of micronutrients and functional ingredients suitable for food matrices as well as the assessment and analysis of perceptions and acceptance of nanotechnology and nano-based products by the general public, agriculture, and food stakeholders using appropriate social science tools.

During the discussion, several research areas in the nutritional sciences that would benefit from nanotechnology applications were highlighted (summarized in Table 1 ). Nutrition scientists may wish to leverage ongoing efforts and collaborate with experts in nanotechnology so that novel approaches can be developed to tackle many of these research questions. The panel discussion provided insight into the research opportunities and challenges concerning applications for nanotechnology so that nutrition and food scientists can be more informed and productive in their research endeavors.

Examples of research areas in nutrition with nanotech enhancement potential

Recent advances in biomedical and agricultural technology will likely assist in advancing our understanding of health and disease processes. The symposium “Nanotechnology Research: Applications in Nutritional Sciences” highlighted new and emerging technologies that are currently, or soon to be, available for nutritional sciences. Examples discussed included: 1 ) nanoscale optical sensors, such as PEBBLE, for intracellular chemical sensing; 2 ) QD technologies to visualize and quantify cellular protein interactions; 3 ) nanoencapsulation of bioactive food components to improve their bioavailability; and 4 ) intelligent food packaging that acts as a biosensor to monitor and detect spoilage or infection ( Fig. 1 ).

Examples of nanotechnology applications and their associated discipline highlighted during the symposium.

Nutrition and food science research areas that might benefit from applying or understanding nanotechnology include research that aims to: 1 ) identify sites of action (molecular targets) for bioactive food components; 2 ) characterize biomarkers that reflect exposure, response, and susceptibility to foods and their components; 3 ) identify new target delivery systems for optimizing health; and 4 ) improve food composition. Because there is little information about the potential health risks of nanoparticles, more research on the toxicology of nanoparticles, both on a case-by-case basis and for general applicability, is also warranted. Nanotechnology has the potential to advance the science of nutrition by assisting in the discovery, development, and delivery of several intervention strategies to improve health and reduce the risk and complications of several diseases. This symposium was designed to enhance knowledge and understanding about technologies that may be utilized or are currently being employed and or/modified for nutrition and food science research. It is hoped that by highlighting these technologies the potential benefit of nanomaterials to revolutionize food and nutrition research is recognized.

Acknowledgments

P.R.S. and S.A.R. wrote the paper and had primary responsibility for final content; M.P., T.Q.V., Q.H., J.L.K., E.S., H.C., C.M.P., K.E.F., C.M-N., V.H., P.S-R., N.M., J.M.B., J.D., and J.M. provided essential materials and information for the creation and revisions of the manuscript. All authors read and approved the final manuscript.

1 Published as a supplement to The Journal of Nutrition . Presented as part of the symposium entitled “Nanotechnology Research: Applications in Nutritional Sciences” given at the Experimental Biology 2009 meeting, April 21, 2009, in New Orleans, LA. This symposium was sponsored the Division of Nutrition Research Coordination, NIH; the Nutritional Science Research Group, Division of Cancer Prevention, National Cancer Institute, NIH; the Office of Science Policy, Office of the Director, NIH; Office of Dietary Supplements, Office of the Director, NIH; the Atherothrombosis and Coronary Artery Diseases Branch, Division of Cardiovascular Sciences, National Heart, Lung, and Blood Institute, NIH; and the Telemedicine and Advanced Technology Research Center, U.S. Army Medical Research and Materiel Command. This symposium was supported by the Division of Nutrition Research Coordination, NIH; the Nutritional Science Research Group, Division of Cancer Prevention, National Cancer Institute, NIH; and the Telemedicine and Advanced Technology Research Center, U.S. Army Medical Research and Materiel Command. The symposium was chaired by Pothur R. Srinivas and Sharon A. Ross. Guest Editor for this symposium publication was Sharon M. Nickols-Richardson. Guest Editor disclosure: Sharon M. Nickols-Richardson had no conflicts to disclose.

2 Author disclosures: P. R. Srinivas, M. Philbert, T. Q. Vu, Q. Huang, J. L. Kokini, E. Saos, H. Chen, C. M. Peterson, K. E. Friedl, C. McDade-Ngutter, V. Hubbard, P. Starke-Reed, N. Miller, J. M. Betz, J. Dwyer, J. Milner, and S. A. Ross, no conflicts of interest.

15 Abbreviations used: NGF, nerve growth factor; NIFA, National Institute for Food and Agriculture; PEBBLE, probes encapsulated by biologically localized embedding; QD, quantum dot; TrkA, tyrosine kinase A.

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Large language models use a surprisingly simple mechanism to retrieve some stored knowledge

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Large language models, such as those that power popular artificial intelligence chatbots like ChatGPT, are incredibly complex. Even though these models are being used as tools in many areas, such as customer support, code generation, and language translation, scientists still don’t fully grasp how they work.

In an effort to better understand what is going on under the hood, researchers at MIT and elsewhere studied the mechanisms at work when these enormous machine-learning models retrieve stored knowledge.

They found a surprising result: Large language models (LLMs) often use a very simple linear function to recover and decode stored facts. Moreover, the model uses the same decoding function for similar types of facts. Linear functions, equations with only two variables and no exponents, capture the straightforward, straight-line relationship between two variables.

The researchers showed that, by identifying linear functions for different facts, they can probe the model to see what it knows about new subjects, and where within the model that knowledge is stored.

Using a technique they developed to estimate these simple functions, the researchers found that even when a model answers a prompt incorrectly, it has often stored the correct information. In the future, scientists could use such an approach to find and correct falsehoods inside the model, which could reduce a model’s tendency to sometimes give incorrect or nonsensical answers.

“Even though these models are really complicated, nonlinear functions that are trained on lots of data and are very hard to understand, there are sometimes really simple mechanisms working inside them. This is one instance of that,” says Evan Hernandez, an electrical engineering and computer science (EECS) graduate student and co-lead author of a paper detailing these findings .

Hernandez wrote the paper with co-lead author Arnab Sharma, a computer science graduate student at Northeastern University; his advisor, Jacob Andreas, an associate professor in EECS and a member of the Computer Science and Artificial Intelligence Laboratory (CSAIL); senior author David Bau, an assistant professor of computer science at Northeastern; and others at MIT, Harvard University, and the Israeli Institute of Technology. The research will be presented at the International Conference on Learning Representations.

Finding facts

Most large language models, also called transformer models, are neural networks . Loosely based on the human brain, neural networks contain billions of interconnected nodes, or neurons, that are grouped into many layers, and which encode and process data.

Much of the knowledge stored in a transformer can be represented as relations that connect subjects and objects. For instance, “Miles Davis plays the trumpet” is a relation that connects the subject, Miles Davis, to the object, trumpet.

As a transformer gains more knowledge, it stores additional facts about a certain subject across multiple layers. If a user asks about that subject, the model must decode the most relevant fact to respond to the query.

If someone prompts a transformer by saying “Miles Davis plays the. . .” the model should respond with “trumpet” and not “Illinois” (the state where Miles Davis was born).

“Somewhere in the network’s computation, there has to be a mechanism that goes and looks for the fact that Miles Davis plays the trumpet, and then pulls that information out and helps generate the next word. We wanted to understand what that mechanism was,” Hernandez says.

The researchers set up a series of experiments to probe LLMs, and found that, even though they are extremely complex, the models decode relational information using a simple linear function. Each function is specific to the type of fact being retrieved.

For example, the transformer would use one decoding function any time it wants to output the instrument a person plays and a different function each time it wants to output the state where a person was born.

The researchers developed a method to estimate these simple functions, and then computed functions for 47 different relations, such as “capital city of a country” and “lead singer of a band.”

While there could be an infinite number of possible relations, the researchers chose to study this specific subset because they are representative of the kinds of facts that can be written in this way.

They tested each function by changing the subject to see if it could recover the correct object information. For instance, the function for “capital city of a country” should retrieve Oslo if the subject is Norway and London if the subject is England.

Functions retrieved the correct information more than 60 percent of the time, showing that some information in a transformer is encoded and retrieved in this way.

“But not everything is linearly encoded. For some facts, even though the model knows them and will predict text that is consistent with these facts, we can’t find linear functions for them. This suggests that the model is doing something more intricate to store that information,” he says.

Visualizing a model’s knowledge

They also used the functions to determine what a model believes is true about different subjects.

In one experiment, they started with the prompt “Bill Bradley was a” and used the decoding functions for “plays sports” and “attended university” to see if the model knows that Sen. Bradley was a basketball player who attended Princeton.

“We can show that, even though the model may choose to focus on different information when it produces text, it does encode all that information,” Hernandez says.

They used this probing technique to produce what they call an “attribute lens,” a grid that visualizes where specific information about a particular relation is stored within the transformer’s many layers.

Attribute lenses can be generated automatically, providing a streamlined method to help researchers understand more about a model. This visualization tool could enable scientists and engineers to correct stored knowledge and help prevent an AI chatbot from giving false information.

In the future, Hernandez and his collaborators want to better understand what happens in cases where facts are not stored linearly. They would also like to run experiments with larger models, as well as study the precision of linear decoding functions.

“This is an exciting work that reveals a missing piece in our understanding of how large language models recall factual knowledge during inference. Previous work showed that LLMs build information-rich representations of given subjects, from which specific attributes are being extracted during inference. This work shows that the complex nonlinear computation of LLMs for attribute extraction can be well-approximated with a simple linear function,” says Mor Geva Pipek, an assistant professor in the School of Computer Science at Tel Aviv University, who was not involved with this work.

This research was supported, in part, by Open Philanthropy, the Israeli Science Foundation, and an Azrieli Foundation Early Career Faculty Fellowship.

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Researchers at MIT have found that large language models mimic intelligence using linear functions, reports Kyle Wiggers for  TechCrunch . “Even though these models are really complicated, nonlinear functions that are trained on lots of data and are very hard to understand, there are sometimes really simple mechanisms working inside them,” writes Wiggers. 

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• Evan Hernandez
• Jacob Andreas
• Language and Intelligence Group
• Computer Science and Artificial Intelligence Laboratory
• Department of Electrical Engineering and Computer Science

Related Topics

• Computer science and technology
• Artificial intelligence
• Human-computer interaction
• Computer Science and Artificial Intelligence Laboratory (CSAIL)
• Electrical Engineering & Computer Science (eecs)

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