Properties of neurodegenerative diseases.
\r\n\tOver the years, the concept of maintenance became more comprehensive, reducing fault occurrence and increasing industrial system availability. Besides, reliability, safety, and criticality requirements were associated with the system or equipment under analysis. Maintenance strategies or schemes can be classified as corrective (run-to-break), preventive (time-based), and predictive (condition-based maintenance). Corrective maintenance is only performed after an occurrence of a fault. Therefore, it involves unexpected breakdowns, high costs, changes in the production chain, and it could lead to catastrophic events. Preventive maintenance and interventions occur based on a scheduled maintenance plan or the equipment's mean time between failures. Although it is more effective than corrective maintenance, unexpected failure may still occur by preventing most failures. Additionally, the process cost is still high, especially the costs associated with labor, inventory, and unnecessary replacement of equipment or components.
\r\n\tOn the other hand, predictive maintenance analyses the equipment condition so that a possible fault can still be identified at an early stage. Predictive maintenance aims to identify a machine anomaly so that it does not result in a fault. Such maintenance involves advanced monitoring, processing, and signal analysis techniques, which are generally performed non-invasively and, in many cases, in real-time. In the case of machines or processes, these techniques can be developed based on vibration, temperature, acoustic emission, or electrical current signal monitoring. It should be noted that monitoring such signals or parameters to verify the operating condition is called condition monitoring. Condition monitoring aims to observe the machine's current operational condition and predict its future condition, keeping it under a systematic analysis during its remaining life. In this sense, a fault condition can be detected and identified from systematic machine condition monitoring. A diagnosis procedure can be established, whereby properly investigating the fault symptoms and prognosis.
\r\n\t
\r\n\tThis book will aim to merge all these ideas in a single volume, aggregate new maintenance experiences, apply new techniques and approaches, and report field experiences to establish new maintenance processes and management paradigms.
\r\n\t
Proteins and peptides are essential complex macromolecules of organisms and participate in actually every process within cells. Three dimensional structures of proteins play a critical role for biological functions. Therefore, they must be properly folded for performing these functions. Three dimensional structures are determined by composition of amino acid sequence. In addition to hydrophobic forces, covalent and weak interactions direct the formation of native protein conformation [1].
Proteins can be exposed to internal and external forces such as protein-protein interactions, various stresses, mutations etc. Since these forces alternates protein conformation, the biological activity of the protein decreases. However, newly synthesized proteins may not fold correctly, or properly folded proteins cannot spontaneously fold. In this case, proteins have a strong tendency to aggregate [1-3]. Especially, heat shock proteins (chaperones) play a key role in correcting protein folding and prevention of protein aggregation [1, 4, 5].
Protein aggregates has toxic effects when accumulated over a certain amount in the cell. The accumulation of abnormal proteins leads to progressive loss of structure and/or function of neurons, including the death of neurons. Many diseases associate with protein aggregation such as prion, Alzheimer’s (AD), Parkinson’s (PD), and Huntington’s diseases (HD). Thus, dysmnesia, mental retardation, and also cancer are seen in these diseases. Many of the neurodegenerative disorders likely occur due to environmental and genetic factors. Especially, probability of AD and PD occurrence rise with increasing age. Briefly, neurodegenerative diseases have similar pathogenesis and cellular mechanisms [6-10].
Nowadays, mechanisms of protein aggregations and generation of neurodegenerative diseases with misfolded proteins are not clear at the molecular level. Thus, protein aggregation is a bone to pick for biotechnology and pharmaceutical industries. The aim of this chapter is to bring a perspective to the role of misfolded proteins in neurodegenerative diseases in terms of molecular and cellular basis.
Formation of neurodegenerative diseases has not been elucidated for many years. To date, a variety of mechanisms have been suggested for explaining protein misfolding and protein aggregation, however we cannot understand the mechanism clearly at the molecular and cellular basis.
Functional proteins must pass a quality control process in terms of folding to perform catalysis, cellular transport, signal transmission and regulation. However, variety of structural and environmental factors influence this process negatively [1-3]. In this section, we will focus on aggregation behavior of proteins and these factors.
The first critical factor is protein structure. Especially, primary and secondary structures of a protein are two of the most important factors for physical and chemical features.
Encoded information in amino acid sequence of a protein determines the three dimensional structure. Position and number of different characteristic amino acid residues in primary structure may lead to an increase or a decrease in aggregation behavior. Number of hydrophobic amino acids in proteins is proportional to tendency of aggregation [2].
Secondary structures of proteins involve in protein misfolding as well as stability. Proteins often fold locally into stable structures that include α-helix and β-sheet. Generally, some β-sheet-rich proteins (such as scrapie infected prion protein) associate with pathological states. During protein aggregation, the secondary structure is converted from α-helix to β-sheet. Thus, protein gets strictness and wide surface area [1, 11, 12].
Mutations play determinative role in protein aggregation and they may dramatically alter solubility, stability, and aggregation tendency of proteins [13].
Thermally stable proteins may change its stability even with a point mutation in its structure. For example, a human lysozyme I56T and D67H mutants greatly decreases the lysozyme stability and as a result the lysozyme aggregates easily upon heating. Further aggregation cause amyloid fibrils and these fibrils are deposited in tissues and are associated with neurodegenerative diseases [2].
Recently, scientists have been suggested a new protein for understanding of ALS (amyotrophic lateral sclerosis), AD, cystic fibrosis (CF) and frontotemporal lobar degeneration (FTLD) mechanisms. The transactive response DNA binding protein 43 (TDP-43) is expressed by all mammalian tissues, conformational changes in this protein cause aggregation and loss of function. TDP-43 has been shown to bind to DNA and mRNA and participate in regulation of transcription and translation. TDP-43 has a glycine rich C-terminal tail and mutation occurs from this region. Consequently, TDP-43 is converted to aggregated form which is accumulated in tissues [14].
After a protein is synthesized, the posttranslational modifications (PTM) of amino acids may increase the diversity of proteins by additional functional groups (acetate, phosphate, various proteins etc.) and structural changes [15]. In particular, phosphorylation plays a significant role in neurodegenerative diseases. It is also known that, occurrence of AD is associated with tauopathy due to aggregation of the tau protein. In brain, tau protein is found in neurons and it can be phosphorylated with kinase enzymes. Thus, aberrant tau aggregates are formed and they can be accumulated in neurons, thereby their toxic effects are caused neuronal loss and synaptic alteration [16, 17].
Glycosylation is an important PTM for protein stability and aggregation potential. Human prion protein has two potential
Hyperphosphorylation and hyperglycosylation are seemed to be required for protein aggregation and misfolding in neurodegenerative diseases. Moreover, the other PTMs such as glycation, nitration, truncation, polyamination etc. involve in protein misfolding diseases [17].
Oxidative stress leads to protein oxidation which is a biomarker for many neurodegenerative diseases. In particular, free radicals and ROS (reactive oxygen species) cause protein oxidation. A variety of oxidants can be occurred in normal aerobic metabolism [20]. Also, lack of antioxidants, excess of oxygen and lipid and metal ions can generate free radicals.
The oxidation of proteins extremely depends on their amino acid compositions. Generally; lysine, histidine, arginine, methionine, cysteine, phenylalanine, tryptophan, threonine, glutamic acid, and proline residues incline oxidation. Some proteins have metal binding regions on its own structure. Metal ions such as copper, zinc, and iron, are capable of redox reactions and electrons are transferred from ions to oxidizing compounds. Therefore, toxic free radicals are formed and proteins can be converted into aggregation forms or proteins can be aggregated by conformational changes [20, 22].
Protein concentration is an important parameter in protein aggregation. High protein concentration can increase the likelihood of aggregation. Protein-protein interactions and intermolecular interactions (especially interactions among hydrophobic amino acids) may generate abnormal protein structures. Some misfolded protein aggregates can be constituted neurodegenerative diseases above a certain concentration. Moreover, proteins are refolded at low concentrations spontaneously. For example, lysozyme and immunoglobulin G refold itself at low protein concentration however, refolding yield decreases with increasing protein concentration. Therefore, the optimum spontaneous protein concentration range is accepted as 10-50 µg/ml. [2, 23].
Environmental pH is to be critical for protein aggregation due to changes in net charge on protein. Protonation state of ionizable sites of protein and positive net charge are increased in acidic conditions. Especially, organization of salt bridges is changed in parallel with composed new secondary structures [2,20]. In prion diseases, acidic pH facilitates generation of PrPSc. At low pH, PrPc gains β-sheet structures and shows aggregation tendency [24]. According to the Finl (2006), α-Syn incubated at different temperature and pH values, and the best formation conditions were determined as pH 7.4 and 37˚C [25]. α-Syn can be lost its native structures and PD is accelerated in these conditions.
In the world, millions of elder people suffer from neurodegenerative diseases and diagnosis and treatment of these diseases costs millions of dollars per year. Unfortunately, the mechanisms of these diseases are still unclear and we don’t have effective treatment methods. Neurodegenerative diseases are identified as protein misfolding diseases, proteopathies and protein conformational disorders. All diseases (prion, AD, PD, and HD) show typical symptoms: loss and deterioration of neurons and synaptic alterations.
Protein misfolding leads to protein aggregation and accumulation of these aggregates is implicated as the main reason of neurodegenerative diseases. In brain, some native proteins (prion, tau, β-amyloid, α-synuclein, and huntington) undergo conformational changes via genetic and environmental factors. Therefore, secondary structures of protein convert from α-helix/random coil to β-sheet (Table 1.). Consequently, neurotoxic misfolded protein aggregates are deposited in central nervous systems and brain damage and neurodegenerative diseases are formed. In this section, we will analyse the most important four neurodegenerative diseases; prion diseases, AD, PD, and HD, on the basis of protein aggregation and its molecular and cellular mechanisms [6, 8-10].
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t
Prion Diseases | \n\t\t\tPrion | \n\t\t\tProtein aggregation | \n\t\t\tβ-sheet | \n\t\t\tSpongiosis | \n\t\t
Alzheimer’s Diseases | \n\t\t\tTau β-amyloid | \n\t\t\tProtein aggregation | \n\t\t\tβ-sheet | \n\t\t\tNeurofibrillary Tangles Senile Plaques | \n\t\t
Parkinson’s Diseases | \n\t\t\tα-Synuclein | \n\t\t\tProtein aggregation | \n\t\t\tβ-sheet | \n\t\t\tLewy Bodies | \n\t\t
Huntington’s Diseases | \n\t\t\tHuntington | \n\t\t\tProtein aggregation | \n\t\t\tβ-sheet | \n\t\t\tHuntington Inclusion | \n\t\t
Properties of neurodegenerative diseases.
The group of prion diseases, including Creutzfeldt-Jakob (CJD), fatal familial insomnia (FFI), Kuru, Gerstmann-Sträussler-Scheinker syndrome (GSS) are seen in humans, and in similar fashion scrapie, bovine spongiform encephalopathy (mad cow disease), chronic wasting diseases (CWD), transmissible mink encephalopathy (TME), feline spongiform encephalopathy (FSE) diseases are observed in animals. All of these diseases give similar neurological symptoms such as dysmnesia, depression, sense disturbances, and psychosis [26].
In 1982, prion term coined by Stanley Prusiner and co-workers from “proteinaceous infectious particle”. Prion protein is found in two different forms: a cellular form of prion protein (PrPc) and scrapie isoform of prion protein (PrPSc). Properly folded form is denoted as PrPc while misfolded form is denoted as PrPSc [27].
The PrPc is an α-helix-rich glycoprotein that is approximately 250 amino acids in length. It is encoded by the
PrPc is highly conserved protein among mammals during evolution (Fig.1.). When we examine the primary structure of the protein, PrPc consist of a signal peptide (1-22), five octapeptide repeats (PHGGGWGQ) (51-91), a highly conserved hydrophobic domain (106-126), and a GPI (glyco-sylphosphatidylinositol) anchor. Furthermore, PrPc contains two N-linked glycosylation sites (181Asn-Ile-Thr and 197Asn-Phe-Thr). Thus, they get dynamic and flexible properties and the glycan covers prevent intermolecular and intramolecular interactions. His96 and His111 are found in metal binding domains of PrPc and they compose coordination sites with metal ions (Cu+2, Zn+2, Mn+2, Ni+2). A disulfide bond between Cys179 and Cys214 play a significant role for proper folding of PrPc [9, 18-20, 24, 27].
Multiple protein sequence alignment of prion proteins. Full length amino acid sequences of rabbit (NP_001075490.1), bovine (GenBank: CAA39368.1), human (UniProtKB/Swiss-Prot: P04156.1), and mouse (NP_035300.1) were aligned using the program Clustal W. PHGGGWGQ repeats are shaded in red. Metal binding sites, His96, and His111 are shaded in blue. Glycosylation sites, 181NIT and 197NFT, are shaded in pink. Finally, Cys179 and Cys214 (disulfide bond sites) are shaded in black.
PrPSc can be defined as an infectious isoform of PrPc and causes fatal prion diseases. PrPSc is formed by misfolding of PrPc with a lost in α-helical content. PrPSc has same amino acid sequence with PrPc, but their secondary, tertiary, and quarternary structures are different. Approximately, PrPc includes 3% β-structure and 47% α-helix structure, but nonetheless PrPSc is composed of 43% β-structure and 30% α-helix structure [24, 29]. It becomes non-soluble and resists to proteolytic degradation with conformational changes, whereas PrPc is soluble and protease sensitive. This insoluble protein accumulates in brain and causes a variety of prion diseases in human and animals.
Previous studies suggested a variety of mechanisms for explaining prion pathology. Oxidative stress and lipid peroxidation are the major factors in prion diseases [20, 30]. In central nervous systems, a variety of oxidative stresses including high level of oxygen and lipid, metal ions, and inadequate antioxidants produce free radicals. In PrPSc infected mice, superoxide anion (O2-) is extremely increased in brain. Therefore, high levels of heme oxygenase-1 and malondialdehyde are observed as oxidative stress markers in brain. Cytochrome c oxidase is a large transmembrane protein in mitochondria and it shows antioxidant activity in mitochondria [12, 31]. The level of lipid peroxidation is increased while Cytochrome c oxidase activities are reduced in scrapie infected animal models. Phospholipase D catalyzes the hydrolysis of phosphatidylcholine to generate choline and phosphatidic acid, and its expression level is induced by H2O2 [12]. According to the studies, activity of phospholipase D is increased in the brains of scrapie infected animals. As a result, PrPc transforms into PrPSc because of the formation of these free radicals.
As we discussed the effect of metal ions on protein misfolding in section 2.1.4, the metal ions also play key roles in prion formation. Cu2+ions play a critical role in prion diseases. PrPc has five conserved octapeptide repeats (PHGGGWGQ) which have an affinity for Cu2+ ions. In contrast, affinity of other metal ions (Mg2+, Mn2+, Ni2+ etc.) is weak or nonexistent. The binding of Cu2+ provides formation of protease resistant form: PrPSc. It is also suggested that, PrPc protects cells from harmful redox activities. Especially, in copper-rich environment, PrPc acts as a “copper buffer” that means it inhibits toxic effects of Cu2+ ions for central nervous system and helps maintaining neurons in high level of cupper ions. Thus, redox damage of PrPc has been involved in prion diseases. In brief, copper can convert the cellular prion protein into a protease-resistant species with conformational changes [31-35].
Glycosylation is a stability-enhancing post translational modification in proteins. PrPc contains two potential glycosylation sites which are Asn181 and Asn197 in human PrPc [36]. Generally, binding of carbohydrates can protect protein surface from proteases and undesired protein-protein interactions. Moreover, N-glycosylated prion protein is anchored to the lipid membranes via GPI [18, 19].
Interaction of PrPc with membrane lipid layers play a significant role in conversion of PrPc to PrPSc. PrPc is localized in cholesterol and sphingomyelin rich area on cell surface (known as lipid raft). PrPc is bound to lipid membranes through its GPI anchor. While leaving PrPc from the membranes by catalysis of phosphatidylinositol phospholipase C (PIPLC), PrPSc show resistance to PIPLC. When binding of PrPc to the lipid membranes, PrPc is degraded or converted into PrPSc form [37-40].
Alzheimer’s disease (AD) is the most frequent type of neurodegenerative disorder in the world. AD is composed of accumulation of aberrant folded tau protein and beta-amyloid protein (Aβ protein) in brain. In 1906, AD was first described by psychiatrist and pathologist Dr. Alois Alzheimer and then the disease was named with his surname [8-10].
To date, there are no effective treatment methods for AD, but some nuclear medicine applications (MRI and PET) are applied in diagnosis of AD. Dramatically, symptoms of AD rise with increasing age and the first sign is memory lapse. Cellular and molecular mechanisms of AD are not well understood yet. Researchers have been reported that AD is associated with genetic and environmental factors and life-style.
A microtubule associated protein, Tau, is a biggest component of AD. In 1975, tau proteins were first discovered by Marc Kirschner in Princeton University. Tau was derived from “
The human
Schematic representation of six human tau isoforms. R1, R2, R3, and R4 (blue boxes) indicate repeat regions. E2 and E3 (orange and yellow box) indicate Exon 2 and Exon 3 respectively (Redrawn from Buee et al., 2000).
Tau protein has four main regions in its primary structures. Acidic region is located in the N-terminal part and it is encoded by exon 2 and exon 3. Prolin-rich region located in the middle of the protein, is encoded by exon 7 and exon 9 and contains several PXXP motifs which can interact with tyrosine kinase. Prolin-rich region works together with acidic region, therefore these two regions are called projection domain which interacts with neural plasma membrane and cytoskeletal elements [16, 17, 41-43].
Tau protein has three to four highly conserved repeats in the C-terminal part for binding to microtubules. Therefore, these repetitive regions are called microtubule binding domains (MBDs) which is encoded by exons 9-12. 275VQJINK280 and 306VQJVYK311are conserved hexapeptides which are located at the beginning of the second and third MBDs. These peptides involve in the generation of β-sheet structure during tauopathy [44].
Microtubules are major proteins of the cytoskeleton. They have hollow and cylindrical structure and participate in intracellular transport, protection cell structure, and continuity of cell viability. The main function of the tau protein is to stabilize microtubules with binding to microtubules and to other proteins [16, 41]. To perform these functions, tau proteins must be phosphorylated at normal level. However, if tau protein hyperphosphorylate, its biological activity can be lost. Moreover, hyperphosphorylation causes conformational changes and aggregation of tau proteins. Other post-translational modifications such as glycosylation, glycation, polyamination, and nitration may play essential roles in AD [17].
The longest isoform of tau protein (441 amino acids) has seventy nine Ser or Thr phosphorylation sites which are mainly found on prolin-rich regions. Also, Ser262, Ser293, Ser324, and Ser356 are located in KXGS motif of R1, R2, R3, and R4 domains. Many of kinases and phosphatases (glycogen synthase kinase-3β (GSK3β), mitogen activated protein kinase (MAPK), tau tubulin kinase 1-2 (TTBK1/2), cyclin dependent kinase 5 (CDK5), microtubule affinity regulating kinase (MARK), and stress activated protein kinase (SAP) are affected in tau phosphorylation [17, 45, 46].
Frontotemporal dementia with parkinsonism-17 (FTDP-17) is a progressive neurodegenerative disease which is caused by mutations in the tau gene. The tau gene is mutated in familial FTDP-17 and this mutation accelerates formation of neurofibrillary tangles (NFTs) in the brain. Furthermore, hyperphosphorylation is promoted by this mutation [47,49].
Excess of NFTs and senile plaques (SPs) are important markers in AD. NFTs are aggregates of hyperphosphorylated tau protein that are most commonly known as a primary marker of AD [50]. NFTs are originated from abnormally hyperphosphorylated tau protein. Normally, tau is a microtubule binding protein that stabilizes and assembles microtubules. However, in AD, tau protein undergoes biochemical changes because it twists into pairs of helical filaments and they twist into tangles. Also, tau is generally located in axons, but in tauopathy, it is located in dendrites. Thus, neuron’s transport system may be disintegrated and microtubule cannot function correctly [16, 50].
Aβ is a relatively small peptide of 4 to 4.4 kDa that is the major component of amyloid deposits. Intracellular Aβ protein is widely found in neurons and it is associated with inflammatory and antioxidant activity, regulation of cholesterol transport, and activation of kinase enzyme. However, Aβ is one of the best known components in formation of neurodegenerative diseases including AD.
Aβ is approximately composed of 36-43 amino acids and it originates from amyloid precursor protein (APP). In human,
APP can be cleaved into fragments by α, β, and γ secretases and Aβ protein is formed by the action of the β and γ secretases. Aβ protein contains two important regions which play a major role in the formation insoluble amyloid fibrils. C-terminal regions (residues 32 to 42) and internal hydrophobic regions (residues 16 to 23) may enhance increasing β-sheet conformation and Aβ protein misfolding [53].
In normal brain, Aβ proteins contain mixture of β-sheet and random coil structures. However, a number of β-sheet structures are increased at high protein concentration. Aβ protein constitutes SPs which are important markers in AD. The formation of SPs is a problem of protein folding because of misfolded and aggregated form of Aβ accumulates and shows toxicity in brain [54].
Genetically, three genes:
Parkinson’s disease (PD) is neurodegenerative movement disorder of the central nervous systems. In 1817, Dr. James Parkinson published “
Natively unfolded α-syncline (α-Syn) is a 14 kDa and highly conserved protein that localize different regions of the brain. The name of protein was preferred as “α-synuclein” because of it shows
Natively, α-Syn is an unfolded protein, but obtains its conformation with biological interactions. In cytoplasm, α-Syn is a soluble and in an unfolded state, but it can be found in α-helical conformation for binding to lipid membranes. Also, α-Syn can be in the form of β-sheet for composing Lewy bodies as explained below [56-58].
α-Syn is encoded with
Primary structure of human α-Syn (Gen Bank: AAL15443.1). Imperfect KTKEGV repeats are colored in blue. Acidic residues are colored in red. Phosphorylation sites (Ser87 and Ser129) are colored in yellow.
Central hydrophobic region contains non-amyloid beta component (NAC) sequences from residue 61 to 95. This region is highly hydrophobic, and it can promote formation of β-sheet structure. The less conserved C-terminal region consists of a large number of acidic amino acids and several prolines [56-60].
At present, biological role and pathogenic processes of Lewy bodies are still unclear. As far as we know, Lewy bodies are aberrant protein aggregates and their deposits cause PD. Lewy bodies are localized not only in PD brains, but also in other neurodegenerative disorders such as AD brains. According to the electron microscopy images, Lewy bodies are 8-30 µm which are consisted of approximately 10 nm amyloidogenic fibrils such as fibrillary α-Syn and neurofilaments. Lewy bodies contain a variety of proteins including α-Syn, neurofilaments, ubiquitinated proteins, and heat shock proteins (Hsp70 and Hsp90). Oxidative stress, mitochondrial dysfunction, inflammation, ubiquitin proteasome system, pH, protein concentration, and high temperature may be affected negatively by Lewy bodies. Therefore, these factors induce misfolding and aggregation of proteins in the Lewy bodies [57, 61].
α-Syn plays crucial role in PD because α-Syn is a major fibrillary component for Lewy bodies. There are many adjuvant and disincentive factors available in α-Synfibrillogenesis. Two mutations, A53T and A30P, in the α-Syn gene and overexpression of wild type α-Syn are increased misfolding processes and aggregation. Also, accumulation of abnormal form of α-Syn can inhibit proteasomal functions [9, 61, 62].
It is known that, α-Syn is natively unfolded as well as predominantly non-phosphorylated
As known, oxidative stress is one of the major factors in many diseases as well as the formation of PD [9, 20]. As a result of oxidation, formed free radicals react rapidly with proteins thus, misfolding and aggregation are generated inside the cells. Among twenty amino acids, methionine and cysteine are capable of being easily oxidized. α-Syn doesn’t have cysteine residues, but high content of methionine residues oxidize to methionine sulfoxide. Thus, due to methionine content of α-Syn, the protein is readily aggregates at oxidation conditions. On the other hand, α-Syn phosphorylation can be increased with oxidative stresses as well [65].
Huntington’s disease (HD) is a genetic neurodegenerative disorder and the disease is caused by autosomal dominant inheritance. In 1872, HD was first described as a genetic disease by Dr. George Huntington. Involuntary muscle contractions, movement, and mental disorders are progressed in HD. The disease is inherited as an autosomal dominant and effects brain and nervous systems. Huntington protein undergoes conformational changes with mutation and it shows aggregation tendency [66].
Huntington (Htt) is a large size protein of 350 kDa that is generally composed of 3144 amino acids. Normal protein is highly expressed in peripheral tissues and brain, and it is involved in endocytosis, cytosketal functions, vesicle trafficking, cellular signal transduction, and membrane recycling. In brains, Htt protein leads to cell damage and toxicity through deposition of misfolded aggregate form of Htt protein [8, 9].
The gene for HD is located on the tip of chromosome 4, and is called the
Htt proteins interact with a variety of peptides including huntington associated protein 1 (HAP1), huntington interacting protein 1 and 2 (HIP1 and HIP2) and huntington yeast partners A, B, and C (HYPA, HYPB, and HYPC). These peptides are functioned in cell signaling, transport, and transcription processes [67, 69].
In HD, the neuropathology is characterized with accumulation of Htt protein aggregates. HD is caused by a number of CAG repeats in the gene. To date, many theories have been suggested in HD, but functions of CAG repeats and mechanisms of HD cannot be understood yet. However, common opinion is long CAG repeats (polyQ) are the most important promoter for toxicity of Htt protein aggregates. The polyQ region starts at residue 18 and the number of glutamine residues are the most important marker in HD. Surprisingly, 40 or more CAG repeats are always generated neuropathy, while 35 or fewer CAG repeats are never generated neuropathy. However, in childhood, CAG repeats from 27 to 35 can develop neuropathy [66, 70-72].
In 1994, Max Perutz put forward a “
Until this section, neurodegenerative diseases have been discussed on the basis of protein aggregation and misfolding. In healthy organisms, a variety of mechanisms work efficiently for prevention of preteopathies. Molecular chaperones are known to be critical for protein folding processes and neurodegenerative diseases. Heat shock proteins (Hsps) are well-known molecular chaperons in living organisms [1, 76-78].
Hsps are highly conserved proteins among living organisms. Hsps are an important class of molecular chaperons and they are located in different parts of the cells such as endoplasmic reticulum, cytosol, and mitochondria. Mainly, Hsps are related with formation of proper protein conformation, and also prevention protein aggregation, misfolding, and oligomerization. Proteins can be exposed a number of cellular and environmental factors including high temperature, inflammation, growth factors, oxidative stress etc. which can cause misfolding and protein aggregation. Overexpression of Hsps has been observed under these stress conditions. Several studies have focused on the neuroprotective role of Hsps. Therefore, the expression levels of Hsps are decreased and misfolded protein accumulation can be occurred in brain [1, 76-78].
Generally, Hsps are divided into six groups on the basis of molecular mass. In this section; Hsp40, Hsp60, Hsp70, Hsp90, Hsp100, and small Hsp (sHsp) have been examined and characterized for association with neurodegenerative diseases and protein folding processes [1].
Hsp70 is a highly conserved protein in all living organisms. It makes complex with unfolded or partially denatured proteins. Hsp70 has two functional domains: ATPase domain and substrate binding domain (SBD). The operation of these domains is controlled with hydrolysis of ATP. ATPase domain binds to ATP and hydrolyzes it to ADP. This energy drives the protein folding function of the Hsp70. Similarly, Hsp70 binding to misfolded peptides, increases the ATP hydrolysis. Also, Hsp70 interacts with Hsp40 and Hsp90 to perform protein folding process. Hsp70 serves a neuroprotective role in all of neurodegenerative diseases [79-81]. Auluck and co-workers indicated that, expression of Hsp70 reduced α-Syn aggregation, accumulation, and toxicity in PD animal models [82]. In HD models, Hsp70 shows protective assignment in polyglutamine-induced toxicity [83]. Also, Hsp70 is involved in the folding and functional maintenance of tau protein. In prion diseases, Hsp70 binds aggregate form of prion proteins and it mediates their degradation by the proteasome [81].
Hsp40 is expressed in variety of organisms in different isoforms. It associates with unfolded polypeptides and prevents protein aggregation. Hsp40 can be found in a cell in three different types. All types of Hsp40 contain highly conserved J domain which interacts with Hsp70 ATPase domain. Thus, ATPase activity of Hsp70 is regulated by this interaction. Hsp40 transmits substrate towards Hsp70 SBD domain with an appropriate conformation. Thus, Hsp70 help substrate peptide in its hydrophobic SBD region and assists the peptide to come to a state of proper three-dimensional structure [1, 84]. Hsp40 is extensively found in neurodegenerated brains due to it is association with Hsp70 as a co-chaperon [83].
Hsp100 participates in counteraction of protein aggregation with Hsp70 and Hsp40. This hexameric 100 kDa protein has substrate and ATP binding regions. Large protein aggregates are broken by Hsp100 and formed small aggregates are carried forward by Hsp70-Hsp40 complex. In yeast, overexpression of Hsp100 leads to disassemble of large prion aggregates and generate the small prion seeds for new rounds of prion propagation [1, 83].
Hsp90 is a highly expressed cellular molecular chaperon and also stabilizes certain proteins and aids protein degradation. Hsp90 is a dimeric protein which has a highly conserved N-terminal domain and a C-terminal domain. Hsp90 is one of the main cytosolic molecular chaperons which is activated with Hsp40 and Hsp70 [1, 85]. Uryu and co-workers demonstrated that expression of Hsp90 is increased in transgenic mouse model of PD. Inhibition of Hsp90 lead to generation of tauopathies because of protein hyperphosphorylation and abnormal neuronal activity can be increased in AD [86].
Hsp60 is a heptameric 60 kDa protein which is located particularly in mitochondria. Hsp60 works with Hsp70 coordinately for protein folding. Furthermore, it plays key roles in mitochondrial protein transport, replication and transmission of mitochondrial DNA, and apoptosis. For actin and tubulin, Hsp60 is a specific chaperon which is decreased in AD. In AD effected neurons, aggregated and misfolded tau protein is increased in contrast with expression of Hsp60 is decreased [1, 83].
sHsp has a molecular mass between 12 and 30 kDa [87]. As a molecular chaperone, sHsp are located at different compartments in the cell and they can protect protein structures and activities. Also, overexpression of sHsp have reported in many studies [87-90]. In HD, the expression level of Hsp27 is increased and it prevents polyglutamine induced toxicity in neurons. Furthermore, Hsp27 reduces α-syn-induced toxicity in PD patient brain [82, 88]. The other sHsps including Hsp10, Hsp12, Hsp20, Hsp26 are associated with protein folding diseases [89].
More than 600 diseases such as Alzheimer\'s disease, Huntington\'s disease, prion diseases, Parkinson\'s disease, multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS) and others are characterized by progressive nervous system dysfunction. In the world, millions of people are affected from these diseases. For example, five million people suffer from Alzheimer\'s disease, one million people from Parkinson’s disease and 30.000 people from Huntington’s diseases in USA. US government spends approximately 50-100 billions of dollars for diagnosis and therapies [91]. Today, we are using effective methods (PET, MRI, SPECT etc.) for diagnosis of neurodegenerative diseases, but we cannot treat the diseases easily as we diagnose them.
All of neurodegenerative diseases are related with protein misfolding and aggregation. Different native proteins lead to formation of diseases, but practically same factors involve in these diseases. Structurally, β-sheet conformation plays a key role in neuropathies. Furthermore, oxidative stress, pH, mutations, post translational modifications etc. lead to protein folding diseases.
New innovations in biochemical and medicinal fields lead to development of a number of mechanisms for protein aggregation and neurodegenerative diseases. Moreover, a variety of analytical techniques such as IR (infrared spectroscopy), NMR (nuclear magnetic resonance), CD (circular dichroism), calorimeters, and electron microscopy have been used for detection of aggregation process. Nevertheless, we cannot identified cellular mechanisms of protein misfolding and related diseases clearly yet. In the future, scientists will concentrate on design of practical and fast methods for detection of protein aggregation in cells.
This work was funded through a seed grant from the Turkish National Academy of Sciences (TUBA GEBIP 2008-29 for YT).
Since the development of the first integrated circuit by J. Kilby in 1958 [1], microchips have advanced enormously growing to include billions of transistors on a single chip. These advances have fueled the growth of the information technology industry with high performance computers and high-speed communications. Data can be communicated at lightning speeds over fiber optic networks and stored in large data centers or in the cloud.
Yet, while these tremendous advancements are available to students attending universities in well-resourced settings, universities in low resource settings often lack even basic information and communication technology (ICT) infrastructure including computers, software, and Internet access. This lack of ICT resources greatly limits the quality of engineering education that can be delivered to students in these low resource settings. Many of the universities with low levels of ICT resources are in developing countries, especially in sub-Saharan Africa, Latin America and the Caribbean, and in parts of Asia. This further exacerbates the digital divide between communities in low resource settings compared to those in higher resource settings. This results in limited innovation and modern economic development opportunities for students in low resource communities. Additionally, the lack of reliable electricity in low resource settings is another barrier to delivering quality education in these environments. Furthermore, the cost and energy requirements for conventional prototyping equipment, e.g. lathes, bandsaws, drill presses, etc. prevents them from being integrated into engineering curricula in low resource settings. Finally, the professors in these low resource settings do not have the training and education in the use of modern technologies. This results in much of the pedagogical approach to teaching engineering in low resource settings to be mostly theoretical and out of date. There has been very little opportunity for students to get hands-on prototyping experience that they can use to innovate engineering solutions to local societal problems.
Recent technology advances in the area of low-cost, open-source hardware and software are opening up new possibilities for professors at universities in low- and middle-income countries (LMICs) to provide their students with hands-on, experiential learning opportunities in developing engineering solutions to real-world problems. Microcontroller and microcomputer hardware platforms, such as the Arduino and Raspberry Pi platforms provide several input/output interfaces for sensors, displays, and transducers, significant memory storage, and quite powerful processing capability. When combined with an array of open-source software tools, such as the Linux and Android (a derivative of Linux) operating systems, Mozilla Firefox, Libre Office, Wikipedia, Khan Academy, Python programming language, etc. a powerful array of capabilities become available to developers at low cost. Furthermore, the cost of solar panels and solar electric systems have also come down dramatically over the last decade to the point where they are competitive with grid-generated electricity in many locations. This allows for reliable power to be provided in areas that have previously lacked access to energy. A fourth technology that has emerged over the last decade is the advent of low cost 3-D printers. This development has also added to the suite of low-cost technologies that are now available for low-cost prototyping of engineered products. Finally, affordable mobile phones are available everywhere. At a minimum, almost everyone in the world has access to feature phones and smart phones are owned by almost 50% of the world’s population [2]. This ubiquitous availability of mobile phones throughout the world has provided relatively low-cost connectivity everywhere.
These five technological advances have opened many new opportunities for ubiquitous, project-based, learning of engineering, even in low resource settings. To fully take advantage of the opportunities afforded by the vision of Industry 5.0, a broader, more diverse array of engineers need to be educated to enhance the creativity needed to address broader challenges as described by the UN Sustainable Development Goals [3] or National Academy of Engineers Grand Challenges [4].
The focus of this chapter is to show how the combination of low-cost energy and information and communication technology (ICT) platforms along with 3D printers offer the opportunity to educate students in engineering in global, low resource settings to create a more inclusive and diverse workforce to support the Industry 5.0 initiative. Examples of hands-on initiatives in various LMICs including Nicaragua, Ecuador, Guatemala, Malawi, Sri Lanka, and Tanzania will be presented.
Low-cost open-source hardware was first introduced by Arduino in 2005 [5]. The philosophy behind the development of the Arduino microcontroller was to make an easy-to-use platform for non-engineers to prototype electronic circuits. The basic Arduino Uno single board microcontroller (see Figure 1) plugs into the USB port of a computer and has its own integrated development environment (IDE) that is relatively easy to program (and can even be programmed with a basic, block-based programming tool). The features of the Arduino microcontroller are provided in Table 1. In addition to the basic device, there are shields that may be added to extend the capabilities of the Arduino microcontroller, such as a Wifi shield that allows for connectivity to a wireless communication network. There are also more powerful versions of the microcontroller, such as the Arduino Mega as well as devices of different form factor, e.g. circular devices that can be housed in circular housings.
Photograph of an Arduino Uno microcontroller [
Feature | Description |
---|---|
Processor type | 8-bit 16 MHz Atmel AVR |
Memory type | 32kB Flash, 1kB EEPROM and 2kB SRAM |
Analog Input/Output pins (includes PWM and SPI interfaces) | 6 |
Digital Input/Output pins | 14 |
Common input devices | Light sensors, temperature sensors, ultrasound sensors |
Common output devices | LED’s, LCD displays, motors, speakers |
Size | Approx. 5 cm. x 7 cm. |
Power supply requirements | 3.3 V or 5 V input; 50 mA |
Cost | ~$20 |
Features of Arduino Uno microcontroller.
A second open-source hardware device that has become very popular is the Raspberry Pi microcomputer. This low-cost device is a fully integrated computer. The features of the Raspberry Pi 3 Model B are illustrated in Figure 2 and provided in Table 2. The Raspberry Pi has a built-in Google Chrome browser and supports programming in Python. There are also many application software packages that come with the basic device including Wolfram’s Mathematica, MIT’s Scratch, and Wikipedia. Many other software packages may be downloaded onto this microcomputer platform.
Features of the Raspberry Pi 3 Model B microcomputer [
Feature | Description |
---|---|
Processor type | Broadcom BCN2837 64-bit Quad Core 1.2 GHz CPU |
Memory type | 1GB RAM + SD Card slot (up to 256GB) |
Analog and Digital Input/Output pins | 40 pin General Purpose I/O bus |
Input ports/common devices | 4 USB ports; Keyboard, mouse, display, camera |
Output ports | Full HDMI video port, audio output port |
Communication port | 10/100 LAN Ethernet RJ45 |
Size | Approx. 9 cm. x 5 cm. |
Power supply requirements | 5 V input; 400 mA |
Cost | ~$35 |
Features of the Raspberry Pi 3 Model B microcomputer.
A third set of open-source hardware technologies that has emerged in the last decade is 3D printers. While 3D printers were available in university research labs in the 1990’s, they were very expensive and so were economically out of reach of members living in low resource communities. The RepRap project was started in 2005 by Dr. Adrian Bowyer with the goal of developing low-cost 3D printers that could be replicated around the world [8]. This has led to the development of low-cost 3D printers that can now be purchased for under $200 in the US. Furthermore, open-source designs are available so that people can make their own units. Figure 3 shows an example of a low-cost 3D printer available on the market today [9]. In addition to the 3D printer hardware, there are many open-source software tools, including 3D builder [10] that are easy to use by beginners. Also, free designs may be downloaded from various websites in standard file formats, such as.stl files. A comprehensive list of resources for 3D printing, including software tools, 3D printer models, example designs, etc. are available from github.com [11].
Lulz Bot Taz 6 low-cost 3D printer [
Many so-called “Fab-Labs” have now opened in many countries to take advantage of these industry trends to support open-source, low-cost design of engineered parts. In addition to 3D printers, these Fab-Labs include other prototyping tools in a workshop setting. A global mapping of Fab-Labs is available at the website: https://www.fablabs.io/labs/map [12].
Finally, the cost of solar panels has dropped dramatically in the past decade as shown in Figure 4 [13]. This allows relatively low-cost solar electric systems (<$2 per Watt) to be installed in remote schools to provide consistent and reliable power even in areas that lack access to grid electricity. An example of a creative approach to setting up a solar computer kiosk is the “Digital Drum” that was developed by UNICEF. The design of the solar-powered computer kiosk employs modified oil drums to create the kiosk. A picture of this implementation at a school in Uganda is shown in Figure 5 [14].
Price of solar panels per watt from 1990 to 2015 [
The “Digital Drum” solar-power computer kiosk in Uganda [
Bringing all these technological advances together offers the opportunity to educate students in low-resource settings in basic engineering skills. These students offer unique creativity and enthusiasm, resulting in a potentially more diverse array of products to emerge from these designers. There is a further trend in global engineering education where students from more privileged communities are interested in doing community service in low resource communities [15]. Students work with rural communities to identify needs and then co-develop engineering solutions for these communities [16]. These needs can span improving basic digital literacy in remote communities to developing applications to detect contaminants in drinking water. The next section describes more detailed case studies of improving engineering education in various universities in low resource settings.
Each of the subsections in this section focus on a particular application area framed by the UN Sustainable Development Goals (UN SDGs). The specific goals to be addressed here are:
UN SDG Goal 3: Good Health and Well Being
UN SDG Goal 4: Quality Education
UN SDG Goal 6: Clean Water and Sanitation
UN SDG Goal 8: Decent Work and Economic Growth
The quality of education in rural communities is often very limited for many reasons including lack of trained teachers, lack of funding for the schools, and lack of technologies in the classrooms (including lack of connectivity). In 2009, World Possible, curated a package of creative commons resources (such as Wikipedia, Khan Academy, CK12 textbooks, etc.) for offline distribution to communities that lacked internet access [17] The organization coupled the content with the open-source web browser, Google Chrome, and created the Remote Area Community Hotspots for Education and Learning (RACHEL). They established this platform on the Raspberry Pi Model 3 and named it the Rachel Pi. The educational content stored in the unit’s memory or on the micro-SD card could be accessed by computers, tablets or smart phones through a wireless router. Content on this device has been further developed in local contexts by local developers. A good example of this is the work done in Guatemala by Israel Quic, a native Mayan who produced materials based on his Mayan heritage in various Mayan languages for the local communities [18].
The Rachel Pi has been deployed all over the world from Tunisia, to Uganda to Papua New Guinea [19, 20]. A specific example is described in more detail next.
Landivar University is a Catholic, Jesuit university which has a campus in Quetzaltenango, Guatemala. The university is well-established and its professors in the Computer Science Department have a reasonably good curriculum including elective topics at a very basic level in the areas of artificial intelligence and Blockchain. The Arduino microcontroller is used in some project work at the university but only to a limited extent. However, the students and professors had not received any exposure to the Raspberry Pi until the author and his students conducted workshops at the university. Students at the university have access to laptop computers and the classrooms are well equipped with projectors and screens.
On the other hand, the region around the town of Quetzaltenango is very poor. Much of the population in the region is indigenous Mayan people who predominantly speak Quechua. The schools in the region of Totonicapan rarely have computer labs and many of them have no access to the Internet, although most of them do have access to electricity. The teachers also have limited technical skills. Catholic Relief Services (CRS) has been supporting a bilingual education program (in Quechua and Spanish) at the schools through a food and nutrition program as well as an infrastructure program (primarily building kitchens and latrines at the schools). The author and his students delivered two workshops on the Raspberry Pi to computer science students and professors at Landivar University in May 2019 and November 2019. Each workshop was held for two days. The first workshop provided an orientation to the Raspberry Pi and the second workshop was a more advanced workshop on configuring the Raspberry Pi for setting up a network and sharing resources from a server to individual computers.
The team from Landivar University working in partnership with a software engineer from CRS were able to obtain funding from the IEEE Humanitarian Activities Committee (IEEE HAC) [21] to establish a computer laboratory in a remote school in the community of Santa Maria Chiquimula in Totonicapan, Guatemala. This system was configured and deployed by the computer science students in early 2020 but because of the COVID-19 situation, has not been accessible to students and teachers at the school because the schools in the region have been closed since then. A photograph showing the students in the computer laboratory in early March 2020 as it was being set up is shown in Figure 6.
Students at a school in Santa Maria Chiqimula, Totonicapan, Guatemala accessing content on a Rachel Pi server.
This example shows how a group of motivated university students in a low resource setting were able to address a local social challenge around the quality of education being delivered to school children in a remote, poor rural community.
A qualitative assessment of the November 2019 workshop on the Raspberry Pi was conducted. Two main questions were asked: What were the positive aspects of the workshop and what were the negative aspects of the workshop? The students indicated that they really enjoyed the practical, hands-on aspects of the workshop and the negative comment was simply that they wish the workshop had been longer!
Engineering using the Arduino microcontroller can also be taught in low resource settings. Since the Arduino microcontroller may be interfaced to a variety of sensors and transducers, there is a large variety of possibilities for performing experiments with these devices. For example, the Arduino microcontroller can be interfaced to a temperature sensor and an LCD display and programmed to show the ambient temperature of the environment. Another simple application is to use a light sensor as the input and display the ambient lighting level on an LCD display. More sophisticated applications, such as a line following robot can be produced by interfacing the unit to a mobile robotic platform and using a light sensor to follow a white line painted on the floor [22]. Another somewhat sophisticated application that offers students the opportunity to demonstrate their creativity is a wearable array of colored LEDs that are programmed to light up based on sound volume (through interfacing with acoustic sensors). There is a block programming interface to the Arduino microcontroller, like Scratch, that can be used with elementary/middle school children who are just beginning to learn basic programming skills for them to perform simple experiments with the Arduino microcontroller.
Bluefields is a town located on the Caribbean coast of Nicaragua. Most of the population in Nicaragua resides in the southwest, Pacific region of the country near the capital city of Managua. This part of the country has the highest economic development in the country while the Caribbean coast is relatively under-developed. The population of Bluefields comprises a variety of indigenous populations who are mostly fisherman. There are many social problems in this region and UNICEF has been working in this part of the country to pilot solutions to address these social problems, particularly as it affects children and youth. Bluefields Indian and Caribbean University (BICU) has as its mission to educate the minority students from the Caribbean coastal region (including Bluefields). Since the social problems affect members of the communities in the indigenous population, UNICEF established an innovation laboratory at BICU to support the university’s students and professors to develop innovative solutions to local problems. While there is a computer science program and a computer laboratory at the university, it is relatively ill-equipped. The quality of education and resources in this university are significantly limited compared to the universities on the Pacific side of the country. In collaboration with UNICEF, the author along with his students delivered a two day workshop to the students and professors at BICU in May 2017. The first day of the workshop was focused on the Arduino microcontroller while the second day was focused on using Android Studio for developing mobile phone applications for Android phones [23, 24]. Arduino microcontroller development kits were donated to the university and the students were able to develop applications after the workshops were delivered. While no formal assessment was conducted following the workshops, the informal feedback provided by the students was that they were very excited by the hands-on, practical experience of building electronic circuits.
The students at BICU were so excited about designing and building electronic devices that they launched a robotics club later in 2017. The students from this robotics club competed and won a national robotics competition in 2018 as underdogs in the competition. As winners of the national competition, they were invited to compete in an international competition [25]. Many of the students at BICU were at-risk youth. Witnessing these underserved students’ ability to embrace and apply electronics technology to win a national competition clearly demonstrates how the quality of education in low resource settings can be dramatically improved using low-cost hardware and effective mentoring.
The quality of health care in rural communities is often very limited. Community health workers (CHWs) with limited medical knowledge and training are often the front-line administrators of local health care to members of their communities. Rural medical clinics may also have limited facilities. Two examples of how quality health care may be improved in these rural settings using technology are described in this section.
The first example focuses on a project conducted in the rural part of northeastern Nicaragua in the area surrounding the town of Waslala. This region of Nicaragua is very poor and the community members in this area tend to be subsistence farmers who grow crops and raise livestock. The mountainous terrain is very rugged with relatively few paved roads as illustrated by the photograph in Figure 7.
A photograph of farmers in the Waslala region of Nicaragua.
The author and his students as well as students and professors from the M. Louise Fitzpatrick College of Nursing at Villanova University, worked with the local Catholic parish and two Nicaraguan universities to develop a telehealth system for this region [26]. The CHWs were trained to make basic measurements of blood pressure, temperature, respirations and, in the case of pregnant women, fundal height. In the case of babies, they were also taught to measure baby head circumference and baby weight. All these trainings were done by the Nursing professors and students from both Villanova University and a partner university, the Universidad Nacional Autonoma de Nicaragua (UNAN) branch in Matagalpa, Nicaragua. The CHWs were then trained in texting the collected vital sign data to a central database on a computer server that was located at the Universidad Nacional de Ingenieria (UNI) in Managua, Nicaragua. They were also trained in using solar chargers to recharge their cell phones since many of the CHWs did not have access to electricity in their communities. An application program was written using an open-source UNICEF software tool, RapidSMS, that could accept text messages and display them as patient records in a database. This data could be reviewed by trained health care professionals and feedback provided to the CHWs in case a patient needed medical attention. While the initial software application was developed by students at Villanova University, further development of the software was conducted by students from UNI. These students were able to use the open source software to again address real world challenges having understood the context of the communities through engagement with the community members and the CHWs. The students performed competently and really enjoyed the experience of doing hands-on, practical application development using open source software to address a social need.
The telehealth project was further expanded to other regions in Nicaragua. One particular expansion was to the under-served Caribbean coast and students from BICU were engaged in the software development. Since RapidSMS requires significant programming skills (that were somewhat lacking at BICU at the time), a simpler cloud-based software tool, Rapid Pro, also from UNICEF, was used in this application. A comparison of these two software tools for telehealth project development is provided in [27]. Health care software tools are growing extensively worldwide to enhance the quality of healthcare in under-served communities. A good example of this is the DHIS 2 health information management system that is being used in many LMICs throughout the world [28].
Repairing medical equipment in low resource settings can be challenging because of the lack of availability of spare parts. This is because, oftentimes, the equipment is old and spare parts may not be available. Furthermore, medical instrumentation can also be difficult to obtain in low resource settings because of lack of funds. In these cases, 3D printing becomes an option to print replacement parts as well as medical instruments. A start-of-the-art review of additive manufacturing of medical instruments was published by a group of researchers from the Delft University of Technology in the Netherlands [29]. While this paper provides a very comprehensive review of a range of medical instruments that may be 3D printed, for the purposes of low resource settings, some basic tools are shown in Figure 8. The figure shows a surgical kit comprising a scalpel, hemostat, forceps, and tweezers. This is particularly important in low resource settings since there may be a very limited supply chain to remote medical clinics. In many developing countries, the medical system is a national system and remote clinics often receive little funding from the central government. Local production of these instruments allows surgeons to be able to have low-cost but very capable tools for their use.
Common medical instruments printed in a 3D printer.
Additionally, local doctors can develop their own instrument designs based on their needs and therefore promotes more local creativity in the design of medical instrumentation.
Chemical and biological contamination of water sources is a major problem all over the world. A low cost means of disinfecting water in remote communities is to put the water into a bottle and place it in the sun for a period of time. In this solar disinfection technique, the UV radiation from the sun kills bacteria in the water resulting in potable water for drinking [30]. Yet, while there are some indicators that can show that the water has received sufficient treatment, these are relatively expensive or may need periodic replacement.
An innovation developed by students at Villanova University uses a UV sensor to accumulate the UV radiation using an Arduino microcontroller. When the accumulated UV radiation crosses a threshold, an indicator displays that the water is safe to drink. This system can be used for several bottles at a time in a community setting [31].
Another example of using an Arduino microcontroller to evaluate the quality of water for potable consumption was described in [32]. The authors of this paper from Brunei used an array of sensors, including a turbidity sensor, a total dissolved solids (TDS) sensor, a pH sensor and a temperature sensor that were interfaced to an Arduino unit as shown in Figure 9. The unit was tested in a stream on the Universiti Brunei Darussalam campus. Preliminary results of their system show good promise for assessing water quality, but they are planning to upgrade the system to incorporate a Raspberry Pi microcomputer to give remote data collection and more powerful computation capabilities.
Picture of Arduino-based water quality sensing unit.
Precision agriculture is becoming an important area in farming. While this technology has been applied to large holder farms it is still in its infancy regarding small holder farmers. One area of importance in small holder farms in developing countries is only irrigating farms when soil moisture content falls below some threshold value. Combining moisture sensing with drip irrigation technology offers the opportunity to minimize the amount of water used in irrigating farms.
Engineering design instruction at the University of Malawi Polytechnic in Blantyre, Malawi used to almost exclusively focus on paper designs because of the lack of prototyping materials and facilities. This meant that the students would just work on the first half of the design process, i.e. understanding the problem, brainstorm design solutions, settle on a particular solution and then sketch out the solution. They did not get to prototype the design, test and troubleshoot it, or iterate on design improvements [33]. Through a collaboration with Rice University in the US, a maker space facility was established at the University of Malawi Polytechnic in 2016. This Polytechnic Innovation Design Studio (PIDS) includes a variety of prototyping equipment Arduinos and Raspberry Pis, 3D printers, a laser cutter, a CNC machine, and hand tools. These tools are used at all levels beginning in the first-year design classes through to the final year capstone design classes in both the electrical engineering (EE) and mechanical engineering (ME) curricula.
Figure 10 shows a highly rated EE student prototype circuit design prior to the establishment of the PIDS facility. The design includes the circuit components mounted to a cardboard backing. After the PIDS facility was established, the designs were significantly improved. Figure 11 shows a moisture sensor using an Arduino microcontroller as part of a drip irrigation system to minimize water use in irrigating farms. Clearly, the quality of the design is much more advanced than the prototype circuit shown in Figure 10.
Pre-PIDS circuit prototype using a cardboard backing and organizational structure for the circuit [
Soil moisture sensor and Arduino reader with LCD display [
An assessment of the quality of the prototype and design process level were conducted for both EE and ME students using a five-point Likert scale. Figure 12 shows the results of this assessment. The prototype quality has been seen to considerably improve by the presence of the PIDS facility. The change in the design process level was also observed to improve but the upper end of the design process levels did not change.
Assessment results for pre-PIDS and post-PIDS designs [
An interesting approach to teaching 3D printing to remote communities is the Fab Bus mobile STEM education platform developed in Aachen, Germany [34]. This mobile education unit is deployed in a converted double decker bus as shown in Figure 13. Eight seats on the upper deck of the bus house 3D printers for students and a teacher’s seat. There are also computers at each station with 3D CAD software tools. The upper deck can be used as a classroom to teach students how to design and print 3D models. A layout of the upper deck is shown in Figure 14. The lower deck houses a showroom with industry-grade machines and various professionally made parts, including metal parts. Short courses are taught in this mobile classroom to high school and university students as well as to small and medium sized businesses. This innovative teaching platform has toured three countries – Germany, Belgium and the Netherlands and has been well received in all three countries.
Mobile 3D printing educational unit (Fab Bus) [
Upper deck layout of the Fab Bus [
In his best-selling book, “The World is Flat”, journalist Tom Friedman observed that a youth with access to a computer and the Internet can contribute to economic development from anywhere in the world [35]. Fifteen years since the first edition of that book, this statement is even more true. Industry 4.0 brought us massively interconnected devices which led to the accumulation of large amounts of data (so-called “big data”) that required artificial intelligence and machine learning to interpret. Industry 5.0 is bringing humans back into the equation to work with machines and is the motivation of this next phase of the industrial revolution. The ubiquity of low-cost ICT and energy technologies as well as low-cost manufacturing technologies, offers an opportunity to bring a more diverse youth, including those from low resource settings, to be educated in engineering product development and to thereby contribute to local economic development.
The technology trends in low-cost ICT technologies, including ubiquitous access to mobile phones, low-cost energy access via solar panels, and open-source software and hardware systems have been reviewed in this chapter. A few application sector examples, built around the UN SDG frameworks, including quality education, clean water and sanitation, good health and wellbeing, and decent work and economic growth have been explored. These technological developments are driving a revolution in global engineering education bringing in historically neglected youth into the worldwide community of engineers. This creates the potential for unique and potentially transformative solutions to global challenges to be invented by students from low resource settings given their unique perspectives on the world.
The author gratefully acknowledges the contributions of his students to the educational outreach programs in the various countries (primarily in Nicaragua, Ecuador and Guatemala) in which he has worked. In particular, he would like to thank Javier Urquizo, Viviana Villavicencio, Nathaly Sanchez, Diego Villacreses, John Beyer, Scarleth Vasconcelos, and Melvin Mendoza. Furthermore, he is very grateful to his colleagues from UNICEF including Chris Fabian, Dr. Rafael Amador and Rinko Kinoshita. He is also grateful to Mr. Edward Tohom of Catholic Relief Services. Finally, he would like to thank professors at various universities with whom he has partnered including Professors Ruth McDermott-Levy, Dr. Betty Keech and Dr. Betty Mariani of Villanova University’s, M. Louise Fitzpatrick College of Nursing, Prof. Jim Klingler of the Villanova School of Business and Prof. Maria Virginia Moncada, retired from UNI, Prof. Kevin Lopez of BICU, Profs. Carlos Leal and Amanda Rodriguez, both formerly of UCA, Drs. Cecilia Paredes, Cesar Martin, and Angel Ramirez as well as Prof. Jimmy Cordova of ESPOL and Prof. Elfego Ovalle of Landivar University in Quetzaltenango, Guatemala. He is also grateful to Villanova University, Venture Well and Halloran Philanthropies for financially supporting his work.
The author declares no conflict of interest.
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At the present time, adult SCs isolated from postnatal tissues are widely used in clinical applications. Their characteristics such as a multipotent differentiation capacity and immunomodulatory activity make them a promising tool to use in patients. Modern material technologies allow for the development of innovative biomaterials that closely correspond to requirements of the current biomedical application. Biomaterials, such as ceramics and metals, are already used as implants to replace or improve the functionality of the damaged tissue or organ. However, the continuous development of modern technology opens new insights of polymeric and smart material applications. Moreover, biomaterials may enhance the SCs biological activity and their implementation by establishing a specific microenvironment mimicking natural cell niche. Thus, the synergistic advancement in the fields of biomaterial and medical sciences constitutes a challenge for the development of effective therapies in humans including combined applications of novel biomaterials and SCs populations.",book:{id:"5951",slug:"biomaterials-in-regenerative-medicine",title:"Biomaterials in Regenerative Medicine",fullTitle:"Biomaterials in Regenerative Medicine"},signatures:"Małgorzata Sekuła and Ewa K. Zuba‐Surma",authors:[{id:"202773",title:"Prof.",name:"Ewa",middleName:null,surname:"Zuba-Surma",slug:"ewa-zuba-surma",fullName:"Ewa Zuba-Surma"},{id:"202775",title:"Dr.",name:"Malgorzata",middleName:null,surname:"Sekula",slug:"malgorzata-sekula",fullName:"Malgorzata Sekula"}]},{id:"56100",doi:"10.5772/intechopen.69718",title:"Properties of Co-Cr Dental Alloys Fabricated Using Additive Technologies",slug:"properties-of-co-cr-dental-alloys-fabricated-using-additive-technologies",totalDownloads:1613,totalCrossrefCites:5,totalDimensionsCites:14,abstract:"The aim of the present paper is to make a review of the properties of dental alloys, fabricated using Additive Technologies (AT). The microstructure and mechanical properties of Co-Cr alloys as well as the accuracy and surface roughness of dental constructions are discussed. In dentistry two different approaches can be applied for production of metal frameworks using AT. According to the first one the wax/polymeric cast patterns are fabricated by 3D printing, than the constructions are cast from dental alloy with as-printed patterns. Through the second one the metal framework is manufactured form powder alloy directly from 3D virtual model by Selective Electron Beam Melting (SEBM) or Selective Laser Melting (SLM). The microstructure and mechanical properties of Co-Cr dental alloys, cast using 3D printed patterns, are typical for cast alloys. Their dimensional and adjustment accuracy is higher comparing to constructions, produced by traditional lost-wax casting or by SLM. The surface roughness is higher than that of the samples, cast by conventional technology, but lower comparing to the SLM objects. The microstructure of SLM Co-Cr dental alloys is fine grained and more homogeneous comparing that of the cast alloys, which defines higher hardness and mechanical properties, higher wear and corrosion resistance.",book:{id:"5951",slug:"biomaterials-in-regenerative-medicine",title:"Biomaterials in Regenerative Medicine",fullTitle:"Biomaterials in Regenerative Medicine"},signatures:"Tsanka Dikova",authors:[{id:"205539",title:"Dr.",name:"Tsanka",middleName:null,surname:"Dikova",slug:"tsanka-dikova",fullName:"Tsanka Dikova"}]},{id:"31995",doi:"10.5772/35937",title:"Air-Solids Flow Measurement Using Electrostatic Techniques",slug:"air-solids-flow-measurement-using-electrostatic-techniques",totalDownloads:5015,totalCrossrefCites:6,totalDimensionsCites:11,abstract:null,book:{id:"1649",slug:"electrostatics",title:"Electrostatics",fullTitle:"Electrostatics"},signatures:"Jianyong Zhang",authors:[{id:"106435",title:"Dr.",name:"Jianyong",middleName:null,surname:"Zhang",slug:"jianyong-zhang",fullName:"Jianyong Zhang"}]}],mostDownloadedChaptersLast30Days:[{id:"69398",title:"New Generation Peptide-Based Vaccine Prototype",slug:"new-generation-peptide-based-vaccine-prototype",totalDownloads:1157,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"Synthetic peptide-based vaccine prototypes are the future potential vaccination. Antigens, which belong to minimal microbial component and produce antibodies such as peptides and polysaccharides, can promote long-term protection against pathogens that can cause infectious diseases. Production of peptides becomes simple with solid phase peptide synthesis and microwave-assisted solid phase peptide synthesis using automatic synthesizers. The use of synthetic peptides was approved by the health authorities for vaccine design. Peptides are themselves very weak immunogens and need adjuvants to provide an effective autoimmune response. For this reason, peptide antigens are conjugated with biopolymers and loaded with nanoparticles. The toxicity of vaccine prototypes is evaluated in cell culture, and non-toxic prototypes are selected for vaccinating experimental animals. The most effective peptide-based vaccine prototype is determined as the one with the highest antibody level. The goal of this book chapter is to illustrate the use of peptides vaccine systems and present their opportunities with their future development.",book:{id:"9048",slug:"current-and-future-aspects-of-nanomedicine",title:"Current and Future Aspects of Nanomedicine",fullTitle:"Current and Future Aspects of Nanomedicine"},signatures:"Öznur Özge Özcan, Mesut Karahan, Palanirajan Vijayaraj Kumar, Shen Leng Tan and Yi Na Tee",authors:[{id:"305705",title:"Dr.",name:"Mesut",middleName:null,surname:"Karahan",slug:"mesut-karahan",fullName:"Mesut Karahan"},{id:"310005",title:"MSc.",name:"Öznur Özge",middleName:null,surname:"Özcan",slug:"oznur-ozge-ozcan",fullName:"Öznur Özge Özcan"},{id:"310006",title:"Prof.",name:"Palanirajan Vijayaraj",middleName:null,surname:"Kumar",slug:"palanirajan-vijayaraj-kumar",fullName:"Palanirajan Vijayaraj Kumar"},{id:"310008",title:"MSc.",name:"Shen Leng",middleName:null,surname:"Tan",slug:"shen-leng-tan",fullName:"Shen Leng Tan"},{id:"310009",title:"MSc.",name:"Yi Na",middleName:null,surname:"Tee",slug:"yi-na-tee",fullName:"Yi Na Tee"}]},{id:"56614",title:"Systematic Study of Ethylene-Vinyl Acetate (EVA) in the Manufacturing of Protector Devices for the Orofacial System",slug:"systematic-study-of-ethylene-vinyl-acetate-eva-in-the-manufacturing-of-protector-devices-for-the-oro",totalDownloads:1706,totalCrossrefCites:3,totalDimensionsCites:4,abstract:"Fracture of facial bones and dental elements, and laceration of soft tissue, have increased in sports over recent years. Dentist is the only professional responsible for the mouth protection design, the knowledge about suitable materials is essential. EVA is a thermoplastic material, available in the market, easy of handling and processing, and low-cost. However, it is important to understand the mechanical properties and ability to absorb and to dissipate the impact energy, when this material is submitted to different environments, such as oral cavity with saliva and different temperatures. This chapter show provides a systematic evaluation of the EVA application in orofacial protectors while focusing on sports. The research comprises two aspects: experimental tests and numerical analyses. During experimental tests, EVA was analyzed in special buccal conditions, concerning temperature and presence of saliva. Regarding the presence of saliva, more specific studies about its influence on the mechanical behavior of EVA were performed. In the numerical analyses of the EVA orofacial protector, the studies focused on its effect on the nasal bone integrity, and in the zygomatic bone protection. However, life cycle should be analyzed, since its performance deteriorates over time. Mainly due to the saliva-originated changes to the EVA mechanical characteristics, it can behave as a rigid material. For facial protection, a better performance is obtained with a combination of rigid and soft EVA material. According to the experimental and numerical results from a systematic study of EVA, its application to orofacial protection can be considered satisfactory.",book:{id:"5951",slug:"biomaterials-in-regenerative-medicine",title:"Biomaterials in Regenerative Medicine",fullTitle:"Biomaterials in Regenerative Medicine"},signatures:"Reinaldo Brito e Dias, Neide Pena Coto, Gilmar Ferreira Batalha and\nLarissa Driemeier",authors:[{id:"204968",title:"Dr.",name:"Neide",middleName:null,surname:"Pena Coto",slug:"neide-pena-coto",fullName:"Neide Pena Coto"}]},{id:"63035",title:"Biological Function of Exosomes as Diagnostic Markers and Therapeutic Delivery Vehicles in Carcinogenesis and Infectious Diseases",slug:"biological-function-of-exosomes-as-diagnostic-markers-and-therapeutic-delivery-vehicles-in-carcinoge",totalDownloads:2209,totalCrossrefCites:12,totalDimensionsCites:23,abstract:"Exosomes are nano-sized vesicles that are formed during inward budding of multivesicular bodies and the maturation of endosomes. They are secreted by almost all cell types under normal, pathological, and physiological conditions. They are found in mostly all biological fluids, such as breast milk, blood, urine, and semen. Exosomes are involved in cell-to-cell communication through the biological transfer of lipids, proteins, DNAs, RNAs, mRNAs, and miRNAs. Exosomes are enriched in tetraspanins, enzymes, heat shock proteins, and membrane trafficking proteins. There are numerous techniques that are used to isolate, purify, and characterize exosomes from biofluids. Isolation/purification techniques include ultracentrifugation, filtration, sucrose density gradient centrifugation, etc. Characterization techniques include flow cytometry, electron microscopy, NanoSight tracking analysis, Western blot, etc. These techniques are often used to help principal investigators understand the properties and biological functions of exosomes. However, some of these techniques can be very complicated and challenging, resulting in various drawbacks. Exosomes can be used as potential carriers for therapeutics. Thus, they can serve as biomarkers to diagnosis various diseases that are associated with cancer, genetics, viruses, bacteria, parasites, etc. Therefore, with advances in science and technology, many innovative techniques have been established to exploit the biological properties of exosomes.",book:{id:"7437",slug:"nanomedicines",title:"Nanomedicines",fullTitle:"Nanomedicines"},signatures:"Brennetta J. Crenshaw, Brian Sims and Qiana L. Matthews",authors:[{id:"254038",title:"Ph.D.",name:"Qiana",middleName:null,surname:"Matthews",slug:"qiana-matthews",fullName:"Qiana Matthews"},{id:"254039",title:"Ms.",name:"Brennetta",middleName:null,surname:"Crenshaw",slug:"brennetta-crenshaw",fullName:"Brennetta Crenshaw"},{id:"266042",title:"Dr.",name:"Brian",middleName:null,surname:"Sims",slug:"brian-sims",fullName:"Brian Sims"}]},{id:"64869",title:"Transethosomes and Nanoethosomes: Recent Approach on Transdermal Drug Delivery System",slug:"transethosomes-and-nanoethosomes-recent-approach-on-transdermal-drug-delivery-system",totalDownloads:1630,totalCrossrefCites:3,totalDimensionsCites:9,abstract:"In the past few decades, an emerging drug delivery system that came into light is transdermal drug delivery system. It has become the talk of the town in the field of drug delivery because of its better and easy accessibility. Though it is one of the attractive routes, transport of drug through the skin has remained a challenge. To overcome the challenge, vesicular system has been adopted so as to have better skin permeation of bioactive agents. Vesicular system like liposome has shown inefficiency to cross the layers of skin. Then transethosomes and nanoethosomes are employed for delivering drug into the deeper layer of skin. Nanoethosomes and transethosomes have same composition that is water, ethanol and phospholipid. Transethosome contains edge activator additionally. Due to the presence of ethanol and edge activator, it displayed enhanced skin permeation. Vesicular system gives a better patient compliance, being a non-invasive method of drug administration. In this chapter, we attempted to provide brief information about methods of preparation, characterization and pharmaceutical uses of nanoethosomes and transethosomes.",book:{id:"7437",slug:"nanomedicines",title:"Nanomedicines",fullTitle:"Nanomedicines"},signatures:"Koushlesh Kumar Mishra, Chanchal Deep Kaur, Shekhar Verma, Anil\nKumar Sahu, Deepak Kumar Dash, Pankaj Kashyap and Saraswati\nPrasad Mishra",authors:[{id:"204256",title:"Dr.",name:"Anil",middleName:"Kumar",surname:"Kumar Sahu",slug:"anil-kumar-sahu",fullName:"Anil Kumar Sahu"},{id:"211230",title:"Mr.",name:"Pankaj",middleName:null,surname:"Kashyap",slug:"pankaj-kashyap",fullName:"Pankaj Kashyap"},{id:"221419",title:"Mr.",name:"Koushlesh",middleName:null,surname:"Mishra",slug:"koushlesh-mishra",fullName:"Koushlesh Mishra"},{id:"221420",title:"Mr.",name:"Sarawati Prasad",middleName:null,surname:"Mishra",slug:"sarawati-prasad-mishra",fullName:"Sarawati Prasad Mishra"},{id:"250558",title:"Dr.",name:"Deepak Kumar",middleName:null,surname:"Dash",slug:"deepak-kumar-dash",fullName:"Deepak Kumar Dash"},{id:"270359",title:"Dr.",name:"Chanchal Deep",middleName:null,surname:"Kaur",slug:"chanchal-deep-kaur",fullName:"Chanchal Deep Kaur"},{id:"270998",title:"Prof.",name:"Shekhar",middleName:null,surname:"Verma",slug:"shekhar-verma",fullName:"Shekhar Verma"}]},{id:"68412",title:"Self-Emulsifying Drug Delivery Systems: Easy to Prepare Multifunctional Vectors for Efficient Oral Delivery",slug:"self-emulsifying-drug-delivery-systems-easy-to-prepare-multifunctional-vectors-for-efficient-oral-de",totalDownloads:1135,totalCrossrefCites:2,totalDimensionsCites:3,abstract:"Self-emulsifying drug delivery systems (SEDDS) have been mainly investigated to enhance the oral bioavailability of drugs belonging to class II of the Biopharmaceutics Classification System. However, in the past few years, they have shown promising outcomes in the oral delivery of various types of therapeutic agents. In this chapter, we discuss the recent progress in the application of SEDDS for oral delivery of protein therapeutics and genetic materials. The role of SEDDS in enhancing the oral bioavailability of P-glycoprotein and cytochrome P450 3A4 substrate drugs is also highlighted. Also, we discuss the most critical evaluation criteria of SEDDS. Additionally, we summarize various solidification techniques employed to transform liquid SEDDS to the more stable solid self-emulsifying drug delivery systems (s-SEDDS) that are associated with high patient compliance. This chapter provides a comprehensive approach to develop high utility SEDDS and their further transformation into s-SEDDS.",book:{id:"9048",slug:"current-and-future-aspects-of-nanomedicine",title:"Current and Future Aspects of Nanomedicine",fullTitle:"Current and Future Aspects of Nanomedicine"},signatures:"Khaled AboulFotouh, Ayat A. Allam and Mahmoud El-Badry",authors:[{id:"299910",title:"Prof.",name:"Mahmoud",middleName:null,surname:"El-Badry",slug:"mahmoud-el-badry",fullName:"Mahmoud El-Badry"},{id:"299914",title:"MSc.",name:"Khaled",middleName:null,surname:"Abulftooh",slug:"khaled-abulftooh",fullName:"Khaled Abulftooh"},{id:"299916",title:"Dr.",name:"Ayat",middleName:null,surname:"Allam",slug:"ayat-allam",fullName:"Ayat Allam"}]}],onlineFirstChaptersFilter:{topicId:"282",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:89,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:104,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:32,numberOfPublishedChapters:318,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:141,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:113,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:105,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:5,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:15,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}},{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}}]},series:{item:{id:"13",title:"Veterinary Medicine and Science",doi:"10.5772/intechopen.73681",issn:"2632-0517",scope:"Paralleling similar advances in the medical field, astounding advances occurred in Veterinary Medicine and Science in recent decades. These advances have helped foster better support for animal health, more humane animal production, and a better understanding of the physiology of endangered species to improve the assisted reproductive technologies or the pathogenesis of certain diseases, where animals can be used as models for human diseases (like cancer, degenerative diseases or fertility), and even as a guarantee of public health. Bridging Human, Animal, and Environmental health, the holistic and integrative “One Health” concept intimately associates the developments within those fields, projecting its advancements into practice. This book series aims to tackle various animal-related medicine and sciences fields, providing thematic volumes consisting of high-quality significant research directed to researchers and postgraduates. It aims to give us a glimpse into the new accomplishments in the Veterinary Medicine and Science field. By addressing hot topics in veterinary sciences, we aim to gather authoritative texts within each issue of this series, providing in-depth overviews and analysis for graduates, academics, and practitioners and foreseeing a deeper understanding of the subject. Forthcoming texts, written and edited by experienced researchers from both industry and academia, will also discuss scientific challenges faced today in Veterinary Medicine and Science. In brief, we hope that books in this series will provide accessible references for those interested or working in this field and encourage learning in a range of different topics.",coverUrl:"https://cdn.intechopen.com/series/covers/13.jpg",latestPublicationDate:"June 17th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:11,editor:{id:"38652",title:"Prof.",name:"Rita",middleName:null,surname:"Payan-Carreira",slug:"rita-payan-carreira",fullName:"Rita Payan-Carreira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRiFPQA0/Profile_Picture_1614601496313",biography:"Rita Payan Carreira earned her Veterinary Degree from the Faculty of Veterinary Medicine in Lisbon, Portugal, in 1985. She obtained her Ph.D. in Veterinary Sciences from the University of Trás-os-Montes e Alto Douro, Portugal. After almost 32 years of teaching at the University of Trás-os-Montes and Alto Douro, she recently moved to the University of Évora, Department of Veterinary Medicine, where she teaches in the field of Animal Reproduction and Clinics. Her primary research areas include the molecular markers of the endometrial cycle and the embryo–maternal interaction, including oxidative stress and the reproductive physiology and disorders of sexual development, besides the molecular determinants of male and female fertility. She often supervises students preparing their master's or doctoral theses. She is also a frequent referee for various journals.",institutionString:null,institution:{name:"University of Évora",institutionURL:null,country:{name:"Portugal"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:3,paginationItems:[{id:"19",title:"Animal Science",coverUrl:"https://cdn.intechopen.com/series_topics/covers/19.jpg",isOpenForSubmission:!0,editor:{id:"259298",title:"Dr.",name:"Edward",middleName:null,surname:"Narayan",slug:"edward-narayan",fullName:"Edward Narayan",profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",biography:"Dr. Edward Narayan graduated with Ph.D. degree in Biology from the University of the South Pacific and pioneered non-invasive reproductive and stress endocrinology tools for amphibians - the novel development and validation of non-invasive enzyme immunoassays for the evaluation of reproductive hormonal cycle and stress hormone responses to environmental stressors. \nDr. Narayan leads the Stress Lab (Comparative Physiology and Endocrinology) at the University of Queensland. A dynamic career research platform which is based on the thematic areas of comparative vertebrate physiology, stress endocrinology, reproductive endocrinology, animal health and welfare, and conservation biology. \nEdward has supervised 40 research students and published over 60 peer reviewed research.",institutionString:null,institution:{name:"University of Queensland",institutionURL:null,country:{name:"Australia"}}},editorTwo:null,editorThree:null},{id:"20",title:"Animal Nutrition",coverUrl:"https://cdn.intechopen.com/series_topics/covers/20.jpg",isOpenForSubmission:!0,editor:{id:"175967",title:"Dr.",name:"Manuel",middleName:null,surname:"Gonzalez Ronquillo",slug:"manuel-gonzalez-ronquillo",fullName:"Manuel Gonzalez Ronquillo",profilePictureURL:"https://mts.intechopen.com/storage/users/175967/images/system/175967.png",biography:"Dr. Manuel González Ronquillo obtained his doctorate degree from the University of Zaragoza, Spain, in 2001. He is a research professor at the Faculty of Veterinary Medicine and Animal Husbandry, Autonomous University of the State of Mexico. He is also a level-2 researcher. He received a Fulbright-Garcia Robles fellowship for a postdoctoral stay at the US Dairy Forage Research Center, Madison, Wisconsin, USA in 2008–2009. He received grants from Alianza del Pacifico for a stay at the University of Magallanes, Chile, in 2014, and from Consejo Nacional de Ciencia y Tecnología (CONACyT) to work in the Food and Agriculture Organization’s Animal Production and Health Division (AGA), Rome, Italy, in 2014–2015. He has collaborated with researchers from different countries and published ninety-eight journal articles. He teaches various degree courses in zootechnics, sheep production, and agricultural sciences and natural resources.\n\nDr. Ronquillo’s research focuses on the evaluation of sustainable animal diets (StAnD), using native resources of the region, decreasing carbon footprint, and applying meta-analysis and mathematical models for a better understanding of animal production.",institutionString:null,institution:{name:"Universidad Autónoma del Estado de México",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null},{id:"28",title:"Animal Reproductive Biology and Technology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/28.jpg",isOpenForSubmission:!0,editor:{id:"177225",title:"Prof.",name:"Rosa Maria Lino Neto",middleName:null,surname:"Pereira",slug:"rosa-maria-lino-neto-pereira",fullName:"Rosa Maria Lino Neto Pereira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bS9wkQAC/Profile_Picture_1624519982291",biography:"Rosa Maria Lino Neto Pereira (DVM, MsC, PhD and) is currently a researcher at the Genetic Resources and Biotechnology Unit of the National Institute of Agrarian and Veterinarian Research (INIAV, Portugal). She is the head of the Reproduction and Embryology Laboratories and was lecturer of Reproduction and Reproductive Biotechnologies at Veterinary Medicine Faculty. She has over 25 years of experience working in reproductive biology and biotechnology areas with a special emphasis on embryo and gamete cryopreservation, for research and animal genetic resources conservation, leading research projects with several peer-reviewed papers. Rosa Pereira is member of the ERFP-FAO Ex situ Working Group and of the Management Commission of the Portuguese Animal Germplasm Bank.",institutionString:"The National Institute for Agricultural and Veterinary Research. 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