bluuebunny/crossref_metadata_2025 huggingface dataset:
Leather and Parchment
Authors: Robinet L.
Published: January 2023

Leather, parchment or rawhide are largely represented in museums, libraries and archive collections as objects for everyday use, and artistic or spiritual expression. Although both made from animal skin, the manufacturing process of leather and parchment differs, thus leading to two different materials from their appearance, properties, use and reactivity towards the environment. The chapter details the different steps of the manufacturing process that is dependent on the desired properties of the finished product, but also on the tradition and materials available in the geographical area. The description of the structural organization of the skin, its main constituent collagen, as well as the tannin for leathers, helps appreciate the complexity of the material with its unique mechanical properties. The different factors of degradation of leather and parchment and their effects on the collagen molecule are also discussed. The chapter introduces the main analytical approaches currently employed to characterize the skin animal species, the tanning process and the collagen degradation state. Finally, a case study on the Chartres fire-damaged medieval manuscripts is given to illustrate the different scientific approaches developed to investigate the parchment conservation state and recover illegible writings.
Metals
Authors: Golfomitsou S.
Published: January 2023

The focus of this chapter is metals in art and heritage collections, from native metals to contemporary alloys, their properties, corrosion and conservation, with reference to the analytical techniques used to facilitate their study and long-term preservation. It includes a short introduction to the use of metals and how alloying alters their working and performance properties. The variability in composition and properties also affects the way objects corrode. Corrosion of a metal is the result of its interaction with its environment resulting in irreversible changes to the chemical, physical and mechanical properties of the material. These changes can result in a wide variety of effects. Different environments, such as soil-based, atmospheric or marine, will be discussed in relation to these corrosion phenomena. Analytical techniques are divided into those which can provide information about the chemical composition and structure of an object (metallography, XRF, SEM–EDS, etc.), and those which provide information about the extent and type of corrosion (e.g. X-ray imaging, XRD, Raman spectroscopy), all of which facilitate conservation treatments. Analytical methods are valuable tools in conservation. Basic conservation approaches and factors affecting them are also discussed.
Paints and Binding Media
Authors: Nevin A.
Published: January 2023

The analysis of binding media in paint is contextualised, and key approaches for the study of media including proteinaceous, lipidic and synthetic polymers used in painting are given. The structure and chemistry of commonly found binding media are reviewed. Examples of analytical strategies for the identification of media based on highly effective Fourier Transform Infrared (FTIR) vibrational spectroscopy and Gas Chromatography/Mass Spectrometry are illustrated for protein and oil-based media. Case studies highlight applications of proteomic analysis to the identification of egg from archaeological wall paintings, the stratigraphic analysis of binding media using synchrotron-based micro-FTIR and FTIR mapping of paint cross-sections, and the analysis of complex oils and modern materials in 20th C. paintings. Advantages, limitations and future trends are described for the analysis of paint, with reference to the degradation of organic media and sample limitations with key texts for further reading provided.
Textiles
Authors: Garside P.
Published: January 2023

Textiles form a vital part of our cultural heritage, but are often overlooked. They have been a ubiquitous part of every culture and society throughout history, and include such items as clothing, household goods, tools and other functional items, decoration and furniture. As a result, they provide insights into social history, trade, agriculture, artistry and technology. However, many textile materials deteriorate relatively rapidly, especially with use, and furthermore they are often discarded, repurposed or recycled. As they are easily lost, it is the role of the textile conservator and the conservation scientist to ensure that these objects will survive for future generations, and can be understood and appreciated for the history they represent. To do so, it is necessary to have a knowledge of their composition, chemistry, microstructure and structure, and the way in which they will interact with one another, with their environment and with any treatments that are carried out. This chapter will discuss these properties for the most common classes of textile fibres, and look at the analytical techniques which can be used to provide these insights.
Plastics
Authors: Richardson E. , Flack C.
Published: January 2023

In recent years there has been growing interest in synthetic materials within the museum environment; both from an identification point of view and in order to determine their condition. Since their development in the late 19th Century, synthetic polymers have moved steadily into almost every area of life, and as a consequence, into a growing number of museum collections. This chapter introduces some of the fundamental microstructures of synthetic polymers and their incorporation in plastic artefacts. The physical properties and processing of plastics are outlined with a view to understanding how and why this class of materials has found widespread application. Analytical strategies for assessing mechanical and thermal characteristics are discussed and put into context through the discussion of a case study. The technical art history case study considers the materials and processes employed in the pyrographies works by Nul artist Henk Peeters, who created a series of works that exploited the thermal properties of polyurethane foam and polyvinyl chloride film through the application of heat.
3D Printed Material
Authors: Beecroft M.
Published: January 2023

3D printing is an emerging technology with an increasing number of artists and designers exploring its potential to create flexible textile-based structures. With growing interest in these 3D printed structures, galleries and museums worldwide have begun to include them in their exhibitions and permanent collections. This chapter discusses the pieces in terms of their structure: multiple assemblies, continuous and discontinuous geometries, their material: nylon, Acrylonitrile Butadiene Styrene (ABS), Thermoplastic Polyurethane (TPU), and their process of fabrication: selective laser sintering (SLS), fused deposition modelling (FDM). Using pieces from Manchester Metropolitan University's Material, Process, Innovation collection, the author's practice-based research Digital Interlooping is used as a case study. The chapter considers the challenges relating to the physical conservation of the pieces in terms of stability and deterioration alongside issues relating to the preservation of digital data. The chapter concludes by summarising the key considerations for 3D printed textile-based pieces as future heritage material.
Practical Work in Higher Level Chemistry Education
Authors: Bennett Stuart W. , Seery Michael K. , Sövegjarto-Wigbers Doris
Published: January 2023

Practical work has an unassailable position in the study of chemistry and, as a consequence, its role, its relevance and most importantly, its nature have rarely been seriously questioned. This chapter seeks to examine what the traditional approach to practical work actually achieves and to expose some of its limitations. A distinction between exercise and experiment is made in the context of an analysis of possible approaches to practical work and ways for optimising the use of costly laboratory resources are suggested. A tighter correspondence between learning outcomes and practical activity can lead to improved and deeper learning as well as to better mapping to assessment.
Cooperative Learning in Higher Level Chemistry Education
Authors: Eilks Ingo , Markic Silvija , Bäumer Marcus , Schanze Sascha
Published: January 2023

Starting with some essential elements from modern learning theory this chapter seeks to justify the use of cooperative learning approaches for teaching chemistry students in higher education. The basic principles of cooperative learning are described, their applications in theoretical and practical courses are discussed and the approach is illustrated using a number of examples taken from higher level chemistry courses. The chapter concludes by considering the potential of computer technology to support cooperative learning environments.
From Computer Assisted to Grid Empowered Teaching and Learning Activities in Higher Level Chemistry Education
Authors: Laganà Antonio , Manuali Carlo , Lago Noelia Faginas , Gervasi Osvaldo , Crocchianti Stefano , Riganelli Antonio , Schanze Sascha
Published: January 2023

This chapter deals with the development and implementation of innovative methods of teaching and learning chemistry based on information and communication technologies (ICT) carried out as part of the activities of the ECTN, and its Association, ECTNA. The chapter starts with some basic methodological considerations on the impact of ICT on teaching and learning chemistry through student-centred cooperative efforts and analyzes in this perspective the evolution from computer- to net-assisted approaches. The analysis of these approaches focuses on their exploitation both to assist students and teachers in making the learning process ubiquitous and continuous and to develop virtual and abstract level networked methodologies specific of the management and the acquisition of scientific knowledge. To this end virtual reality and learning management systems, which are already enabling new ways of representing and handling chemical concepts and categories, are discussed in detail on the base of some case studies. Further implementations of ICT for broadband transmissions and grid networking are discussed in order to highlight the resulting empowering of data high availability and cooperative concurrent computing. The related discussion lends itself to the formulation of a proposal for establishing a grid-based virtual organization aimed at ferrying European higher education institutions into the telematic era.
Learning from Industry and Employment
Authors: Adams Keith , Gros Leo , Wallace Ray
Published: January 2023

The focus of this chapter is on the learning benefits of activities outside the lecture hall centred on the world of work. In particular we examine the merits of a period of industrial placement and propose a model for its successful integration into the syllabus. Apart from providing practical experience with particular laboratory techniques, industrial placement has considerable potential to develop a broad range of personal skills which are difficult to incorporate into a conventional academic course. Anecdotal evidence presented here indicates that students recognize the value of industrial placement even several years after completing their studies.
Molecular Descriptors from Two-Dimensional Chemical Structure
Authors: Maran U. , Sild S. , Tulp I. , Takkis K. , Moosus M.
Published: January 2023

This chapter presents a review of whole-molecule descriptors obtained from two-dimensional chemical structure. The sections include a short overview of the mathematical foundation (graph theory) that is behind the calculation of topological descriptors. A concise overview, together with practical calculated examples, is provided for major classes of 2-D descriptors, including topological indices, information content descriptors, electrotopological descriptors, and autocorrelation descriptors. Numerous examples of their practical use in QSAR modelling are presented. The examples are dedicated to in silico toxicology modelling applications, including toxicities towards Pimephales promelas, Tetrahymena pyriformis, Daphnia magna, Vibrio fischeri, Chlorella vulgaris, rodents and humans. Also the role of 2-D descriptors in the modelling of soil sorption coefficients is presented. Emphasis is given to the interpretation of topological descriptors in QSAR models. Finally, a state-of-the art overview of available applications for the calculation of molecular descriptors is given together with an extensive bibliography of the relevant literature.
Morita–Baylis–Hillman Reaction
Authors: Zhao Mei-Xin , Wei Yin , Shi Min
Published: January 2023

This Chapter will describe the origin and growth of Morita-Baylis-Hillman reaction, the reactant classes and reaction conditions, and also discuss the general catalytic mechanisms.
Transformations of Functional Groups in Morita–Baylis–Hillman Adducts
Authors: Zhao Mei-Xin , Wei Yin , Shi Min
Published: January 2023

This chapter will mainly describe the transformations of hydroxyl group in MBH adducts and the MBH adducts related Friedel-Crafts reaction, isomerization, Heck reaction, hydrogenation, Diels-Alder reaction as well as a variety of nucleophilic additions such as carbon nucleophiles, nitrogen nucleophiles and so on. Moreover, radical reaction and metathesis reaction of MBH adducts will also be discussed.
Morita–Baylis–Hillman Adducts or Derivatives for the Construction of Cyclic Frameworks
Authors: Wang Fei-jun , Wei Yin , Shi Min
Published: January 2023

This chapter will generally reviewed the transformations of MBH adducts or derivatives to construct various cyclic frameworks.
Application of Morita–Baylis–Hillman Reaction for the Synthesis of Natural Products
Authors: Wang Fei-Jun , Wei Yin , Shi Min
Published: January 2023

This chapter will generally describe MBH reaction applied in the synthesis of a series of natural products such as furaquinocins, salinosporamides.
Catalytic Nucleic Acid Biosensors for Environmental Monitoring
Authors: Nagraj Nandini , Lu Yi
Published: January 2023

The discovery that nucleic acids can perform catalytic functions in addition to being genetic information carriers has opened doors to a new paradigm in chemistry and biology. It was thought previously that all biological enzymes were proteins, but discoveries made over the last 30 years have changed this perception. In this chapter the properties of RNAzymes, DNAzymes, and aptazymes are illustrated. The application of these novel catalytic molecules to environmental monitoring is discussed.
New Trends in DNA Sensors for Environmental Applications: Nanomaterials, Miniaturization, and Lab-on-a-Chip Technology
Authors: Escosura-Muniz Alfredo de la , Medina Mariana , Merkoçi Arben
Published: January 2023

The purpose of this chapter is to review the latest trends in the use of nanomaterials (nanoparticles, quantum dots, nanotubes, etc.) as well as miniaturization and lab-on-a-chip technologies for nucleic acid based biosensing systems with interest for environmental applications. Although most of the principles of nanomaterial-based sensors have been addressed earlier, in this chapter we aim to focus on the DNA and nanomaterial-based systems that are of interest for environmental applications. In addition to nanomaterials the chapter will also consider lab-on-a-chip systems involving DNA as a novel trend in environmental monitoring. Due to the lack of relevant reports in the literature on specific DNA-based systems, other analytes will be also discussed for some of the detection modes reviewed here, keeping in mind future extension of these methods as possible alternatives for DNA-based environmental monitoring.
Phase Transition under Confinement
Authors: Singh Jayant K. , Docherty Hugh , Cummings Peter T.
Published: January 2023

In this chapter, we focus on advanced Monte Carlo and molecular dynamics techniques to study vapour-liquid phase equilibria, cross-over behaviour of critical properties and solid-liquid phase transition under confinement. The state of the art in the field is demonstrated by reviewing selected results of our recent computer simulations. We present Monte Carlo studies of cross-over behaviour of critical properties, in different geometries, from 3D to 2D. In the second part of the chapter, we list various issues pertaining to the study of solid-liquid transitions under confinement in the context of lubrication at the nanoscale. We also provide recent molecular dynamics results which provide more clarity in understanding the effect of surface texture on the solid structure of confined fluids. We end the chapter with an introduction to analysis and techniques to evaluate liquid-solid phase transitions and structure formation in cylindrical pores.
Simulating Thermomechanical Phenomena of Nanoscale Systems
Authors: Alex Greaney P. , Grossman Jeffrey C.
Published: January 2023

Using nanoscale structures, systems have the potential to radically alter the way that we use, and think of heat. It is a field that abounds with opportunity, from expanding the limits of thermal conductivity, to diagnostics, phononics, and adding worth to heat beyond its face caloric value. In this chapter we give a brief survey of recent experimental progress, and a discussion of computational approaches to nanoscale thermal problems. Explored are the merits of calculation (theory) versus simulation. In the second part of the chapter a set of case studies are used to demonstrate a selection of computational methods for simulating and analyzing heat transfer and dissipation in nanoscale systems. Despite much progress in advancing methodology for computing and simulating heat, numerous important challenges are yet to be surmounted. Our aim in this chapter is to encourage and spur much-needed further work in this exciting field.
Electron Transport Theory for Large Systems
Authors: Sanvito Stefano
Published: January 2023

Electron transport is a ubiquitous phenomenon in modern technology, which underpins the operation of transistors, read heads for hard-disk drives and a multitude of chemical and biological sensors. The rapid approach of the typical device size to the nanoscale makes standard device simulators, based on effective Hamiltonian, inadequate and novel atomistic and materials specific transport theories are needed. Density functional theory combined with the non-equilibrium Green's functions scheme (NEGF+DFT) for electron transport provides today the most accurate and still numerically practical approach to the problem. In particular it is the only fully ab initio method which is currently capable of tackling systems with a large number of degrees of freedom. How this is achieved will be the subject of this Chapter, where I will also mention the pitfalls of such a method and the proposed remedies. Furthermore I will provide a glance over possible applications where transport theory has been demonstrated useful and efficient.
Theoretical Strategies for Functionalisation and Encapsulation of Nanotubes
Authors: Seifert GotThard , Baldoni Matteo , Mercuri Francesco , Enyashin Andrey
Published: January 2023

Nanotubular materials like carbon nanotubes (CNTs) and inorganic nanotubes (INNTs) were proposed as promising materials for a large variety of nanotechnological applications. Due to intrinsic experimental limitations, the theoretical modeling plays a crucial role in the understanding of the properties of these materials. The present chapter is intended to provide a comprehensive overview of some theoretical concepts for modeling of CNTs functionalization and the encapsulation of inorganic material into CNTs and INNTs. The work is divided into two main parts. In the first, a methodological background is given along with some basic structural features of the “nano-objects” taken into account. In particular the application of the Clar sextet theory to the case of CNTs is analyzed in detail. Several applications of this concept are reported in the second part. Some basic electronic properties of the CNTs are analyzed from the Clar sextet theory point of view. DFT calculations on Clar-consistent CNTs models provide a suitable route for the understanding of the chemical reactivity of semiconducting chiral CNTs. Another possible field of application of NTs concerns the development of novel materials by making use of NTs as nano-sized templates of nanostructured materials. A detailed overview of theoretical understanding of capillary properties of carbon and inorganic BN and MoS2 nanotubes is given. Therein, results from classical MD simulations on the imbibition process for a molten salt into a nanotube and on the crystallization of the melt within the nanotubular cavity are shown.
Density Functional Calculations of NMR Chemical Shifts in Carbon Nanotubes
Authors: Zurek Eva , Autschbach Jochen
Published: January 2023

Computations of spectroscopic parameters of nanosystems can serve as an aid in experimental characterization. The focus of this article is on NMR (nuclear magnetic resonance) since in general this is one of the most versatile tools to study the structures, and properties of molecules and solids. After outlining the theory behind first–principles calculations of NMR parameters, it is illustrated that detailed information about the structure of carbon nanosystems can be obtained from these calculations. Theoretical studies of pristine SWNTs have indicated that 13C NMR may be used to determine the diameter distribution of a bulk sample. NICS (nucleus independent chemical shifts) have provided information about the aromaticity of various tubes, and the NMR chemical shifts of small molecules trapped in nanotubes have been calculated. Work on amine functionalized SWNTs has suggested that 13C NMR may be used to determine which nanotube carbons are derivatized, and perhaps even yield information about the diameter of the tubes. 13C NMR can potentially be useful to quantify the degree of fluorination. Theoretical studies on Stone-Wales defects have indicated that characteristic NMR signals may arise from atoms in the defect site. The tensor properties of nanotube NMR shielding is discussed.
Open-shell organometallics: reactivity at the ligand
Authors: Dzik Wojciech I. , de Bruin Bas
Published: January 2023

The purpose of this review is to show that (cooperative) ligand radical reactivity can be effectively employed in synthetic organometallic chemistry and catalysis to achieve selectivity in radical-type transformations. The ‘redox non-innocence’ of ligands, and the controlled reactivity of ‘ligand radicals’ – giving rise to new, intriguing substrate transformations – allow unusual and selective radical-type substrate coupling reactions, ligand rearrangements and C-Y bond formations. In this review, several examples of fast and selective ligand-centered radical transformations in the open-shell organometallic chemistry of transition metals are described, focussing on radical-type reactions of olefin-, vinylidene-, vinyl-, alkyne-, allyl-, propargyl-, carbonyl-, and carbene ligands. Intriguing and selective substrate-substrate coupling reactions, (covalent) carbon-metal bond formations and hydrogen atom transfer reactions from and to ligand radicals are summarized. To conclude this chapter, an overview of recently disclosed new insights in the catalytic mechanism of CoII(por) catalysed olefin cyclopropanation is presented, showing that enzyme-like cooperative metal-ligand-radical reactivity is no longer reserved to real enzymes, but is a useful new concept to steer and control radical-type transformations in future bio-inspired organometallic catalysis.
Alkali/coinage metals – organolithium, organocuprate chemistry
Authors: Haywood Joanna , Wheatley Andrew E. H.
Published: January 2023

Part 1 of this chapter reviews coordination compounds of the alkali metals that contain a carbon-metal bond, looking firstly at the application of mixed alkali metal-zinc compounds in the directed metallation of a variety of compounds. The use of alkynyl, N-donor and N-heterocyclic carbene ligands is also discussed. Compounds of the coinage metals, copper, silver and gold, are discussed in Part 2 of the review. Discussion is broken down by metal, with copper being discussed first. Compounds containing, among others, alkene, amido and phosphido ligands are discussed, along with the significant amount of work on carbene complexes. This interest in carbene complexes is also noted within the silver and gold sections which follow, with a large number of new compounds being described. 2D and 3D networks containing silver centres have also attracted a great deal of interest and are described, along with the luminescent properties of a selection of novel gold species. This part of the review is completed by coverage of mixed-coinage metal structures, where many of the species are found to be polymeric in nature. Here again, the compounds discussed contain at least one carbon-metal bond.
Highlights in low-coordinate group 14 organometallic chemistry
Authors: Layfield Richard A.
Published: January 2023

This chapter summarizes the key advances that have been made in the organometallic (or ‘organo-element’) chemistry of silicon, germanium, tin(II) and lead(II) in the period 2008-2009. Compounds in which the group 14 element resides in a low-coordinate environment are the main focus, which allows the chapter to be conveniently divided under the headings of: multiply bonded compounds; small molecule activation chemistry; heavy group 14 elements as ligands at transition metal centres; and heteroaromatic compounds. Since an important highlight review article summarizing key developments in the study of heavy group 14 radical species was published in 2008 by Lee, Nakamoto and Sekiguchi,1 this topic will not be covered herein.2
Pyrethrins and Pyrethroid Insecticides
Authors: Schleier III* Jerome J. , Peterson Robert K. D.
Published: January 2023

Pyrethrum is one of the oldest and most widely used botanical insecticides and its insecticidal properties have been known for more than 150 years. The commercial limitations of pyrethrum extracts, which are collectively known as pyrethrins, have long been recognized because of their high rate of photodegradation and a short “knockdown” (rapid paralysis) effect. After the discovery of the constituents of pyrethrins, researchers searched for derivatives of pyrethrins that had a higher resistance to photodegradation. This search directly led to the synthesis of pyrethroids. The advantages of pyrethrins and pyrethroids in pest management are that they are highly lipophilic, have a short half-life in the environment, have a low terrestrial vertebrate toxicity, and do not biomagnify like older chemical classes such as organochlorines. This chapter reviews the chemistry, mode of action, metabolism, environmental fate, and human-health and environment risks for pyrethrins and pyrethroids.
The Spinosyn Insecticides
Authors: Dripps J. E. , Boucher R. E. , Chloridis A. , Cleveland C. B. , DeAmicis C. V. , Gomez L. E. , Paroonagian D. L. , Pavan L. A. , Sparks T. C. , Watson G. B.
Published: January 2023

The spinosyns are unique insecticidal secondary metabolites produced by two soil bacteria, Saccharopolyspora spinosa and S. pogona. Spinosad and spinetoram, the two active ingredients developed from the spinosyns, received Presidential Green Chemistry Challenge Awards in 1999 and 2008, respectively. Spinosad is derived entirely from fermentation, whereas spinetoram is created by making two synthetic modifications to fermentation-derived spinosyn starting materials. These modifications resulted from innovative approaches to quantify spinosyn structure-activity relationships, and the modifications make spinetoram more active and enable it to provide longer-lasting control than spinosad. The spinosyn mode of action involves a unique site on the nicotinic acetylcholine (nACh) receptor. Low toxicity to mammals and most other non-target species provides a wide margin of safety for agricultural workers and the environment. The spinosyns have short environmental persistence and degrade by physical and microbial processes into simpler fragments containing only carbon, oxygen, nitrogen, and hydrogen. Spinosyn insecticide manufacturing is a green, fermentation-based process using renewable agricultural feedstocks. The spinosyn insecticides have had a huge impact on agriculture by providing control of a broad range of important arthropod pests across more than 250 crops in more than 80 countries. Spinosad and spinetoram are generally compatible with Integrated Pest Management (IPM) programs. Spinosad's natural origin has enabled certification for organic agriculture in a growing number of countries, and it has significant noncrop uses in stored grain protection, animal health, and public health. Further research and advances in delivery systems technology will open an even wider range of uses for the spinosyns.
The Bisacylhydrazine Insecticides
Authors: Gomez Luis E. , Hastings Kerry , Yoshida Harvey A. , Dripps James E. , Bailey Jason , Rotondaro Sandra , Knowles Steve , Paroonagian Doris L. , Dhadialla Tarlochan Singh , Boucher Raymond
Published: January 2023

The bisacylhydrazine (BAH) insecticides are a class of green chemistry compounds very specific to the target insect pests that induce a premature molting process in the affected insects. The BAH insecticides bind to the ecdysone receptors in the target pests with a greater affinity than that observed for the natural hormone, 20-hydroxyecdysone. This confers a greater level of selectivity towards most non-target organisms present in the ecosystems where the BAH insecticides are used. The BAH insecticides act directly on immature stages of the target insects (eggs and larvae) and cause some sublethal effects, such as delayed developmental rates and reduced fecundity and fertility on the adult stage of the pests. These insecticides have very good ecotoxicological profile, having virtually no impact on most non target organisms including beneficial insects and pollinators, (bees, predators and parasitoids), birds, fish and terrestrial invertebrates. The BAH insecticides also have low-toxicity to mammals making them reduced risk materials for humans handling the products. The most widely registered BAH is methoxyfenozide, which has registrations in more than 50 countries in a variety of crops ranging from vegetables to specialty uses such as forestry and tea. Due to their characteristics, the BAH insecticides can be incorporated in insecticide resistance and integrated pest management programs. Data related to these aspects of BAH insecticides are presented.
The Contribution of Transgenic Models to the Understanding of Alzheimer's Disease Progression and Therapeutic Development
Authors: Chabrier Meredith A. , Neely Kara M. , Castello Nicholas A. , LaFerla Frank M.
Published: January 2023

Transgenic mouse models of Alzheimer disease (AD) have been invaluable in unraveling the mechanisms of disease progression and for testing potential therapeutic interventions. Since the cause of sporadic AD is unknown, transgenic models of AD are primarily based on mutations found only in patients with familial AD. These mutations produce pathological and cognitive changes that resemble sporadic AD, and thus these transgenic mice are still extremely useful for studying this more common form of AD. Here we discuss notable advances in our understanding of AD pathogenesis that have directly resulted from studies with transgenic models of AD, such as the finding from 3xTg-AD mice and other models demonstrating that tau pathology is facilitated by amyloid-beta. We also discuss several promising therapeutics that were largely characterized using transgenic mice, including immunotherapy, HDAC inhibitors, and M1 receptor agonists.
Animal Models of Amyloid/PS-1 Pathology
Authors: Takashima Akihiko
Published: January 2023

Senile plaques and neurofibrillary tangles (NFTs) are major pathological proteinaceous anomalies that occur in the brains of Alzheimer's disease (AD) patients. Motivated by the amyloid hypothesis, animal models exhibiting Aβ deposition have been produced by crossbreeding mice overexpressing human mutant amyloid precursor protein (hAPP) with mice overexpressing mutant PS-1, the latter of which accelerates Aβ deposition in the brain. Most mouse models exhibiting Aβ deposition show memory deficits associated with synaptic plasticity impairments and synapse loss. In this chapter, I introduce the most commonly used amyloid/PS-1 transgenic mouse models that exhibit Aβ deposition and discuss some limitations of using these animal models to understand the devastating condition of AD.
The Ying and Yang of the Reelin Signalling Pathway in Alzheimer's Disease Pathology
Authors: Soriano Eduardo , Rossi Daniela , Pujadas Lluís
Published: January 2023

Reelin is an extracellular protein crucial for brain development. To study Reelin functions in the adult forebrain we generated a transgenic mouse model that overexpress Reelin under the control of the CaMKIIα promoter (pCaMKII-Reelin-OE; Tg1/Tg2)l. Studies on Tg1/Tg2 mice indicate that Reelin regulates adult neurogenesis and migration, as well as the structural and functional properties of synapses. These observations suggest that Reelin controls developmental processes that remain active in the adult brain.
Transgenic Mice Overexpressing GSK-3β as Animal Models for Alzheimer's Disease
Authors: Hernández Félix
Published: January 2023

Alzheimer's disease (AD) is characterized by two neuropathological hallmarks, senile plaques and neurofibrillary tangles (NFT). Senile plaques are extracellular deposits of amyloid fibrils composed of the β-amyloid peptide. NFT are intraneuronally generated aggregates of paired helical filaments (PHF), which are assembled from hyperphosphorylated forms of the microtubule-associated protein tau. Glycogen synthase kinase-3β (GSK3β) has been proposed as the link between these two neuropathological hallmarks of AD and deregulation of GSK3β activity in neurons has been postulated as a key feature in AD pathogenesis. This is based on the interaction of GSK3 with many of the cellular components related to the neuropathology of AD, such as the amyloid precursor protein, the β-amyloid peptide, the metabolic pathway leading to acetylcholine synthesis, the presenilins, which are mutated in many cases of familial AD, and tau protein. In this chapter, a resume of transgenic GSK3 mice overexpressing wild-type and different mutant isoforms as well as the additional AD models that results from the breeding of these GSK3 mice with mice overexpressing proteins altered in AD are summarized. The possibility of using these animal models to test novel therapeutic interventions aimed at blocking GSK3 to ameliorate AD pathology is also discussed.
Invertebrate and Vertebrate Models of Tauopathies
Authors: Götz Jürgen , Ittner Lars M. , Götz Naeman N. , Lam Hong , R. Nicholas Hannah
Published: January 2023

Animal models are widely used in neurodegenerative research. With the identification of pathogenic mutations in familial cases of disease, animal models have been generated that model key aspects of the human pathology. This chapter reviews what has been achieved in both vertebrate and invertebrate models, with a focus on the microtubule-associated protein tau and its interaction with amyloid-β. While an initial focus was on reproducing the human pathology in vivo, today's challenge lies in understanding what causes disease in the first place.
Animal Models for ALS
Authors: Fujii Ritsuko , Takumi Toru
Published: January 2023

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by selective motor neuron loss in the motor cortex and spinal cord, eventually leading to progressive paralysis and death. Despite many discoveries of ALS-related genes, the cause and pathogenesis of the disease remains to be elucidated. The motor neuron degeneration in ALS appears to be caused by multiple factors. To unravel a complex molecular basis of the disease, ALS animal models should be useful tools to monitor progression of the disease over the time and to determine crucial neurodegenerative events during the early disease course. To date, there are growing numbers of reports on ALS animal models. Most of them are rodent transgenic models overexpressing ALS-associated mutant genes, either constitutively or conditionally. In this chapter, we review recent advances in transgenic ALS animal models and discuss about their pathological features that may help our understanding of selective motor neuron degeneration in ALS.
A Non-transgenic Rat Model of Sporadic Alzheimer's Disease
Authors: Iqbal Khalid , Wang Xiaochuan , Blanchard Julie , Grundke-Iqbal Inge
Published: January 2023

Alzheimer's disease occurs both in familial and or sporadic forms. The familial AD accounts for less than 1% of the cases and is caused by specific mutations in amyloid precursor protein, presenilin 1 or presenilin 2 genes. The nature of the etiological factors for the sporadic form of AD, which accounts for over 99% of the cases, is at present not well understood. To date most of the animal models are transgenic mice which express the familial AD mutations alone or in combination with tau mutations of frontotemporal dementia. This chapter discusses the sparseness of animal models of sporadic AD and describes a novel adeno associated virus (AAV) vector-induced experimental rat model of this disease. This model replicates the overexpression of the C-terminal fragment of I2PP2A, I2CTF, in rat brain using the AAV vector. The AAV-I2CTF rats show intraneuronal accumulation of Ab1–42 and abnormally hyperphosphorylated tau but no Ab plaques or neurofibrillary tangles by nine months, studied so far, but are cognitively impaired in Morris water maze spatial reference memory task. As compared with generation of transgenic animals, the AAV-induced expression system is rapid, highly reproducible, and within the reach of most research laboratories as well as allows the expression of the desired gene in a spatial and temporal controlled manner.
Extracellular and Intracellular Signaling – a New Approach to Diseases and Treatments
Authors: Adams, Jr. James David , Lien Eric J. , Parker Keith
Published: January 2023

Hormones, neurotransmitters, cytokines and a number of extracellular ligands participate in extracellular signaling mechanisms that modify cellular biochemistry. Intracellular ligands are involved in an array of intracellular signaling processes that increase or decrease the effects of extracellular ligands. Both extracellular and intracellular mechanisms are important in drug effects, maintaining health and treating chronic disease. The management of chronic diseases is becoming a very common process for many people. Many questions remain to be answered about chronic diseases. What causes them? Is it possible to prevent them? How are they best treated?
One Receptor for Multiple Pathways: Focus on Leptin Signaling
Authors: Gómez Rodolfo , Conde Javier , Scotece Morena , Gualillo Oreste
Published: January 2023

The adipokine leptin, due to its dual nature as hormone and cytokine, can be described as a cytokine-like hormone with pleiotropic actions. It exerts a multitude of regulatory functions including energy homeostasis, regulation of various endocrine axes, bone metabolism, thermoregulation and modulation of immune and inflammatory response. Leptin exerts its biological influence by binding to its receptors, which are encoded by the diabete gene (db). Leptin receptors belong to the class I cytokine receptor superfamily. Alternative splicings of the db gene give rise to multiple isoforms, but only the long form Ob-Rb appears to be capable of transducing the leptin signal. The JAK-STAT pathway seems to be the main route by which Ob-Rb transmits the extracellular signal it receives. Other alternative pathways, however, are also involved. Here, we discuss the most recent advances on leptin biology with particular attention to its receptor signaling.
Regulation of Muscle Proteostasis via Extramuscular Signals
Authors: Atherton Philip J. , Szewczyk Nathaniel J.
Published: January 2023

Muscle protein synthesis and degradation are dynamic processes, the balance of which has been recently termed proteostasis. At any one time muscle has to balance outputs in synthesis and degradation from “inputs” of both extra- and intramuscular derived signals including those of hormones, autocrine/paracrine factors, metabolites, mechanical loading and attachment to the extracellular matrix. If there is a disturbance in whole-body/muscle homeostasis (i.e. due to illness, altered mechanical activity), the concentration of these inputs is altered. The resultant integration of these signaling inputs stimulates reprogramming of proteostasis. If the balance is tipped toward net synthesis or degradation muscles undergo hypertrophy or atrophy, respectively. The first aim of this chapter is to discuss what is currently known about how input signals, largely in isolation, regulate muscle protein turnover and encapsulates evidence from both animal and human work and both in vivo and in vitro studies. The second aim is to describe what is understood about the regulation of muscle proteostasis by extracellular-intracellular signaling with specific attention paid to the key regulators of proteostasis in healthy humans (i.e. responses to feeding, ambulation). The third aim is to discuss the regulation of muscle atrophy under pathological conditions of trauma, illness, disuse and aging.
Intracellular Signaling Pathways in Parkinson's Disease
Authors: Contreras Monica Sanchez , Cardozo-Pelaez Fernando
Published: January 2023

Parkinson's disease (PD) is a chronic neurodegenerative disease that involves the selective loss of dopaminergic neuronal cells in the substantia nigra (SN) in the midbrain. The studies in PD-affected individuals as well as animal, cellular and toxicant-based disease models have provided information about the mechanisms involved in PD etiology. Intracellular signaling pathways offer a mechanistic explanation for how an initial event may induce selective cell death in PD and also specific targets for therapeutic intervention in PD.
Force Evaluation for Bingham Fluids Using Multiple-relaxation-time Lattice Boltzmann Model
Authors: Chen S. , Sun Q. , Jin F.
Published: January 2023

Bingham fluids are widely encountered in engineering practices. In this paper, the Papanastasiou's model for Bingham fluids was solved using the multiple-relaxation-time lattice Boltzmann model (MRT-LB). We applied the MRT-LB model to simulate the flows around a spherical particle. Beside the rich flow structures obtained in this work, the dynamic fluid force on the spherical particle was calculated. It was found that both Reynolds number Re and Bingham number Bn affect drag coefficients CD. The relationship of Bn with the ratio of the un-yielded zone thickness to particle diameter was analyzed.
Granular Flows in Fluid
Authors: Kumar K. , Soga K. , Delenne J.-Y.
Published: January 2023

Underwater avalanches are a major risk to offshore structures. The mechanisms involved in the initiation and propagation of underwater granular avalanches are complex. They depend mainly on the slope angle, density, and quantity of material destabilised. Characterising the risk induced by such catastrophic flows requires the development of reliable models. Most models of submarine landslides assume a single homogeneous phase representing the grain-fluid mixture that is governed by a non-Newtonian fluid behaviour. Although successful in accounting for general phenomenology in a small computation time, such models, defined at a large scale, are limited in describing all features of seabed granular flows. Hence, it is important to understand the mechanism of underwater granular flows at the particle scale to develop a better up scaling model. A pending research issue is the parameterization of interactions between the water phase and the sediment phase. Owing to the number of flow variables involved and measurement imprecision, estimating such parameters from laboratory experiments remains difficult. In the present study, sub-particle scale numerical simulations are performed to understand the local phenomena of underwater granular flows. The Discrete Element Method (DEM) is coupled with the Lattice Boltzmann Method (LBM) for fluid-particle interactions in order to study the collapse of granular columns in fluids. The coupling of DEM and LBM enables the introduction of water phase to the solid phase and calculation of hydrodynamic forces on grains. D2Q9 Model in LBM is used to simulate the fluid phase. A parametric analysis is performed to assess the influence of permeability on the evolution of flow and run-out distances. The effect of hydrodynamic forces on the run-out evolution is analysed by comparing the mechanism of energy dissipation and flow evolution in dry and immersed granular flows.
A Study of the Influence of Surface Energy on the Mechanical Properties of Lunar Soil Using DEM
Authors: Modenese C. , Utili S. , Houlsby G.T.
Published: January 2023

DEM was employed to investigate the mechanical behaviour of Lunar Soil, generally defined as the finest fraction of the Lunar Regolith, taking into account the main effects of the lunar environment (e.g. high vacuum, low gravity and high temperature fluctuations). The purpose is to inform the planning of future lunar exploration, both manned and robotic. The investigation has focussed on the origins of the observed cohesion of Lunar Soil, whose explanation has proved elusive until now. The effects on the stress-strain behaviour of inter-particle attractive van der Waals forces (quantified by the surface energy) were investigated by means of triaxial compression tests in a periodic cell containing 5000 spherical particles. The particle radii vary according to the typical Particle Size Distribution of the Lunar Regolith. Very dense samples, with relative density approaching 100%, were prepared under isotropic compression. Triaxial tests were then carried out at constant mean pressure for very small confining stresses in the range of 0.1 kPa to 10 kPa, corresponding to a depth from the lunar surface of approximately 0.04 m to 4 m, respectively. To assess the effect of surface energy, simulations were run with and without the presence of inter-particle adhesion, which was introduced at the contact level by implementing the JKR model. The results show that the surface energy is responsible for an apparent macroscopic cohesion at the peak of the deviatoric stress-strain curve, but does not affect the tangent friction angle. However, at the critical state, very little cohesion (if any) was observed. Furthermore, an increase of the secant friction angle is apparent only at stresses less than 5 kPa. Physical explanations of these complex phenomena are postulated, and a link between microscopic and macroscopic physical variables is proposed.