Name, abbreviation, structure, molecular weight (MW), density (
\r\n\tFood insecurity results in fear of hunger and starvation that ultimately affects one’s ability to work for sustainability and economic growth of the country. In addition to this, food insecurity results in various chronic diseases due to reduce immunity that ultimately, a burned on the county economy. Therefore, this book will intend to discuss in detail about the food insecurity challenges and their effect on the quality of life. This book will also aim to provide an overview about the new trends and future prospective that help to resolve the food security issues.
",isbn:"978-1-80356-942-0",printIsbn:"978-1-80356-941-3",pdfIsbn:"978-1-80356-943-7",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,hash:"090302a30e461cee643ec49675c811ec",bookSignature:"Dr. Muhammad Haseeb Ahmad, Dr. Muhammad Imran and Dr. Muhammad Kamran Khan",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11475.jpg",keywords:"Nutrition, Poverty, Hunger, Food Waste Utilization, Innovative Technologies, Food Processing, Genetically Modified Food, Policy Making, Trade Reforms, Climate Change, Agriculture Productivity, Disease Resistant Crops",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"April 7th 2022",dateEndSecondStepPublish:"May 5th 2022",dateEndThirdStepPublish:"July 4th 2022",dateEndFourthStepPublish:"September 22nd 2022",dateEndFifthStepPublish:"November 21st 2022",remainingDaysToSecondStep:"15 days",secondStepPassed:!0,currentStepOfPublishingProcess:3,editedByType:null,kuFlag:!1,biosketch:"An emerging scientist in the field of food science and technology with special expertise in development of rapid and nondestructive technologies, chemometrics and data mining.",coeditorOneBiosketch:"Muhammad Imran has expertise in extrusion technology, microencapsulation, lipids chemistry, sensory evaluation and food process engineering.",coeditorTwoBiosketch:"A renowned scientist with expertise in Novel food processing technologies.",coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"292145",title:"Dr.",name:"Muhammad",middleName:null,surname:"Haseeb Ahmad",slug:"muhammad-haseeb-ahmad",fullName:"Muhammad Haseeb Ahmad",profilePictureURL:"https://mts.intechopen.com/storage/users/292145/images/system/292145.png",biography:"Dr. Muhammad Haseeb Ahmad is currently an assistant professor in the Department of Food Science, Government College University Faisalabad, Pakistan. He also served as an assistant professor for one year at the National Institute of Food Science and Technology, University of Agriculture Faisalabad, Pakistan. He received his doctoral degree from Hohenheim University, Stuttgart, Germany, in 2016. During his stay there, he also worked as a research associate for research projects relevant to various food disciplines. Dr. Ahmad is the author of about thirty five research publications and twelve book chapters. He has also presented his research work at various national and international conferences (25). 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He won the Indigenous and IRSIP (Department of Food Science and Human Nutrition, Michigan State University, East Lansing, USA) Fellowships for completion of doctorate research funded by HEC, Islamabad, Pakistan. Dr. Muhammad Imran has expertise in extrusion technology, microencapsulation, lipids chemistry, sensory evaluation, and food process engineering. Until today, Dr. Muhammad Imran has authored 80 publications (International & National) in various Impact Journals of Scientific repute and written 15 Book Chapters as principal author and co-author. Dr. Muhammad Imran has attended several International Conferences (held nationally and locally) as an Invited and Keynote Speaker and also participated as an organizing member to conduct International Conferences, Seminars Workshops, etc. Dr. Muhammad Imran is a Life Time Member of PSFST.",institutionString:"Government College University, Faisalabad",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Government College University, Faisalabad",institutionURL:null,country:{name:"Pakistan"}}},coeditorTwo:{id:"208645",title:"Dr.",name:"Muhammad",middleName:null,surname:"Kamran Khan",slug:"muhammad-kamran-khan",fullName:"Muhammad Kamran Khan",profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:"Government College University Faisalabad",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"0",institution:null},coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"5",title:"Agricultural and Biological Sciences",slug:"agricultural-and-biological-sciences"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"429339",firstName:"Jelena",lastName:"Vrdoljak",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/429339/images/20012_n.jpg",email:"jelena.v@intechopen.com",biography:"As an Author Service Manager, my responsibilities include monitoring and facilitating all publishing activities for authors and editors. From chapter submission and review to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review, and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. Whether that be identifying an exceptional author and proposing an editorship collaboration, or contacting researchers who would like the opportunity to work with IntechOpen, I establish and help manage author and editor acquisition and contact."}},relatedBooks:[{type:"book",id:"6418",title:"Hyperspectral Imaging in Agriculture, Food and Environment",subtitle:null,isOpenForSubmission:!1,hash:"9005c36534a5dc065577a011aea13d4d",slug:"hyperspectral-imaging-in-agriculture-food-and-environment",bookSignature:"Alejandro Isabel Luna Maldonado, Humberto Rodríguez Fuentes and Juan Antonio Vidales Contreras",coverURL:"https://cdn.intechopen.com/books/images_new/6418.jpg",editedByType:"Edited by",editors:[{id:"105774",title:"Prof.",name:"Alejandro Isabel",surname:"Luna Maldonado",slug:"alejandro-isabel-luna-maldonado",fullName:"Alejandro Isabel Luna Maldonado"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10359",title:"Landraces",subtitle:"Traditional Variety and Natural Breed",isOpenForSubmission:!1,hash:"0600836fb2c422f7b624363d1e854f68",slug:"landraces-traditional-variety-and-natural-breed",bookSignature:"Amr Elkelish",coverURL:"https://cdn.intechopen.com/books/images_new/10359.jpg",editedByType:"Edited by",editors:[{id:"231337",title:"Dr.",name:"Amr",surname:"Elkelish",slug:"amr-elkelish",fullName:"Amr Elkelish"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1591",title:"Infrared Spectroscopy",subtitle:"Materials Science, Engineering and Technology",isOpenForSubmission:!1,hash:"99b4b7b71a8caeb693ed762b40b017f4",slug:"infrared-spectroscopy-materials-science-engineering-and-technology",bookSignature:"Theophile Theophanides",coverURL:"https://cdn.intechopen.com/books/images_new/1591.jpg",editedByType:"Edited by",editors:[{id:"37194",title:"Dr.",name:"Theophile",surname:"Theophanides",slug:"theophile-theophanides",fullName:"Theophile Theophanides"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3161",title:"Frontiers in Guided Wave Optics and Optoelectronics",subtitle:null,isOpenForSubmission:!1,hash:"deb44e9c99f82bbce1083abea743146c",slug:"frontiers-in-guided-wave-optics-and-optoelectronics",bookSignature:"Bishnu Pal",coverURL:"https://cdn.intechopen.com/books/images_new/3161.jpg",editedByType:"Edited by",editors:[{id:"4782",title:"Prof.",name:"Bishnu",surname:"Pal",slug:"bishnu-pal",fullName:"Bishnu Pal"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3092",title:"Anopheles mosquitoes",subtitle:"New insights into malaria vectors",isOpenForSubmission:!1,hash:"c9e622485316d5e296288bf24d2b0d64",slug:"anopheles-mosquitoes-new-insights-into-malaria-vectors",bookSignature:"Sylvie Manguin",coverURL:"https://cdn.intechopen.com/books/images_new/3092.jpg",editedByType:"Edited by",editors:[{id:"50017",title:"Prof.",name:"Sylvie",surname:"Manguin",slug:"sylvie-manguin",fullName:"Sylvie Manguin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"371",title:"Abiotic Stress in Plants",subtitle:"Mechanisms and Adaptations",isOpenForSubmission:!1,hash:"588466f487e307619849d72389178a74",slug:"abiotic-stress-in-plants-mechanisms-and-adaptations",bookSignature:"Arun Shanker and B. Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"72",title:"Ionic Liquids",subtitle:"Theory, Properties, New Approaches",isOpenForSubmission:!1,hash:"d94ffa3cfa10505e3b1d676d46fcd3f5",slug:"ionic-liquids-theory-properties-new-approaches",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/72.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"314",title:"Regenerative Medicine and Tissue Engineering",subtitle:"Cells and Biomaterials",isOpenForSubmission:!1,hash:"bb67e80e480c86bb8315458012d65686",slug:"regenerative-medicine-and-tissue-engineering-cells-and-biomaterials",bookSignature:"Daniel Eberli",coverURL:"https://cdn.intechopen.com/books/images_new/314.jpg",editedByType:"Edited by",editors:[{id:"6495",title:"Dr.",name:"Daniel",surname:"Eberli",slug:"daniel-eberli",fullName:"Daniel Eberli"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"57",title:"Physics and Applications of Graphene",subtitle:"Experiments",isOpenForSubmission:!1,hash:"0e6622a71cf4f02f45bfdd5691e1189a",slug:"physics-and-applications-of-graphene-experiments",bookSignature:"Sergey Mikhailov",coverURL:"https://cdn.intechopen.com/books/images_new/57.jpg",editedByType:"Edited by",editors:[{id:"16042",title:"Dr.",name:"Sergey",surname:"Mikhailov",slug:"sergey-mikhailov",fullName:"Sergey Mikhailov"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1373",title:"Ionic Liquids",subtitle:"Applications and Perspectives",isOpenForSubmission:!1,hash:"5e9ae5ae9167cde4b344e499a792c41c",slug:"ionic-liquids-applications-and-perspectives",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/1373.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"52686",title:"Behavior of Ionic Liquids Under Nanoconfinement Greatly Affects Actual Friction",doi:"10.5772/65758",slug:"behavior-of-ionic-liquids-under-nanoconfinement-greatly-affects-actual-friction",body:'\nIonic liquids (ILs) are expected to be promising candidate materials for new lubricants [1–5]. In particular, their stability under severe conditions, such as ultrahigh vacuum [6, 7] and high temperatures [8], has attracted increasing interest. To choose ILs suitable for use as lubricants, it is important to understand the characteristics of the target materials. However, currently, the details of the lubrication mechanism of ILs are not clearly understood.
\nThe tribological properties of ILs have been studied using a macroscopic tribotester. Most previous research has focused on the lubricating behavior of ILs in the boundary lubrication regime at high loads of several GPa and on their tribochemical reactions with solid surfaces [9–13]. The formation of tribochemical layers on metal surfaces from ILs containing a halogen such as fluorine under sliding conditions has been studied by X-ray photoelectron spectroscopy (XPS) [9–12], scanning electron microscope with energy dispersive X-ray spectroscopy (SEM-EDS) [9–11], and time-of-flight secondary ion mass spectrometry (TOF-SIMS) [12]. Therefore, ILs have also been used as additives for the formation of a tribochemical layer under high loads of several GPa [14–16]. When used, these layers have been considered to contribute to the reduction of friction in the system.
\nOn the other hand, due to the interest in applying ILs as lubricants, the properties of ILs confined in a nanoscale space have also been studied by atomic force microscopy (AFM) [17–19] and the surface force apparatus (SFA) [20, 21]. The oscillating forces observed by both AFM and SFA demonstrated the layered structure of ILs in narrow gaps. However, the relationship between these nanoscale properties and the macrolubrication properties is still not fully understood even for the same surface and ILs. Motivated by this problem, we have recently used resonance shear measurement (RSM) to show that some ILs form a layered structure in the nanoscale space created by the sliding surface [21, 22]. We also revealed that a nanostructure consisting of only several IL layers had a large influence on macroscale friction.
\nIn this chapter, we describe the nano- and macrolubrication properties of some ILs (Table 1) with different anions by using RSM and a conventional ball-on-plate-type tribotester, respectively. This study reveals that ILs with different structures form different nanolayered structures and that their nanoscale behaviors are correlated with their macroscale tribology. In addition to providing information related to the lubrication mechanism of ILs, we also describe the principles for choosing an IL as a lubricant.
\nName, abbreviation, structure, molecular weight (MW), density (
RSM was performed using an in-house resonance shear system based on an SFA [22], as shown schematically in Figure 1. The experimental setup and procedures for RSM are described in detail in a previous publication [21]. Silica sheets used as samples were prepared following the procedure reported by Horn et al. [24]. The root mean square (RMS) roughness value measured by AFM (Toyo Corporation, Agilent 5100 AFM/SPM Microscope) over an area of 5 × 5 μm2 for the silica sheets was 0.31 nm. Using RSM, the resonance curve between the molecularly smooth silica sheets was measured across IL films at a surface separation
Schematic of the RSM system. The surfaces are in the crossed-cylinder geometry.
The RSM system measured the surface force and resonance shear response by continuously changing the thickness of the liquid film confined between two solid surfaces with a nanometer resolution. The liquid thickness was controlled and determined using interferometric methods in the surface force apparatus. The shear response via resonance method provided a sensitive method for detecting the tiny changes in the liquid properties between the substrates, allowing us to evaluate the viscosity change associated with liquid structuring, frictional/lubricational property, as well as other properties, by simply changing the liquid film thickness.
\n\nFigure 2 shows the typical resonance shear curves for different surface separations. The resonance curves for the two reference states of separation in air (AS) and for silica-silica contact (SC) were measured prior to the RSM of a liquid (Figure 2). In the absence of a liquid, the system parameters (mass, damping parameter, and spring constant for the apparatus) determined the AS and SC resonance curves. In the presence of a liquid, the resonance curve at long distances showed a peak at a low frequency that was almost the same as the AS peak. The peak intensity
Typical resonance shear curves with different surface separations.
The RSM system described above was used to study the nanolubrication properties of ILs between smooth silica surfaces. Figure 3(a) and (b) shows the resonance curves for [DEME][TFSI] and [DEME][BF4] ILs confined between silica surfaces at various separation distances. For reference, the resonance curves for AS and SC were measured prior to the resonance shear measurement of the ILs (Figure 3). In the absence of the ILs, the system parameters (mass, damping parameter, and spring constant for the apparatus) determined the AS and SC resonance curves. In the presence of [DEME][TFSI], the resonance curve at
Resonance curves for (a) [DEME][TFSI] and (b) [DEME][BF4] confined between the silica surfaces at various separation distances under an applied load
The resonance shear behavior of [DEME][BF4] (Figure 3(a)) was similar to that of [DEME][TFSI], except in the small
Profiles of normal force normalized by surface curvature radius (
Figure 5 plots the relative intensity (
We analyzed the resonance curves using a previously developed physical model [27] to obtain a quantitative understanding of the properties of the confined ILs. The details of the analytical procedure are described in the literature [21, 27]. Figure 6 plots the effective viscosity (
Relative intensity (peak intensity confined ILs/SC peak intensity) versus the applied load for [DEME][TFSI] (●) and [DEME][BF4] (□) [
Effective viscosity
We suppose that the rapid increase in the effective viscosity with decreasing distance observed in Figure 6 corresponds to the distance at which the formation of a solid-like structure due to the confinement is initiated. For [DEME][BF4], the sharp viscosity increase began at a clearly shorter distance than that for [DEME][TFSI], indicating that this ammonium salt restructures more readily than the TFSI salt, or in other words, that the BF4 salt is more easily crystallized. This consideration is also supported by the results of the crystallization temperature measurement using differential thermal calorimetry (DSC) [28]. As indicated by the DSC measurements, [DEME][BF4], for which the viscosity increases at a relatively long distance, shows a distinct crystallization temperature, whereas the TFSI salt only shows a glass transition temperature but not a crystallization temperature. The same trend is found for aromatic ILs. The viscosity of [BMIM][TFSI], which has a specific crystallization temperature, rises rapidly at a large distance, whereas the viscosity of [BMIM][BF4], which does not show a crystallization temperature, rises rapidly only at a short distance [29].
\n\nFigure 7 plots
Plots of the effective viscosity
In the RSM, the facing silica surfaces were completely separated to avoid partial contact and to allow the analysis of the boundary lubrication property of the confined liquid at a certain separation distance. In this configuration, an increase in the viscosity of the lubricant layer under confinement directly leads to increased friction at the sliding interface. The results obtained from RSM showed that the
Friction measurements were carried out using a conventional reciprocating tribotester, TRIBOGEAR TYPE 38 (Shinto Scientific Co. Ltd., Tokyo), using a glass ball of 10 mmφ and a glass plate. To obtain a clean surface, the glass ball and glass plate were treated in fresh nitric acid at 373 K for 75 min. The RMS roughness values measured by AFM for the glass ball and plate were 9.9 and 1.2 nm over an area of 5 × 5 μm2, respectively. A schematic of the tribotester is shown in Figure 8. The measurements were performed at a movement distance of 10 mm, with a sliding velocity ranging from 5.0 × 10−4 to 3.0 × 10−2 m s−1 under an applied load of 196–980 mN at room temperature (295 ± 0.5 K). The friction force was measured by an all-in-one load converter from a gauge attached to the sample holder and was recorded as a function of time. The friction coefficient (
Schematic of reciprocating-type tribotester.
The Stribeck diagram of the friction behavior is used to explain the rubbing phenomena occurring in lubricated contacts [30]. A schematic representation of the Stribeck diagram is shown in Figure 9. For high values of
Schematic of Stribeck diagram; friction coefficient as a function of the lubrication parameter:
We studied the boundary lubrication properties of ILs between a glass ball and a glass plate by using a macroscopic tribotester. Figure 10 plots the friction coefficients between a glass ball and a glass plate in [DEME][TFSI] or [DEME][BF4] versus the sliding velocity (
For a confined IL, boundary lubrication is dominant, and the contribution of hydrodynamic lubrication due to the change in lubricant thickness is not effective. Therefore, the difference in boundary lubrication under the measurement conditions between [DEME][BF4] and [DEME][TFSI] can be explained based on the effective viscosity obtained from RSM. The obtained RSM results showed that the
Friction coefficient between a glass ball and a glass plate in [DEME][TFSI] (●), in [DEME][BF4] (□), by sliding the glass plate over a distance range of 10 mm at sliding velocity of 5.0 × 10−4 m s−1–3.0 × 10−2 m s−1 and under an applied load of 196–980 mN at 298 K. Dashed lines are guides to the eyes [
We now discuss the possible structural origin for the observed viscosity effects. Canova et al. studied the layering structure of ILs ([BMIM][TFSI] and [BMIM][BF4]) confined to a silica contact plane using molecular dynamics simulations. For [BMIM][TFSI], it was found that ion pairs orient alternately to form a checker-board structure. This means that each ion is forced to contact ions with the same charge during shearing [31]. The repulsive force between the ions with the same sign of the charge destabilizes the crystal structure of the IL and triggers an overall restructuring of inner molecular layers to form a more stable configuration, resulting in high friction. In contrast, [BMIM][BF4] formed a layer-by-layer structure where cations and anions did not suffer from such repulsions because each ion layer is sandwiched between the oppositely charged layers, leading to smooth shearing and low friction. Even though the cations used in our study are different from those studied by Canova et al., based on this insight, we ascribe the better boundary lubrication performance of [DEME][BF4] relative to that of [DEME][TFSI] to the differences in the layered structures of these ILs under confinement.
\nThe RSM showed that ILs were maintained between the silica surfaces at a surface separation of 2.5 nm for [DEME][TFSI] and 2.1 nm for [DEME][BF4], which are usually referred to as hard-wall thicknesses. Assuming a cubic packing geometry and following Horn et al.’s [23] method, the diameters of the ion pairs determined from the density were 0.79 nm for [DEME][TFSI] and 0.69 nm for [DEME][BF4]. Based on these values, we determined that in both systems, three layers of ILs were trapped between the silica surfaces. The dramatic reduction in the friction coefficient in “the boundary lubrication region” with ILs was presumably due to the presence of the three layers of ILs between the silica surfaces under an applied load of 196 mN.
\nThese results indicated that the tribotester macroscopic tribological properties correspond to the nanoscale lubrication properties obtained from nanoscopic RSM.
\nWe performed RSM and reciprocating-type tribotests to evaluate the friction properties of lubrication systems consisting of some types of ILs between the silica surfaces. In the case of [DEME][BF4] and [DEME][TFSI], the RSM results revealed that IL layers with a thickness of ca. 2 nm remained between the silica surfaces under applied loads. For these conditions, the effective viscosity of the IL including BF4 anion was smaller than that of the IL including the TFSI anion. Similarly, in the boundary lubrication regime, the friction coefficient
This work was supported in part by the “Green Tribology Innovation Network” Advanced Environmental Materials Area, Green Networks of Excellence (GRENE) program and Grants-in-Aid for Scientific Research (nos. 25810091, 26820034, and 30399258) sponsored by the Ministry of Education, Culture, Sports, Science and Technology (MEXT) in Japan.
\nLearning disability (LD) is an umbrella term that includes
Currently, all treatments for LD involve medications and rehabilitative techniques that focus on managing the symptoms. Thus, there is a need to explore other treatments which will work at the cellular level. Stem cell therapy is a new evolving field of regenerative medicine and has shown great potential as a treatment strategy for various disorders such as autism, intellectual disability, and cerebral palsy among many neuro-developmental conditions. It addresses the core underlying pathology of LD. In experimental studies, stem cell therapy has been shown to repair the hypoxia-damaged neural networks and restore the lost neuronal connections [7]. Stem cells, when injected, migrate to the target tissue and differentiate into mature cells. Along with regenerating and restoring the neurons and glial cells, they have a neuroprotective effect [8]. Several vertebrates regenerate tissues and organs, like the salamanders, regenerate lost body parts through the de-differentiation of specialized cells into new precursor cells. These de-differentiated cells then proliferate and later form new specialized cells of the regenerated organ. Stem cells or progenitor cells are the common denominators for nearly all types of regeneration [9]. The goal of stem cell therapy is thus to enable the localization of therapeutic cells to impaired/injured regions of the brain, to stimulate tissue repair and maintenance via a paracrine effect, and potentially even to generate new neurons [10]. Therefore, stem cells, through re-perfusion of the damaged brain regions in SLD can lead to improved neurological functions. This can increase academic performance and chances of employability in the future. Stem cell therapy has shown improved brain function and quality of life in similar neurological impairments such as autism spectrum disorder, cerebral palsy, intellectual disability.
This chapter focuses on the Regenerative capacity of Stem Cell Therapy in learning disability. It has a detailed description of what stem cells are, where they are obtained from, how they are injected into the body, and their mechanism of action. Furthermore, it explains how stem cell therapy results in a positive outcome in children with learning disabilities. We have included neuroimaging techniques such as PET CT brain scan as a monitoring tool to study the effect of stem cell therapy.
With increasing awareness, the prevalence of learning disability has risen considerably. Most often LD is managed with medications and rehabilitative therapies which include behavioral therapy, alternate methods of learning like remedial education, individualized education plan (IEP), and intervention programs. However, these treatment strategies do not address the underlying neuropathology of LD. Hence, there is a need for a treatment that focuses on cellular repair and further addresses the cognitive deficit.
Stem cells provide the building blocks for every organ in the body. They have the unique ability to divide asymmetrically and to differentiate into the various cell types of the body. They simultaneously replicate to maintain a stem cell lineage. Stem cells are present in almost every human tissue. In embryos, they differentiate into all the tissues and organs of the body and provide a renewal capacity in most organs in fully developed humans. In neurological disorders wherein the neurons are damaged or defective, stem cell therapy repairs and replaces damaged/lost neurons [10]. Cell therapy is based on allogenic (patient receives stem cells from a healthy donor), or autologous transplantation (patient receives their own stem cells) of cells, with the goal of regenerating the damaged tissue or organ of the patient and replenishing specific stem cell populations [11].
Classification of stem cells depend on major characteristics such as (Figure 1):
Types of stem cells based on differentiation potential and source.
Intra-arterial—Cell delivery involves endovascular infusion of progenitor cells directly in the artery perfusing the ischemic tissue. This route of cell delivery bypasses the peripheral filtering organs, thereby increasing cell delivery. It is less invasive than intracerebral transplantation, it is repeatable, it would allow for a systemic biological effect, and could lead to a widespread distribution in the affected brain regions [38]. Bioluminescent Imaging has shown that intra-arterial injected neural cells engraft in the hypoxia/ischemia-injured brain and engraftment efficiency for intra-arterial injection was 12× higher compared with intravenous delivery [39]. However, it is an invasive procedure with an increased risk of complications.
Stem cells have a unique property of homing and targeting specific damaged areas on administration. The homing mechanism is attributed to the expression of growth factors, chemokine, and extracellular matrix receptors on the surface of cells. On administration, they survive, migrate, proliferate, and differentiate into the required cell types [40]. They not only replace the damaged cells but also carry out the repair process via paracrine mechanisms [41]. Transplanted stem cells express paracrine signaling factors including cytokines and other growth factors, which are involved in the repair process through neuroprotection, increasing angiogenesis, decreasing inflammation, preventing apoptosis, activation of resident/satellite cells, etc. (Figure 2).
Mechanism of action of stem cells.
Stem cells secrete a vast array of neuroprotective growth factors including BDNF, nerve growth factor (NGF), neurotrophin-3 (NT-3), glial cell line-derived neurotrophic factor (GDNF), fibroblast growth factor-2, and insulin-like growth factor type 1. These growth factors activate signaling pathways, enhance the differentiation, survival of neurons and maintain neuronal functions [42].
Stem cells secrete signaling molecules like vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), and basic fibroblast growth factor (FGF2) resulting in improved perfusion, regional blood flow, enhanced angiogenesis, and oxygenation [43].
Stem cells impart an immunomodulatory effect as they reduce the levels of pro-inflammatory molecules TNF-α, IL-1β, IL-1α, IL-6 and increase levels of anti-inflammatory molecules such as IL-10 therefore, enhancing endogenous brain repair [44].
The resident stem cells may possess growth factor receptors that can be activated to induce their migration and proliferation and promote both the restoration of dead tissue and the improved function in damaged tissue. Transplanted cells stimulate these endogenous cells to carry out the repair process [45].
To our knowledge, there are no clinical studies of stem cell therapy in learning disability. However, it has been greatly explored in various pediatric neurological disorders such as autism, cerebral palsy, and intellectual disability [46].
Sharma et al. have established the safety and efficacy of bone marrow-derived mononuclear cells in autism and intellectual disability. In 254 cases of autism spectrum disorder, 95.27% of patients showed an improved score on CARS while 94.48% of cases showed improvement in ISAA. Symptomatic improvements were observed in eye contact, attention and concentration, hyperactivity, sitting tolerance, social interaction, stereotypical behavior, aggressiveness, communication, speech, command following, and self-stimulatory behavior. Eighty six patients who underwent a repeat PET CT scan showed improved brain metabolism after intervention in areas that correlated to the symptomatic changes [47].
In intellectual disability, the outcome of 29 patients of the intervention group was compared to that of 29 patients from only the rehabilitation group and it was found that all patients in the intervention group showed improvement while there was no improvement in 20.69% of patients from only the rehabilitation group. Improvement was noted in cognition, memory, problem-solving, understanding of relationships, social inhibitions, toilet training, command-following, eye contact, aggressive behavior, and attention and concentration. Comparative PET-CT scan study in patients of the intervention group showed improved metabolism in the frontal, parietal cortex, thalamus, mesial temporal structures, and cerebellum. No serious adverse events were recorded [48].
We have studied the outcome of autologous bone marrow-derived mononuclear cells in 20 individuals diagnosed with learning disability.
Demographically, 14 male and 6 female patients were included, where 6 patients were within ages 1–10 years, 13 within 11–20 years, and 1 patient in the 21–30 years age range. Symptomatically, these patients presented with dysfunctions in academic performance, attention and concentration, reading, writing and mathematical skills, spelling, comprehension and recognizing words, problem-solving, and memory issues. Their functional capacity was measured by functional independence measure (FIM) and intelligence and/or social quotient through various tests such as BKT and VSMS measures.
For the procedure of stem cell transplantation, autologous bone marrow mononuclear stem cells (BMMNCs) were selected as they were easily obtainable, safe, and did not involve any ethical issues. Intrathecal route of administration is a minimally invasive, safe, and effective procedure as compared to other routes. Studies have also shown that a mixture of cells exhibits more benefits as compared to a single subfraction of cells [49]. Hence, intrathecal autologous BMMNC transplantation was carried out in our study.
The patients were administered Granulocyte Colony Stimulating Factor (GCSF) before the harvest and transplantation of BMMNCs. On the day of the transplantation, 80–100 ml bone marrow was aspirated using a bone marrow aspiration needle from the right anterior superior iliac spine. This was collected in heparinized tubes and transported to the laboratory. Thereafter, in the culture laboratory, MNCs were separated by the density gradient technique. CD34 counts were performed and transported back to the operation theater in a cool sterile container. With the patient in a left lateral position, using a spinal needle, the thecal sac was punctured at L4-L5 space and the cells were injected through that spinal needle. Following this, Methylprednisolone 500 ml isolyte P was given intravenously, and the patient was observed for any adverse events.
After the stem cell transplantation, all patients underwent specialized rehabilitation such as special education, occupational and physical therapy, psychological counseling, and speech therapy.
No major procedure-related adverse events were recorded. One patient reported a slight increase in absence seizures, which was controlled with medications. On an average follow-up of 26 months, 94.7% patients showed an improved clinical status. Reading skills improved in 75% patients, writing skills in 88% patients and mathematical skills improved in 70% affected patients, attention increased in 94% patients, memory skills in 78.5% patients, problem-solving skills improved in 69% patients, and comprehension skills in 72.7% patients. Spelling and vocabulary skills improved in 75% and 60% patients respectively. Overall increased academic performance was reported in 70% patients (Figure 3).
Improvements were seen in various areas in 20 patients with learning disability post stem cell transplantation.
Evidence suggests that exercise induces mobility in the injected stem cells, thereby helping in the migration of the cells and helping upregulate neural plasticity [50]. Exercise also improves oxygenation and blood supply to the brain. Hence, the synergistic effect of stem cell therapy and neurorehabilitation brings about maximum functional recovery. Post stem cell therapy, the aim of rehabilitation in individuals with LD is to address the specific deficits that impair their ability to learn through sensory integration therapy, context-specific training, psychological counseling, and vocational training. Occupational therapy interventions use sensory integration methods to enhance sensory processing skills such as understanding, attention, sitting tolerance, and memory skills along with higher cognitive skills like judgment and problem-solving skills. Focusing on fine motor hand functions, handwriting grip, and writing skills are facilitated. Making use of visual schedules and timers to enhance time organization. Some studies showed direct instruction and modeling of letter formation, combined with memory retrieval, self-evaluation, fluency, and/or orthographic coding activities, led to improvements in students’ legibility and writing fluency in the studies [51, 52, 53], and improvements in correct word sequences [54]. Speech therapists may collaborate with instructors to incorporate instruction that involves multiple modalities to facilitate connections between letters and sounds, as well as between written and oral language that incorporates visual and auditory cues. Students with LD benefit from explicit and systematic instruction that is closely related to their area of instructional need [55]. Special education differs from general education for students with LD when it is more explicit, intensive, and supportive [49]. Some ways of facilitating improved academic performance and life skills are through controlling task difficulty, teaching students in small, interactive groups, modeling and teaching strategies for generating questions and thinking aloud while reading, writing, or working on a scientific or mathematical problem, direct and explicit instructional practices, higher-order processing skills and problem-solving along with learning when, where, and how to apply strategies, ongoing progress monitoring of specific skills, teaching the building blocks of reading and writing like phonemic awareness, writing speed, the process of writing and the organizational and mechanical aspects of writing [56, 57, 58, 59, 60]. These strategies enhance the specific skills of reading, writing, arithmetic and inculcate generalization of strategies in life. Alternatively, Art therapy can be used in people with SLD who have difficulties in expressing themselves. It is a form of psychotherapy using art media as its primary mode of communication. Making artwork can facilitate expression and communication for people who find it difficult to express their thoughts and feelings verbally, and it is an accessible approach for children and adults with learning disabilities [61].
Brain tissue requires glucose for functional activity. The PET-CT scan records brain metabolism by using fluorodeoxyglucose (FDG) uptake. The active neural tissue absorbs glucose in direct proportion to its function. In turn, FDG uptake measures glucose metabolism and detects neuronal activity, which is the level of brain function. It is a promising technology to detect cellular effects of neurorestoration [62, 63]. In our study, a PET-CT scan was performed for all patients prior to cell transplantation to determine the dysfunctions in the brain. In the patients who underwent a repeat stem cell transplantation, PET images were compared to study the changes in brain metabolism after cell therapy. The images prior to stem cell therapy revealed hypo-metabolism in bilateral cerebellar hemispheres, medial temporal lobe, anterior and posterior cingulate gyri, and bilateral thalami with basal ganglia involvement, whereas hyper-metabolism was seen in the prefrontal cortex in many cases. These areas showed improved metabolism after cell therapy (Figures 4 and 5).
Improvements were seen in reduced hypometabolism in areas of cerebellum and basal ganglia 12 months post stem cell therapy (the blue hypometabolic areas turn green post cellular therapy).
Improvements were seen in reduced hypometabolism in areas of the cerebellum, temporal and parietal lobes 8 months post stem cell therapy.
Stem cell therapy in combination with standard treatment and rehabilitation is a novel therapeutic option for learning disability. Its safety and efficacy have already been established in other incurable pediatric conditions such as autism, cerebral palsy, intellectual disability. Likewise, the results of our study conducted on patients with a learning disability have demonstrated a positive outcome and is an excellent foundation upon which future research can be advanced. Future studies should focus on analyzing the benefits of different cell types, the number of cells, and the route of administration for optimal use of cell therapy in learning disability.
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In this work, we are interested in the Neuromate robot. The latter uses the procedure of stereotaxic surgery but with better planning, greater precision and simpler execution. The Neuromate robot allows in particular the registration with intraoperative images (ventriculographies, and especially angiographies) in order to perfect the planning. In this book, we focus on the contact force measurement system required for the effectiveness of the stimulation between the robot probe and the patient’s head and thus ensure the safety of the patient. A force sensor is integrated upstream of the wrist, the pressure sensor is part of a silicon matrix that has been bonded to a metal plate at 70°C. The study was carried out under the software COMSOL Multiphysics, ideally suited for the simulation of applications (Microelectromechanical systems) “MEMS”. After electromechanical stationary survey, deflection of the quadrant when the pressure difference across the membrane was 25 kPa, as expected, the deviation was expected to be greatest at the center of the membrane. The proposed sensor structure is a suitable selection for MEMS capacitive pressure sensors.",book:{id:"6865",slug:"becoming-human-with-humanoid-from-physical-interaction-to-social-intelligence",title:"Becoming Human with Humanoid",fullTitle:"Becoming Human with Humanoid - From Physical Interaction to Social Intelligence"},signatures:"Hacene Ameddah",authors:[{id:"302678",title:"Dr.",name:"Hacene",middleName:null,surname:"Ameddah",slug:"hacene-ameddah",fullName:"Hacene Ameddah"}]},{id:"70653",title:"Living and Interacting with Robots: Engaging Users in the Development of a Mobile Robot",slug:"living-and-interacting-with-robots-engaging-users-in-the-development-of-a-mobile-robot",totalDownloads:795,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Mobile robots such as Aldebaran’s humanoid Pepper currently find their way into society. Many research projects already try to match humanoid robots with humans by letting them assist, e.g., in geriatric care or simply for purposes of keeping company or entertainment. However, many of these projects deal with acceptance issues that come with a new type of interaction between humans and robots. These issues partly originate from different types of robot locomotion, limited human-like behaviour as well as limited functionalities in general. At the same time, animal-type robots—quadrupeds such as Boston Dynamic’s WildCat—and underactuated robots are on the rise and present social scientists with new challenges such as the concept of uncanny valley. The possible positive aspects of the unusual cooperations and interactions, however, are mostly pushed into the background. This paper describes an approach of a project at a research institution in Germany that aims at developing a setting of human–robot-interaction and collaboration that engages the designated users in the whole process.",book:{id:"6865",slug:"becoming-human-with-humanoid-from-physical-interaction-to-social-intelligence",title:"Becoming Human with Humanoid",fullTitle:"Becoming Human with Humanoid - From Physical Interaction to Social Intelligence"},signatures:"Valerie Varney, Christoph Henke and Daniela Janssen",authors:[{id:"299092",title:"Dr.",name:"Valerie",middleName:null,surname:"Varney (neé Stehling)",slug:"valerie-varney-(nee-stehling)",fullName:"Valerie Varney (neé Stehling)"},{id:"299578",title:"Dr.",name:"Daniela",middleName:null,surname:"Janssen",slug:"daniela-janssen",fullName:"Daniela Janssen"},{id:"299580",title:"MSc.",name:"Christoph",middleName:null,surname:"Henke",slug:"christoph-henke",fullName:"Christoph Henke"}]},{id:"66784",title:"Physical Interaction and Control of Robotic Systems Using Hardware-in-the-Loop Simulation",slug:"physical-interaction-and-control-of-robotic-systems-using-hardware-in-the-loop-simulation",totalDownloads:966,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Robotic systems used in industries and other complex applications need huge investment, and testing of them under robust conditions are highly challenging. 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The mathematical model is developed using MATLAB software and the virtual animation setup of the robot is developed using the Virtual Robot Experimentation Platform (V-REP) robot simulator. 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