List of treatments received by each of the five groups of rats.
\\n\\n
Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\\n\\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\\n"}]',published:!0,mainMedia:{caption:"Highly Cited",originalUrl:"/media/original/117"}},components:[{type:"htmlEditorComponent",content:'IntechOpen is proud to announce that 191 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
\n\nThroughout the years, the list has named a total of 261 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\nReleased this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\n\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\n'}],latestNews:[{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"},{slug:"intechopen-identified-as-one-of-the-most-significant-contributor-to-oa-book-growth-in-doab-20210809",title:"IntechOpen Identified as One of the Most Significant Contributors to OA Book Growth in DOAB"}]},book:{item:{type:"book",id:"3484",leadTitle:null,fullTitle:"State of the Art in Biosensors - Environmental and Medical Applications",title:"State of the Art in Biosensors",subtitle:"Environmental and Medical Applications",reviewType:"peer-reviewed",abstract:"The main challenge in biosensor development is their application for various practical tasks to provide a continuous and reliable flow of information about the indicators of natural and industrial processes and the surroundings, so enabling adequate feedback and control. 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Dr. Rinken's research activities are focused on the studies and development of biosensing systems for automatic monitoring along with testing and application of biosensor based analytical systems.",institutionString:"University of Tartu",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"5",totalChapterViews:"0",totalEditedBooks:"5",institution:{name:"University of Tartu",institutionURL:null,country:{name:"Estonia"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"693",title:"Environmental Biotechnology",slug:"environmental-biotechnology"}],chapters:[{id:"43538",title:"Recent Progress in Optical Biosensors for Environmental Applications",doi:"10.5772/52252",slug:"recent-progress-in-optical-biosensors-for-environmental-applications",totalDownloads:3192,totalCrossrefCites:2,totalDimensionsCites:8,hasAltmetrics:0,abstract:null,signatures:"Feng Long, Anna Zhu, Chunmei Gu and Hanchang Shi",downloadPdfUrl:"/chapter/pdf-download/43538",previewPdfUrl:"/chapter/pdf-preview/43538",authors:[{id:"154702",title:"Dr.",name:"Feng",surname:"Long",slug:"feng-long",fullName:"Feng Long"},{id:"155353",title:"Dr.",name:"Chunmei",surname:"Gu",slug:"chunmei-gu",fullName:"Chunmei Gu"},{id:"155354",title:"Prof.",name:"Hanchang",surname:"Shi",slug:"hanchang-shi",fullName:"Hanchang Shi"},{id:"165332",title:"Dr.",name:"Anna",surname:"Zhu",slug:"anna-zhu",fullName:"Anna Zhu"}],corrections:null},{id:"43539",title:"Biomimetic Sensors for Rapid Testing of Water Resources",doi:"10.5772/52438",slug:"biomimetic-sensors-for-rapid-testing-of-water-resources",totalDownloads:2093,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:null,signatures:"Jill M. 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There are different motor topologies to meet the requirements of such application, for instance, permanent magnet synchronous motors (PMSM), induction motors (IM), switched reluctance motors (SRM), and synchronous reluctance motors (SynRM). PMSMs have the best power density ratio and can maintain the power in a wide speed range. However, the material cost due to the rare-earth magnets and concerns about availability and supply of the magnets makes it necessary to use other type of motors. In this context, the concept of rare-earth-free-motors gains attention [1]. Synchronous reluctance motors are good candidates in terms of material and manufacture cost; however, the power density and power factor are low. Then, the idea of permanent magnet-assisted synchronous reluctance motors (PMa-SynRM) appears, since they improve the performances of SynRMs by using ferrite magnets. Ferrite magnets have lower electrical conductivity than rare-earth magnets, so the eddy current losses are much lower, and thus the temperature rise due to eddy current losses. Although ferrite magnets exhibit a lower remanent magnetic flux density compared to neodymium magnets, ferrite magnets have a higher Curie temperature. As a consequence, ferrite magnets are well suited to be applied in high-temperature environments, such as electric vehicles, thus offering improved reliability with respect to the use of rare-earth permanent magnets.
The design of a motor usually consists of a multi-physics analysis where the thermal, electric, magnetic, and mechanic domains are analyzed. In the electromagnetic pre-design stage, the geometry of the machine is often calculated based on criteria taking into account different domains. The electromagnetic domain allows calculating the necessary amount of the magnet, the thermal domain settles the size of the slots of the stator, and the mechanical domain settles the size of the radials ribs.
The final geometry of the motor is obtained after an optimization process, where the values of the motor’s parameters are variated to determine the best solution. However, the starting point of the design is based on the electromagnetic pre-design. This work aims at guiding the electromagnetic pre-design of the PMa-SynRM.
The pre-design is performed with the basic specifications of the machine, such as mechanical power, corner speed, phase current, pole number, or efficiency required, among others. Since FEA is often not applied to speed up the design process, the parameters calculated must be very accurate, so several refinement loops are introduced. In this context, the whole process is a combination of analytical equations with iterative loops to refine the estimated parameters, which are required to start the electromagnetic pre-design.
The starting point consists of estimating some parameters, such as efficiency, power factor, air gap flux density, or back EMF, in order to determine the required phase current, electrical power, or number of turns per phase, among others. These estimated values depend on the machine type, for instance in the SynRM, the power factor can be selected around 0.7, and the efficiency around 95%.
The initial set of equations is given by:
where “
Being, “
To finalize with the electrical part of the design, the number of turns per phase can be calculated according to (3):
where “
Considering a sinusoidal flux density, the value of “
Note that the effective length and the pole pitch cannot be determined since the air gap volume is unknown. The mains dimensions must be calculated before the number of turns per phase.
The first step to calculate the motor geometry is the determination of the main dimensions of the motor. These parameters are the outer and inner diameter of the rotor, the outer and inner diameter of the stator, and the stack length. It is worthy to mention that depending on the restrictions of the application, the outer dimensions can be fixed. Figure 1 shows several motor’s parameters, such as inner and outer rotor radius (
Motor basic geometry.
The calculation of the motor’s geometry starts determining the air gap volume/surface or the outer volume/surface of the machine. In this context, different approaches can be found in the literature to calculate the motor geometry using the data obtained from the specifications. On the one hand, Bianchi et al. [3] and Gamba [4] calculate the exterior geometry, which is represented by the outer stator diameter and the stack length. The first one uses a relation between the torque generated and the volume (Kv), meanwhile the second one relates the losses generated with the outer surface (Kj). According to Bianchi et al. [3], the Kv for these kinds of machines is around 10 Nm/L. However, these values can change depending on the value of the torque. In the second approach, the thermal loading depends on the coolant system, so it is required to determine the outer motor geometry. If the outer geometry is fixed, the thermal loading determines the coolant system required [5]. On the other hand, the electrical loading (
This approach is based on the mechanical constant [2, 7], which is given by:
where “
The proposed pre-design starts with the mechanical constant, so a further explanation of the different values of such constant is required. The value of the mechanical constant is obtained by analyzing several motors of the same typology and coolant systems. Figure 2, extracted from [1], shows the relation between the mechanical constant and efficiency for different motor types.
Machines comparison based on the maximum efficiency point and machine constant of mechanical power. Data presented have been collected from [
Nevertheless, when using the electrical loading, mechanical constant, or other parameters to obtain the volume or surface of the air gap, the relation between diameter and length is required. The form factor “
“
Using (5) and (6), the effective length
In order to maximize the saliency ratio, the air gap thickness must be as low as possible [3]. According to Pyrhönen et al. [2], the air gap should be smaller compared to induction machines. The air gap in induction machines is given by:
where “
The stator geometry is completed when the size of the slot, teeth, and yoke are determined. The width of the teeth (
A) Approximate geometry using the most restricted dimensions. B) Flux lines in teeth.
In order to calculate the size of the slots, the number of conductors in each slot and the tooth size are required. Then, (3) can be solved since the pole pitch is known. When the number of turns in series per phase is calculated, the number of conductors in each slot (
being, “
Note that “
In this point, the estimated flux density within the air gap changes, so it is calculated as:
Considering a sinusoidal magnetic flux distribution within the air gap and how this magnetic flux distributes through the stator, the size of the teeth and yoke are calculated to obtain a magnetic saturation below a pre-defined value. The teeth have to be sized to withstand the magnetic flux that comes from the air gap. The magnetic flux will enter in the teeth instead of the slots, so the magnetic flux in the pole is divided in the different teeth. However, the teeth are dimensioned considering the worse scenario. Figure 3B shows the magnetic fluxes lines of air gap entering in the teeth. The sinusoidal magnetic flux density is superimposed to understand the different quantity or density of magnetic flux (blue arrows) in both teeth. Then, the width of teeth is calculated considering the teeth with higher magnetic flux. In order to oversize the teeth, the magnetic flux density is considered constant at the maximum value as can be observed in Figure 3B (blue line in the teeth):
where “
“
In order to obtain a correct size of teeth, the maximum allowed magnetic flux density on this motor part is fixed between 1.5 and 1.8 T. Therefore:
where “
On the other hand, the yoke’s width must be calculated to drive half of the air gap’s magnetic flux on one magnetic pole as can be observed in Figure 4.
Detail of the magnetic flux in the yoke.
Then, the magnetic flux in the air gap is calculated as follows:
where the term “
Then, the width of the yoke is:
where “
According to Figure 3A, when the width of the teeth is known, the slot’s width can be determined as:
Then, height of the slot is determined by:
where “
The height of the teeth is given by:
Then, the outer stator diameter is obtained as:
The rotor of the SynRMs is punched to create the anisotropy. The insulation, which is the air cavity created in the rotor’s perforation, is called flux barrier. The magnetic steel material between flux barriers is called segment or flux carrier. The rotor structure is completed by ribs; there are two different ribs. The first one is the tangential rib, which connects the segments. The other type is the radial rib, which increases the mechanical integrity of the machine. The mentioned parts are depicted in Figure 5.
(A) Basic geometry of the rotor of SynRM. (B) Flux barriers distribution.
A good saliency ratio can be enhanced by a correct design of the rotor [25]. It starts choosing the proper number of flux barriers [3, 26, 27, 28], which is given by:
Note that according to (22), there are two possibilities for
Then, the positioning of the barriers is realized to obtain a good distribution of the magnetic flux, that is, a reduction of the torque ripple. The ripple reduction is obtained by means of an optimization process, where the angle of the barriers is changed to find the best solution [29, 30, 31]. However, during the pre-design stage, the angle between the end points of the barriers is fixed according to [28, 32]:
Note that (23) calculates the angle between barriers. The angle between the last barrier and the pole center is
The magnetic flux flows through the segments, so a correct sizing is mandatory. Note that the low reluctance of the magnetic steel is related to the magnetic saturation of the segments. Then, the calculation of the width of the flux carriers considers the rotor position with the highest magnetic flux. In this position, which it is called direct axis (d-axis), the maximum magneto-motive force (MMF) in the stator is located between the magnetic poles, meanwhile the zero MMF is in the middle of the magnetic pole, as can be observed in Figure 6A. It is worthy to mention that the MMF is considered sinusoidal in order to simplify the calculation of the rotor’s geometry.
MMF distribution in the dq-positions. The blue arrows represent the magnetic flux in the rotor. (A) d-position (B) q-position.
The widths of the different segments (Si) are dimensioned to obtain the same magnetic saturation in each segment. In order to estimate the magnetic saturation, the magnetic flux (φ) must be calculated. Considering the geometry shown in Figure 6A, an equivalent magnetic circuit can be built to determine the relation between the magnetic fluxes, as depicted in Figure 7A. Only one-half of the pole is represented due to the magnetic symmetry.
d-Axis equivalent magnetic circuit used to determine the width of the segments. (A) d-position (B) q-position.
Note that the reluctance of the air gap is much bigger than the segments’ reluctances, so the latter can be disregarded. Then, the magnetic fluxes are given by:
Therefore, the value of fluxes depends on the MMF. The MMF of each segment is represented by stairs function where the value is the average value of the MMF distribution shown in Figure 6A. Since all position angles of the barriers have been fixed, the average MMF of each segment can be calculated as follows:
Then, taking into account (24), where the flux is proportional to the MMF, and the condition of obtaining an equal magnetic saturation on each segment, the relation of segment’s width is given by:
The magnetic saturation is calculated using the magnetic flux and the cross section, so (26) is deducted as follows:
In addition, it is worthy to mention that (26) must be adapted in segment 1, since the magnetic flux is divided in the two magnetic poles, so the final equation to determine the relationship between S1 and S2 is given by:
Finally, there are one more unknowns that equations, so one more equation is required to find out the width of the segments. Since the width of all the segments is equal to the total iron length in the rotor, the last equation results in:
where “
“
On the other hand, the flux barriers must be designed to offer a large magnetic resistance to the flow of the magnetic flux. In this context, the sizing of the flux barriers is carried out when the magnetic flux is positioned in the quadrature position, as can be observed in Figure 6B. The MMF distribution in the q-position is calculated as in the d-position, that is, using the average value of the MMF considering a sinusoidal distribution, as shown in Figure 6B. In this case, the MMF is given by:
Figure 7B depicts the equivalent magnetic circuit in the q-position to calculate the size of the different flux barriers.
Note that the MMFq1 is zero, so the path of flux 1 can be removed. As can be observed, the magnetic flux in the q-axis is given by the addition of fluxes 1–4. Then, the purpose of the barriers’ sizing is to minimize the q-flux. Then, the relation between the widths of each barrier is given by:
A demonstration of the procedure to obtain (32) is further developed. However, the following example is realized with two barriers for the sake of simplification. Figure 8 shows a rotor with two flux barriers, the magnetomotive force in each segment, which has been calculated with (31), and the variable to optimize, which is the size of the first barrier.
Example of two barriers to determine the relation between the widths of the barriers.
As mentioned before, the sizing of the barriers aims to reduce the total flux in the q-axis (blue arrows). Then, the flux in each barrier is given by:
The reluctance of the barriers is given by:
Therefore, the total flux is given by:
Note that the total flux is a function of the reluctances of the flux barriers, that is, the total flux is a function of the variable “x” (see Figure 8). Hence:
where the total width of air in the rotor is given by:
Then, the minimization of the flux is obtained as follows:
Then, the final result is:
Finally, the permeance of each barrier can be assumed constant in order to obtain a better distribution of the flux in the air gap:
Finally, by introducing (40) in (39), (32) appears.
It is worthy to mention that there is another approach [27, 28], which relates the size of the barriers as follows:
As can be observed in Figure 6B, there is another variable to define, which it is the width of the flux barrier in the lateral location (
Note that one more equation is required to solve the sizing of the barriers. The total length of the barriers can be determined by using the insulation ratio in the d-axis:
“
In this point, the sizing of the rotor is explained. However, there are several uncertain points. These undefined variables are the inner rotor diameter and the insulation ratios (
On the one hand, the inner rotor diameter (
Then, the inner rotor diameter is defined as:
“
Iterative loop to size the rotor segments and barriers in the q-position.
On the other hand, the d-axis insulation ratio is not defined. As explained before, this insulation ratio is determined to locate the barriers according to Figure 5. Then, the value of this variable is swept to obtain the final design. In this case, the criterion to halt the iterative process is the correct position of the last barrier (the angle is
Rotor iterative loop to size the segments and barriers in d-position.
It is noted that a posterior mechanical verification is required to ensure a suitable mechanical strength of the rotor configuration obtained in this step.
After the calculation of the rotor size, the magnet quantity must be determined in order to obtain a suitable behavior of the machine during the operation. The north of the magnet is located in the negative direction of the q-axis (see Figure 11) in order to improve the motor capabilities, such as torque, base speed, and angle between voltage and current (see Figure 11B).
(A) Magnet orientation in the rotor. (B) Phasor diagram with and without magnets.
The motor capability within the flux-weakening region is related with the magnet contribution [33, 34]. It means that the magnets can be or not be inserted in all the barriers, depending on the requirements. In the case of not inserting magnets in all barriers, it is recommended to put the magnets in the innermost barrier, since the outset barriers are more magnetically stressed, so the magnet can suffer demagnetization [3, 35].
To compute the inductances and the magnet flux linkage, a fast and simple magnetic model is introduced. It is important to mention that a complex magnetic model is required in the optimization stage [36, 37]; however, in the electro-magnetic pre-design, the proposed magnetic model is good enough to calculate the magnet and improve the accuracy of the geometry.
The magnetic model based on two reluctance networks (RN) not only calculates the magnetic flux linkage but also estimates the
There are two reluctance networks to analyze, the d- and q-axis. The q-reluctance network (RN) allows calculating the q-inductances and the magnet flux linkage. Figure 12 shows an equivalent magnetic model to determine the mentioned parameters of the machine.
Simple reluctance network in q-axis.
Note that, the magnet is only located in the innermost barrier, however, it can be removed or more magnets can be introduced in the remaining barriers. The RN is formed by MMF generators and reluctances. The first one is created by the coils and magnets:
“
It is worthy to be mentioned that this magnetic model is not complete. The winding MMF generator is only represented in one tooth, so the whole contribution of the different teeth has to be added. In [38], there is more information to calculate the MMFwinding according to a given winding distribution:
where “
where “
On the other hand, the d-axis RN is shown in Figure 13. In this case, the magnet is not reflected since it only influences the q-axis. The magnetic saturation of the magnetic steel must be considered. The magnetic saturation in the teeth and yoke can be fixed at the value chosen in the design stage (13) and (17), and in the rotor can be fixed at 1 T.
Simple reluctance network in d-axis.
The unknown magnetic flux is calculated using two different equations. The first one (49) relates the MMF obtained in a closed path with the reluctances and the magnetic flux in this path:
The second one relates the total magnetic fluxes in a node (see Figure 12):
The q-axis is solved twice; the first one only considers the MMF generated by the magnets in order to calculate the magnet flux linkage (
By using these values, the motor performances can be deducted, so the process could be re-started with these new values. The back EMF is calculated as follows:
The current angle is given according to the MTPA rule, so the d- and q-currents are known. Then, the power factor can be deducted by calculating the phase shift between the current and voltage. Finally, the torque and output power can be calculated:
Then, the losses, which are composed by copper and iron losses, are given by:
“
In this point, the thermal behavior of the machine has been considered in the sizing of the slot. The magnetic behavior is analyzed by using the proposed simple magnetic model. Then, the oversize of the slots and the magnet compensated situation ensure the reliability of the motor in terms of magnetic and thermal behaviors. However, the mechanical stress has to be considered to ensure the correct behavior of the machine, since the rotor structure reduces the mechanical integrity.
The mechanical problems are solved by the correct sizing of the radial ribs. Several authors deal with this problem [39, 40, 41]. The centrifugal force is given according to:
where “
Then, the width of the radial ribs (Wr) is given as:
where “
In this point, the whole process to obtain the electromagnetic pre-design according to the given requirements is realized. A summary detailing the parameters and equations required in each step is shown in Algorithm 1.
1: Introduce the desired performances (power, rated speed) 2: Introduce the fixed parameters (pole pairs, phase number, slots, Bus DC) 3: Start electro-magnetic pre-design process 4: Estimate parameters (efficiency, power factor, back EMF, saturation factor) 5: 6: Basic parameters calculation: Electric power (1), phase current (2) 7: Estimate Cmec according to Figure 2 8: Calculate 9: Estimate number of turns in series 10: Calculates the number of conductors in slot (8) 11: Calculates the number of turns in series 12: Calculates the stator geometry (teeth, yoke, and slots dimensions) (11–21) 13: Chose the number of flux barriers (22) 14: Calculates the position of the barriers (23) 15: 16: Define 17: Calculates the width of the segments and barriers (25–30) and (31–32) 18: Evaluates stop criterion 19: (Figure 10 20: 21: Define 22: Calculates the width of the barriers in d-axis(42–43) 23: Evaluates stop criterion 24: 25: 26: Calculates Inductances, magnetic flux linkage (51) 27: Calculates losses (55–56) 28: Calculates motor performances: Torque (53), output power (54) 29: Calculates the estimated values: Back EMF (52), efficiency (57), power factor, saturation factor, peak air gap flux density (using the d-flux from magnetic model). 30: Evaluates stop criterion (error of estimated parameters) 31: 32: Calculates the thickness of the radial ribs (58–59) |
Due to the harsh operating conditions, electric vehicles require highly reliable and resilient electric motors. To this end, rare-earth-free PMaSynRMs are appealing candidates. In this chapter, a design procedure of PMaSynRMs has been presented, which includes electromagnetic, thermal, and mechanical restrictions in order to ensure a reliable and resilient operation within extended operational limits. For example, in the event of a major demagnetization failure, the PMaSynRM designed following the proposed approach is able to work as a synchronous reluctance machine, thus providing about 75% of the rated torque. In addition, the use of ferrite magnets allows the machine to operate in higher temperature environments.
Alzheimer’s disease (AD) is a neurodegenerative disorder, which present mainly in the elderly patients. It is characterized by progressive loss of cognitive functions, amyloid β (Aβ) deposition, and formation of paired-helical-filament (PHF) tau and neurofibrillary tangles (NFTs) in the brain cells. NFTs are formed inside the cell bodies of the neurons. These NFTs cause shrinkage of neurons and resultant loss of cognition and learning [1, 2].
Tau protein is a highly soluble microtubule-associated protein found abundantly in the neuronal cells of the central nervous system (CNS). Tau proteins are the product of alternative splicing from a single gene, designated for microtubule-associated protein tau (MAPT) in humans, located on chromosome 17. There are six isoforms of tau found in the human brain. They can be distinguished by their binding domains. Tau has 79 potential phosphorylation sites on the longest isoform [3]. Tau is the major microtubule-associated protein of a mature neuron. The other two neuronal MAPs are MAP1 and MAP2, which are involved in tubulin interaction and promotion of its assembly into microtubules and stabilization of the microtubule network [4].
Normal adult human brain contains 2–3 moles of phosphorylated tau protein. Hyperphosphorylation of tau decreases its normal function. In Alzheimer’s disease, brain tau is approximately three- to fourfold more hyperphosphorylated than the normal adult brain. This hyperphosphorylated state polymerized into paired-helical-filament tau and when mixed with straight filaments (SF) formed neurofibrillary tangles (NFT). The hyperphosphorylated tau in AD brain has the ability to sequester normal tau, MAP1, and MAP2, to disrupt microtubules, and to self-assemble into PHF/SF. Abnormal hyperphosphorylated tau, in the cytosol, does not polymerized into PHF [5]. The cytosolic hyperphosphorylated tau is involved in tubulin assembly but inhibiting its normal assembly and disrupting microtubule [6]. In addition, with hyperphosphorylation of tau, conformational changes and abnormal cleavage of tau may contribute to the pathogenesis of AD [7, 8]. Tau hyperphosphorylation has been reported in AD and other tauopathies; thus, the inhibition of abnormal hyperphosphorylation of tau offers a promising therapeutic target for AD and related tauopathies [9].
Similarly, oxidative stress is also strongly linked to neuronal dysfunction and neuronal cell death [10]. It is suggested that oxidative stress plays a significant role in the pathological conditions of AD by enhancing Aβ deposition, tau phosphorylation, and loss of synapses and neurons [11].
Reactive oxygen species (ROS) are by-products of biochemical and physiological processes in the body and can cause oxidative damage to macromolecules in an uncontrolled manner that may lead to many chronic diseases. Thus, overproduction of ROS is a hallmark of neurodegenerative disorders and other diseases [12, 13].
Neuroinflammation also causes neurodegeneration in the vulnerable regions of the brain such as the hippocampus. Microglia and astrocytes play important roles in neuroinflammation and contribute to neurological disorders [14, 15].
Previous studies showed that curcumin acts as an antioxidant by activating macrophages to remove ROS-like, superoxide anions, H2O2, and nitrite radicals. Its anti-inflammatory properties were tested in vivo and in vitro on animals in acute and chronic inflammatory conditions [16]. Moreover, vitamin D also reported to play a part in the cerebral processes of detoxification by interacting with reactive oxygen and nitrogen species in the rat brain and by regulating the activity of glutamyl transpeptidase [17, 18], which is a key enzyme in the metabolism of glutathione. Vitamin D3 is the active form of vitamin D. This study investigated the effects of curcumin and vitamin D3 on memory and learning, by assessing the behavioral responses of scopolamine-induced learning-impaired rats through assays involving the locomotive and maze activities and histological and protein analysis in the rat brain tissues. The findings of this study show that inducing learning impairment in rats by using scopolamine followed by treatment with curcumin and vitamin D3 results in neuroprotection and attenuation of cognitive deficits as shown by reduced brain tissue damage in histoanalysis, decreased accumulation of abnormal proteins with immunoblot analysis and increased in the numbers of correct responses to behavioral stimuli during locomotive and maze tests.
Aging is the primary risk factor for AD development. Aged population is prone to oxidative stress that results in the degeneration of their brains [19, 20]. Diets containing saturated fat and less intake of vitamin E and C are linked with the risk of AD [20]. AD patients suffer from memory impairment along with other cognitive deficits such as language, visuospatial skills, insight, and apraxia. Most patients may suffer from other symptoms such as depression, hallucination, apathy, and delusions at later stages of AD [21]. Numerous studies have indicated that accumulation of amyloid beta proteins (A
Vitamin D is a group of fat-soluble secosteroids that helps to absorb calcium, magnesium, phosphate, iron, and zinc. Vitamin D protects the brain from the degenerative processes of AD by binding itself with vitamin D receptors [27]. Vitamin D deficiency has been associated with neurological and psychiatric disorders. Previous studies revealed that it controls Ca2+ homeostasis in the hippocampus by regulating intracellular Ca2+. It also controls neurotrophic agents and protects the brain from Aβ-42 accumulation by stimulating phagocytosis. It also protects acetylcholine deficiency by increasing the activity of choline acetyltransferase in the brain. Due to its multiple biological targets, vitamin D can be used as an aide with the standard anti-dementia treatment. Among vitamin Ds, the most important compound is vitamin D3, also known as cholecalciferol. Increasing evidence highlights the impact of vitamin D deficiency as an important factor in various central or peripheral neurological diseases, especially multiple sclerosis and other neurodegenerative diseases, such as amyotrophic lateral sclerosis, Parkinson’s disease, and Alzheimer’s disease [28].
Curcumin (
Donepezil is available with the trade name “Aricept” developed by Eisai Inc. in 1983. It is a reversible AChE inhibitor, used for the treatment of mild to moderate dementia in AD patients. It has a long plasma half-life of 70 h. It is a noncompetitive reversible inhibitor of AChE that improves the function of cholinergic transmission. It increases the concentration of acetylcholine by preventing its hydrolysis. Animal studies have shown its selectivity for brain tissues and inhibition of AChE activities in smooth, striated, cardiac muscles. It can also inhibit AChE in red blood cells similar to its effect at synapses in CNS. AChE inhibition in red blood cells has been used as an indicator of the clinical effectiveness of donepezil in Alzheimer’s disease patients [36].
Scopolamine is a tropane alkaloid that acts as a muscarinic receptor antagonist. Scopolamine is used to study memory and cognition in animal model of AD. Studies have shown that scopolamine provides a suitable pharmacological model of memory defect. Scopolamine administration characterizes cognitive deficits resulting in the impairment of verbal learning, spatial learning, and reaction time [37]. Scopolamine can also have an influence on other neurotransmitter systems due to the functional interaction of cholinergic neurons with other neurotransmitter systems [38]. Cholinergic transmission is blocked, resulting in cognitive impairment in a rat model of AD [39]. Histological studies of the brain of Alzheimer’s patients have revealed the presence of activated microglia and reactive astrocytes around the Aβ plaques. The chronic activation of microglia secretes cytokines and some reactive substances that exacerbate Aβ pathology; thus, neuroglia plays an important part in the pathogenesis of AD [40]. Curcumin has a lipophilic property that is capable of passing through all cell membranes and thus exerts its intracellular effects. Curcumin has antiproliferative actions on microglia. A minimal dose of curcumin affects the neuroglial proliferation and differentiation. The overall effect of curcumin on neuroglial cells involves decreased astrocytes proliferation, improved myelogenesis, and increased activity and differentiation of oligodendrocytes [40].
This study was conducted with the following objectives:
To determine the effects of curcumin, vitamin D3, and donepezil on behavioral responses of scopolamine-induced memory and learning-impaired rats.
To examine the structure of brain tissues obtained from scopolamine-treated rats with and without curcumin or vitamin D3 or donepezil.
To investigate the concentration of hyperphosphorylated tau protein in scopolamine-treated rat brain tissues with donepezil, curcumin, or vitamin D3.
Male Sprague Dawley rats of 200 ± 25 g were obtained from the animal house (PAPRSB Institute of Health Sciences Animal Facility, University Brunei Darussalam). Thirty animals were divided into five groups of six animals per group and reared under a standard laboratory condition with free access to food and water. Rats were acclimatized in a laboratory condition for a minimum of 1 week before undergoing behavioral test. The food was restricted under a daily feeding regime to maintain the weight of the rats.
All experiments were performed during daylight for 27 days, and all groups except group I (saline control) received daily scopolamine injection (2.5 mg/kg) to induce excitotoxicity. Curcumin, vitamin D3, and donepezil were administered to rats orally (Table 1). All experiments were conducted in accordance with institutional ethics guidelines for animal care and use (Table 2).
Group | Treatment |
---|---|
Group 1 | Saline control (0.9% saline) |
Group 2 | Scopolamine (2.5 mg/kg) injection |
Group 3 | Scopolamine (2.5 mg/kg) injection and curcumin (80 mg/kg) oral |
Group 4 | Scopolamine (2.5 mg/kg) injection and donepezil (2.5 mg/kg) oral |
Group 5 | Scopolamine (2.5 mg/kg) injection and vitamin D3 (0.0179 mg/kg) oral |
List of treatments received by each of the five groups of rats.
Control | Scopolamine | Curcumin | Vitamin D3 | Donepezil | |
---|---|---|---|---|---|
Mean | 17.42607 | 176.1054 | 27.29171 | 33.8713571 | 34.12914 |
SEM | 1.261983 | 71.34413 | 14.49811 | 11.5630538 | 12.12356 |
Data expressed as mean ± standard error of the mean (SEM), expressed as the mean of time taken by different groups to reach the reward chamber each alternate day for 27 days.
This test was used to investigate learning and memory. The maze consisted of a rectangular box with an entry and a reward chamber with food, which were placed at the opposite ends of the box (Figure 1). All groups were given training in rectangular maze 1 week before drug administration. Each animal was placed in the same spot, recording the time taken by the animal to reach the reward chamber (transfer latency). Five readings were taken for each animal, and the average was calculated as their learning score [41, 42, 43].
Rectangular maze test.
Actophotometer was used to measure the locomotor activity (Figure 2). Each animal was treated with their respective compound, was placed in actophotometer, and was given 2 min in activity cage. When the beam of light falling on photocell was cut off due to the movement of the animal, an activity count was recorded. The increase or decrease in locomotor activity was then calculated [42, 43].
Actophotometer for locomotor activity.
After the behavioral study was conducted, the animals were anesthetized, and their brains were removed and stored in 4% paraformaldehyde (Figure 3). The brains were embedded in paraffin and kept in the refrigerator. Paraffin sections (5 μm) were prepared using rotary microtome (Figure 4) and stained with hematoxylin and eosin [44]. Photographs were taken for each section.
Freshly dissected rat brains.
Paraffin embedding for immunohistochemistry.
Curcumin, donepezil, and vitamin D3 reduce tau phosphorylation in the brains of a scopolamine-treated rat model of Alzheimer’s disease.
The brain tissues were dissected from the coronal area with clean tools and put on ice as quickly as possible to prevent protein degradation by proteases. The tissues were placed in microcentrifuge tubes and immersed in liquid nitrogen to snap-freeze. They were homogenized on ice after adding 1× ice-cold lysis buffer, rinsed twice with the same buffer, and agitated on a shaker for 2 h at 4°C. After centrifugation for 20 min at 12,000 rpm at 4°C, the supernatant was transferred into a fresh tube kept on ice discarding the pellet. A small volume of lysate was sampled to perform a protein quantification assay.
After boiling each cell lysate in Tris-buffered saline, 0.1% Tween 20 (TBST) at 100°C for 5 min, 50 μg of protein was loaded into the wells of the sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) gel for immunoblot analysis. After gel running for 1–2 h at 100 V, the proteins were then transferred onto the membrane and blocked for 1 h at room temperature. The membrane was then incubated with 1:1000 dilution of primary antibody in blocking buffer followed by washing three times with TBST for 5 min each wash. The membrane was incubated with the 1:1000 dilution of conjugated secondary antibody in blocking buffer at room temperature for 1 h and washed three times with TBST at 5 min each wash. Excess reagents were removed, and the membrane was covered with transparent plastic wrap. The image was acquired using the darkroom development techniques for chemiluminescence detection.
Data were expressed as mean ± standard error of the mean (SEM). The analysis of variance (ANOVA, single factor) was used to measure transfer latency with statistical significance set at p < 0.05.
The effects of curcumin and vitamin D3 on scopolamine-induced rats were investigated using the rectangular maze test comparing the results obtained with that of donepezil, a widely accepted AD standard drug. Rats that were injected with scopolamine showed significantly higher transfer latency, indicating the longer time for rats to reach the food (nearly 200 s). Also, there was no sign of improvement during the successive days (Figure 5). Rats treated with curcumin and vitamin D3 displayed significant reduction in transfer latency, which means that treated rats did not take a longer time to reach the food, less than 50 s as shown in Figure 6. Furthermore, there was a slight reduction in the latency time from day to day. The effect of these two compounds was also comparable to that of donepezil.
Effect of curcumin, vitamin D3, and donepezil on latency time compared with the disease control group (mean, n = 6). The histogram shows the mean of latency time in seconds.
Time taken to reach the reward chamber in the rectangular maze. Y-axis represents time in second. Data expressed as mean ± SEM.
Actophotometer was used to measure locomotor activity by counting total photocell counts per rat for 2 min. Rat injected with scopolamine showed progressive decline in their locomotor activity (Figure 7), and average values were shown in Table 3 and Figure 8. Rats treated with curcumin and vitamin D3 showed an initial increase in locomotor activities then slightly declined after 7 days followed by leveling off in the succeeding days. In contrast, rats treated with curcumin and vitamin D3 showed high locomotor activity compared with the non-treated control rats treated with donepezil that exhibited similar response as those treated with curcumin and vitamin D3, suggesting that these two compounds had triggered alertness and excitatory activities in scopolamine-treated rats.
Effect of curcumin, vitamin D3, and donepezil on latency time compared to scopolamine-treated group (mean, n = 6). Graph shows mean latency time in seconds.
Control | Scopolamine | Curcumin | Vitamin D3 | Donepezil | |
---|---|---|---|---|---|
Mean | 12.88686 | 6.161643 | 9.911429 | 11.77929 | 12.0664286 |
SEM | 3.712271 | 6.766518 | 2.502838 | 3.992999 | 3.23978538 |
Data expressed as mean ± SEM for the total number of photocell counts for each group.
Locomotor activities of all rats except scopolamine-treated rats in actophotometer showed no significant difference. Data expressed as mean of photocell count (mean ± SEM, n = 6) of animals on each alternate day for 27 days.
Non-treated rats injected with scopolamine revealed prominent degeneration of cells and decrease number of nuclei in their brain tissues as compared to those treated with curcumin and vitamin D3. Moreover, treatment with curcumin, vitamin D3, and donepezil showed similar cell morphology similar to the control group demonstrating brain cells that appeared normal (Figure 9).
Hematoxylin and eosin staining of rat brain tissues: A, control; B, scopolamine-induced; C, curcumin-treated; D, vitamin D3-treated; and E, donepezil. The images show no significant difference in the cellular histology of the hippocampal area (cornu ammonis) (CA3) in the experimental groups (curcumin, vitamin D3, and donepezil) as compared with those of scopolamine group, which showed less number of nuclei stained as revealed by H and E staining. Arrows in scopolamine slide B indicated the gaps around the neuronal cells of coronal sections (5 μm) at magnification 40×.
See Figure 10.
Western blot analyses of scopolamine-treated and other treatments (curcumin and vitamin D3 and donepezil) groups showing difference in the levels of hyperphosphorylated tau in a rat model of AD. (a) Immunoblot of hippocampus homogenates from treated rats (scopolamine, vehicle, treated with curcumin and vitamin D3) using the PHF monoclonal antibodies and (b) normalized with β actin.
See Tables 4, 5 and Figure 11.
S/No. | Area | Percent |
---|---|---|
1 | 13690.4 | 17.975 |
2 | 22076.4 | 28.986 |
3 | 16481.8 | 21.641 |
4 | 10,292 | 13.513 |
5 | 13,621 | 17.884 |
Densitometry data were obtained using image J software, exhibiting relative density of protein from all groups.
S/No. | Area | Percent |
---|---|---|
1 | 4240.34 | 23.631 |
2 | 3502.99 | 19.522 |
3 | 1857.51 | 10.352 |
4 | 4913.31 | 27.381 |
5 | 3429.87 | 19.114 |
Densitometry data were obtained using image J software. Representing relative density of Tau protein for all groups.
Densitometry data obtained from image J software, presented as relative density of tau protein present in all groups.
This study investigated the effects of curcumin and vitamin D3 on learning and memory and locomotion. The first part of the study involved subjecting the rats to several behavioral tests and examining their memory competencies and locomotor responses. Histological studies were also done on rats’ brains to observe the changes that have occurred in the brain tissues after various treatments. The results obtained from rats treated with curcumin and vitamin D3 were compared with donepezil-treated rats. Scopolamine (muscarinic cholinergic antagonist) was used to induce memory impairment in rats [45]. Curcumin was selected as the previous research showed that curcumin could be used to recover learning and memory abilities in rats in AD and other inflammatory conditions [46]. Literature also reported that curcumin facilitates learning and memory functions by diminishing or preventing lipid peroxidation in the brains of aged rats [47]. In general, curcumin is a well-known oxygen free radical scavenger [46].
Vitamin D plays an important role in the regulation of numerous neurotransmitters including acetylcholine, dopamine, serotonin, and gamma aminobutyric acid. Several studies have also been reported that vitamin D deficiency is associated with neurological dysfunction and that supplementation of vitamin D may induce a protective effect against neurological disorders [48]. Based on the results of this study, the rats that were injected with scopolamine only revealed a gradual increase in the latency time until day 9, indicating a longer time required for rats to reach the end of the maze where food as a source of attractive stimuli was placed. After the ninth day, the latency time remained high and was three times higher than that of curcumin, vitamin D3, and donepezil. Rats treated with curcumin and vitamin D3 exhibits reduced latency time. A slight increase in time was observed between days 1 and 7 and gradually decreased up to day 27. The daily decrease in the latency time represented the effects of these two compounds on long-term memory. When comparing between curcumin and vitamin D3, rats treated with curcumin had slightly lower latency time than vitamin D3, suggesting that curcumin was comparatively more effective than vitamin D3 and donepezil in improving learning and memory among rats. Rats treated with donepezil initially showed low latency time, but remained constant until the 27 days. The similarity of latency time values obtained among curcumin, vitamin D3, donepezil, and the control suggested that curcumin and vitamin D3 have comparable effects like that of donepezil and may reverse the memory impairment induced by scopolamine.
The locomotor activity of rats was investigated by placing each rat in an actophotometer for 2 min and then assessing their movement as compared with those treated with curcumin and vitamin D3. Furthermore, the results indicated a decline in daily activities suggesting signs of slowing down. Vitamin D3 showed an increase in locomotor activity, which was comparable with those of donepezil and the controls confirming previous studies on the role of vitamin D in motor activities [49].
Curcumin exhibited slightly less action when compared to vitamin D3, donepezil treated, and control rats but was still exhibiting higher movements than scopolamine only. After 9 days, the locomotor activity for each treatment except scopolamine became relatively stable throughout 27 days and did not show any signs of slowing down, indicating that rats treated with vitamin D3 and curcumin exhibited signs of alertness that continued for a longer time.
The effects of each treatment were also histologically examined in rat brains. Sections of the brain tissue from the region of hippocampus were stained to investigate histological appearance before and after the treatment with selected compound. The cells in the brain tissue treated only with scopolamine exhibited less number of nuclei that appeared to be shrunken and smaller than with those of the control group. Treatment with curcumin and vitamin D3 showed no difference as compared with those of the brain tissue treated with donepezil and control group, suggesting that the brain tissues seemed to have recovered after the rats were treated with curcumin and vitamin D3. The difference in the levels of tau protein was also assessed using immunoblotting. In scopolamine-induced group, phosphorylated tau proteins were relatively higher than other groups indicating a state of proliferation in the brain tissues. Previous studies reported that accumulation of phosphorylated tau protein is one of the hallmarks of AD [50]. Western blot images were also assessed visually by making comparisons between bands in different lanes (Figure 10). Densitometry data obtained from image J software presented as relative density of tau protein found in all groups (Tables 4 and 5). After the rats were treated with curcumin and vitamin D3, the levels of tau proteins were reduced suggesting an attenuation of phosphorylated tau proteins in the rat brains, confirming the earlier studies (Figures 10 and 11) [51, 52].
We concluded that Alzheimer’s disease is a progressive neurodegenerative disorder characterized by gradual memory loss and shrinkage of neuronal cells particularly in the hippocampus and basal forebrain regions. Curcumin and vitamin D3 have biomedical qualities that protect the brain from degeneration associated with AD. In this study, the behavioral tasks involving rectangular maze test and locomotor activity were used to determine if curcumin and vitamin D3 could improve learning and memory among rats subjected to scopolamine-induced impaired cognition. With cognitive impairment, the correct response rate of animals during acquisition and retention period was significantly lower than that of the control group. However, treatment with curcumin and vitamin D3 has increased their correct response rate for both tasks that became equal with those of the control group (p < 0.05). Tissue analysis by H and E staining of the rat brain from the scopolamine group showed less number of cells, which was improved upon the treatment with curcumin and vitamin D3, resulting in significantly increase in the number of cells with no gap around them. This was accompanied by reduced level of abnormal tau proteins detected via immunoblot analysis. Together, these findings demonstrate that curcumin and vitamin D3 have the potential to reverse some cognitive deficits, correct memory impairment, and protect the brain from degeneration.
The animal model of AD has shown improvement in learning and memory after exposure to curcumin and vitamin D3 treatment, which slowed down the progress of AD pathologies delaying the onset of AD. With potential as a treatment for AD in future, the active structure and the target of both curcumin and vitamin D3 can be further investigated to elucidate the molecular mechanism by which their beneficial effects can be enhanced for the improvement of AD patients. Vitamin D due to its multiple biological targets can be used as an adjunct to standard anti-dementia treatment in AD. Curcumin has intensively been studied for the improvement of AD symptoms, and existing investigations on inhalable curcumin and ar-turmerone on neural stem cells (NSCs) are currently under clinical trials.
"Open access contributes to scientific excellence and integrity. It opens up research results to wider analysis. It allows research results to be reused for new discoveries. And it enables the multi-disciplinary research that is needed to solve global 21st century problems. Open access connects science with society. It allows the public to engage with research. To go behind the headlines. And look at the scientific evidence. And it enables policy makers to draw on innovative solutions to societal challenges".
\n\nCarlos Moedas, the European Commissioner for Research Science and Innovation at the STM Annual Frankfurt Conference, October 2016.
",metaTitle:"About Open Access",metaDescription:"Open access contributes to scientific excellence and integrity. It opens up research results to wider analysis. It allows research results to be reused for new discoveries. And it enables the multi-disciplinary research that is needed to solve global 21st century problems. Open access connects science with society. It allows the public to engage with research. To go behind the headlines. And look at the scientific evidence. And it enables policy makers to draw on innovative solutions to societal challenges.\n\nCarlos Moedas, the European Commissioner for Research Science and Innovation at the STM Annual Frankfurt Conference, October 2016.",metaKeywords:null,canonicalURL:"about-open-access",contentRaw:'[{"type":"htmlEditorComponent","content":"The Open Access publishing movement started in the early 2000s when academic leaders from around the world participated in the formation of the Budapest Initiative. They developed recommendations for an Open Access publishing process, “which has worked for the past decade to provide the public with unrestricted, free access to scholarly research—much of which is publicly funded. Making the research publicly available to everyone—free of charge and without most copyright and licensing restrictions—will accelerate scientific research efforts and allow authors to reach a larger number of readers” (reference: http://www.budapestopenaccessinitiative.org)
\\n\\nIntechOpen’s co-founders, both scientists themselves, created the company while undertaking research in robotics at Vienna University. Their goal was to spread research freely “for scientists, by scientists’ to the rest of the world via the Open Access publishing model. The company soon became a signatory of the Budapest Initiative, which currently has more than 1000 supporting organizations worldwide, ranging from universities to funders.
\\n\\nAt IntechOpen today, we are still as committed to working with organizations and people who care about scientific discovery, to putting the academic needs of the scientific community first, and to providing an Open Access environment where scientists can maximize their contribution to scientific advancement. By opening up access to the world’s scientific research articles and book chapters, we aim to facilitate greater opportunity for collaboration, scientific discovery and progress. We subscribe wholeheartedly to the Open Access definition:
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\\n\\nLicense
\\n\\nBook chapters published in edited volumes are distributed under the Creative Commons Attribution 3.0 Unported License (CC BY 3.0). IntechOpen upholds a very flexible Copyright Policy. There is no copyright transfer to the publisher and Authors retain exclusive copyright to their work. All Monographs/Compacts are distributed under the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). Read more
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\\n\\nAll scientific works are Peer Reviewed prior to publishing. Read more
\\n\\nOA Publishing Fees
\\n\\nThe Open Access publishing model employed by IntechOpen eliminates subscription charges and pay-per-view fees, enabling readers to access research at no cost. In order to sustain operations and keep our publications freely accessible we levy an Open Access Publishing Fee for manuscripts, which helps us cover the costs of editorial work and the production of books. Read more
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\\n\\nIntechOpen is committed to ensuring the long-term preservation and the availability of all scholarly research we publish. We employ a variety of means to enable us to deliver on our commitments to the scientific community. Apart from preservation by the Croatian National Library (for publications prior to April 18, 2018) and the British Library (for publications after April 18, 2018), our entire catalogue is preserved in the CLOCKSS archive.
\\n\\nOpen Science is transparent and accessible knowledge that is shared and developed through collaborative networks.
\\n\\nOpen Science is about increased rigour, accountability, and reproducibility for research. It is based on the principles of inclusion, fairness, equity, and sharing, and ultimately seeks to change the way research is done, who is involved and how it is valued. It aims to make research more open to participation, review/refutation, improvement and (re)use for the world to benefit.
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The Open Access publishing movement started in the early 2000s when academic leaders from around the world participated in the formation of the Budapest Initiative. They developed recommendations for an Open Access publishing process, “which has worked for the past decade to provide the public with unrestricted, free access to scholarly research—much of which is publicly funded. Making the research publicly available to everyone—free of charge and without most copyright and licensing restrictions—will accelerate scientific research efforts and allow authors to reach a larger number of readers” (reference: http://www.budapestopenaccessinitiative.org)
\n\nIntechOpen’s co-founders, both scientists themselves, created the company while undertaking research in robotics at Vienna University. Their goal was to spread research freely “for scientists, by scientists’ to the rest of the world via the Open Access publishing model. The company soon became a signatory of the Budapest Initiative, which currently has more than 1000 supporting organizations worldwide, ranging from universities to funders.
\n\nAt IntechOpen today, we are still as committed to working with organizations and people who care about scientific discovery, to putting the academic needs of the scientific community first, and to providing an Open Access environment where scientists can maximize their contribution to scientific advancement. By opening up access to the world’s scientific research articles and book chapters, we aim to facilitate greater opportunity for collaboration, scientific discovery and progress. We subscribe wholeheartedly to the Open Access definition:
\n\n“By “open access” to [peer-reviewed research literature], we mean its free availability on the public internet, permitting any users to read, download, copy, distribute, print, search, or link to the full texts of these articles, crawl them for indexing, pass them as data to software, or use them for any other lawful purpose, without financial, legal, or technical barriers other than those inseparable from gaining access to the internet itself. The only constraint on reproduction and distribution, and the only role for copyright in this domain, should be to give authors control over the integrity of their work and the right to be properly acknowledged and cited” (reference: http://www.budapestopenaccessinitiative.org)
\n\nOAI-PMH
\n\nAs a firm believer in the wider dissemination of knowledge, IntechOpen supports the Open Access Initiative Protocol for Metadata Harvesting (OAI-PMH Version 2.0). Read more
\n\nLicense
\n\nBook chapters published in edited volumes are distributed under the Creative Commons Attribution 3.0 Unported License (CC BY 3.0). IntechOpen upholds a very flexible Copyright Policy. There is no copyright transfer to the publisher and Authors retain exclusive copyright to their work. All Monographs/Compacts are distributed under the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). Read more
\n\nPeer Review Policies
\n\nAll scientific works are Peer Reviewed prior to publishing. Read more
\n\nOA Publishing Fees
\n\nThe Open Access publishing model employed by IntechOpen eliminates subscription charges and pay-per-view fees, enabling readers to access research at no cost. In order to sustain operations and keep our publications freely accessible we levy an Open Access Publishing Fee for manuscripts, which helps us cover the costs of editorial work and the production of books. Read more
\n\nDigital Archiving Policy
\n\nIntechOpen is committed to ensuring the long-term preservation and the availability of all scholarly research we publish. We employ a variety of means to enable us to deliver on our commitments to the scientific community. Apart from preservation by the Croatian National Library (for publications prior to April 18, 2018) and the British Library (for publications after April 18, 2018), our entire catalogue is preserved in the CLOCKSS archive.
\n\nOpen Science is transparent and accessible knowledge that is shared and developed through collaborative networks.
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\n\nOpen Science refers to doing traditional science with more transparency involved at various stages, for example by openly sharing code and data. It implies a growing set of practices - within different disciplines - aiming at:
\n\nWe aim at improving the quality and availability of scholarly communication by promoting and practicing:
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On September, 29th 2006 he has won a post PhD fellowship from the university of Bologna (from October 2006 to October 2008), at the competitive examination he was ranked first in the industrial engineering area. He extensively served as referee for several international journals. He is author/coauthor of more than 100 research papers. He has been involved in some projects supported by MURST and European Community. 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After finishing his P. hD degree in 1992, he served in the Industry as a Scientific Officer and continued his academic career as a visiting scholar for a number of educational institutions. In 1996 he joined National University of Science & Technology Pakistan (NUST) as an Associate Professor; NUST is one of the top few universities in Pakistan. In 1999 he joined an International Company Lineo Inc, Canada as Manager Compiler Group, where he headed the group for developing Compiler Tool Chain and Porting of Operating Systems for the BLACKfin processor. The processor development was a joint venture by Intel and Analog Devices. In 2002 Lineo Inc., was taken over by another company, so he joined Aalborg University Denmark as an Assistant Professor.\nProfessor Akbar has truly a multi-disciplined career and he continued his legacy and making progress in many areas of his interests both in teaching and research. 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Behind these definitions are hidden all the aspects of normal and pathological functioning of all processes that the topic ‘Metabolism’ will cover within the Biochemistry Series. 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Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. Currently, proteomics relies mainly on mass spectrometry (MS) combined with electrophoretic (1 or 2-DE-MS) and/or chromatographic techniques (LC-MS/MS). MS is an excellent tool that has gained popularity in proteomics because of its ability to gather a complex body of information such as cataloging protein expression, identifying protein modification sites, and defining protein interactions. 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