Discretization analysis.
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Barely three months into the new year and we are happy to announce a monumental milestone reached - 150 million downloads.
\n\nThis achievement solidifies IntechOpen’s place as a pioneer in Open Access publishing and the home to some of the most relevant scientific research available through Open Access.
\n\nWe are so proud to have worked with so many bright minds throughout the years who have helped us spread knowledge through the power of Open Access and we look forward to continuing to support some of the greatest thinkers of our day.
\n\nThank you for making IntechOpen your place of learning, sharing, and discovery, and here’s to 150 million more!
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In twentyfive chapters it covers the most important topics related to Autism Spectrum Disorders in the efficient way and aims to be useful for health professionals in training or clinicians seeking an update. Different people with autism can have very different symptoms. Autism is considered to be a "spectrum" disorder, a group of disorders with similar features. Some people may experience merely mild disturbances, while the others have very serious symptoms. This book is aimed to be used as a textbook for child and adolescent psychiatry fellowship training and will serve as a reference for practicing psychologists, child and adolescent psychiatrists, general psychiatrists, pediatricians, child neurologists, nurses, social workers and family physicians. 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From chapter submission and review to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review, and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. 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CMGs are momentum exchange devices commonly used for spacecraft maneuvers. The studied configuration was a 3/4 CMG pyramid scheme with a balance mass configuration as shown in Figure 1. Rotation about the x-axis is denoted as roll, y-axis pitch, and z-axis yaw, respectively.
\nCMG orientation schematic.
This paper explores the maximum available momentum for a mixed skew angle, non-redundant, constant-speed, single-gimballed CMG configuration. Mixed skew angles provide the opportunity to bias CMG momentum in a particular direction. This may enhance maneuverability of a spacecraft and improve performance for various mission sets.
\nThis study assumes a spacecraft has a proper attitude control system that includes some form of singularity avoidance or penetration logic; this is necessary to utilize the full momentum of a CMG in the studied configuration.
\nA Simulink model was used to develop, test, and simulate a spacecraft attitude control system. The system topology is shown in Figure 2.
\nAttitude control system topology.
The attitude control system, shown in Figure 2, begins with a user input attitude maneuver, the system then generates a trajectory for the maneuver, and the trajectory is fed to a controller and actuator to generate desired torque. The dynamics describes the kinematics of the spacecraft motion. For more information on the spacecraft kinematics, see [1]. Sensors and observers are used to determine the state of the spacecraft and the information is fed back to the controllers. This process continues until the spacecraft completes the maneuver.
\nGiven a desired maneuver, trajectory generation is the first phase of attitude control. The trajectory provides a path and input for the controllers. It is unrealistic for a spacecraft to instantly move from one position to the desired end state; therefore, a trajectory must be generated that provides time for the spacecraft to maneuver.
\nA sine curve can be used as a rule of thumb trajectory. It provides time for the spacecraft to accelerate, reach a maximum rate, and then gradually decelerate to land at the desired endpoint. More advanced trajectory generation techniques can be found in [2].
\nCMGs, depicted in Figure 3, are torque devices used to maneuver spacecraft. They operate by rotating a mass to establish angular momentum (
Simplified schematic of a CMG [
Shown in Figure 3 is the angular momentum vector,
The Euler’s momentum exchange torque equation is shown in Eq. (1).
\nIn Eq. (1),
where \n
Applying the Law of Momentum Conservation, the torque a CMG applies will result in an opposite effect on the spacecraft. The application of this concept is shown in Eq. (4)
\nwhere
With the configuration shown in Figure 1, β depicts the CMG skew angle, θ is the rotation of the CMG about the gimbal axis, and
In a real system, there must be some form of commanded torque generation. Controllers take the state as an input and generate the torque command, u. There are two primary forms of controllers, feedforward and feedback.
\nThe feedforward controller takes the state as an input and generates a torque command. A physics-based feedforward controller, pioneered by Lorenz, is the ideal form of a controller and is far more accurate than a linearized controller [4, 5, 6]. The feedforward controller for the system analyzed is shown in Eq. (8).
\nBy equating coefficients between Eqs. (8) and (1), it is clear that the feedforward controller is based exactly on the dynamics of a rotational system where \n
Feedforward control is effective because it is based exactly on the dynamics of the spacecraft. In addition, proper application of the feedforward controller can eliminate phase lag [7]. However, the basic feedforward, as shown in Eq. (8), has no ability to account for imperfections in the maneuver. Various advances in adaptive feedforward control have been developed to advance the ability of a physics-based feedforward controller and can be found in [8, 9, 10, 11, 12, 13].
\nThe feedback controller is a method to create a control command based on an error signal between the current and desired state. This proves incredibly useful to correct for imperfections in a maneuver. Imperfections or disturbances can be a result of various things such as an inaccurate estimate of
A PID controller creates a control command based on a linearized dynamic model with proportional, integral, and derivative gains as shown in Eq. (9).
\nwhere, \n
There are various tuning methods utilized for PID controllers. Some common methods are iterative/experimental, Zeigler, and Liner Quadratic Regulator (LQR).
\nA first order approach to tuning is simply to choose gains through iteration. This experimental approach is simply to vary gains until the system performs within the acceptable parameters.
\nA second approach, Zeigler tuning, was developed empirically over time and can be considered a basic rule-of-thumb approach. Zeigler tuning requires first to determine the ultimate gain that creates stable oscillations. The ultimate gains, along with the oscillation period, are then used to calculate the gains for a PID controller. The equation for calculating Zeigler PID gains is given in Eq. (10).
\nLQR tuning is theoretically the optimal tuning method for linearized systems. It utilizes an optimization algorithm such that an engineer can input a linear state-space model and the optimal, minimum-cost, gains will be given [18].
\nThe PDI controller is a variant of the PID controller. David Luenberger developed an approach to avoid differentiating within the controller to reduce error. Rather than differentiating to provide derivative gain as shown in Eq. (9), the observed derivative state is fed to the controller after PI command calculation, the derivative state and gain are then summed after an integrator. The approach induces derivative action while avoiding differentiation within the controller. In addition, the PDI controller utilizes R.D. Lorenz’ approach to eliminate virtual zero references in a cascaded topology. For more information on Luenberger and Lorenz’ PID variations, see [17].
\nThe actuator takes the torque command and converts it into a gimbal rate for the CMGs to apply the desired torque. Rearranging Eq. (6) and substituting Eq. (7) yields
\nTherefore, for a given desired torque, \n
As shown in Eq. (11), \n
where s, c, and t are sin, cos, and tan, respectively. There are numerous CMG orientations in which the denominator for a given term in [A] may be zero—this results in a numerical singularity.
\nSensors are used to measure the actual state of the spacecraft. Ideally, a spacecraft would have enough sensors to provide full state feedback for the controllers. However, the number of sensors required to provide full state feedback may be cost or space prohibitive. Regardless, sensors are not ideal and induce noise into a system.
\nAs a result, generally a state sensor will be used in conjunction with filters and observers. Filters, such as Lowpass or Kalman filters, are used to remove noise from the sensed state signal. Observers, as duals to the controller, take the state and differentiate to provide full state feedback. A number of space system identification algorithms can be found in [20].
\nThere are various definitions of a singularity for a non-redundant CMG system. Physically, singularities are situations in which at least a single CMG torque vector is perpendicular to the commanded torque direction. As a result, the commanded torque cannot be applied and, in general, control systems attempt to calculate and send infinite results to the CMGs and lose control of the spacecraft.
\nNumerically, singularities occur when
\nIn general, for the configuration shown in Figure 1,
\nEqs. (7), (13), and (14) show that singularities are dependent on both β and θ. For any spacecraft configuration, β is fixed upon CMG installation and singularities become a function of θ alone. Therefore, it is required to clearly define the effect of β on singularities and available CMG momentum.
\nIt is essential to note that singularities are instantaneous positions—this means that an infinitesimal shift in angle will result in a position theoretically capable of producing torque. However, though positions like this are theoretically capable of producing torque, the required commanded \n
As shown in Eq. (12), CMGs are coupled in all three axes [21]. Consequently, if one CMG is singular, the resulting [A]−1 would technically be singular. However, in many situations, even if one CMG is singular resulting in a singular [A]−1, the other CMGs are capable of providing useable torque.
\nWith this in mind, to effectively maneuver a spacecraft using CMGs, singularities and singularity-like regions near singularities must be characterized and avoided or penetrated. The industry standard is to operate only in totally singular-free regions, however the number of singularities for any CMG system is often large and as a result, the control space for CMG maneuvers is highly restrictive. Without singularity controller logic, for example, a benchmark 54.73° CMG skewed array has a minimum singularity free momentum of 0.15 H (shown in Figure 4) where H is maximum momentum of one CMG [22].
\nSingularity free momentum.
One approach for singularity control logic is singularity avoidance as shown in [23]. The newest, state-of-the-art solution for CMG singularities is singularity penetration with unit delay (SPUD). SPUD was invented to expand the CMG operating area and protect the spacecraft from losing control near singularities. SPUD’s basic premise is to recognize when the CMG is approaching a singularity and hold the last useful command until the CMG passes through the singularity [24].
\nWith the assumption that sufficient singularity avoidance or penetration logic is in place, a spacecraft attitude control system has the opportunity to utilize the entirety of a CMG’s momentum.
\nFigure 5 shows the maximum available CMG momentum for a homogeneous skew angle CMG array. However, there are many possible configurations in which the skew angle for all CMGs may not be able to be equal. There is a lack of characterization of available CMG momentum for mixed skew angle CMG arrays.
\nHomogeneous skew angle maximum momentum.
MATLAB code and a Simulink model, based on the CMG fundamentals described, were utilized as tools to analyze the maximum available momentum for mixed skew angle CMG arrays. For the momentum analysis, CMG #1 was held constant while CMG #2 and #3 were iterated from 0° to 90° with a step size of 1°. Then, CMG #1 was stepped 5° and the process repeated until CMG #1 cycled from 0° to 90°.
\nA discretization analysis was conducted to ensure accurate results were being recorded. A step size analysis for the homogeneous skew angle array was conducted and is shown in Table 1.
\nStep size (°) | \nStandard deviation | \nComputation time (s) | \n
---|---|---|
0.1 | \n0.2541 | \n182.09 | \n
0.5 | \n0.2592 | \n39.86 | \n
1 | \n0.2652 | \n19.20 | \n
2 | \n0.2815 | \n10.10 | \n
5 | \n0.3250 | \n4.35 | \n
Discretization analysis.
It was clear that as step size decreased, the standard deviation decreased. As the step size approached 0.1°, the standard deviation began to reach asymptotic behavior. However, as the step size approached 0.1°, computational time increased exponentially.
\nThe analysis in Table 1 was conducted iterating one skew angle from 0° to 90°. With the knowledge that the mixed skew angle study would increase the iteration dimensionality from one to two while holding CMG #1 constant, the number of iterations would increase by the power of two. Taking into account computation time, a 1° step size was chosen for the study.
\nThe maximum available momentum for a non-redundant mixed skew array is shown in Figure 6.
\nMaximum available momentum.
For each image in Figure 6, the horizontal axis shows β3 from 0° to 90° and the vertical shows β2 from 0° to 90°. The top left image shows β1 at 0°, top right 30°, bottom left 60°, and bottom right 90°. Table 2 shows the significant skew angle combinations and resulting maximum available momentum.
\nCMG 1-2-3 β angles (°) | \nMaximum momentum (H) | \n
---|---|
0-0- | \n3 | \n
0- | \n3 | \n
30-0- | \n3 | \n
60-0- | \n3 | \n
90-0- | \n3 | \n
90- | \n3 | \n
0-90-90 | \n2.449 | \n
30-90-60 | \n2.449 | \n
60-90-30 | \n2.449 | \n
90-90-0 | \n2.449 | \n
Significant CMG skew angles and momentum.
Table 2 shows that if β2 is zero, any combination of β1 and β3 will result in the maximum available momentum being 3 H. In addition, when β2 is 90, the complimentary angle between β1 and β3 results in the lowest maximum available momentum for all mixed skew combinations.
\nAs depicted in Figure 1, CMG #1 and #3 are opposite one another while CMG #2 is offset by 90°. This orientation is critical for momentum space rotation. As shown in Figure 6, when β1 and β3 are 90°, β2 does not affect the maximum available momentum. An investigation of the effect of β2 on the array momentum space was conducted.
\nIt is known from [25] that certain combinations of 0° and 90° mixed skew angles can shift the momentum space for an array without affecting the shape of the singularity surface. Figures 7, 8, 9 show the momentum space and singularities for a 90-0-90 CMG array configuration. It has a donut shape with the maximum available momentum of 1, 3, and 2 H for x, y, and z, respectively.
\nCMG skew 1-2-3 of 90-0-90 degrees respectively.
CMG skew 90-0-90 in the x-z plane.
CMG skew 90-0-90 in the y-z plane.
Changing β2 to 30° maintains the same singularity surface shape, however, the donut rotates 30° up in the y-z plane as shown in Figure 10.
\nCMG skew 90-30-90 in the y-z plane.
With a 90-30-90 configuration, rather than having 3 H available in the y axis, 3 H is available in the axis 30° up from the y-z plane. This momentum space tilt occurs for all values of β2 when β1 and β3 are 90°.
\nβ2 alone can point the direction of maximum available momentum. This behavior is purely a function of geometry. Figure 1 and Eq. (7) show that when β1 and β3 are 90°, CMG #1 and #3 can put their full momentum anywhere in the y-z plane, therefore by changing the skew of CMG #2, the axis of 3 H momentum can shift from the y axis up towards the z axis without affecting the momentum surface shape.
\nShifting the angle momentum axis occurs for any combination of skew angles. However, for other mixed skew angles, as shown in Figure 6, the ability to provide a full 3 H is no longer preserved and the singularity surface changed. Physically, as β1 and β3 decrease from 90, they no longer have the ability to provide their full momentum in the y-z plane. As an example, the resulting change in available momentum for a 60-X-30 configuration is shown in Figure 11 and Figure 12.
\nCMG skew 60-30-30 singularity surface.
CMG skew 60-60-30 singularity surface.
As β2 increases from 30° to 60°, the maximum available momentum shifts up from 30° to 60°, but the magnitude of momentum in that axis shrinks.
\nFor spacecraft that depend on off axis rotations, mixed skew angles can provide the benefit of tilted momentum space to maximize the CMGs’ ability to rotate about that axis. A 90-X-90 configuration (where X is the angle of the desired rotation axis) is recommended because it allows the momentum space to tilt without changing shape or sacrificing available momentum. To achieve an off-axis 3 H momentum space, the CMGs must be oriented as shown in Figure 1 such that two CMGs are located on the x axis and one is located on the y axis where the desired axis of rotation is angled in the y-z plane.
\nCMGs are a useful momentum exchange tool to maneuver spacecraft. There are many configurations of mixed skew angle arrays that allow for a maximum 3 H available momentum. If β2 is 0°, any combination of β1 and β3 will allow a full 3 H to be available in a given direction. For a 90-X-90 configuration, β2 can be used to tilt the maximum momentum space in the y-z plane without altering the shape of the momentum space. This configuration could be useful for spacecraft requiring off axis rotations.
\nType I interferonopathies are congenital genetic disorder of the interferon (IFN) system, characterized by certain clinical symptoms resulting from the overproduction of IFNα [1, 2, 3]. In our opinion, the term interferonopathy means a general pathology of the interferon system, congenital or acquired, which includes the following types of disorders of the IFN system:
The main role of type I interferons is to control viral infection. The synthesis and secretion of type I IFN is activated when our immune cells come in contact with viruses. Type I IFN is synthesized by epithelial cells, many cells of the immune system, including plasmacytoid dendritic cells (pDC) that recognize foreign or auto nucleic acids. Although both epithelial and pDC synthesize type I IFN simultaneously in different tissues, pDC-derived type I IFN actually exerts various immune responses through its cognate receptors on target cells. This results in modulation of diverse processes such as antigen presentation and activation of adaptive immunological process involving B and T cells [5]. For the synthesis of interferons in the body, cell activation is necessary. Toll-like receptors (TLRs); RIG-like receptors (RLRs), RIG-I; melanoma differentiation-associated protein 5 (MDA5); and cyclic GMP-AMP synthase (cGAS) participate in the recognition of foreign and host nucleic acid sites [6]. The main inducers of the synthesis of type I interferons are double-stranded and single-stranded RNA of viruses, as well as bacterial DNA [7]. RIG-like receptors recognize both single- and double-stranded viral RNAs, whereas cGAS (cyclic GMP-AMP synthase), in contrast, recognizes double-stranded DNA and RNA: DNA duplexes are formed during the replication of retroviruses and catalyze the synthesis of cGMP-AMP, which is the main agonist of the adapter protein—STING. After binding RNA, RIG-I and MDA5 bind the mitochondrial antiviral-signaling (MAVS) adapter protein. Both STING and MAVS stimulate downstream signaling cascades that include multiple kinases and finally lead to phosphorylation of IRF3 and induction of interferon synthesis [8]. Then type I IFN binds to the corresponding IFNAR receptors located on the cell membrane, which leads to the activation of Tyk2 and Jak1 kinases, which undergo phosphorylation and activate signal transduction and transcription activation proteins (STAT1 and STAT2). As a result, a heterotrimeric complex is formed, known as IFN-stimulating gene factor-3 (ISGF3), which includes IFN regulatory factor 9 (IRF9). Janus kinase (Jak) activation is negatively regulated by IFNα-inducible proteins SOCS1 and SOCS3. The binding of ISGF3 promotes interferon-stimulated genes (ISGs), which leads to their transcriptional activation and the collective actions of hundreds of ISGs, resulting in the production of a large number of induced IFN, which inhibits both viral replication and the spread of viruses. Rapid type I IFN secretion and then rapid synthesis induce activity of congenital and adaptive immunity cells by activation of pro-inflammatory cytokines that activate cellular and humoral antiviral immune response [9] (Figure 1).
Molecular mechanisms of the induction of type I and III interferon synthesis. PAMPs: dsRNA, double-stranded RNA; ssRNA, single-stranded RNA. Nucleic acid sensors: cGAS, cyclic GMP-AMP synthase;
During acute viral infection, IFN level is significantly elevated, and more than 70% of cells acquire antiviral status, i.e., they are protected against virus penetration and are able to efficiently neutralize them. Type I IFN has several very important positive effects: direct and indirect antiviral effect, protective antiviral effect, antitumor effect, and immunomodulatory effect. At the same time, it was shown that increased production of IFN can lead to negative consequences similar to autoimmune reactions.
The information presented by several authors about interferon system pathologies is vast and diverse but is not well-systematized. All known defects of IFN system, including type I and II IFN, whether congenital or acquired, including various disorders (deficiency; inadequate response to contact with viruses, bacteria, and mutated or tumor cells; IFN system paralysis; IFN overexpression), are pathologies of IFN system. All those defects of IFN system are collectively known as interferonopathies. There is an urgent need to create a classification of congenital and acquired disorders of the IFN system. We believe that the classification of IFN pathology would help in determining the correct approaches to the differentiated choice of adequate treatment tactics.
Based on our own and others’ experience, we have developed the interferonopathies classification as per the following table [1, 2, 3, 10, 11, 12, 13, 14, 15] (Table 1).
Recently several studies have presented genetic and molecular disorders accompanying rare Mendelian diseases that are associated with type I IFN overexpression resulting from defects in intracellular nucleic acid metabolism, DNAse deficiency, or defects in sensor nucleic acid recognition. Genetic disorders—Mendelian diseases (Aicardi-Goutières syndrome, familial chilblain lupus, spondyenchondromatosis, proteasome-associated autoinflammatory syndrome, Singleton-Merten syndrome)—resulting in inadequately high type I IFN overexpression accompanied by a certain range of clinical disorders are called type I interferonopathies. Interferonopathies have rare pathology; their occurrence varies from 1:10,000 to 1:1,000,000 people. According to the literature, the most common syndrome is Aicardi-Goutières [16]. The frequency of some recently described genetic disorders (e.g., PRAAS2) cannot be counted [17]. Such disorders cause a great number of own nucleic acids in cell cytoplasm to appear. It results in active DNA recognition and pathological overexpression of type I IFN which launch autoimmunity hyperactivation, thus leading to autoimmune inflammation affecting the central and peripheral nervous system. It also results to skin and vessel damage (vasculitis), lung damage, etc. Therefore rapid and efficient immune reaction to alien nucleic acids is positive when it causes type I IFN activation during pathogen invasion and antimicrobial protection. It becomes deleterious when it responds to own DNA which is due to the defect of own nucleic acid metabolism. Some neurological, vascular, and skin symptoms which are typical for type I interferonopathies are reviewed in such multifactorial diseases as exanthematous lupus erythematosus, widespread vasculitis, and autoimmune multiple myositis [6, 7, 18] (Table 2).
I. Congenital interferonopathies | II. Acquired—secondary interferonopathies |
---|---|
1.1 Interferon α deficiency (IFNα) 1.2 Interferon β deficiency (IFNβ) 1.3 Interferon γ deficiency (IFNγ) 2.1 IFNα overexpression 2.1.1 Autoinflammatory syndromes and autoimmune diseases (systemic lupus erythematosus (SLE), systemic angiitis, dermatomyositis), Down syndrome 2.1.2 Type I interferonopathies: Aicardi-Goutières syndrome (AGS), familial chilblain lupus (FCL), spondyenchondromatosis, proteasome-associated autoinflammatory syndrome (PRAAS), Singleton-Merten syndrome (SMS) | 1. 1.1 IFNα deficiency 1.2 IFNβ deficiency 1.3 IFNγ deficiency 2.1 Blockage IFNα adequate response 2.2 Blockage IFNβ adequate response 2.3 Blockage IFNγ adequate response 3.1 Cytokine storm |
Classification of interferonopathies.
Syndrome | Responsible gene | Phenotypes |
---|---|---|
Aicardi-Goutières syndrome | TREX1, RNASEH2B, RNASEH2C, RNASEH2A, SANHD, ADAR, IFIH1 | Encephalopathy, muscular dystonia, microcephaly, calcification of the basal ganglia in the substance of the brain, cramps, fever, increased acute phase blood markers, cytopenia, increased levels of interferon in the cerebrospinal fluid |
Singleton-Merten syndrome | IFIH1 DDX58 RIG-I | Cardiovascular diseases with aortic calcification, osteoporotic manifestations, dental and skeletal abnormalities, psoriatic skin lesions |
Proteasome-associated autoinflammatory syndromes Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) | PSMB4 PSMB3 PSMB8 PSMB9 POMP | Erythematous skin lesions, panniculitis, lipodystrophy, arthritis with the development of joint contractures, myalgia, hepatomegaly, splenomegaly, calcification of the basal ganglia in the brain, fever, increased acute phase blood markers Recurrent fevers in the first months of life, along with characteristic skin lesions, lipodystrophy, violaceous swollen eyelids, arthralgias, extremity contractures, and delayed physical development as well as systemic inflammation markers have been identified as CANDLE-related clinical manifestations |
STING-associated vasculopathy with onset in infancy (SAVI) | TMEM173 | Vasculopathy with the formation of distal gangrene; necrosis; erythematous rash on the face, tip of the nose, and auricles; interstitial lung disease, arthralgia, fever |
Spondyloenchondrodysplasia (SPENCD) | ACP5 | Spondylometaphyseal dysplasia, stunting, calcification of the basal ganglia in the substance of the brain, arthropathy, thrombocytopenia, deficiency of cellular and humoral immunity |
ISG15 deficiency | ISG15 | Calcification of the basal ganglia in the substance of the brain, convulsions, mycobacterial infections |
USP18 deficiency (pseudo-TORCH syndrome) | USP18 | Cerebral hemorrhage and calcification, hepatomegaly, thrombocytopenia |
Trichohepatoenteric syndrome 2 | SKIV2L | Watery diarrhea, brittle and tangled hair, liver damage, mental retardation |
Retinal vasculopathy with cerebral leukodystrophy (RVCL) | TREX1 | The main characteristics of RVCL include the middle-age onset, the progressive visual loss due to retinal vasculopathy (telangiectasias, microaneurysms, and retinal capillary obliteration around the macula), and variable neurological manifestations such as dementia or migraine |
Familial chilblain lupus | TREX1 | Rare monogenic form of cutaneous lupus erythematosus; partly ulcerating acral lesions or painful bluish-red papules located in the fingers, toes, nose, and ears; arthralgias, affecting mainly large joints, without evidence of true arthritis; photosensitivity; or mouth ulcers |
X-linked reticulate pigmentary disorder (XLPDR) | POLA1 | Generalized hyperpigmentation intermingled with small hypomelanotic macules during early childhood, a distinctive face characterized by an upswept frontal hairline and arched eyebrows, as well as severe photophobia, recurrent respiratory infections, and severe gastrointestinal disorders |
Genetic disorders associated with immune dysregulations and clinical characteristics of interferonopathies associated with type I IFN overexpression.
Data available on genetic defects of intracellular nucleic acid metabolism greatly facilitate understanding of the mechanisms of insufficient immune activation, which can help in the development of new therapeutic approaches to the treatment of autoinflammatory and autoimmune diseases [1, 2, 3]. The progress in understanding immunopathogenesis mechanism makes it possible to set the exact targets for new therapeutic strategy development [1, 2]. The immune dysregulation syndrome is characterized by a high level of IFNα, a deficiency of regulatory T-lymphocytes, impaired functioning of B cells, and low content of low-density neutrophils. These neutrophils easily form neutrophilic extracellular traps (NET), and the resulting DNA complexes provoke an increase in IFNα synthesis, and then pDC recognizes autoDNA and produces IFNα [10, 11, 19]. These disorders are observed primarily in systemic lupus erythematosus. New approaches in treatment of SLE and other type I interferonopathies have been developed. Monoclonal antibody therapy in type I interferonopathies treatment with SLE is sifalimumab, rontalizumab against IFNα, and anifrolumab against IFNα receptor (IFNAR). Baricitinib (JAK1/JAK2 inhibitor) is currently at clinical studies (phases 2 and 3) in small cohort of patients with interferonopathies [20, 21, 22]. It is also known that treatment with baricitinib decreased disease signs and symptoms and allowed a significant reduction of corticosteroid treatment in patients with CANDLE and SAVI [23] (Figure 2).
Target therapies by biologics in the treatment of type I IFN overproduction. IFNAR, IFNα receptor; ISGs, interferon-stimulated genes; Tyk, tyrosine kinase; Jak, Janus kinase; pDC, plasmacytoid dendritic cell; STAT, signal transducer and activator of transcription.
There are genetic defects in the synthesis of IFNα/IFNβ and IFNγ and defects in the receptors for IFNα and IFNγ (IFNAR and IFNGR) including genetic disorders associated with low IFN production according to recent studies. Those genetic defects of IFNs are accompanied by clinical signs of severe recurrent viral and/or mycobacterial infection.
Congenital defects of type I IFN are associated with mutation of genes participating in synthesis of IFNα/IFNβ resulting to deficiency of various molecules (STAT1, UNC93B1, MCM4, TLR3, TRAF3, TRIF, TBK1) and decline level of IFNα/IFNβ. Deficiency of IFNγ, its receptor IFNGR (IFNγR1), and IL-12 plays an important role in IFNγ regulation [12, 24, 25]. Congenital defects of type I IFN have been globally systematized in 2015 by Bousfiha et al. [24]. It has been proven that it causes severe viral and bacterial intracellular infections which are the cause of deaths. Such patients are needed in replacement therapy with recombinant IFNα2b in complex with antioxidants. Congenital defects of IFNγR1 receptor are associated with severe intracellular mycobacterial infections. Combined genetic defects leading to deficiency of IFNα and IFNγ are associated with an autosomal recessive mutation in the STAT1 gene, which causes severe viral and mycobacterial infections [12, 24, 25] (Table 3).
Predominant susceptibility to viral infection | ||
---|---|---|
Syndrome | Responsible gene | Phenotypes |
Herpes simplex encephalitis (HSE) | AR (autosomal recessive inheritance): UNC 9381 TLR3 TRIF AD (autosomal dominant inheritance): TLR3 TRIF TRAF3 TBK1 | Dominant clinical phenotype is HSE during primary infection with HSV1, usually between 3 months and 6 years of age Specific tests examining the TLR3 pathway marked decrease on the ability of patient’s fibroblasts to produce IFNβ/IFNλ in response to TLR3 agonists and HSV1 infection |
Warts, hypogammaglobulinemia, infection, myelokathexis (WHIM) syndrome | AD: CCXR4 | Warts/human papilloma virus infection Neutropenia, reduced B cell numbers |
Epidermodysplasia verruciformis | EVER1/TMC6, EVER2/TMC8 | Human papilloma virus (group B1) infection and skin cancer |
STAT1 deficiency STAT2 deficiency | Viral infections | |
CD16 deficiency | Severe viral infections | |
IRF7 deficiency | Severe influenza disease | |
Syndrome | Responsible gene | Phenotypes |
IRF8 deficiency | AR: IRF8 | Susceptibility to mycobacteria, |
RORc deficiency | RORc | Susceptibility to mycobacteria, |
MSMD IL-12-IFNγ axis deficiency | AD: IFNGR1 Complete AR IFNGR1 and AR IFNGR2 Partial STAT1 LOF (AD), partial IFNGR1, partial IFNGR2, complete IL-12R1, complete IL-12B, complete ISG15, XL CYBB, IRF8, Tyk2, XL NEMO | Mycobacterial osteomyelitis Serious disseminated BCG and environmental mycobacteria infections (soft tissue, bone marrow, lungs, skin, bones, and lymph nodes), Usually less severe |
Genetic disorders and clinical characteristics of interferonopathies associated with type I IFN deficiency.
There are secondary acquired disorders in the IFN system, which cause a weakening of antiviral resistance in adults and children [12]. Different viruses can damage synthesis and production of IFN at various interferonogenesis stages. These secondary defects of the type I IFN lead to the occurrence of severe viral infections (herpesviral encephalitis), recurrent acute respiratory viral infections (recARVI), chronic recurrent HSV1 infection, atypical chronic EBV infections, and other atypical cases of virus infection. It was shown that viruses can avoid the effects of IFN and inhibit the action and synthesis of IFN using various molecular mechanisms. Numerous studies demonstrated that a lot of viruses (all herpesviruses, majority of respiratory viruses, hepatitis B and C viruses, etc.) produce proteins capable of inhibiting synthesis and production of IFNα/IFNβ and IFNγ. Viruses can damage each stage of the expression of ISGs [9] (Figure 3).
Blockage of signaling pathways for the induction of interferon by viruses (red hexagons indicate the points of application of all herpesviruses, majority of respiratory viruses, chronic hepatitis B and C viruses, etc.). dsRNA, double-stranded RNA; IRF, IFN regulatory factor; IFNAR, IFNα receptor; ISGs, interferon-stimulated genes; Tyk, tyrosine kinase; Jak, Janus kinase; NF-kB, nuclear factor kappa-light-chain-enhancer of activated B cells; cGAS, cyclic GMP-AMP synthase; MAVS, mitochondrial antiviral-signaling protein;
Patients with recurrent acute respiratory viral infections and various chronic herpesvirus infections including recurrent herpes viral infections have secondary defects of IFN system. Immunocompromised children of various ages and adults may suffer from recARVI with the frequency of 10 to 16–24 and more times annually; almost in 100% of cases, it is associated with the presence of mono and mixed herpes viral infection. The frequency of recurrent chronic HSV1/HSV2 infection of facial and/or genital location in those patients may reach 16–24 times per year. Epstein-Barr virus may cause atypical virus infection associated with chronic fatigue syndrome [12].
The problem of developing new approaches to the treatment of congenital and acquired defects of the IFN system is very acute [12, 26, 27, 28]. Acquired defects in the IFN system (93–96%) and impaired functioning of neutrophilic granulocytes (NG) are most often detected in patients with recurrent chronic herpes virus infections.
We conducted experiment in vitro to study the effect of recombinant IFNα2b (rIFNα2b) on NG in viral (cells from patients with HSV1/HSV2 infection) and bacterial (model infection by fMLP) infections. The study showed positive regulation of the negatively charged IFNαβR1+IFNγR+TLR4+NG phenotype in patients with various chronic herpesvirus infections under the influence of rIFNα2b in vitro. It was noted that the number of NGs carrying IFNαβR1 and IFNγR and expression density of IFNαβR1 is increasing, wherein expression density of IFNγR and TLR4 is decreased [29]. rIFNα2b modulating effects on CD16+CD66b+CD33+CD11b+NG phenotype transformed by fMLP in experimental model of bacterial process in vitro, to promote remodeling of the pro-inflammatory NG phenotype into anti-inflammatory, have been shown [30]. Thus rIFNα2b has a protective effect on the NG phenotype according to experimental data.
In clinical practice, the use of parenteral IFN to correct disorders in the IFN system is very difficult due to the presence of numerous side effects. One should also bear in mind the inefficiency of short courses of IFN therapy for restoration of the normal IFN system functioning in recARVI, recurrent chronic herpes viral infection of facial or genital location, and papilloma virus infection of the skin and mucosa characterized by recurrent episodes when the frequency of recARVI and/or recurrent attacks of HSV1/HSV2 infection may reach 14–24 and more per year. For over 20 years, we have been developing interferon therapy programs using drugs in Russian production—rectal suppositories and gel of recombinant human IFNα2b (rIFNα2b+aox) in combination with antioxidants (vitamins E and C) (Viferon) [12, 13, 14, 15, 26, 27]. During that period, we managed to demonstrate safety, antiviral, and immunomodulatory efficiency of this kind of IFN therapy, total absence of any side effects that are typical for parenteral IFN therapy, and total absence of antibodies against IFNα2b. Replacement therapy with rIFNα2b + aox is prescribed to patients with primary, genetically preconditioned, congenital or acquired IFN system disorders. In case of primary IFN system disorders, patients need a basic recovery therapy making it possible to eliminate viral antigens as much as possible; and then it is required to select dosage for permanent replacement therapy with rIFNα2b+aox. In case of acquired interferon deficiency, patients are prescribed with differentiated therapy with high, medium, and low doses of rIFNα2b+aox (Figure 4).
Dynamics of changes in the system of IFN in immunocompromised children against the background of therapy with rIFNα2b+aox (Viferon).
At the same time, in case when we had treated the group of patients with combined immunodeficiency (defects of induced production of IFNα and IFNγ and dysfunctions of phagocytic and microbicidal activities of neutrophilic granulocytes) that was associated with recurrent acute respiratory viral infection and different chronic herpes viral coinfections, combined interferon and immunomodulatory therapy was used. The aim was to restore the levels of induced production of IFNα and IFNγ and to reconstruct dysfunctions of phagocytic and microbicidal activities of neutrophilic granulocytes and other deficient chains in antiviral immunity. One group of children, group 1, received an interferon therapy program (rIFNα2b+aox), and patients in group 2 received a program of combined interferon therapy (rIFNα2b+aox) and immunotherapy (glucosaminylmuramyldipeptide). The use of replacement and immunomodulatory mono-rIFNα2b+aox or in combination with immunotherapy (glucosaminylmuramyldipeptide) has helped us to receive very good clinical efficacies and has reached restoration of interferon status and normal functioning of neutrophilic granulocytes (p < 0.05) (Figure 5). At the same time, it is required to take into account both uneven viral infection syndrome manifestation and the rate of IFNα deficiency as well as peculiarities of immune system disorders in case of secondary immune deficiency [12, 13, 14, 15, 27].
The state of the interferon system in immunocompromised children with recurrent respiratory infections on the background of differentiated programs interferon and immunotherapy. Note: group 1 received an interferon therapy program (rIFNα2b+aox); group 2 received a program of combined interferon therapy (rIFNα2b+aox) and immunotherapy (glucosaminylmuramyldipeptide); (*p < 0.05, reliability in relation to control).
Here is an example illustrating the change in clinical, immune, and interferon status in immunocompromised children with recurrent acute respiratory viral infections under the influence of interferonotherapy.
Clinical case. Patient X, 3 years old. The child suffers from repeated acute respiratory viral infections 1–2 times per month (14–16 episodes per year); the duration of the acute period of respiratory viral infection is 7–10 days. The clinical symptoms of the disease were acute rhinitis, acute pharyngitis, acute laryngitis, acute tracheitis, febrile and subfebrile body temperature for 2–4 days, and severe symptoms of intoxication. The duration of the frequent incidence of acute respiratory viral infections is 2 years. The defects of the immune system are a decrease of CD3+CD4+ lymphocytes and CD3+CD8+ lymphocytes; a decrease of immunoregulatory index; neutropenia; a decrease of bacteria absorption and digestion processes by neutrophils; and a decrease of microbicidal activity of neutrophils. We tested spontaneous and Newcastle disease virus-induced IFN production during the incubation of peripheral blood (24 h, t 37°C in 5% CО2). The level of induced IFNα in the patient was 4 IU/ml versus 58 IU/ml in control. The patient was prescribed rIFNα2b+aox therapy with a total duration of 2.5 months.
Treatment program:
Local intranasal use of rIFNα2b+aox (Viferon gel, 36,000 IU/g), two to three times a day, 6 weeks.
Systemic rectal application of rIFNα2b+aox suppositories according to a “step-by-step” scheme:
300,000 IU per day, 10 days.
300,000 IU per day three times a week, 2 weeks.
300,000 IU per day two times a week, 2 weeks.
150,000 IU per day two times a week, 2 weeks.
150,000 IU per day once a week, 2 weeks.
Conducted local and systemic interferon therapy led to a reduction in the frequency of acute respiratory viral infections to three episodes per year lasting 5–7 days, proceeding in a milder form. Rehabilitation of immunity parameters occurred after 2.5 months of interferonotherapy, and the level of induced IFNα was normalized to 64 IU/ml.
Summing up the above information, we may conclude that new biological drugs based on mAb are effective and safe, and they are able to neutralize IFNα overexpression in type I interferonopathies, both in Mendelian’s diseases and in autoimmune disorders. At the same time, local and system use of rIFNα2b+aox (Viferon) in congenital and acquired IFN system defects associated with viral infection syndrome, where a differential dosage is selected individually taking into account the rate of deficiency and an adequate, extended course of therapy is optimal because it is associated with positive clinical and immunological effects without any negative and side effects. Our more than 20-year experience has shown that using recIFNα2b+aox in patients with congenital or acquired IFN system defects had demonstrated positive clinical effect and is safe [31]. IFN (rIFNα2b+aox) therapy can be used with very good clinical efficacy in cases of primary or secondary defects of induced production of IFNα and IFNγ. From the other side, it is very important that in patients with a genetic predisposition to the manifestation of autoimmune diseases, primarily vasculitis and systemic lupus erythematosus, we do not recommend to use IFN therapy.
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",metaTitle:"Edited Volumes",metaDescription:"The Edited Volume, also known as the InTechOpen Book, is an InTechOpen pioneered publishing product. Edited Volumes make up the core of our business - and as pioneers and developers of this Open Access book publishing format, we have helped change the way scholars and scientists publish their scientific papers - as scientific chapters. ",metaKeywords:null,canonicalURL:"/pages/edited-volumes",contentRaw:'[{"type":"htmlEditorComponent","content":"WHY PUBLISH IN AN INTECHOPEN EDITED VOLUME?
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\n\nOut of all of the publishing options available to researchers, why choose to contribute your research to an IntechOpen Edited Volume? The reasons are simple. IntechOpen has worked exceptionally hard over the past years to fine tune the Open Access book publishing process and we continue to work hard to deliver the best for all of our contributors. The quality of published content is of utmost importance to us, followed closely by speed, and of course, availability and accessibility. To view current Open Access book projects that are Open for Submissions visit us here.
\n\nQUALITY CONTENT
\n\nOver the years we have learned what is important. What makes a difference to the researchers that work with us, what they value. Something that is very high not only on their lists, but our own, is the quality of the published content.
\n\nOur books contain scientific content written by two Nobel Prize winners, two Breakthrough Prize winners and 73 authors who are in the top 1% Most Cited.
\n\nWith regular submission for coverage in the single most important database, the Book Citation Index in the Web of Science™ Core Collection (BKCI), and no rejected submissions to date, over 43% of all Open Access books indexed in the BKCI are IntechOpen published books.
\n\nIn addition to BKCI, IntechOpen covers a number of important discipline specific databases as well, such as Thomson Reuters’ BIOSIS Previews.
\n\nACCESS
\n\nThe need for up to date information available at the click of a mouse is one thing that sets IntechOpen apart. By developing our own technologies in order to streamline the publishing process, we are able to minimize the amount of time from initial submission of a manuscript to its final publication date, without compromising the rigor of the editorial and peer review process. This means that the research published stays relevant, and in this fast paced world, this is very important.
\n\nYOUR WORK, YOUR COPYRIGHT
\n\nThe utilization of CC licenses allow researchers to retain copyright to their work. Researchers are free to use, adapt and share all content they publish with us. You will never have to pay permission fees to reuse a part of an experiment that you worked so hard to complete and are free to build upon your own research and the research of others. The Edited Volume helps bring together research from all over the world and compiles that research into one book - accessible for all. The research presented in chapter one can inspire the author of chapter three to take his or her research to the next level. It is about sharing ideas, insights and knowledge.
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\n\n3,332 OPEN ACCESS BOOKS
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His studies in robotics lead him not only to a PhD degree but also inspired him to co-found and build the International Journal of Advanced Robotic Systems - world's first Open Access journal in the field of robotics.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"441",title:"Ph.D.",name:"Jaekyu",middleName:null,surname:"Park",slug:"jaekyu-park",fullName:"Jaekyu Park",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/441/images/1881_n.jpg",biography:null,institutionString:null,institution:{name:"LG Corporation (South Korea)",country:{name:"Korea, South"}}},{id:"465",title:"Dr.",name:"Christian",middleName:null,surname:"Martens",slug:"christian-martens",fullName:"Christian Martens",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Rheinmetall (Germany)",country:{name:"Germany"}}},{id:"479",title:"Dr.",name:"Valentina",middleName:null,surname:"Colla",slug:"valentina-colla",fullName:"Valentina Colla",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/479/images/358_n.jpg",biography:null,institutionString:null,institution:{name:"Sant'Anna School of Advanced Studies",country:{name:"Italy"}}},{id:"494",title:"PhD",name:"Loris",middleName:null,surname:"Nanni",slug:"loris-nanni",fullName:"Loris Nanni",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/494/images/system/494.jpg",biography:"Loris Nanni received his Master Degree cum laude on June-2002 from the University of Bologna, and the April 26th 2006 he received his Ph.D. in Computer Engineering at DEIS, University of Bologna. 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. His research interests include pattern recognition, bioinformatics, and biometric systems (fingerprint classification and recognition, signature verification, face recognition).",institutionString:null,institution:null},{id:"496",title:"Dr.",name:"Carlos",middleName:null,surname:"Leon",slug:"carlos-leon",fullName:"Carlos Leon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Seville",country:{name:"Spain"}}},{id:"512",title:"Dr.",name:"Dayang",middleName:null,surname:"Jawawi",slug:"dayang-jawawi",fullName:"Dayang Jawawi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Technology Malaysia",country:{name:"Malaysia"}}},{id:"528",title:"Dr.",name:"Kresimir",middleName:null,surname:"Delac",slug:"kresimir-delac",fullName:"Kresimir Delac",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/528/images/system/528.jpg",biography:"K. Delac received his B.Sc.E.E. degree in 2003 and is currentlypursuing a Ph.D. degree at the University of Zagreb, Faculty of Electrical Engineering andComputing. His current research interests are digital image analysis, pattern recognition andbiometrics.",institutionString:null,institution:{name:"University of Zagreb",country:{name:"Croatia"}}},{id:"557",title:"Dr.",name:"Andon",middleName:"Venelinov",surname:"Topalov",slug:"andon-topalov",fullName:"Andon Topalov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/557/images/1927_n.jpg",biography:"Dr. Andon V. Topalov received the MSc degree in Control Engineering from the Faculty of Information Systems, Technologies, and Automation at Moscow State University of Civil Engineering (MGGU) in 1979. He then received his PhD degree in Control Engineering from the Department of Automation and Remote Control at Moscow State Mining University (MGSU), Moscow, in 1984. From 1985 to 1986, he was a Research Fellow in the Research Institute for Electronic Equipment, ZZU AD, Plovdiv, Bulgaria. In 1986, he joined the Department of Control Systems, Technical University of Sofia at the Plovdiv campus, where he is presently a Full Professor. He has held long-term visiting Professor/Scholar positions at various institutions in South Korea, Turkey, Mexico, Greece, Belgium, UK, and Germany. And he has coauthored one book and authored or coauthored more than 80 research papers in conference proceedings and journals. His current research interests are in the fields of intelligent control and robotics.",institutionString:null,institution:{name:"Technical University of Sofia",country:{name:"Bulgaria"}}},{id:"585",title:"Prof.",name:"Munir",middleName:null,surname:"Merdan",slug:"munir-merdan",fullName:"Munir Merdan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/585/images/system/585.jpg",biography:"Munir Merdan received the M.Sc. degree in mechanical engineering from the Technical University of Sarajevo, Bosnia and Herzegovina, in 2001, and the Ph.D. degree in electrical engineering from the Vienna University of Technology, Vienna, Austria, in 2009.Since 2005, he has been at the Automation and Control Institute, Vienna University of Technology, where he is currently a Senior Researcher. His research interests include the application of agent technology for achieving agile control in the manufacturing environment.",institutionString:null,institution:null},{id:"605",title:"Prof",name:"Dil",middleName:null,surname:"Hussain",slug:"dil-hussain",fullName:"Dil Hussain",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/605/images/system/605.jpg",biography:"Dr. Dil Muhammad Akbar Hussain is a professor of Electronics Engineering & Computer Science at the Department of Energy Technology, Aalborg University Denmark. Professor Akbar has a Master degree in Digital Electronics from Govt. College University, Lahore Pakistan and a P-hD degree in Control Engineering from the School of Engineering and Applied Sciences, University of Sussex United Kingdom. Aalborg University has Two Satellite Campuses, one in Copenhagen (Aalborg University Copenhagen) and the other in Esbjerg (Aalborg University Esbjerg).\n· He is a member of prestigious IEEE (Institute of Electrical and Electronics Engineers), and IAENG (International Association of Engineers) organizations. \n· He is the chief Editor of the Journal of Software Engineering.\n· He is the member of the Editorial Board of International Journal of Computer Science and Software Technology (IJCSST) and International Journal of Computer Engineering and Information Technology. \n· He is also the Editor of Communication in Computer and Information Science CCIS-20 by Springer.\n· Reviewer For Many Conferences\nHe is the lead person in making collaboration agreements between Aalborg University and many universities of Pakistan, for which the MOU’s (Memorandum of Understanding) have been signed.\nProfessor Akbar is working in Academia since 1990, he started his career as a Lab demonstrator/TA at the University of Sussex. 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. He has contributed in stochastic estimation of control area especially, in the Multiple Target Tracking and Interactive Multiple Model (IMM) research, Ball & Beam Control Problem, Robotics, Levitation Control. He has contributed in developing Algorithms for Fingerprint Matching, Computer Vision and Face Recognition. He has been supervising Pattern Recognition, Formal Languages and Distributed Processing projects for several years. He has reviewed many books on Management, Computer Science. Currently, he is an active and permanent reviewer for many international conferences and symposia and the program committee member for many international conferences.\nIn teaching he has taught the core computer science subjects like, Digital Design, Real Time Embedded System Programming, Operating Systems, Software Engineering, Data Structures, Databases, Compiler Construction. 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Patients who do not respond to conservative treatments and have significant spinal stenosis should be referred for surgery.",book:{id:"7540",slug:"different-areas-of-physiotherapy",title:"Different Areas of Physiotherapy",fullTitle:"Different Areas of Physiotherapy"},signatures:"Shu-Yan Ng, Tsz-Ki Ho and Yin-Ling Ng",authors:[{id:"204673",title:"Dr.",name:"Shu Yan",middleName:null,surname:"Ng",slug:"shu-yan-ng",fullName:"Shu Yan Ng"}]},{id:"62969",title:"Non-Pharmacological Pain Management",slug:"non-pharmacological-pain-management",totalDownloads:2968,totalCrossrefCites:7,totalDimensionsCites:9,abstract:"Non-pharmacological pain therapy refers to interventions that do not involve the use of medications to treat pain. The goals of non-pharmacological interventions are to decrease fear, distress and anxiety, and to reduce pain and provide patients with a sense of control. When deciding the most effective non-pharmacological technique, take into consideration the patient’s age, developmental level, medical history and prior experiences, current degree of pain and/or anticipated pain. The advantage of non-pharmacological treatments is that they are relatively inexpensive and safe.",book:{id:"7289",slug:"pain-management-in-special-circumstances",title:"Pain Management in Special Circumstances",fullTitle:"Pain Management in Special Circumstances"},signatures:"Ahmed El Geziry, Yasser Toble, Fathi Al Kadhi, Muhammad Pervaiz\nand Mohammad Al Nobani",authors:null},{id:"63463",title:"Clinical Classification of Cerebral Palsy",slug:"clinical-classification-of-cerebral-palsy",totalDownloads:2643,totalCrossrefCites:3,totalDimensionsCites:4,abstract:"The classification of cerebral palsy (CP) remains a challenge; hence the presence of so many classifications and a lack of consensus. Each classification used alone is incomplete. Therefore, a multiaxial classification gives a more comprehensive description of a child with CP. The recent WHO International Classification of Functioning, Disability and Health (ICF) emphasizes the importance of focusing on the functional consequences of various states of health and has stimulated the development of newer functional scales in CP. It is widely accepted that the functional classification is the best classification for the patient because it guides management. The objectives of this chapter are to review the various classifications of CP, to highlight the clinical features used in the various classifications, to outline the recent functional classifications of CP and to highlight how these recent classifications guide current management. It is expected that at the end of this chapter, the reader should be able to understand the difficulties in classifying CP, enumerate and discuss the various classifications of CP, understand the merits and shortcomings of each classification scheme, clinically evaluate and classify a child with CP multiaxially and understand how functional scales predict current and future needs of children with CP.",book:{id:"7072",slug:"cerebral-palsy-clinical-and-therapeutic-aspects",title:"Cerebral Palsy",fullTitle:"Cerebral Palsy - Clinical and Therapeutic Aspects"},signatures:"Christian Chukwukere Ogoke",authors:[{id:"250398",title:"Dr.",name:"Christian",middleName:"Chukwukere",surname:"Ogoke",slug:"christian-ogoke",fullName:"Christian Ogoke"}]},{id:"70770",title:"Ambulatory Devices: Assessment and Prescription",slug:"ambulatory-devices-assessment-and-prescription",totalDownloads:1203,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"Injuries or disabilities associated with the lower extremities and aging frequently result in ambulation difficulty and this usually necessitates the prescription of ambulatory assistive device (e.g., cane, crutch and walker) in an attempt to restore locomotory function. Ambulatory devices are orthotic devices that provide support, stability and balance for users to able to move from one point to another. Users can progress or retrogress from one ambulatory device to another while some are permanently fit on a particular device throughout lifetime. The progression is dependent on the medical condition, user’s abilities, user’s anthropometric and environment. Physiotherapist prescribes ambulatory device to users and helps with the fitting and proper use of the ambulatory device. A correct prescription and well fitted ambulatory device minimize functional limitation and promote functional ability and improve quality of life. 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He has both an MS and Ph.D. in Biomedical Engineering. He was previously a research scientist at the University of California Los Angeles (UCLA) and visiting professor and researcher at the University of North Dakota. He is currently working in artificial intelligence and its applications in medical signal processing. In addition, he is using digital signal processing in medical imaging and speech processing. Dr. Asadpour has developed brain-computer interfacing algorithms and has published books, book chapters, and several journal and conference papers in this field and other areas of intelligent signal processing. 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Dr. Gaiceanu is a member of the National Council for Attesting Titles, Diplomas and Certificates, an expert of the Executive Agency for Higher Education, Research Funding, and a member of the Senate of the Dunarea de Jos University of Galati. He has been the head of the Integrated Energy Conversion Systems and Advanced Control of Complex Processes Research Center, Romania, since 2016. He has conducted several projects in power converter systems for electrical drives, power quality, PEM and SOFC fuel cell power converters for utilities, electric vehicles, and marine applications with the Department of Regulation and Control, SIEI S.pA. (2002–2004) and the Polytechnic University of Turin, Italy (2002–2004, 2006–2007). He is a member of the Institute of Electrical and Electronics Engineers (IEEE) and cofounder-member of the IEEE Power Electronics Romanian Chapter. He is a guest editor at Energies and an academic book editor for IntechOpen. He is also a member of the editorial boards of the Journal of Electrical Engineering, Electronics, Control and Computer Science and Sustainability. Dr. Gaiceanu has been General Chairman of the IEEE International Symposium on Electrical and Electronics Engineering in the last six editions.",institutionString:'"Dunarea de Jos" University of Galati',institution:{name:'"Dunarea de Jos" University of Galati',country:{name:"Romania"}}},{id:"4519",title:"Prof.",name:"Jaydip",middleName:null,surname:"Sen",slug:"jaydip-sen",fullName:"Jaydip Sen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/4519/images/system/4519.jpeg",biography:"Jaydip Sen is associated with Praxis Business School, Kolkata, India, as a professor in the Department of Data Science. His research areas include security and privacy issues in computing and communication, intrusion detection systems, machine learning, deep learning, and artificial intelligence in the financial domain. 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Ms. Mehtab has published seven papers in international conferences and one of her papers has been accepted for publication in a reputable international journal. She has won the best paper awards in two prestigious international conferences – BAICONF 2019, and ICADCML 2021, organized in the Indian Institute of Management, Bangalore, India in December 2019, and SOA University, Bhubaneswar, India in January 2021. Besides, Ms. Mehtab has also published two book chapters in two books. Seven of her book chapters will be published in a volume shortly in 2021 by Cambridge Scholars’ Press, UK. Currently, she is working as the joint editor of two edited volumes on Time Series Analysis and Forecasting to be published in the first half of 2021 by an international house. Currently, she is working as a Data Scientist with an MNC in Delhi, India.",institutionString:"NSHM College of Management and Technology",institution:{name:"Association for Computing Machinery",country:{name:"United States of America"}}},{id:"226240",title:"Dr.",name:"Andri Irfan",middleName:null,surname:"Rifai",slug:"andri-irfan-rifai",fullName:"Andri Irfan Rifai",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/226240/images/7412_n.jpg",biography:"Andri IRFAN is a Senior Lecturer of Civil Engineering and Planning. He completed the PhD at the Universitas Indonesia & Universidade do Minho with Sandwich Program Scholarship from the Directorate General of Higher Education and LPDP scholarship. He has been teaching for more than 19 years and much active to applied his knowledge in the project construction in Indonesia. His research interest ranges from pavement management system to advanced data mining techniques for transportation engineering. He has published more than 50 papers in journals and 2 books.",institutionString:null,institution:{name:"Universitas Internasional Batam",country:{name:"Indonesia"}}},{id:"314576",title:"Dr.",name:"Ibai",middleName:null,surname:"Laña",slug:"ibai-lana",fullName:"Ibai Laña",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314576/images/system/314576.jpg",biography:"Dr. Ibai Laña works at TECNALIA as a data analyst. He received his Ph.D. in Artificial Intelligence from the University of the Basque Country (UPV/EHU), Spain, in 2018. He is currently a senior researcher at TECNALIA. His research interests fall within the intersection of intelligent transportation systems, machine learning, traffic data analysis, and data science. He has dealt with urban traffic forecasting problems, applying machine learning models and evolutionary algorithms. He has experience in origin-destination matrix estimation or point of interest and trajectory detection. Working with large volumes of data has given him a good command of big data processing tools and NoSQL databases. He has also been a visiting scholar at the Knowledge Engineering and Discovery Research Institute, Auckland University of Technology.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"314575",title:"Dr.",name:"Jesus",middleName:null,surname:"L. Lobo",slug:"jesus-l.-lobo",fullName:"Jesus L. Lobo",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314575/images/system/314575.png",biography:"Dr. Jesús López is currently based in Bilbao (Spain) working at TECNALIA as Artificial Intelligence Research Scientist. In most cases, a project idea or a new research line needs to be investigated to see if it is good enough to take into production or to focus on it. That is exactly what he does, diving into Machine Learning algorithms and technologies to help TECNALIA to decide whether something is great in theory or will actually impact on the product or processes of its projects. So, he is expert at framing experiments, developing hypotheses, and proving whether they’re true or not, in order to investigate fundamental problems with a longer time horizon. He is also able to design and develop PoCs and system prototypes in simulation. He has participated in several national and internacional R&D projects.\n\nAs another relevant part of his everyday research work, he usually publishes his findings in reputed scientific refereed journals and international conferences, occasionally acting as reviewer and Programme Commitee member. Concretely, since 2018 he has published 9 JCR (8 Q1) journal papers, 9 conference papers (e.g. ECML PKDD 2021), and he has co-edited a book. He is also active in popular science writing data science stories for reputed blogs (KDNuggets, TowardsDataScience, Naukas). Besides, he has recently embarked on mentoring programmes as mentor, and has also worked as data science trainer.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"103779",title:"Prof.",name:"Yalcin",middleName:null,surname:"Isler",slug:"yalcin-isler",fullName:"Yalcin Isler",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRyQ8QAK/Profile_Picture_1628834958734",biography:"Yalcin Isler (1971 - Burdur / Turkey) received the B.Sc. degree in the Department of Electrical and Electronics Engineering from Anadolu University, Eskisehir, Turkey, in 1993, the M.Sc. degree from the Department of Electronics and Communication Engineering, Suleyman Demirel University, Isparta, Turkey, in 1996, the Ph.D. degree from the Department of Electrical and Electronics Engineering, Dokuz Eylul University, Izmir, Turkey, in 2009, and the Competence of Associate Professorship from the Turkish Interuniversity Council in 2019.\n\nHe was Lecturer at Burdur Vocational School in Suleyman Demirel University (1993-2000, Burdur / Turkey), Software Engineer (2000-2002, Izmir / Turkey), Research Assistant in Bulent Ecevit University (2002-2003, Zonguldak / Turkey), Research Assistant in Dokuz Eylul University (2003-2010, Izmir / Turkey), Assistant Professor at the Department of Electrical and Electronics Engineering in Bulent Ecevit University (2010-2012, Zonguldak / Turkey), Assistant Professor at the Department of Biomedical Engineering in Izmir Katip Celebi University (2012-2019, Izmir / Turkey). He is an Associate Professor at the Department of Biomedical Engineering at Izmir Katip Celebi University, Izmir / Turkey, since 2019. In addition to academics, he has also founded Islerya Medical and Information Technologies Company, Izmir / Turkey, since 2017.\n\nHis main research interests cover biomedical signal processing, pattern recognition, medical device design, programming, and embedded systems. He has many scientific papers and participated in several projects in these study fields. He was an IEEE Student Member (2009-2011) and IEEE Member (2011-2014) and has been IEEE Senior Member since 2014.",institutionString:null,institution:{name:"Izmir Kâtip Çelebi University",country:{name:"Turkey"}}},{id:"339677",title:"Dr.",name:"Mrinmoy",middleName:null,surname:"Roy",slug:"mrinmoy-roy",fullName:"Mrinmoy Roy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/339677/images/16768_n.jpg",biography:"An accomplished Sales & Marketing professional with 12 years of cross-functional experience in well-known organisations such as CIPLA, LUPIN, GLENMARK, ASTRAZENECA across different segment of Sales & Marketing, International Business, Institutional Business, Product Management, Strategic Marketing of HIV, Oncology, Derma, Respiratory, Anti-Diabetic, Nutraceutical & Stomatological Product Portfolio and Generic as well as Chronic Critical Care Portfolio. A First Class MBA in International Business & Strategic Marketing, B.Pharm, D.Pharm, Google Certified Digital Marketing Professional. Qualified PhD Candidate in Operations and Management with special focus on Artificial Intelligence and Machine Learning adoption, analysis and use in Healthcare, Hospital & Pharma Domain. Seasoned with diverse therapy area of Pharmaceutical Sales & Marketing ranging from generating revenue through generating prescriptions, launching new products, and making them big brands with continuous strategy execution at the Physician and Patients level. Moved from Sales to Marketing and Business Development for 3.5 years in South East Asian Market operating from Manila, Philippines. Came back to India and handled and developed Brands such as Gluconorm, Lupisulin, Supracal, Absolut Woman, Hemozink, Fabiflu (For COVID 19), and many more. In my previous assignment I used to develop and execute strategies on Sales & Marketing, Commercialization & Business Development for Institution and Corporate Hospital Business portfolio of Oncology Therapy Area for AstraZeneca Pharma India Ltd. Being a Research Scholar and Student of ‘Operations Research & Management: Artificial Intelligence’ I published several pioneer research papers and book chapters on the same in Internationally reputed journals and Books indexed in Scopus, Springer and Ei Compendex, Google Scholar etc. Currently, I am launching PGDM Pharmaceutical Management Program in IIHMR Bangalore and spearheading the course curriculum and structure of the same. I am interested in Collaboration for Healthcare Innovation, Pharma AI Innovation, Future trend in Marketing and Management with incubation on Healthcare, Healthcare IT startups, AI-ML Modelling and Healthcare Algorithm based training module development. I am also an affiliated member of the Institute of Management Consultant of India, looking forward to Healthcare, Healthcare IT and Innovation, Pharma and Hospital Management Consulting works.",institutionString:null,institution:{name:"Lovely Professional University",country:{name:"India"}}},{id:"310576",title:"Prof.",name:"Erick Giovani",middleName:null,surname:"Sperandio Nascimento",slug:"erick-giovani-sperandio-nascimento",fullName:"Erick Giovani Sperandio Nascimento",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0033Y00002pDKxDQAW/ProfilePicture%202022-06-20%2019%3A57%3A24.788",biography:"Prof. Erick Sperandio is the Lead Researcher and professor of Artificial Intelligence (AI) at SENAI CIMATEC, Bahia, Brazil, also working with Computational Modeling (CM) and HPC. He holds a PhD in Environmental Engineering in the area of Atmospheric Computational Modeling, a Master in Informatics in the field of Computational Intelligence and Graduated in Computer Science from UFES. He currently coordinates, leads and participates in R&D projects in the areas of AI, computational modeling and supercomputing applied to different areas such as Oil and Gas, Health, Advanced Manufacturing, Renewable Energies and Atmospheric Sciences, advising undergraduate, master's and doctoral students. He is the Lead Researcher at SENAI CIMATEC's Reference Center on Artificial Intelligence. In addition, he is a Certified Instructor and University Ambassador of the NVIDIA Deep Learning Institute (DLI) in the areas of Deep Learning, Computer Vision, Natural Language Processing and Recommender Systems, and Principal Investigator of the NVIDIA/CIMATEC AI Joint Lab, the first in Latin America within the NVIDIA AI Technology Center (NVAITC) worldwide program. He also works as a researcher at the Supercomputing Center for Industrial Innovation (CS2i) and at the SENAI Institute of Innovation for Automation (ISI Automação), both from SENAI CIMATEC. He is a member and vice-coordinator of the Basic Board of Scientific-Technological Advice and Evaluation, in the area of Innovation, of the Foundation for Research Support of the State of Bahia (FAPESB). He serves as Technology Transfer Coordinator and one of the Principal Investigators at the National Applied Research Center in Artificial Intelligence (CPA-IA) of SENAI CIMATEC, focusing on Industry, being one of the six CPA-IA in Brazil approved by MCTI / FAPESP / CGI.br. He also participates as one of the representatives of Brazil in the BRICS Innovation Collaboration Working Group on HPC, ICT and AI. He is the coordinator of the Work Group of the Axis 5 - Workforce and Training - of the Brazilian Strategy for Artificial Intelligence (EBIA), and member of the MCTI/EMBRAPII AI Innovation Network Training Committee. He is the coordinator, by SENAI CIMATEC, of the Artificial Intelligence Reference Network of the State of Bahia (REDE BAH.IA). He leads the working group of experts representing Brazil in the Global Partnership on Artificial Intelligence (GPAI), on the theme \"AI and the Pandemic Response\".",institutionString:"Manufacturing and Technology Integrated Campus – SENAI CIMATEC",institution:null},{id:"1063",title:"Prof.",name:"Constantin",middleName:null,surname:"Volosencu",slug:"constantin-volosencu",fullName:"Constantin Volosencu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/1063/images/system/1063.png",biography:"Prof. Dr. Constantin Voloşencu graduated as an engineer from\nPolitehnica University of Timișoara, Romania, where he also\nobtained a doctorate degree. He is currently a full professor in\nthe Department of Automation and Applied Informatics at the\nsame university. Dr. Voloşencu is the author of ten books, seven\nbook chapters, and more than 160 papers published in journals\nand conference proceedings. He has also edited twelve books and\nhas twenty-seven patents to his name. He is a manager of research grants, editor in\nchief and member of international journal editorial boards, a former plenary speaker, a member of scientific committees, and chair at international conferences. His\nresearch is in the fields of control systems, control of electric drives, fuzzy control\nsystems, neural network applications, fault detection and diagnosis, sensor network\napplications, monitoring of distributed parameter systems, and power ultrasound\napplications. He has developed automation equipment for machine tools, spooling\nmachines, high-power ultrasound processes, and more.",institutionString:'"Politechnica" University Timişoara',institution:null},{id:"221364",title:"Dr.",name:"Eneko",middleName:null,surname:"Osaba",slug:"eneko-osaba",fullName:"Eneko Osaba",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/221364/images/system/221364.jpg",biography:"Dr. Eneko Osaba works at TECNALIA as a senior researcher. He obtained his Ph.D. in Artificial Intelligence in 2015. He has participated in more than twenty-five local and European research projects, and in the publication of more than 130 papers. He has performed several stays at universities in the United Kingdom, Italy, and Malta. Dr. Osaba has served as a program committee member in more than forty international conferences and participated in organizing activities in more than ten international conferences. He is a member of the editorial board of the International Journal of Artificial Intelligence, Data in Brief, and Journal of Advanced Transportation. He is also a guest editor for the Journal of Computational Science, Neurocomputing, Swarm, and Evolutionary Computation and IEEE ITS Magazine.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"275829",title:"Dr.",name:"Esther",middleName:null,surname:"Villar-Rodriguez",slug:"esther-villar-rodriguez",fullName:"Esther Villar-Rodriguez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/275829/images/system/275829.jpg",biography:"Dr. Esther Villar obtained a Ph.D. in Information and Communication Technologies from the University of Alcalá, Spain, in 2015. She obtained a degree in Computer Science from the University of Deusto, Spain, in 2010, and an MSc in Computer Languages and Systems from the National University of Distance Education, Spain, in 2012. Her areas of interest and knowledge include natural language processing (NLP), detection of impersonation in social networks, semantic web, and machine learning. Dr. Esther Villar made several contributions at conferences and publishing in various journals in those fields. Currently, she is working within the OPTIMA (Optimization Modeling & Analytics) business of TECNALIA’s ICT Division as a data scientist in projects related to the prediction and optimization of management and industrial processes (resource planning, energy efficiency, etc).",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"49813",title:"Dr.",name:"Javier",middleName:null,surname:"Del Ser",slug:"javier-del-ser",fullName:"Javier Del Ser",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49813/images/system/49813.png",biography:"Prof. Dr. Javier Del Ser received his first PhD in Telecommunication Engineering (Cum Laude) from the University of Navarra, Spain, in 2006, and a second PhD in Computational Intelligence (Summa Cum Laude) from the University of Alcala, Spain, in 2013. He is currently a principal researcher in data analytics and optimisation at TECNALIA (Spain), a visiting fellow at the Basque Center for Applied Mathematics (BCAM) and a part-time lecturer at the University of the Basque Country (UPV/EHU). His research interests gravitate on the use of descriptive, prescriptive and predictive algorithms for data mining and optimization in a diverse range of application fields such as Energy, Transport, Telecommunications, Health and Industry, among others. In these fields he has published more than 240 articles, co-supervised 8 Ph.D. theses, edited 6 books, coauthored 7 patents and participated/led more than 40 research projects. He is a Senior Member of the IEEE, and a recipient of the Biscay Talent prize for his academic career.",institutionString:"Tecnalia Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"278948",title:"Dr.",name:"Carlos Pedro",middleName:null,surname:"Gonçalves",slug:"carlos-pedro-goncalves",fullName:"Carlos Pedro Gonçalves",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRcmyQAC/Profile_Picture_1564224512145",biography:'Carlos Pedro Gonçalves (PhD) is an Associate Professor at Lusophone University of Humanities and Technologies and a researcher on Complexity Sciences, Quantum Technologies, Artificial Intelligence, Strategic Studies, Studies in Intelligence and Security, FinTech and Financial Risk Modeling. He is also a progammer with programming experience in:\n\nA) Quantum Computing using Qiskit Python module and IBM Quantum Experience Platform, with software developed on the simulation of Quantum Artificial Neural Networks and Quantum Cybersecurity;\n\nB) Artificial Intelligence and Machine learning programming in Python;\n\nC) Artificial Intelligence, Multiagent Systems Modeling and System Dynamics Modeling in Netlogo, with models developed in the areas of Chaos Theory, Econophysics, Artificial Intelligence, Classical and Quantum Complex Systems Science, with the Econophysics models having been cited worldwide and incorporated in PhD programs by different Universities.\n\nReceived an Arctic Code Vault Contributor status by GitHub, due to having developed open source software preserved in the \\"Arctic Code Vault\\" for future generations (https://archiveprogram.github.com/arctic-vault/), with the Strategy Analyzer A.I. module for decision making support (based on his PhD thesis, used in his Classes on Decision Making and in Strategic Intelligence Consulting Activities) and QNeural Python Quantum Neural Network simulator also preserved in the \\"Arctic Code Vault\\", for access to these software modules see: https://github.com/cpgoncalves. He is also a peer reviewer with outsanding review status from Elsevier journals, including Physica A, Neurocomputing and Engineering Applications of Artificial Intelligence. Science CV available at: https://www.cienciavitae.pt//pt/8E1C-A8B3-78C5 and ORCID: https://orcid.org/0000-0002-0298-3974',institutionString:"University of Lisbon",institution:{name:"Universidade Lusófona",country:{name:"Portugal"}}},{id:"241400",title:"Prof.",name:"Mohammed",middleName:null,surname:"Bsiss",slug:"mohammed-bsiss",fullName:"Mohammed Bsiss",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/241400/images/8062_n.jpg",biography:null,institutionString:null,institution:null},{id:"276128",title:"Dr.",name:"Hira",middleName:null,surname:"Fatima",slug:"hira-fatima",fullName:"Hira Fatima",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/276128/images/14420_n.jpg",biography:"Dr. Hira Fatima\nAssistant Professor\nDepartment of Mathematics\nInstitute of Applied Science\nMangalayatan University, Aligarh\nMobile: no : 8532041179\nhirafatima2014@gmal.com\n\nDr. Hira Fatima has received his Ph.D. degree in pure Mathematics from Aligarh Muslim University, Aligarh India. Currently working as an Assistant Professor in the Department of Mathematics, Institute of Applied Science, Mangalayatan University, Aligarh. She taught so many courses of Mathematics of UG and PG level. Her research Area of Expertise is Functional Analysis & Sequence Spaces. She has been working on Ideal Convergence of double sequence. She has published 17 research papers in National and International Journals including Cogent Mathematics, Filomat, Journal of Intelligent and Fuzzy Systems, Advances in Difference Equations, Journal of Mathematical Analysis, Journal of Mathematical & Computer Science etc. She has also reviewed few research papers for the and international journals. She is a member of Indian Mathematical Society.",institutionString:null,institution:null},{id:"414880",title:"Dr.",name:"Maryam",middleName:null,surname:"Vatankhah",slug:"maryam-vatankhah",fullName:"Maryam Vatankhah",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Borough of Manhattan Community College",country:{name:"United States of America"}}},{id:"414879",title:"Prof.",name:"Mohammad-Reza",middleName:null,surname:"Akbarzadeh-Totonchi",slug:"mohammad-reza-akbarzadeh-totonchi",fullName:"Mohammad-Reza Akbarzadeh-Totonchi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Ferdowsi University of Mashhad",country:{name:"Iran"}}},{id:"414878",title:"Prof.",name:"Reza",middleName:null,surname:"Fazel-Rezai",slug:"reza-fazel-rezai",fullName:"Reza Fazel-Rezai",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"American Public University System",country:{name:"United States of America"}}},{id:"426586",title:"Dr.",name:"Oladunni A.",middleName:null,surname:"Daramola",slug:"oladunni-a.-daramola",fullName:"Oladunni A. Daramola",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Federal University of Technology",country:{name:"Nigeria"}}},{id:"357014",title:"Prof.",name:"Leon",middleName:null,surname:"Bobrowski",slug:"leon-bobrowski",fullName:"Leon Bobrowski",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Bialystok University of Technology",country:{name:"Poland"}}},{id:"302698",title:"Dr.",name:"Yao",middleName:null,surname:"Shan",slug:"yao-shan",fullName:"Yao Shan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Dalian University of Technology",country:{name:"China"}}},{id:"354126",title:"Dr.",name:"Setiawan",middleName:null,surname:"Hadi",slug:"setiawan-hadi",fullName:"Setiawan Hadi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Padjadjaran University",country:{name:"Indonesia"}}},{id:"125911",title:"Prof.",name:"Jia-Ching",middleName:null,surname:"Wang",slug:"jia-ching-wang",fullName:"Jia-Ching Wang",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"National Central University",country:{name:"Taiwan"}}},{id:"332603",title:"Prof.",name:"Kumar S.",middleName:null,surname:"Ray",slug:"kumar-s.-ray",fullName:"Kumar S. Ray",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Statistical Institute",country:{name:"India"}}},{id:"415409",title:"Prof.",name:"Maghsoud",middleName:null,surname:"Amiri",slug:"maghsoud-amiri",fullName:"Maghsoud Amiri",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Allameh Tabataba'i University",country:{name:"Iran"}}},{id:"357085",title:"Mr.",name:"P. Mohan",middleName:null,surname:"Anand",slug:"p.-mohan-anand",fullName:"P. Mohan Anand",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Kanpur",country:{name:"India"}}},{id:"356696",title:"Ph.D. Student",name:"P.V.",middleName:null,surname:"Sai Charan",slug:"p.v.-sai-charan",fullName:"P.V. Sai Charan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Kanpur",country:{name:"India"}}},{id:"357086",title:"Prof.",name:"Sandeep K.",middleName:null,surname:"Shukla",slug:"sandeep-k.-shukla",fullName:"Sandeep K. Shukla",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Kanpur",country:{name:"India"}}}]}},subseries:{item:{id:"17",type:"subseries",title:"Metabolism",keywords:"Biomolecules Metabolism, Energy Metabolism, Metabolic Pathways, Key Metabolic Enzymes, Metabolic Adaptation",scope:"Metabolism is frequently defined in biochemistry textbooks as the overall process that allows living systems to acquire and use the free energy they need for their vital functions or the chemical processes that occur within a living organism to maintain life. 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. Thus all studies on metabolism will be considered for publication.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/17.jpg",hasOnlineFirst:!0,hasPublishedBooks:!0,annualVolume:11413,editor:{id:"138626",title:"Dr.",name:"Yannis",middleName:null,surname:"Karamanos",slug:"yannis-karamanos",fullName:"Yannis Karamanos",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002g6Jv2QAE/Profile_Picture_1629356660984",biography:"Yannis Karamanos, born in Greece in 1953, completed his pre-graduate studies at the Université Pierre et Marie Curie, Paris, then his Masters and Doctoral degree at the Université de Lille (1983). He was associate professor at the University of Limoges (1987) before becoming full professor of biochemistry at the Université d’Artois (1996). He worked on the structure-function relationships of glycoconjugates and his main project was the investigations on the biological roles of the de-N-glycosylation enzymes (Endo-N-acetyl-β-D-glucosaminidase and peptide-N4-(N-acetyl-β-glucosaminyl) asparagine amidase). From 2002 he contributes to the understanding of the Blood-brain barrier functioning using proteomics approaches. He has published more than 70 papers. His teaching areas are energy metabolism and regulation, integration and organ specialization and metabolic adaptation.",institutionString:null,institution:{name:"Artois University",institutionURL:null,country:{name:"France"}}},editorTwo:null,editorThree:null,series:{id:"11",title:"Biochemistry",doi:"10.5772/intechopen.72877",issn:"2632-0983"},editorialBoard:[{id:"243049",title:"Dr.",name:"Anca",middleName:null,surname:"Pantea Stoian",slug:"anca-pantea-stoian",fullName:"Anca Pantea Stoian",profilePictureURL:"https://mts.intechopen.com/storage/users/243049/images/system/243049.jpg",institutionString:null,institution:{name:"Carol Davila University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}},{id:"203824",title:"Dr.",name:"Attilio",middleName:null,surname:"Rigotti",slug:"attilio-rigotti",fullName:"Attilio Rigotti",profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institutionString:null,institution:{name:"Pontifical Catholic University of Chile",institutionURL:null,country:{name:"Chile"}}},{id:"300470",title:"Dr.",name:"Yanfei (Jacob)",middleName:null,surname:"Qi",slug:"yanfei-(jacob)-qi",fullName:"Yanfei (Jacob) Qi",profilePictureURL:"https://mts.intechopen.com/storage/users/300470/images/system/300470.jpg",institutionString:null,institution:{name:"Centenary Institute of Cancer Medicine and Cell Biology",institutionURL:null,country:{name:"Australia"}}}]},onlineFirstChapters:{paginationCount:7,paginationItems:[{id:"82777",title:"Sustainability and Social Investment: Community Microhydropower Systems in the Dominican Republic",doi:"10.5772/intechopen.105995",signatures:"Michela Izzo, Alberto Sánchez and Rafael Fonseca",slug:"sustainability-and-social-investment-community-microhydropower-systems-in-the-dominican-republic",totalDownloads:4,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Globalization and Sustainability - Recent Advances, New Perspectives and Emerging Issues",coverURL:"https://cdn.intechopen.com/books/images_new/11476.jpg",subseries:{id:"91",title:"Sustainable Economy and Fair Society"}}},{id:"82387",title:"Kept Promises? 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