Pemphigus forms and target antigens.
\r\n\tTo this end, erectile dysfunction affects the health, well-being and quality of life of the affected person. Perhaps, due to cultural reasons, most of them feel great unease to seek medical care in spite of the overwhelming need to do so. Some of them have yet to understand that their suffering is a medical condition. In most cases, a hospital visit is usually encouraged and sometimes pressured by the spouse or partner.
\r\n\tFrom available studies, a number of factors can cause erectile dysfunction, including, general medical conditions, emotional disturbance and psychiatric disorders. However, more researches on the subject are expected and bigger is the need of people to be adequately health-informed and educated about the condition.
\r\n\tThis book is a compilation of the state-of-the art overview on erectile dysfunction. The book equally intends to provide the reader with comprehensive understanding and overview of the current trends about erectile dysfunction.
Bullae are formed as a result of the damage of skin integrity due to various reasons, including bacterial or viral infections, trauma, genetic disorders and autoantibodies and fluid accumulation in the different layers of the skin; subcorneal, suprabasilar, dermal-epidermal junction and upper dermis [1]. Autoimmune bullous diseases (ABD) are a heterogeneous group of rare but fatal or debilitating skin diseases characterized by varying degrees of mucosal and cutaneous blister formation due to autoantibodies directed against the structural proteins of epidermis or the dermal-epidermal junction [2, 3]. ABD are classified according to the location of the bullae in the skin and the antigens targeted by the antibodies. They are simply examined in four main groups: pemphigus, pemphigoid, acquired epidermolysis bullosa and dermatitis herpetiformis [1].
\nIt is important to know the structure of the skin and antigens targeted by autoantibodies in order to better understand the ABD. The epidermal stratified squamous epithelium is a complex structure which includes several layers of keratinocytes. Cohesion among these cells is needed to preserve the epidermal architecture and function [4]. Epidermal integrity is provided by three types of junctional structures: (1) anchoring junctions (desmosomes and adherens junctions), major adhesive cell–cell junctions of epithelial cells that function with each other to hold epithelial sheets together. Both are connected with the cytoskeleton and represent sites of mechanical coupling between cells. (2) Tight junctions (zonula occludens) that constitute a diffusion barrier. (3) Gap junctions, where intercellular channels allowing for the direct exchange of small molecules between cells [4, 5]. While suprabasal, differentiating keratinocytes adhere to each other, undifferentiated basal keratinocytes are anchored to the dermis and interact with extracellular matrix. Basal cell surfaces not in contact with basement membrane have desmosomes which attach adjacent keratinocytes [1].
\nDesmosomes are disc-like strong cell–cell adhesion complexes that act as anchors linking the intermediate filament (IF) cytoskeletons of neighboring cells in tissues that undergo large amounts of mechanical strain such as the heart and skin [6, 7]. In addition to their adhesive role, desmosomes are dynamic structures that regulate normal physiological processes such as proliferation and differentiation during development, tissue morphogenesis and wound healing [3, 6, 8–10].
\nDesmosomes are described as small dense nodules at the contact points between neighboring cells. “Desmos” means “bond” and “soma” means “body.” Electron microscopic investigations and newly developed procedures have supplied detailed knowledge about their structures and major protein components [3].
\nDesmosomes are 0.2–0.5 μm in diameter in human epidermis and consist of dense plaques located symmetrically on the plasma membranes of adjoining cells. Extracellular domain, a dense midline separates the membranes [8, 11].
\nDesmosomes, calcium-dependent junctions, have five major component proteins such as the desmosomal cadherins (DCs) [desmoglein (dsg) and desmocollin (dsc)], the plakin family [desmoplakins, (DP)], and the armadillo proteins [plakoglobin (PK) and plakophilin (PP)] [6, 8].
\nDsg and dsc are desmosomal adhesion molecules, and there are four dsg (1–4) and three dsc (1–3) in different tissues in humans. Dsg2 and dsc2 are present in all tissues that contain desmosomes such as simple epithelia, myocardium and are present in low amounts in basal layer of complex epithelia like epidermis [4, 6]. While dsg4 is present in both stratified epithelia and hair, dsg1/3 and dsc1/3 are found only in stratified epithelia. Dysregulation of desmosomal cadherins causes skin, hair, heart and digestive tract disorders and cancer because of their roles in epithelial morphogenesis and differentiation [6].
\nExtracellular domains of dsg and dsc are highly homologous to those of classical cadherin, E-cadherin, which have five extracellular cadherin repeats containing Ca2+ binding sites and a cell-adhesion recognition (CAR) site [4, 8]. The cytoplasmic domains of dsg have a membrane proximal region, including an intracellular cadherin-typical region and a dsg-specific region [8].
\nDsg 1 expression is higher in suprabasal layers in the skin epithelium. Dsg1 can support keratinocyte differentiation. Extracellular regions of dsg1 do not play a role in this function; they are needed for adhesion. In the recent years, mutations in dsg1 that cause severe skin dermatitis, multiple allergies and metabolic wasting syndrome (SAM) have been identified [6].
\nIn the epidermis, dsg1 and 3 show inverse distribution patterns, dsg3 is present in high levels in the basal layer but dsg1 is found in low levels in this layer. However, the upper layers have high levels of dsg1 and low levels of dsg3. Therefore, pemphigus foliaceus causes bullae only in the most superficial layers of the skin while pemphigus vulgaris leads to blisters in the basal layers of the skin. Because dsg1 and dsg3 are both found in the intermediate layers, blisters do not typically occur in these layers (compensation hypothesis) [6].
\nThe armadillo-repeat family members which are PG and the PP are characterized by their central arm-repeat domains. PG, together with PP, provides the adhesion of DP to keratin intermediate filaments and mediates important signal transduction pathways and regulates the clustering of desmosomal components [12].
\nİ. Plakoglobin: PG has three structural components as an N-terminal and a C-terminal domain which are separated by the central 12 arm-repeat domain and is homologous to b-catenin. Despite this homology, PG and b-catenin are differently distributed at cell–cell contacts. b-catenin normally is not a component of desmosomes and is only present in adherens junctions unlike PG [5]. PG plays an important role in heart, skin and hair development. Pg−/− mice show severe cardiac defects and Naxos disease that presents with arrhythmogenic right ventricular cardiomyopathy, wooly hair and keratoderma due to the mutation in the gene encoding PG [8].
\nii. Plakophilins: PP are members of armadillo-repeat family, and PP1 was originally isolated as an accessory desmosomal plaque protein in stratified and complex epithelia binding to keratin. Later, PP2 and 3 and their subtypes were defined. PP are present both at desmosomes and in the nucleus [5]. While PP1 is mostly expressed in the suprabasal layer, PP2 is located in lower layers of stratified epithelia and heart [12]. All PP have diverse biological and pathological roles [6]. PP1 has an important role in desmosomal plaque formation and stability. PP1 mutation causes ectodermal dysplasia-skin fragility syndrome in which skin fragility, inflammation, ectodermal development abnormalities such as scant hair, hypohidrosis and astigmatism are seen [8]. Also, PP1 is elevated in the head and neck cancers and Ewing sarcoma. Therefore, it has been thought that PP1 regulates cell proliferation and growth.
\nPP2 has a role in the regulation of actin cytoskeletal dynamics, cell migration and tumorigenesis in addition to modulation of intercellular adhesion. PP2 is a new positive regulator for EGFR activation. Knockdown of PP2 causes the attenuation of EGFR-mediated signals and tumor development [6].
\nAlso, the mutations in PP2 have been identified as a cause of arrhythmogenic right ventricular cardiomyopathy.
\nPP3 mutations have not yet been identified in humans but pp3 deficient mice developed cutaneous inflammation and hair abnormalities [8]. This protein mRNA expression has been found to be significantly higher in gastrointestinal cancer patients than controls. Also, its level increased in advanced stages and metastatic cancer. Moreover, it was found that PP3 was increased in breast and pancreatic cancers [6].
\nPlakins presents with a family of very large cytolinker proteins of 200–700 kDa. They have important role in the cross-linking of actin microfilaments, microtubules and/or intermediate filaments to each other and provide the connection of adhesive junctions with the cytoskeleton. There are seven identified plakin proteins and four of them, desmoplakin (DP), plektin, envoplakin and periplakin are localized in the desmosomes [5].
\ni. Desmoplakin: DP is an essential desmosomal component in the connection of desmosomal proteins with intermediate filament (IF) cytoskeleton. DP has a critical role in the heart and skin. Global knockout of DP in mouse causes lethality at embryonic days leading to a dramatic decrease in the desmosome numbers [6].
\nThe N-terminal plakin domain peptide (DP-NTP) is essential to target DP to desmosomal plaques and contains binding sites for PPs and PG. The carboxy terminal domain of DP is composed of three plakin repeat domains (PRDs) named A, B and C and is responsible for the attachment of IF [5, 12]. The molecular interactions within the desmosomal plaque protein network are much complicated. It has been shown that the PP1 head domain acts as a lateral linker and allows the recruitment of additional DP molecules to the desmosomal plaque. Moreover, there is evidence that DP might bind directly to desmosomal cadherins in the absence of PG and PPs. But, in cells expressing PP1 and PG, DP preferentially binds to PP1. While dsg1 is the only desmosomal cadherin that interacts with the PP1 head domain PP2 interacts directly with dsg1 and 2, and dsc1a and 2a. In contrast to PP1, PP2 binds to PG. Together with the different tissue distribution of the PPs, the different binding specificities may be involved in the regulation of the size and cadherin composition of desmosomes and the efficiency of IF binding to desmosomes [5].
\nTwo major isoforms of DP were identified: DP1 and DP2. Both are widely expressed in numerous tissues but DP2 is absent/reduced in the heart and simple epithelia [12]. The loss of DP2 causes a more severe adhesion defect due to mechanical stress [6]. DP2 has a more significant role than DP1 in maintaining the adhesion of keratinocytes [12]. Sarcoendoplasmic reticulum Ca+2-ATPase isoform 2 (SERCA2) regulates DP translocation to sites of cell–cell adhesion and SERCA2 is often mutated in Darier’s disease. If mutation in DP leads to complete loss of protein or loss of the IF-binding C terminus, it results in lethal acantholytic epidermolysis bullosa with or without apparent associated cardiomyopathy. DP missense mutation can lead to Carvajal/Naxos syndrome that is characterized by keratoderma, wooly hair and cardiomyopathy [6, 8]. Consequently, desmosome mutations can lead to aberrant gap junctions and abnormal heart and epidermal functions, abnormal barrier homeostasis of skin. The loss of DP may also be associated with some cancers and/or their local invasion because of the loss of desmosomal function [6].
\nii. Plectin: Plectin, a huge protein, was an originally IF-binding protein and was identified in hemidesmosomal and focal adhesion structures in the basal membrane of keratinocytes in the basal layer of the skin and striated, smooth and cardiac muscles. Later, it was shown that plectin is also expressed in desmosomes. However, it has an auxiliary role and is not a major component of desmosomes. It has major function in the organization of microtubules, actin and IF by coordinated cross-linking and the regulation of their dynamics. Plectin gene mutation does not cause blistering in the epidermis but cause blister formation in the epidermal basal layer by affecting hemidesmosomes. Plectin gene mutation causes autosomal recessive epidermolysis bullosa simplex (EBS) associated with muscular dystrophy [5].
\niii. Envoplakin: Envoplakin was originally identified as a plakin protein family member. It was found along IFs and is partially colocalized with DP at desmosomes in terminally differentiating keratinocytes. Similar to plectin, envoplakin is not a major component of desmosomes. Envoplakin knockout mice normally develop but they have only a slight delay in barrier acquisition. No disorders due to the envoplakin mutations have been defined in humans yet [5].
\niv. Periplakin: Similar to envoplakin, periplakin is upregulated during terminal differentiation of keratinocytes in cornified envelope. It is distributed more extensively than envoplakin, but there is little knowledge about its role in other tissues. Plectin, envoplakin and periplakin play a role as auxiliary factors in strengthening IF attachment to desmosomes at the desmosomal plaque [5].
\nData have shown that adhesive binding between dsc2 and 3 and dsg2 and 3 are both homophilic and isoform specific. Dsg3 can mediate weak homophilic adhesion. Dsc3 shows homophilic binding. While there is a heterophilic interaction between dsc3 and dsg1, there is no interaction between dsc3 and dsg3 [8].
\nHyperadhesion, a strongly adhesive state is a distinctive property of desmosomes from other intercellular junctions. Adoption of hyperadhesion is a property of dsc. Keratinocytes proliferate in low Ca2+ medium but do not contact adjacent cells. At the early stage of desmosomal development, desmosomal adhesion is Ca2+ −dependent, and chelating agents may induce the loss of adhesion and splitting of desmosomes. A rise in Ca2+ concentration induces assembly of AJ and desmosomes and in the late stage, epithelial desmosome becomes resistant to low Ca2+, and hyperadhesion is characterized by Ca2+ independence [5]. Hyperadhesion is associated with the ordered arrangement of the dsc. Phosphokinase (PK) Ca may regulate Ca2+ dependence and inhibit hyperadhesion. Phosphorylation of desmosomal plaque components or different cytoplasmic signals may cause rearrangement in the plaque and transmit a signal to EC domains [8].
\nThe cell–cell contact and specific adhesive interaction are essential components for desmosome assembly. Any disorders of these components caused by low extracellular Ca2+, antibodies and blocking peptide inhibit desmosomal assembly. It was shown that intercellular adhesion starts in AJ and then stabilized by desmosomes. Antibodies to E and P cadherin block AJ and also inhibit desmosome formation [5]. PG plays an essential role in desmosomal assembly by providing interaction between AJ and desmosomes (cross-talk). Other components of desmosomal assembly are PP, dsc, dsg and DP [5, 8]. However, desmosomal assembly can also be induced by protein kinase C signaling in case of lacking of AJ. In the first step, dsg3 is transported to the cell surface, and in the second step, IF attached and half-desmosome-like structures are developed and they intermediate desmosome formation. If half desmosomes are not finally stabilized by interactions with half desmosomes on the adjacent cells they undergo endocytosis and degrade [5].
\nThe role of desmosomes in maintaining tissue integrity is defined by the large number of diseases in which one or more of its constituents are impaired [4]. The impairment of adhesive functions of desmosomal cadherins results from either development of autoantibodies against desmosomal cadherins or by gene mutations. Pemphigus is a family of blistering skin disorders caused by autoantibodies against desmosomal cadherins [5].
\nPemphigus vulgaris (PV) and pemphigus foliaceus (PF) are two most common forms of pemphigus family and potentially fatal disorders characterized by blister formation in skin and mucous membranes (in PV) due to the acantholysis, loss of keratinocytes cell–cell adhesion. Immunochemical studies showed that in PV, autoantibodies are immunoglobulin (Ig) G type and are directed against dsg3, 130 kD glycoprotein, or both dsg3 and dsg1, 160 kD antigen [5, 13], while in PF, they directed to only dsg1 [1, 12–14]. IgG1 and 4 type autoantibodies are indicators for active disorder while IgG2 is found in remission [1, 3]. Dsg3 and dsg1 show different expression patterns throughout epidermis. Dsg1 is expressed throughout epidermis and oral mucosa but it is more predominant in superficial epidermis than in deep epidermis. In contrast, dsg3 is expressed throughout the oral mucosa but it is only present in basal and lower epidermal cells. In PF, anti-dsg IgG antibodies cause blistering in the superficial epidermis, but not in the mucosa or deep epidermis because dsg3 expression compensates loss of function due to the anti-dsg1 antibodies. In PV, anti-dsg3 antibodies cause blister development in the deepest layer of mucosa, where dsg1 expression is minimal. Mucocutaneous type PV results from both anti-dsg1 and anti-dsg3 antibodies [14–16]. But, in this type, diffuse intercellular blisters throughout epidermis do not occur. A cause of it may be that cell–cell adhesion might be weaker at the basal and intermediate suprabasal layers, where there are fewer desmosomes. Another reason may be that the lower layer of epidermis might have better access for autoantibodies which penetrate from the dermis. The main postulate of this monopathogenic theory (compensation theory) is that anti-dsg3 and 1 antibodies-dependent disabling of cell–cell adhesion is adequate to cause detachment of keratinocytes and form the blisters [3, 17]. However, data demonstrated that inactivation of dsg3 gene or depletion of dsg3 from keratinocytes could not induce gross blistering in the skin. In striate palmoplantar keratoderma which is due to N-terminal deletion of dsg1 acantholysis or skin blisters are not seen. Thus, compensation theory is still controversial [3, 15, 18]. Multipathogenic theory works to explain blister formation by multiple hit hypothesis. According to this hypothesis, a simultaneous and synchronized inactivation of physiological mechanisms of cell–cell adhesion causes disruption of epidermal detachment. Non-dsg antibodies may be pathogenic because they cause cell shrinkage, loss of adhesion at keratinocytes and/or proapoptotic signaling [17]. Additionally, IgA and IgE classes of Anti-dsg3 antibodies have been found in the sera of PV patients [3].
\nT-helper cells have critical role in the formation of pemphigus autoantibodies. Activation of autoreactive T cells (losing self-tolerance to dsg) responsive to pemphigus antigens lead to induction of IgG antibodies from B cells [3, 19]. Autoimmunity to certain epitopes of dsg3, dsg-reactive T and B cells may be seen in normal individuals particularly, the relatives of PV patients. There are dsg3 reactive Th1 cells in healthy relatives but there are Th2 cells in PV patients. Th2 reactive cells are detected at similar frequencies in the acute, chronic active and remittent phases of the disease but Th1 cells are increased in chronic active PV. It was demonstrated that Treg cells were decreased in the serum of PV patients [3, 18]. However, there is no decrease in Treg cells in PV skin lesions because Treg cells accumulate in the skin lesions and the draining lymph nodes. It has been thought that pemphigus autoimmunity can be triggered by Toll-like receptors (TLR) because of the activation of PF by TLR7 agonist, imiquimod [3].
\nIt was shown that the number and size of desmogleins are reduced in PV and PF [19]. Data demonstrated that pemphigus autoantibodies bind to conformational epitopes formed by the N-terminal 161 amino acids and stabilized by calcium on desmogleins, and that these binding areas are responsible for the pathogenicity but C-terminal extracellular domain is not the pathogenic domain [14]. Previous data showed that PV IgG most likely directly cause the loss of adhesion via the disruption of desmogleins by steric hindrance (cis or trans interaction) [12, 13, 18]. Interestingly, the detachment of keratinocytes from each other first occurs in the interdesmosomal area, and desmosomal detachment is seen in late acantholysis. Recent studies have demonstrated that the loss of desmosomal function is not only related to the steric hindrance, it may be related with other mechanisms [5, 13]. PV IgG bound to unassembled desmosomal cadherins does not prevent desmosomal generation rather, it causes internalization and degradation of IgG-antigen complex [15].
\nIt has been shown that polyclonal PV IgG causes the retraction of keratin IF and intercellular detachment in vitro in keratinocytes obtained from wild type mice. But PG has critical importance for keratin retraction and detachment of cells [14]. PV IgG binding results in the depletion of dsg3 from keratinocytes and is followed by its internalization and degradation and depriving the not yet assembled desmosome of dsg3 [12, 14]. This suggestion was supported by the demonstration of a reduction in dsg3 levels in cell lysates. In contrast, some studies showed that dsg3 levels increase in cell lysates due to the reduction of anchorage of dsg3 to the cytoskeleton caused PV IgG antibodies [15]. Recent studies in mice have not shown the loss of dsg3 in split desmosomes or keratin retraction in acantholytic areas and that dsg3 is not depleted from desmosome before acantholysis [14].
\nEarly studies showed that non-lysosomal proteases like plasminogen activator released by antibody binding caused the development of blisters but later, investigations in mice did not support this hypothesis and demonstrated that plasmin and plasminogen activators were not necessary for IgG-mediated acantholysis in mice in PV. Recent studies in vivo and in vitro have shown that selective proteases such as MMPs disrupt the adhesion of keratinocytes leading to proteolysis of adhesion molecules. While dsg3 is digested by MMP-9, a member of MMPs family, cell adhesion molecules like dsg1 and E-cadherin are digested by members of ADAM family of MMP during apoptosis [15]. In cultured keratinocytes, it has been shown that PV IgG induces apoptosis resulting in acantholysis. Apoptotic keratinocytes, reduced antiapoptotic factors and increased proapoptotic factors were detected in the epidermis in PF. Thus, induction of apoptosis may be a primary factor responsible for acantholysis and loss of intercellular adhesion. Caspases, apoptosis enzymes that have a role in acantholysis, are the other proteases. It was shown that activated caspase 3 was found in the epidermis before the blister formation, and it could cleave desmosomal proteins such as dsg1, dgs2 and dsg3. Caspases also cause the disruption of plaque proteins such as PP and DP1 and DP2, plektin and periplakin [8, 15]. Moreover, caspase inhibitors may block blister formation [8]. Shortly, these data suggested that caspases have fundamental role in apoptolysis [15]. FasL and CytC activate both extrinsic and intrinsic apoptotic signaling pathways in keratinocytes treated with PV IgGs [17]. Tumor necrosis factor alpha receptor superfamily member 5 and NADAH dehydrogenase-like protein are involved in the extrinsic and intrinsic apoptotic pathways, respectively [3].
\nAcantholysis is an active and complex process. Interaction of cell and PV IgG causes activation of phosphatidylcholine-specific phospholipase C, an increase in inositol 1,4,5 triphosphate (IP3) and diacylglycerol production and protein kinase C (PKC) activity. It also causes an increase in intracellular calcium concentration [15]. It has been shown that PV IgG causes serine-phosphorylation of dsg3, and the phosphorylation leads to the loss of PG binding. Data suggested that PG, a cytoplasmic plaque constituent, plays a critical role in keratin retraction because PG binding is essential for targeting dsg3 to desmosomes [8, 14]. Recently, a lot of protein kinase and signaling molecules, including p38 MAPK, PKC, c-myc, Src, Rho A, PERK, FAK, Akt/mTOR, and cdk2 have been demonstrated [11, 15]. For example, it was shown that p38 phosphorylation facilitates the retraction of IF and detachment of the cells [13]. Desmocollin genes encoded N-glycosylated type 1 transmembrane proteins belong to Ca-dependent cell adhesion molecules of cadherin family. Similar to dsg3, dsc3 is expressed in the basal and suprabasal layers of the epidermis. It was demonstrated that anti-dsc3 antibodies might induce the loss of adhesion of epidermal cells and contribute to blister development in pemphigus. In addition to dsg and dsc3 antibodies, reactivity to dsc1, several muscarinic and nicotinic acetylcholine receptor subtypes, HLA molecules, a number of mitochondrial proteins, thyroid peroxidase and hSPCA1 encoded ATP2C1 gene were shown. Moreover, anti-non-dsg antibodies may show the synergistic effects with anti-dsg antibodies, in other words, they may potentially amplify the activity of anti-dsg antibodies [17].
\nAnti-mitochondrial antibodies (AMA) target the mitochondrial nicotinic acetylcholine receptors that prevent apoptolysis in keratinocytes. AMA with anti-dsg antibodies can induce acantholysis, AMA/anti-dsg1 induces subcorneal splitting and AMA/anti-dsg3 induces suprabasal acantholysis. Recent studies showed that FcRn receptors exist on the keratinocytes and are a single target for PV IgG. PVIgG/FcRn complexes become internalized and are transmitted to mitochondria. Mitochondria are damaged via AMA and apoptotic signals are triggered for cell shrinkage. This shrinkage resulting in cytoskeleton collapse is an outcome of energy failure due to the damaged mitochondria [17].
\nAccording to a recent hypothesis, anti-dsg antibodies are not the reason but the result because reactivity to dsg1/3 develops in both extracellular and intracellular domains, and this gives rise to the thought that dsg molecules are released to intercellular space from damaged keratinocytes and become available to antigen presenting cells [3]. Consequently, pemphigus autoimmunity is directed to multiple organ-specific and non-organ-specific proteins.
\nParaneoplastic pemphigus (PNP) is a rare and serious form of pemphigus. It is different from other OBD because it can affect multiple organs as well as skin [11, 20]. It has unusual clinical features, including severe mucosal involvement, bronchiolitis and a wide range of skin rash (pemphigus-like, bullous pemphigoid-like, erythema multiforme-like, graft versus host disease-like and lichen planus-like) [21]. It also shows unusual histopathological and immunological findings. PNP lesions are extremely painful and may be localized on the palm and soles, conjunctiva and simple squamous epithelia. The lesions are resistant to therapy. PNP is usually associated with malignancies such as lymphoma and leukemia. The mortality rate of PNP is high (90%) [11]. It may also be associated with myasthenia gravis and thymomas [22]. Because of cutaneous and noncutaneous pathologies associated with neoplasia it is called as paraneoplastic autoimmune multiorgan syndrome [21].
\nIn PNP, targets of autoantibodies are more than one: dsgs, dscs, DP1 and 2, bullous pemphigoid antigen (BPAg)1, PF, PP, envoplakin, plectin, epiplakin and alpha-2-macroglobulin-like-1 (A2ML-1) that is a broad range protease inhibitor expressed stratified epithelia and other damaged tissues in PNP [11, 20, 22]. Characteristic autoantibodies in PNP target the plakin family proteins that are molecules localized in the intracellular plaque of desmosomes and hemidesmosomes [20]. Also, anti-acetylcholine receptor autoantibodies and acetylcholinesterase autoantibodies were detected in 35 and 28% of PNP patients, respectively. High levels of these autoantibodies correlated with dyspnea in PNP patients. These antibodies target not only epidermal proteins but also other antigens in neural and bronchial tissues [22].
\nIt is currently unclear why there are multiple autoantibodies in PNP. In patients associated with thymoma, it has been thought that defective thymocyte maturation might lead to the production of autoreactive T cells that can induce B-cell proliferation and autoantibody production. In hematologic malign tumors, aberrant immunological conditions caused by tumors might cause the production of many autoantibodies [22]. Another theory is that autoantibodies against the neoplastic antigens cross-react to epithelial antigens [21]. In PNP, responsible immunity is not solely humoral immunity, also cellular immunity plays a role in the pathogenesis. Therefore, histopathology shows individual keratinocyte necrosis with lymphocyte exocytosis in addition to deposits of autoantibodies in direct immunofluorescence (DIF) examination [20].
\nLymphoid tumors may produce antibodies to desmosome and hemidesmosome components. But this solely cannot be explained with the pathogenesis of PNP. It is thought that tumors may express proteins that cross-react with epithelial proteins such as plakins. Another mechanism is dysregulated cytokine production by the tumor cells. The levels of interleukin (IL)-6 which promotes B-cell differentiation and Ig production is increased in PNP. Epitope spreading may explain antibodies against multiple proteins found in PNP [20].
\nIn PNP, accumulation of activated CD8+ T cells and increased interferon gamma and tumor necrosis factor alpha levels were shown in the epidermis locally. Also, natural killer cells were detected in the affected tissues. Consequently, both humoral and cellular immunity play a role in the development of PNP [20].
\nAnother subtype of pemphigus is IgA pemphigus characterized by IgA antibodies to desmosomal and non-desmosomal keratinocyte cell surface constituents. It has two subtypes: subcorneal pustular dermatosis type in which there are antibodies to dsc1 and very rarely to dsc 2 and 3, and intraepidermal neutrophilic type in which target antigen is still unknown but in rare cases, anti-dsg1 and 3 antibodies are the target antigens [11, 21, 23]. The mechanism of the development of skin lesions is not clear. It is thought that IgA antibodies might bind to the Fc receptor CD89 on monocytes and granulocytes resulting neutrophil chemotaxis and subsequent proteolytic cleavage of keratinocyte cell–cell junction [21]. Recently, IgG/IgA pemphigus which is an overlapping variant of classic IgG pemphigus and IgA pemphigus has been defined. Histopathological findings are acantholysis, blister formation localized on subcorneal or entire layer of epidermis and neutrophilic infiltration [11].
\nPemphigus herpetiformis (PH) is a pemphigus form clinically resembling dermatitis herpetiformis and histopathologically pemphigus. In PH, autoantibodies against dsg1, dsg3, both dsg1 and dsg3 and more recently, dsc1, dsc3 and an unknown 178-kDa protein were recognized. PH autoantibodies may recognize functionally less important epitopes of dsg1 or 3; therefore, it does not lead acantholysis directly. It is thought that autoantibodies cause the attraction of the inflammatory cells to tissue inducing by signaling pathway of cytokine production by keratinocytes [21] (Table 1).
\nPemphigus form | \nTarget antigens | \n
---|---|
PV | \ndsg3 or dsg3 and 1, dsc1, muscarinic and, nicotinic | \n
\n | acetylcholine receptor, several HLA molecules, hSPCA | \n
\n | mitochondrial proteins, thyroid peroxidase | \n
\n | subtypes | \n
PF | \ndsg1 | \n
PH | \ndsg1, dsg3, dsc 1, dsc3, unknown 178-kDa protein | \n
PNP | \ndsgs, dscs, DP1 and 2, BPAg1, PF, PP, envoplakin, | \n
\n | plectin, epiplakin and A2ML-1 | \n
IgA pemphigus | \n\n |
SCP | \nmostly dsc1 rarely dsc2,dsc3 | \n
IEN | \nmostly unknown, some dsg1, dsg3 | \n
Pemphigus forms and target antigens.
Basement membranes are highly specialized forms of extracellular matrix composed of a distinct set of glycoproteins and proteoglycans [24]. They underlie all epithelia and endothelia, enveloping nerves, muscle fibers, distinct cell compartments and whole organs [24]. Basement membranes of various tissues differ ultrastructurally, biochemically and functionally. They act as substrates for attachment of cells, templates for tissue repair, matrices for cell migration, substratum to influence differentiation, morphogenesis and apoptosis of epithelial cell layers and permeability barriers for cells and macromolecules [25]. Basement membranes consist of lamina densa, a central electron-dense region, adjacent to a less dense area which is lamina lucida or lamina rara [24].
\nHuman skin is the body’s largest organ, which provides mechanical and immunological barrier against the external environment [26]. The interface between the lower part of the epidermis and the top layer of dermis is the dermoepidermal basement zone (BMZ) which maintains the structure and integrity of the skin by anchoring the overlying epidermis to the dermal matrix below [27]. The importance of the correct assembly of the components of BMZ for skin integrity is apparent from the multiple skin blistering disorders caused by mutations in genes coding for proteins associated with the epidermal BMZ and from autoimmune disorders where autoantibodies target these molecules. These proteins are also important in tissue homeostasis, repair and regeneration [28].
\nThe epidermal BMZ can be divided into four zones. The first zone contains the cytoskeleton, hemidesmosomes and plasma membranes of basal keratinocytes. The second zone is lamina lucida which contains filaments connecting hemidesmosomes in basal keratinocytes to the lamina densa. The third zone is lamina densa and the fourth zone is sublamina densa region which contains anchoring fibrils, anchoring plaques and fibrillin containing microfibrils [25, 29]. The biochemical components of BMZ are synthesized by basal keratinocytes and dermal fibroblasts [30]. Molecular components of epidermal BMZ are shown in Table 2.
\nCytoskeleton of basal keratinocytes | \n
Keratin 5 | \n
Keratin 14 | \n
Hemidesmosome-anchoring filament complexes | \n
Plectin | \n
230 kDa bullous pemphigoid antigen (BP230/BPAG1) | \n
Type XVII collagen (180 kDa bullous pemphigoid antigen/BP AG2) | \n
α6 ß4 integrin | \n
Tetraspan CD151 | \n
Laminin 332 | \n
Type XIII collagen | \n
Syndecans 1 and 4 | \n
α3 ß1 integrin | \n
Lamina densa | \n
Laminin 332 (formerly laminin 5) | \n
Laminin 311 (formerly laminin 6) | \n
Laminin 511(formerly laminin 10) | \n
Nidogen | \n
Type 4 collagen | \n
BM-40/SPARC | \n
Perlecan | \n
Sublamina densa region | \n
Type VII collagen | \n
Type IV collagen | \n
Elastin | \n
Fibulins | \n
Fibrillins | \n
Latent TGF-ß-binding proteins | \n
Linkin | \n
Type III collagen | \n
Type I collagen | \n
Molecular components of epidermal BMZ.
The basal keratinocytes are anchored to the basal lamina via the keratin intermediate filaments and hemidesmosomes. The molecules within the basal lamina connect the basal keratinocyte to the basal lamina which anchors the BMZ to the underlying collagenous matrix of the superficial dermis [31]. Hemidesmosomes are small, regularly spaced electron dense structures on the inner surface of the basal pole of the keratinocytes [32]. They extend from the intracellular compartment of basal keratinocytes to the lamina lucida in the upper portion of the dermal epidermal basement membrane. The intracellular domains within the basal keratinocytes attach to the keratin intermediate filament network, and within the lamina lucida, they are contiguous with anchoring filaments [30]. The anchoring filaments transverse the lamina lucida and insert it into the lamina densa. Beneath the lamina densa, the anchoring fibrils extend beneath the basement membrane within the papillary dermis. The hemidesmosomes, anchoring fibrils and anchoring filaments form the hemidesmosome-anchoring filament complex [25, 32]. The hemidesmosome-anchoring filament complex forms a continuous link between the basal keratinocyte intermediate keratin filaments and the underlying BMZ and dermal components [32, 33].
\nThere is a structural framework known as the cytoskeleton within each basal keratinocyte which is composed of three main types of filaments: microfilaments, microtubules and intermediate filaments [31]. Basal keratinocytes express intermediate filament keratins 5 and 14 which are the major keratins in the adult epidermis [32]. Intermediate filaments form an intracellular cytoskeletal network throughout the epidermis and help to maintain the cell shape and epithelial structural integrity both through the formation of a cell scaffold and through their connection to desmosomes and hemidesmosomes [27, 32]. Mutations in genes coding K5 and K14 interfere with the assembly of the tonofilament cytoskeleton and connection of intermediate filaments to desmosomes and hemidesmosomes [27]. Autosomal dominant mutations in K5 and K14 underlie epidermolysis bullosa simplex (EBS) localized to hands and feet [26].
\nPlectin is an epidermal plakin protein and is a component of hemidesmosome [34]. In the epidermis, the N-terminal of plectin includes binding sites for the cytoplasmic region of integrin ß4, BP180 and actin filaments and the C-terminal connects to keratin filaments [27]. It plays a key role in linking the keratin filament network to hemidesmosomes at the plasma cell membrane [34]. Mutations in plectin gene lead to various forms of EBS, including EBS associated with muscular dystrophy or with pyloric atresia and EBS-Ogna [27].
\nThe first specific target antigen of circulating autoantibodies identified in bullous pemphigoid patients, 230 kDa bullous pemphigoid antigen, which is also called the bullous pemphigoid antigen (BPAG) 1 isoform e (BPAG1e) is an intracellular, hemidesmosomal protein and a member of plakin family [33].
\nIt is the major component of the hemidesmosomal inner dense plaque [29]. BPAG1e interacts with cytoplasmic domain of type XVII collagen, keratin intermediate filaments, erbin and integrin ß4. It links the keratin intermediate cytoskeleton to multiple hemidesmosome components [32]. The N-terminal of BP230 has a role in the integration of BP230 into the desmosomes and has binding sites for BP180 and ß4 integrin, and the C-terminal has binding sites for intermediate keratin filaments [27].
\nThough BP230 is a major target antigen in BP, the pathogenic relevance of BP230 in BP is not clear due to its intracellular localization [35]. In a study in 1995 in BPAG1e knockout mice, hemidesmosomes were otherwise normal, but they lacked the inner plate and had no cytoskeleton attached. The cell growth or substratum adhesion was also not affected indicating that BPAG1e was not absolutely essential for hemidesmosome or BMZ assembly. The mice also developed severe dystonia and sensory nerve degeneration [36]. In 2014, Feldrihan et al. demonstrated that antibodies against BP230 were nonpathogenic in experimental models of bullous pemphigoid [37].
\nType VII collagen, which is also known as 180-kDa bullous pemphigoid antigen, is a transmembrane collagenous protein which is located within the hemidesmosome and lamina lucida [26, 30]. Its intracellular ligands are plectin, BPAG1e and ß4 integrin, and the extracellular ligands are α6 integrin and laminin 332 [29]. Collagen XVII spans almost the entire length of the BMZ and it is a major component of the hemidesmosome [31]. It is thought to play a role in the structure or stability of anchoring filaments, and it has an important function in maintaining the integrity of dermoepidermal junction [32].
\nAutoantibodies from patients with BP, pemphigoid gestationis (PG) and linear IgA bullous disease (LABD) target the NC16a domain of BPAG2 and from patients with mucous membrane pemphigoid (MMP) tend to target the distal carboxy terminus of BPAG2, which extends deeper into basement membrane as well as NC16A [25].
\nThe ectodomain of BP180 can be proteolytically shed from the cell surface through cleavage within the NC16A domain generating neoepitopes and the resulting 120 kDa fragment is LAD-1 that can be further processed into a 97 kDa fragment, which is targeted in linear IgA disease and also in BP and pemphigoid gestationis [35].
\nMutations in COL17A1 gene encoding type VII collagen cause non-Herlitz subtypes of junctional EB [27].
\nIntegrins are a family of cell adhesion receptors, which have important roles in ligand binding and signaling [11]. The primary integrin in the cutaneous BMZ is α6β4 integrin, which is critical in the adhesion of basal cells to the underlying BMZ [30]. It links the intracellular hemidesmosomal plaque to the extracellular matrix and plays an important role in initiating signaling pathways involved in cell migration, differentiation and survival. The large intracellular domain of β4 integrin interacts with cytoplasmic domain of BP180 and provides linkage to keratin filaments via plectin. The extracellular domain of α6 and β4 integrins provides binding sites for various laminin isoforms, including laminin 332 [27]. Mutations in either α6 or β4 chains result in autosomal recessive junctional EB associated with pyloric atresia [31].
\nAutoantibodies against α6 and β4 integrins have been detected in a subgroup of patients with MMP. Autoantibodies recognizing the α6 subunit were found in patients with oral lesions, and autoantibodies recognizing the ß4 subunit were found in patients with ocular involvement [35].
\nCD151 is a member of the tetraspanin family of cell surface proteins [28]. It is expressed on the basolateral surface of basal keratinocytes concentrated within desmosomes [27, 28]. The possible interaction partners of CD151 are the α3β1 and α6β1 integrins [32]. CD151 is thought to play a role in the organization and stability of hemidesmosomes by facilitating the formation of stable laminin-binding complexes with integrin α6β4 as well as being involved in cellular signaling [27, 28].
\nLaminins are a heterogeneous family of noncollagenous glycoproteins within the lamina lucida/lamina densa of all basement membranes. The laminin molecule is formed by three different polypeptide subunits: α, β and γ [38]. Laminins have a cruciform structure containing both globular- and rod-like segments which are implicated in interactions with other extracellular matrix molecules, like the hemidesmosomal components and type VII collagen, as well as in cell attachment [30]. Laminins are the major components of all the basement membranes along with collagen IV and exist in several isoforms which have been shown to self-assemble into independent networks that are cross-linked by nidogen and perlecan [38]. To date, 16 laminin isoforms have been identified, and some of the laminin isoforms are expressed in the epidermal BMZ [30, 32]. Laminins 5,6 and 10 are the main epidermal BMZ-specific laminins [32]. Laminins promote basement membrane assembly and maintain cell and tissue integrity. Laminins within basement membranes serve as ligands for overlying cell surface receptors, thereby providing signals regarding the epithelial microenvironment [25]. The integrins, a family of cellular receptors, are major receptors that mediate cell adhesion to laminins [38].
\nPreviously known as laminin 5, laminin 332 (epiligrin, kalinin, nicein, GB3 antigen, BM600) is the major laminin within the cutaneous BMZ [25, 30]. It consists of α3, ß3 and γ 2 laminin polypeptide chains [26]. It is found at the upper lamina densa/lamina lucida border at the base of anchoring filaments [32]. It plays an essential role in dermal-epidermal attachment and can be regarded as a bridge between hemidesmosomal proteins (α6ß4 integrin and type XVII collagen) and the anchoring fibrils (Type VII collagen) on the dermal site [27, 35].
\nThe mutations in LAMA3, LAMB3 and LAMC2 genes encoding laminin 332 cause Herlitz type of junctional EB [35].
\nAutoantibodies against laminin 332 mainly directed against the α3 chain and can be detected in 20% of patients with MMP. This subgroup is termed anti-laminin 332 MMP, and it is associated with a solid malignancy in 30% of the cases [35].
\nLaminin γ 1 is a component of various laminin heterotrimers, including laminin 311, 321 and 511. It has been described as a target in anti-laminin γ1 pemphigoid, previously known as anti-p200 pemphigoid [35].
\nThe integrin α3 subunit may dimerize with ß1 integrin in the dermoepidermal junction and contribute to epithelial-mesenchymal signaling [27]. Integrin α3 is a transmembrane integrin receptor subunit that mediates signals between the cells and their microenvironment. Muta-tions in the gene for the integrin α3 subunit causes an autosomal recessive multiorgan disorder characterized with interstitial lung disease, nephrotic syndrome and junctional EB [39].
\nNidogens (previously known as entactin) are ubiquitous BM glycoproteins [24, 25]. The predominating nidogen is nidogen-1, and nidogen-2 was discovered as second mammalian isoform [24]. They interact with many other BMZ molecules, in particular with laminin and collagen IV, and their primary function appears to be stabilizing interactions between laminins and collagen IV with the lamina densa [35].
\nNidogens are not required for epidermal BMZ formation because of the overlapping functions of many of the BMZ components [31].
\nType IV collagen is found only in basement membranes and consists of three α-chain subunits which can be identical or genetically distinct but structurally related [25, 31]. Collagen IV’s primary role in the basement membrane is structural, as its three-dimensional lattice superstructure forms the basal lamina [31]. It is linked to laminins 5/6/10 complex by nidogen [32]. Collagen IV also has been associated with angiogenesis, tissue remodeling and cancer progression. There are many genetic diseases attributed to collagen IV, including Goodpasture syndrome, Alport syndrome, diffuse esophageal leiomyomatosis, benign familial hematuria [25].
\nHeparan sulfate proteoglycans are glycoproteins which are found at the cell surface and in the extracellular matrix, where they interact with a plethora of ligands [40]. Characteristically, three proteoglycans are present in vascular and epithelial basement membranes, including perlecan, agrin and collagen XVIII [29]. They are present within, just above and just below the lamina densa of the epidermal basement membrane [25]. They can interact with various components of lamina densa, including type IV collagen and nidogen, and they are believed to contribute to the overall architecture of the basement membrane as well as tissue-specific functions [25, 29]. Their high sulfate charge contributes to the negative charge of basement membranes and restricts the permeability of these matrices [25].
\nType VII collagen is the major component of anchoring fibrils, and it provides mechanical strength by linking the basal lamina and the underlying connective tissue [35]. Anchoring fibrils lie beneath the basal lamina, and they are fan-like, cross-banded structures extending into the papillary dermis that form semicircular loops [32]. They extend from the lower part of the lamina densa to the upper reticular dermis [25].
\nType VII collagen consists of three identical α-chains that self-organize into a triple-helical collagenous structure. Each triple helical domain is flanked by a noncollagenous N-terminal and a C-terminal [27]. It contains a large globular noncollagenous domain termed NC1 in the amino terminal and a smaller domain termed NC2 in the carboxy terminal [25].
\nA large number of type VII collagen molecules laterally aggregate to form anchoring fibrils in which NC1 domains bind the lamina densa at one end and either loop back into lamina densa or else connect to anchoring plaques in sublamina densa region [25, 30]. The anchoring plaques are electron-dense structures which contain collagen IV and laminin 332 [29]. Specific subdomains within the NC1 domains have affinity for type I fibrillar collagen in the dermis and type IV collagen in the lamina densa and anchoring plaques. It also interacts with laminin 332 [25].
\nThe importance of anchoring fibrils in securing the adhesion of the dermal-epidermal basement membrane to the underlying dermis is seen in mutations in COL7A1 encoding type VII collagen which underlie both autosomal dominant and autosomal recessive forms of dystrophic EB in which the blister formation occurs in the sublamina densa region [34].
\nIgG autoantibodies directed against type VII collagen also results in epidermolysis bullosa acquisita which is a severe, acquired autoimmune bullous disease [41].
\nType VII collagen has also been described as autoantigen in a small subgroup of patients with MMP, bullous systemic lupus erythematosus and LABD [35] (Table 3).
\nBasement membrane zone molecules | \nAcquired subepidermal blistering disease | \n
---|---|
BPAG1e | \nBullous pemphigoid Mucous membrane (cicatricial) pemphigoid Pemphigoid gestationis Linear IgA disease Lichen planus pemphigoides | \n
Collagen XVII | \nBullous pemphigoid Pemphigoid gestationis Mucous membrane (cicatricial) pemphigoid Lichen planus pemphigoides Linear IgA disease | \n
Laminin 332 | \nMucous membrane (cicatricial) pemphigoid associated with malignancy | \n
Laminin 311 | \nMucous membrane (cicatricial) pemphigoid | \n
Laminin γ1 | \nAnti-laminin γ1 pemphigoid, (anti-p200 pemphigoid) | \n
Integrin α6β4 | \nMucous membrane (cicatricial) pemphigoid | \n
Type VII collagen | \nEpidermolysis bullosa acquisita Bullous lupus erythematosus | \n
Targeted molecules and the corresponding acquired subepidermal blistering disease.
Satellite control system (SCS) is a core, essential subsystem that provides to the satellite capabilities to control its orbit and attitude with a certain performance that is required for satellite mission and proper functioning of satellite payload operation. However, the first mandatory task for SCS is assuring satellite safe functionality; providing sufficient electric power, thermal and communication conditions to be able for nominal functioning during specified life time at different sun lightening conditions (including potential eclipse periods), protecting against life critical failures proving to satellite safe attitude in Safe Hold Mode (SHM). Without SCS or satellite guidance, navigation and control (GN&C) system, any Earth-orbiting satellite could be considered just as artificial space body, demonstrating the launcher capability for the satellite launch. As soon as a satellite is assigned to perform a certain space mission, it has to have SCS and a kind of special device (s)-payload (s), performing scientific, commercial or military tasks that are dedicated to this mission. Today, the widespread satellite and SCS design philosophy [1, 2, 3] is based on the concept that satellite is a platform (bus or transportation vehicle) for the very important person (VIP) passenger, which is the payload, and this platform is aimed just to deliver and carry it in space. This approach has been proven as successful or, at least, satisfactory from the commercial point of view. However, the first Soviet satellite “Sputnik” and further Soviet/Russian satellites were built and launched under the different philosophy that satellite is the main “personage” performing a space mission and the payload (unlikely the ballistic rocket war head (s)) is just one of the satellite subsystems that should be integrated into the satellite board under the satellite chief designer guidance, who is responsible for the mission performance. From the author’s point of view, this approach has certain advantages following from the Aerospace System Engineering, integration and distribution functions, and responsibilities between the space mission participants. In this chapter, SCS is presented from this point of view, integrating conventionally separate satellite GN and C subsystems and devices into the joint integrated system, attitude and orbit determination and control system (AODCS). The main principles and features of this system are presented in this chapter.
The first human-made Earth-orbiting satellite (Soviet Sputnik), Simplest Satellite (SS-1), was launched on October 4, 1957. This satellite was launched following the development of the Soviet intercontinental ballistic rocket R-7 (8 K71). Nevertheless, it started a new era of space human exploration (Figure 1).
Soviet designers-creators of the first earth-orbiting artificial satellite SS-1.
SS-1 technical characteristics are as follows [4, 5]:
Mass 83.6 kg; sealed from two identical hemispheres with a diameter of 0.58 m; life time 3 months; payload, two 1 W transmitters (HF, 20.005 and VHF, 40.002 MHz) with four unidirectional deployable antennas (four 2.4–2.9 m metallic rods); electrical batteries, silver-zinc; sufficient for 2 weeks.
Orbit: perigee 215 km, apogee 939 km, period 96.2 min, eccentricity 0.05, inclination angle 65.10 deg.
Inside, the satellite sphere was filled by nitrogen, and the temperature was kept within 20–23 deg. C with automatic thermoregulation-ventilation system (thermometer-ventilator).
The satellite had no attitude control and was free rotated around its center of mass in orbit, keeping initial angular speed, provided by the separation pulse after the separation from the launch rocket. However, thanks to the four rod antennas that provided unidirectional radio transmission in the two-radio bends, HF and VHF, SS-1 evidently indicated its presence in space for all people over the world. Even amateur radio operators with amateur receivers could receive famous now signals: BIP, BIP, BIP…!! (Figure 2).
Since SS-1, about 8378 satellites were launched to year 2018 [6]. Early satellite launches were extraordinary events and demonstrated tremendous achievement of the launched state, the USSR (4 Oct. 1957, SS-1), the USA (31 Jan. 1958, Explorer 1) and Canada (29 Sep. 1962, Alouette, launched by Thor-Agena, a US two-stage rocket), but with time, satellite launches became ordinary and usually pursue a certain military or civil mission.
SS-1, assembled (left). Open two semispheres (right).
Among the civil missions (satellites), the following types can be determined as already conventional: navigation, communication, Earth observation, scientific, geophysics and geodetic, technology demonstration and developers training. These satellites are usually equipped with a kind of payload system(s) (radio/TV transmitter/transducer, radar, telescope or different scientific instrument, etc.) to perform certain dedicated space mission(s). For example, the first Canadian Earth observation satellite RADARSAT-1 (Nov 4, 1995–May 10, 2013; Figure 3) was equipped with a side-looking synthetic aperture radar (SAR) on board the International Space Station (November 1998, ISS; Figure 4) was installed a Canadian robotic arm for its assembling and maintenance.
The first Canadian earth observation satellite RADARSAT-1.
International Space Station (ISS).
According to the satellite altitude (h), their orbits can be classified as low-altitude (LEO), 200–2000 km; medium-altitude (MEO), 5000–20,000 km; and high-altitude (HEO), h > 20,000 km; according to eccentricity as: close to circular e < 0.01; elliptical 0.01 < e < 0.3; highly elliptical 0.3 < e < 0.8.
There are satellites with special type of orbit such as polar (i = 90 deg), equatorial geostationary (GEO, i = 0 and h = 35,800 km) and Sun-synchronous provide orbital precession equal to Sun annual rate (i depends on satellite period) (Figure 5).
Satellite orbit types (“tundra” and “Molniya” are Russian communication satellites in highly ecliptic orbits).
Miniaturized low-cost satellites are as follows: small satellites (100–500 kg), microsatellite (below 100 kg) and nanosatellite (below 10 kg).
A large diversity of satellites serving for different missions is in space now. A widespread point of vew is that all of them are transportation platforms delivering and carrying in orbit dedicated to the planned space mission payload system, like a VIP passenger. For example, it could be the postman for the postal horse carriage for many years ago. Namely, the satellite with its control system (SCS) provides to the payload all conditions required for the mission performance (orbit, attitude, power, pressure, temperature, radiation protection and communication with ground mission control center (MCC)). That is why from the mission integration point of view, the SCS can be seen as the space segment integration bases that set their development and operation process in corresponding order. In turn, SCS as satellite subsystem also can be reviled and established in satellite onboard equipment architecture, combining the group of subsystems that are dedicated to orbit and attitude determination and control tasks. It could be done rather from the System Engineering than from the commercial practice point of view and would significantly streamline satellite development order and the degree of responsibility of all the developers.
It should be mentioned that such group of aircraft equipment in aviation has been named as GN&C Avionics; hence, for space, it can be named as the Spacetronics, and the heritage of system development and integration wherever it is possible should be kept. Essential difference with Avionics for the Spacetronics is that it should work for specified life time in space environment (dedicated orbit) after mechanical start-up impacts (overload, vibration) connected to the launch into the orbit. The verification of this capability is usually gained in special space qualification ground tests that imitate launch impact and space environment with thermo-vacuum and radiation chambers, mechanical load and vibration stands [7, 8].
Today, for many satellites, GN&C onboard equipment can be presented by the following subsystems, performing related functions listed below:
Global Positioning System (GPS)—onboard satellite orbit and time determination
Propulsion system—orbit/attitude control system
Attitude Determination and Control System (ADCS)—satellite attitude determination and control
Integration of these subsystems can be named as attitude and orbit determination and control system or Spacetronic system. Typically, AODCS includes the following components:
Onboard computer system (OBCS) or dedicated to AODCS electronic cards (plates) in Central Satellite Computer System (e.g., command and data handling computer (C&DH))
Sensors
Actuators
Basic AODCS architecture is presented in Figure 6.
Satellite AODCS system.
OBCS, onboard computer system; TLM, telemetry data and commands; PL, payload; PS, propulsion system; RW, inertia reaction wheels; MTR, magnetic torque rods; GPS, satellite navigation Global Positioning System; MAG, 3-axis magnetometer; SS, 2-axis Sun sensor; HS, horizontal plane sensor; ST, star tracker; RS, angular rate sensor; EP, electric power; TR, temperature regulation; VP, vacuumed protection; RP, radiation protection.
Depending on required reliability and life time, each component can be a single or redundant unit. Unlike airplanes, satellite is an inhabitant space vehicle that is operated from the ground. The operation is usually performed via a bidirectional telemetry radio link (TLM) in S-band (2.0–2.2 GHz). Payload data downlink radio link (unidirectional) is usually performed via X-band (7.25–7.75 GHz;). For both links, usually the same data protocol standards are applied Figure 7.
Satellite communications with ground stations.
Two subsystems can be allocated in AODCS architecture, namely, orbit determination and control subsystem (ODCS) and attitude determination and control subsystem (ADCS). Practically both subsystems are dynamically uncoupled; however, orbital control requires the satellite to have a certain attitude (as well as orbital knowledge itself), and attitude control requires orbit knowledge also. Hence, orbit (its knowledge) is essentially continuously required on satellite board where it is propagated by special orbit propagator (OP). Due to orbital perturbations (residual atmospheric drag, gravity and magnetic disturbances and solar pressure), satellite orbit changes over time and OP accumulates errors; its accuracy is degraded.
Before the application of satellite onboard GPS receivers, the satellite position and velocity were periodically determined on ground by the ground tracking radio stations (GS, dish antenna), and calculated on-ground orbital parameters were periodically uploaded to satellite OBCS to correct OP, to provide available accuracy. Now with GPS satellite, orbit can be calculated onboard autonomously, and OP can propagate data only during relatively short GPS outage periods. For some applications, orbital data uploaded from the ground still can be used, at least, for fusion with GPS-based OP.
For newly developed satellites with GPS, orbit maneuvers (correction, deorbiting, collision avoidance, special formation flying and orbit servicing missions) can be executed autonomously onboard at planned time or from ground operators using orbital knowledge and TLM commands to activate satellite orbit control thrusters.
Below AODCS components are presented to show their generic principles that can help for the system understanding and modeling. Generic design requirements are presented in [3]. Some design examples can be found in many sources, for example, [1, 9, 10, 11, 12].
AODCS sensors are designed to measure satellite orbital and attitude position and velocity. From the most general point of view, they can be considered as the vector measuring devices (VMD). The device can measure in space a physical vector
Vector R¯ in the Cartesian coordinate system XYZ.
Satellite GPS SRG-10. Double redundant with a pair of zenith and nadir antennas.
Vector module and its orientation can be expressed as functions of its projections
It can be noted that measurement of referenced vectors can be used for the determination of satellite position or angular orientation. A minimum of three vectors is required to determine satellite position and two to determine its attitude. If more vectors are measured providing informational redundancy, then such statistical estimation methods as least square method (LSM) and Kalman filter (KF) can be applied. Satellite velocity and angular rate can be derived by the differentiation of its position and attitude applying a kind of filter recommended by the filtering and estimation theory [13, 14, 15]. It should also be noted that if vector orientation is measured for the position determination, then satellite attitude should be known and vice versa.
Especial autonomous satellite navigation system (sensor) is the inertial navigation system (INS/inertial measurement unit (IMU)). It can be used for the determination of satellite position, velocity, orientation and angular rate simultaneously. INS is based on measuring with linear accelerometers and angular rate sensors (“gyros”) the two vectors: satellite linear active acceleration
Today, satellite GPS can provide onboard accurate data about position, velocity and time [19] (Figure 9).
Accuracy: position, 15 m (
GPS receiver is a radio range measuring device that measures distance from the desired satellite to navigation satellite constellation (NAVSTAR, USA; GLONASS, Russia; and GALILEO, Europe) and computes its position and velocity. GPS measures the distance R (
A minimum of three navigation satellites should be simultaneously traced by the receiver to determine position and velocity. Then satellite position is the cross-point of three spherical surfaces of the position equation
where
The TRIAD method [10] is applied when two different vectors are measured. They usually can be any of the three pairs combined with the following three vectors: Earth magnetic induction vector
Let us assume that two different physical nature not collinear vectors
These unit vectors expressed at a given time by measured values in measured frame or body frame and reference values in a reference frame define two rotation matrixes,
where vectors
Rotation matrix
Three Euler angles of rotation, roll (
where
Vector measured sensors
If a pair from the three vectors (B, S, r-write as vectors) is measured, then following VMD in the pair can be used: SS (Figure 10), HS (Figure 11) and MAG (Figure 12).
If more than two vectors are measured and available for attitude determination, then LSM-BATCH method [10] can be applied to use informational redundancy for increasing the stochastic estimation accuracy. This method basically can be applied for any set of VMD but is specifically convenient for the star tracker (ST), when some number (
S-vector sensor Bradford fine sun sensor, accuracy, 0.2 deg. (2σ).
r-vector sensor HS CMOS/SRAM-modular infrared horizon sensor, accuracy, 0.4 deg. (2σ).
B-vector sensor MAG TFM100-S, accuracy, 10mG (2σ).
Star direction R-vector measured sensor (optic and computer units). Advanced stellar compass, accuracy, 2\'\'−16\'\'2σ.
Let us consider the transformation of the referenced vector
where
If the ST is in the tracking mode keeping in its FOV some
where
Then subtracting from (8)
where
Transforming in (10) matrix product and taking into account random measurement errors, this equation can be represented in the following form:
where
Then this equation can be considered as a “standard” linear algebraic equation:
where,
If
where
Direct measurement
Satellite angular rate
Measurement of satellite angular velocity ω¯ with three rate sensors RSx,RSy,RSz.
Measured angular velocity vector
where
Body rate estimator
Often, specifically for attitude stabilization (keeping or aka pointing) mode, satellite angular rate is estimated by using the so-called body rate estimator and is not measured directly by the RS. Indeed, using for attitude keeping mode small angles and linear approximation, we can simplify satellite attitude dynamics model [9] to three single-axis state equations and present it with the stochastic influences as follows:
where
The linear KF can be applied to synthesize the estimator for the optimal estimation of the vector angle
where
Matrix KF (16) is separated in three independent scalar channels for
It can be shown that in the considering case, the steady-state (
where
where
or in other words, the time constant is in inverse proportionality to the filterability index (in ¼ degree) and the specific damping coefficient is conventional for such a second-order unit 0.707 for each of the three channels.
As it can be seen from the consideration above, the use of directly measuring devices (e.g., ST and RS) for attitude and body rate determination has a disadvantage. The random noises are at the devices output, and they have to be filtered in the closed control loop of satellite attitude control that puts some constraints to choose the control law coefficients. However, using indirect body rate measurement, the state estimator (filter) unavoidably introduces additional phase delay in the control loop because of the consecutive inclusion of this filter in the control loop. To use the RS (gyro) and the integrator for body rate and attitude determination autonomously for a long time is not possible because of the accumulated attitude errors caused by the integration of the gyro drift. The following scheme (that is common in Aviation) can be considered as free from the disadvantages above. Let us assume that satellite attitude is determined in two ways: continuous integration of RS angular velocity (IMU) and using VMD, for example, ST. Then this ST is used to correct the attitude derived by the integration of RS output. The idea of MSU is shown in Figure 16.
Integration of multisensory sensor unit (MSU) single-axis channel.
In integrated IMU attitude (IMU = RS + integrator) as in Figure 14 above (three identical channels),
where
where KF coefficients
Satellite propulsion system [9, 10] is usually designed for satellite orbital and/or angular control. In the first case, PS is commanded from the ground OC by TLM commands in some cases when satellite orbit has to be changed (orbit correction, deorbiting, collision avoidance), in the second controlled automatically from onboard AODCS. It consists of such typical elements as orbital and attitude thrusters (number and installation scheme depending on certain application), propulsion tank with associated pipes, valves, regulators, and electronics. General principles of PS act independently of the type (ion thrusters (0.01–0.1 N), liquid propellant and solid motor (100–10,000 N), cold gas (1-3 N)).
Figure 15 illustrates the satellite control with PS thruster principles. The principle of the formation of the propulsion jet force can be presented by the following equation of variable mass body dynamics that from Russian sources, for example, [23], is known as Prof. I. Meshchersky’s equation:
ω¯-vector sensor RS, BEI QRS-11 single-axis body rate sensor, accuracy, 7deg/h=0.0019deg/s2σ.
where
Satellite control with PS thruster principles.
In Section 3.2.2.1.2, it is always
The expelled propulsion mass
where
Discrete pulse modulation control is usually used to minimize the consumption of the propellant for attitude control [9]. Examples of the gas thruster and the tank are presented in Figures 20 and 21.
Magnetorquers are essentially sets of electromagnets. A conductive wire is wrapped around a ferromagnetic core which is magnetized when excited by the electric current caused by the control voltage applied to the coil. The disadvantage of this design is the presence of a residual magnetic dipole that remains even when the coil is turned off because of the hysteresis in the magnetization curve of the core. It is therefore necessary to demagnetize the core with a proper demagnetizing procedure. Normally, the presence of the core (generally consisting of ferromagnetic) increases the mass of the system. The control voltage is controlled by AODCS control output (Figures 18–20). The magnetic dipole generated by the magnetorquer is expressed by the formula:
Prof. I. Meshchersky (1859–1935).
K. Tsiolkovsky (1857–1935).
Cold gas GN-2 thruster, nominal thrust 3.6 N (230 psi), specific impulse 57 s.
where n is the number of turns of the wire,
where
Typically, three coils are used; the three-coil assembly usually takes the form of three perpendicular coils, because this setup equalizes the rotational symmetry of the fields which can be generated; no matter how the external field and the craft are placed with respect to each other, approximately the same torque can always be generated simply by using different amounts of current on the three different coils (Figure 22).
60 liter propulsion gas tank.
3D orthogonal magnetic torque rods.
It can be seen from Eq. (26) that MTR cannot generate the magnetic torque in the direction that is parallel to Earth magnetic field
However, the following approach can be used to find required vector
Another MTR control method is the so-called B-dot control [25].
where
As the result of (29) control, the satellite will reduce its body rate and is finally slow rotated along Earth’s geomagnetic field line (vector
If the redundancy is required, it is provided by additional (redundant) coil with the same core (Figure 23).
Magnetic torque rod SSTL MTR-30, magnetic moment, M=30Am2.
Reaction wheels (RW), aka momentum exchange devices [9] or reaction-momentum wheels (RMW), have massive rotated rotor with big axial moment of inertia with respect to the axis of rotation. They are electrically controlled by the electric motors and the rotor is installed on the rotating motor shaft. The controlled voltage, applied to the control winding of the motor, controls its rotor angular speed. The product of the rotor angular acceleration
Three orthogonal reaction wheels (RW).
RW can generate control inertia torques
In general case, RW can be run around in some nominal angular speed
where
Then differentiating (31) in rotating with angular velocity satellite axis
where
where
Eq. (33) can be represented in the following form:
where
The torque
where
In the operator Laplace s-form (transfer function), Eq. (36) can be rewritten as follows:
where
It should be noted that sometimes the RW control loop is more sophisticated. Special integrators could be connected into the loop to memorize and compensate the dry friction torques acting in bearings. Some small nominal rotating speed can be set for all three RMW to eliminate the dry friction torque having a pike when the wheel speed is zero
However, more representative case is when
Indeed, if we put in (32) that
where
Reaction/momentum wheel HR-0610, torque, 75⋅10−3Nm; momentum, 4−12Nms.
Independently of sytem arhitecture; it is separate dedicated to AODCS computer, or a special AODCS card within central satellite C&DH computer, it is the integration element of AODCS [1, 11]. AODCS system may consist of the computer (computer card) itself (OBC) and auxiliary intercommunication electronic units (electronic cards) AEU carrying DC/DC electric power conversion and I/O (analog and digital) interface and commutation functions.
OBC can be divided into two parts: the hardware (HW, power convertor, processor, input/output [I/O] convertors, non-volatile and volatile memory) and the software (SW, operation system [OS] and vital or functional software [VS/FS]) (Figure 26).
Satellite OBCS, MAC-200 (C&DH unit with AODCS card) comprises of two OBC: Prime and redundant (cold reserve).
What makes the satellite OBC essentially different for the airplane OBC is that its SW can be uploaded and updated from the ground and during operation and scheduled maintenance. OS OBC includes generic computer programs: program of I/O interface, time schedule (dispatcher), embedded test, timer and standard mathematic functions. Satellite SW often is considered as satellite SW subsystem that is verified during development (with mathematical high-fidelity Matlab/Simulink simulators and semi-natural processor-in-the-loop (PIL) simulators). SW subsystem should be tested to meet SW requirements [26, 27]. The flight version of the SW subsystem is supported with operation real-time satellite simulators (RSS) [1, 11] located in operation center. It should be mentioned that only final AODCS (OBC (HW + SW), sensors, and actuators) functional test [2] that should be performed in the Space Qualification Laboratory [7] during satellite Space Qualification and Acceptance campaign can really minimize the risk of launching a not ready satellite and prevent against AODCS refinishing in orbit during commissioning and operation.
VS can be separated in two parts, ODCS SW and ADCS SW. For both parts, I/O interface with sensors and actuators is determined in special interface control document(s) (ICD), describing type, certain connectors, and electrical parameters of the exchanging data. These data before using them for functional tasks are pre-processed in OBC with special algorithms.
This group of algorithms performs the following common tasks:
Convert data into required physical parameters and units, taking into account certain sensor input–output scale function.
Transform data in certain device frame and compensate device misalignment, bias and scale function errors if it is possible, monitor device state, establishing “on/off,” “work/control,” “data bad/good” flags.
Transfer to C&DH TLM data about sensor/actuator state and their data.
Perform some other auxiliary functions if they are required.
Main functional tasks ODCS SW and ADCS SW can be listed as below.
To understand the idea of propagation of satellite orbit in Earth gravity field to the simplest, Keplerian motion propagator based on spherical Earth gravity field model might be used [9]; however more realistic results can be obtained with more accurate propagator, taking into account the second zonal harmonic
where
These equations can propagate satellite position and velocity (
where
Satellite orbit in the inertial ECI (XYZ) coordinate system.
If orbit maneuver is required, then it can be commanded by AODCS SW autonomously, or special control commands TLM (uploaded command tables) are sending to satellite AODCS, and in predetermined time they are executed activating at scheduled time for the calculated period
This group of algorithms was presented above in 3.2.1.2 and can be used here.
For example, let us consider single-axis stabilized satellite that should keep one axis (e.g.,
Satellite pointed by the Z-axis to the sun.
In Figure 28,
The following formula represents the mathematical transformation of the Sun vector from the reference into the body frame:
where
Then from (41), (42) can derive the following formulas:
From (43), desired angles and can be derived that can be used for satellite attitude control.
Let us also assume that the satellite does not have angular velocity sensors RS and its angular velocities should be derived from the measured angles
where
If not the optimization criterion to characterize the control quality [13] is required, then conventional negative feedback closed control loop with linear PID (proportional, integral, and damping) control law [9] that provides a good performance for many practical satellite control applications can be used to satisfy the requirements. They are typical for any automatic control system requirements: such as transfer process decay time and overshooting, residual static error caused by the permanent external disturbance, etc. Today, attitude control system performance can be verified mainly on ground with simulation. If we try to evaluate it in flight, then only onboard attitude sensors TLM data can be used for postprocessing, and it should be taken into account that mainly sensors that detect high-frequency noise (perceived errors) will be observable and low-frequency components (sensor biases) are compensated in the closed control attitude stabilization loop. Simple example of single-axis satellite attitude stabilization control loop is presented below. It is a simplified linear model; however, it presents the stabilization principle and essential features. Let us assume that a simple, positional, and damping control law is used to stabilize satellite axis
where
where
where
Let us take a ball-shaped satellite with the inertia matrix as follows:
where
Let us divide all terms in Eq. (50) by the coefficient
where
As it follows from Eq. (52), steady-state error in attitude stabilization can be calculated with the formula:
where
For Eq. (52), the optimal damping coefficient is
Numerical example
Let us evaluate satellite time constant
and MTR has the following parameters: maximal magnetic moment
For the data above, it has the value of
as for a homogeneous sphere. Substituting into Eq. (55) the data above, we can calculate that for SS-1
Now damping coefficient can be calculated with the following formula:
It has the following value:
Finally,
When
Simulation
Eqs. (51) and (52) were simulated using Simulink (see Figure 29).
Satellite single-axis attitude control Simulink block scheme.
Blocks in the pink color present the satellite model, the dark green color is for control law blocks, the cyan blocks are registration oscilloscopes, and the display and the orange color are the disturbances. The red manual switch allows to implement the differentiating filter, transforming the scheme from the approximation (52) to the accurate presentation (51). Disturbing external torque
Response to initial deviation angle αx0=10. (a) without dif. filter and (b) with dif. filter.
Response to initial angular velocity α̇x0=0.01deg/s.
Response to external disturbance torque Td=10−5Nm. Static error αx∗=0.898∘.
Response to attitude sensor bias Δx0=1∘ plus white noise σV=0.1∘,TV=1s. Satellite attitude stabilization errors, ALP.
Satellite attitude measured errors ALPm.
Simulation of ACS (Figure 29) is presented in Figures 30–34. Units: vertical axis (deg), horizontal axis: (s).
Decay time:
As it can be seen, measured noise is filtered effectively in the control loop, and stabilization error is equal to the sensor bias with opposite sign.
In Figure 34, we can see that the measured (perceived) errors that TLM data provide to ground after the decay time do not present sensor bias and present only measured noise. It is because satellite stabilization error with opposite sign compensates the bias. In general, it can also be seen that the simulation of the approximate second-order model (52) is very close to the accurate model (51). Hence, at least for the analytical representation, (52) can be successfully used.
Part I of this chapter presents an overview of practical satellite control system, satellite guidance, navigation and control equipment. The work presented here is based on the author’s point of view of integration of this GN&C equipment in the integrated AODCS system (satellite GN&C Spacetronics System). Main work principles, architecture, and components of the satellite control system were briefly highlighted.
The chapter can serve to a wide pool of space system specialists as an introduction to satellite control system development.
The author wishes to express his sincere gratitude to the Canadian Space Agency, where he had the opportunity to learn and possess the knowledge and experience related to the writing of this chapter. As well, he is very thankful to many of his colleagues from Canadian Magellan Aerospace Company (Bristol Aerospace Division) with whom he discussed and analyzed satellite AODCS design projects and issues that helped him to work out the system analysis and its principal concepts presented in this chapter. Additionally, he cannot forget that his experience and background in Aerospace Technology were also accumulated from the former USSR (Moscow Aviation Institute, Moscow Aviapribor Corporation, Moscow Experimental Design Bureau Mars, Institute in Problems in Mechanic of RAN) and Israel (IAI, Lahav Division and Tashan Engineering Center), where he could observe and learn from diverse and wealthy engineering and scientific schools led by great scientists and designers such as Prof. BA. Riabov, Prof. V.P. Seleznev, V.A. Yakovlev, G. I. Chesnokov, V.V. Smirnov, Dr. A. Syrov, Acad. F. Chernousko, A. Sadot and Dr. I. Soroka.
This chapter was written as a solo author since his friend and regular coauthor Prof. George Vukovich from York University of Toronto passed away 2 years ago. For many years, Prof. Vukovich served as Director of his Department of Spacecraft Engineering in CSA. He will always keep good memories of Prof. Vukovich who helped and encouraged him continue his scientific and engineering work.
The author also acknowledges the copyrights of all publishers of the illustrations that were extracted from the open sources in the Internet.
Dedicated to Prof. G. Vukovich.
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She performed research in perioperative autotransfusion and obtained the degree of PhD in 1993 publishing Peri-operative autotransfusion by means of a blood cell separator.\nBlood transfusion had her special interest being the president of the Haemovigilance Chamber TRIP and performing several tasks in local and national blood bank and anticoagulant-blood transfusion guidelines committees. Currently, she is working as an associate professor and up till recently was the dean at the Albert Schweitzer Hospital Dordrecht. She performed (inter)national tasks as vice-president of the Concilium Anaesthesia and related committees. \nShe performed research in several fields, with over 100 publications in (inter)national journals and numerous papers on scientific conferences. \nShe received several awards and is a member of Honour of the Dutch Society of Anaesthesia.",institutionString:null,institution:{name:"Albert Schweitzer Hospital",country:{name:"Gabon"}}},{id:"83089",title:"Prof.",name:"Aaron",middleName:null,surname:"Ojule",slug:"aaron-ojule",fullName:"Aaron Ojule",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Port Harcourt",country:{name:"Nigeria"}}},{id:"295748",title:"Mr.",name:"Abayomi",middleName:null,surname:"Modupe",slug:"abayomi-modupe",fullName:"Abayomi Modupe",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/no_image.jpg",biography:null,institutionString:null,institution:{name:"Landmark University",country:{name:"Nigeria"}}},{id:"94191",title:"Prof.",name:"Abbas",middleName:null,surname:"Moustafa",slug:"abbas-moustafa",fullName:"Abbas Moustafa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94191/images/96_n.jpg",biography:"Prof. Moustafa got his doctoral degree in earthquake engineering and structural safety from Indian Institute of Science in 2002. He is currently an associate professor at Department of Civil Engineering, Minia University, Egypt and the chairman of Department of Civil Engineering, High Institute of Engineering and Technology, Giza, Egypt. He is also a consultant engineer and head of structural group at Hamza Associates, Giza, Egypt. Dr. Moustafa was a senior research associate at Vanderbilt University and a JSPS fellow at Kyoto and Nagasaki Universities. He has more than 40 research papers published in international journals and conferences. He acts as an editorial board member and a reviewer for several regional and international journals. His research interest includes earthquake engineering, seismic design, nonlinear dynamics, random vibration, structural reliability, structural health monitoring and uncertainty modeling.",institutionString:null,institution:{name:"Minia University",country:{name:"Egypt"}}},{id:"84562",title:"Dr.",name:"Abbyssinia",middleName:null,surname:"Mushunje",slug:"abbyssinia-mushunje",fullName:"Abbyssinia Mushunje",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Fort Hare",country:{name:"South Africa"}}},{id:"202206",title:"Associate Prof.",name:"Abd Elmoniem",middleName:"Ahmed",surname:"Elzain",slug:"abd-elmoniem-elzain",fullName:"Abd Elmoniem Elzain",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Kassala University",country:{name:"Sudan"}}},{id:"98127",title:"Dr.",name:"Abdallah",middleName:null,surname:"Handoura",slug:"abdallah-handoura",fullName:"Abdallah Handoura",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"École Supérieure des Télécommunications",country:{name:"Morocco"}}},{id:"91404",title:"Prof.",name:"Abdecharif",middleName:null,surname:"Boumaza",slug:"abdecharif-boumaza",fullName:"Abdecharif Boumaza",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Abbès Laghrour University of Khenchela",country:{name:"Algeria"}}},{id:"105795",title:"Prof.",name:"Abdel Ghani",middleName:null,surname:"Aissaoui",slug:"abdel-ghani-aissaoui",fullName:"Abdel Ghani Aissaoui",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/105795/images/system/105795.jpeg",biography:"Abdel Ghani AISSAOUI is a Full Professor of electrical engineering at University of Bechar (ALGERIA). He was born in 1969 in Naama, Algeria. He received his BS degree in 1993, the MS degree in 1997, the PhD degree in 2007 from the Electrical Engineering Institute of Djilali Liabes University of Sidi Bel Abbes (ALGERIA). He is an active member of IRECOM (Interaction Réseaux Electriques - COnvertisseurs Machines) Laboratory and IEEE senior member. He is an editor member for many international journals (IJET, RSE, MER, IJECE, etc.), he serves as a reviewer in international journals (IJAC, ECPS, COMPEL, etc.). He serves as member in technical committee (TPC) and reviewer in international conferences (CHUSER 2011, SHUSER 2012, PECON 2012, SAI 2013, SCSE2013, SDM2014, SEB2014, PEMC2014, PEAM2014, SEB (2014, 2015), ICRERA (2015, 2016, 2017, 2018,-2019), etc.). His current research interest includes power electronics, control of electrical machines, artificial intelligence and Renewable energies.",institutionString:"University of Béchar",institution:{name:"University of Béchar",country:{name:"Algeria"}}},{id:"99749",title:"Dr.",name:"Abdel Hafid",middleName:null,surname:"Essadki",slug:"abdel-hafid-essadki",fullName:"Abdel Hafid Essadki",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"École Nationale Supérieure de Technologie",country:{name:"Algeria"}}},{id:"101208",title:"Prof.",name:"Abdel Karim",middleName:"Mohamad",surname:"El Hemaly",slug:"abdel-karim-el-hemaly",fullName:"Abdel Karim El Hemaly",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/101208/images/733_n.jpg",biography:"OBGYN.net Editorial Advisor Urogynecology.\nAbdel Karim M. A. El-Hemaly, MRCOG, FRCS � Egypt.\n \nAbdel Karim M. A. El-Hemaly\nProfessor OB/GYN & Urogynecology\nFaculty of medicine, Al-Azhar University \nPersonal Information: \nMarried with two children\nWife: Professor Laila A. Moussa MD.\nSons: Mohamad A. M. El-Hemaly Jr. MD. Died March 25-2007\nMostafa A. M. El-Hemaly, Computer Scientist working at Microsoft Seatle, USA. \nQualifications: \n1.\tM.B.-Bch Cairo Univ. June 1963. \n2.\tDiploma Ob./Gyn. Cairo Univ. April 1966. \n3.\tDiploma Surgery Cairo Univ. Oct. 1966. \n4.\tMRCOG London Feb. 1975. \n5.\tF.R.C.S. Glasgow June 1976. \n6.\tPopulation Study Johns Hopkins 1981. \n7.\tGyn. Oncology Johns Hopkins 1983. \n8.\tAdvanced Laparoscopic Surgery, with Prof. Paulson, Alexandria, Virginia USA 1993. \nSocieties & Associations: \n1.\t Member of the Royal College of Ob./Gyn. London. \n2.\tFellow of the Royal College of Surgeons Glasgow UK. \n3.\tMember of the advisory board on urogyn. FIGO. \n4.\tMember of the New York Academy of Sciences. \n5.\tMember of the American Association for the Advancement of Science. \n6.\tFeatured in �Who is Who in the World� from the 16th edition to the 20th edition. \n7.\tFeatured in �Who is Who in Science and Engineering� in the 7th edition. \n8.\tMember of the Egyptian Fertility & Sterility Society. \n9.\tMember of the Egyptian Society of Ob./Gyn. \n10.\tMember of the Egyptian Society of Urogyn. \n\nScientific Publications & Communications:\n1- Abdel Karim M. El Hemaly*, Ibrahim M. Kandil, Asim Kurjak, Ahmad G. Serour, Laila A. S. Mousa, Amr M. Zaied, Khalid Z. El Sheikha. \nImaging the Internal Urethral Sphincter and the Vagina in Normal Women and Women Suffering from Stress Urinary Incontinence and Vaginal Prolapse. Gynaecologia Et Perinatologia, Vol18, No 4; 169-286 October-December 2009.\n2- Abdel Karim M. El Hemaly*, Laila A. S. Mousa Ibrahim M. Kandil, Fatma S. El Sokkary, Ahmad G. Serour, Hossam Hussein.\nFecal Incontinence, A Novel Concept: The Role of the internal Anal sphincter (IAS) in defecation and fecal incontinence. Gynaecologia Et Perinatologia, Vol19, No 2; 79-85 April -June 2010.\n3- Abdel Karim M. El Hemaly*, Laila A. S. Mousa Ibrahim M. Kandil, Fatma S. El Sokkary, Ahmad G. Serour, Hossam Hussein.\nSurgical Treatment of Stress Urinary Incontinence, Fecal Incontinence and Vaginal Prolapse By A Novel Operation \n"Urethro-Ano-Vaginoplasty"\n Gynaecologia Et Perinatologia, Vol19, No 3; 129-188 July-September 2010.\n4- Abdel Karim M. El Hemaly*, Ibrahim M. Kandil, Laila A. S. Mousa and Mohamad A.K.M.El Hemaly.\nUrethro-vaginoplasty, an innovated operation for the treatment of: Stress Urinary Incontinence (SUI), Detursor Overactivity (DO), Mixed Urinary Incontinence and Anterior Vaginal Wall Descent. \nhttp://www.obgyn.net/urogyn/urogyn.asp?page=/urogyn/articles/ urethro-vaginoplasty_01\n\n5- Abdel Karim M. El Hemaly, Ibrahim M Kandil, Mohamed M. Radwan.\n Urethro-raphy a new technique for surgical management of Stress Urinary Incontinence.\nhttp://www.obgyn.net/urogyn/urogyn.asp?page=/urogyn/articles/\nnew-tech-urethro\n\n6- Abdel Karim M. El Hemaly, Ibrahim M Kandil, Mohamad A. Rizk, Nabil Abdel Maksoud H., Mohamad M. Radwan, Khalid Z. El Shieka, Mohamad A. K. M. El Hemaly, and Ahmad T. El Saban.\nUrethro-raphy The New Operation for the treatment of stress urinary incontinence, SUI, detrusor instability, DI, and mixed-type of urinary incontinence; short and long term results. \nhttp://www.obgyn.net/urogyn/urogyn.asp?page=urogyn/articles/\nurethroraphy-09280\n\n7-Abdel Karim M. El Hemaly, Ibrahim M Kandil, and Bahaa E. El Mohamady. Menopause, and Voiding troubles. \nhttp://www.obgyn.net/displayppt.asp?page=/English/pubs/features/presentations/El-Hemaly03/el-hemaly03-ss\n\n8-El Hemaly AKMA, Mousa L.A. Micturition and Urinary\tContinence. Int J Gynecol Obstet 1996; 42: 291-2. \n\n9-Abdel Karim M. El Hemaly.\n Urinary incontinence in gynecology, a review article.\nhttp://www.obgyn.net/urogyn/urogyn.asp?page=/urogyn/articles/abs-urinary_incotinence_gyn_ehemaly \n\n10-El Hemaly AKMA. Nocturnal Enuresis: Pathogenesis and Treatment. \nInt Urogynecol J Pelvic Floor Dysfunct 1998;9: 129-31.\n \n11-El Hemaly AKMA, Mousa L.A.E. Stress Urinary Incontinence, a New Concept. Eur J Obstet Gynecol Reprod Biol 1996; 68: 129-35. \n\n12- El Hemaly AKMA, Kandil I. M. Stress Urinary Incontinence SUI facts and fiction. Is SUI a puzzle?! http://www.obgyn.net/displayppt.asp?page=/English/pubs/features/presentations/El-Hemaly/el-hemaly-ss\n\n13-Abdel Karim El Hemaly, Nabil Abdel Maksoud, Laila A. Mousa, Ibrahim M. Kandil, Asem Anwar, M.A.K El Hemaly and Bahaa E. El Mohamady. \nEvidence based Facts on the Pathogenesis and Management of SUI. http://www.obgyn.net/displayppt.asp?page=/English/pubs/features/presentations/El-Hemaly02/el-hemaly02-ss\n\n14- Abdel Karim M. El Hemaly*, Ibrahim M. Kandil, Mohamad A. Rizk and Mohamad A.K.M.El Hemaly.\n Urethro-plasty, a Novel Operation based on a New Concept, for the Treatment of Stress Urinary Incontinence, S.U.I., Detrusor Instability, D.I., and Mixed-type of Urinary Incontinence.\nhttp://www.obgyn.net/urogyn/urogyn.asp?page=/urogyn/articles/urethro-plasty_01\n\n15-Ibrahim M. Kandil, Abdel Karim M. El Hemaly, Mohamad M. Radwan: Ultrasonic Assessment of the Internal Urethral Sphincter in Stress Urinary Incontinence. The Internet Journal of Gynecology and Obstetrics. 2003. Volume 2 Number 1. \n\n\n16-Abdel Karim M. El Hemaly. Nocturnal Enureses: A Novel Concept on its pathogenesis and Treatment.\nhttp://www.obgyn.net/urogynecolgy/?page=articles/nocturnal_enuresis\n\n17- Abdel Karim M. El Hemaly. Nocturnal Enureses: An Update on the pathogenesis and Treatment.\nhttp://www.obgyn.net/urogynecology/?page=/ENHLIDH/PUBD/FEATURES/\nPresentations/ Nocturnal_Enuresis/nocturnal_enuresis\n\n18-Maternal Mortality in Egypt, a cry for help and attention. The Second International Conference of the African Society of Organization & Gestosis, 1998, 3rd Annual International Conference of Ob/Gyn Department � Sohag Faculty of Medicine University. Feb. 11-13. Luxor, Egypt. \n19-Postmenopausal Osteprosis. The 2nd annual conference of Health Insurance Organization on Family Planning and its role in primary health care. Zagaziz, Egypt, February 26-27, 1997, Center of Complementary Services for Maternity and childhood care. \n20-Laparoscopic Assisted vaginal hysterectomy. 10th International Annual Congress Modern Trends in Reproductive Techniques 23-24 March 1995. Alexandria, Egypt. \n21-Immunological Studies in Pre-eclamptic Toxaemia. Proceedings of 10th Annual Ain Shams Medical Congress. Cairo, Egypt, March 6-10, 1987. \n22-Socio-demographic factorse affecting acceptability of the long-acting contraceptive injections in a rural Egyptian community. Journal of Biosocial Science 29:305, 1987. \n23-Plasma fibronectin levels hypertension during pregnancy. The Journal of the Egypt. Soc. of Ob./Gyn. 13:1, 17-21, Jan. 1987. \n24-Effect of smoking on pregnancy. Journal of Egypt. Soc. of Ob./Gyn. 12:3, 111-121, Sept 1986. \n25-Socio-demographic aspects of nausea and vomiting in early pregnancy. Journal of the Egypt. Soc. of Ob./Gyn. 12:3, 35-42, Sept. 1986. \n26-Effect of intrapartum oxygen inhalation on maternofetal blood gases and pH. Journal of the Egypt. Soc. of Ob./Gyn. 12:3, 57-64, Sept. 1986. \n27-The effect of severe pre-eclampsia on serum transaminases. The Egypt. J. Med. Sci. 7(2): 479-485, 1986. \n28-A study of placental immunoreceptors in pre-eclampsia. The Egypt. J. Med. Sci. 7(2): 211-216, 1986. \n29-Serum human placental lactogen (hpl) in normal, toxaemic and diabetic pregnant women, during pregnancy and its relation to the outcome of pregnancy. Journal of the Egypt. Soc. of Ob./Gyn. 12:2, 11-23, May 1986. \n30-Pregnancy specific B1 Glycoprotein and free estriol in the serum of normal, toxaemic and diabetic pregnant women during pregnancy and after delivery. Journal of the Egypt. Soc. of Ob./Gyn. 12:1, 63-70, Jan. 1986. Also was accepted and presented at Xith World Congress of Gynecology and Obstetrics, Berlin (West), September 15-20, 1985. \n31-Pregnancy and labor in women over the age of forty years. Accepted and presented at Al-Azhar International Medical Conference, Cairo 28-31 Dec. 1985. \n32-Effect of Copper T intra-uterine device on cervico-vaginal flora. Int. J. Gynaecol. Obstet. 23:2, 153-156, April 1985. \n33-Factors affecting the occurrence of post-Caesarean section febrile morbidity. Population Sciences, 6, 139-149, 1985. \n34-Pre-eclamptic toxaemia and its relation to H.L.A. system. Population Sciences, 6, 131-139, 1985. \n35-The menstrual pattern and occurrence of pregnancy one year after discontinuation of Depo-medroxy progesterone acetate as a postpartum contraceptive. Population Sciences, 6, 105-111, 1985. \n36-The menstrual pattern and side effects of Depo-medroxy progesterone acetate as postpartum contraceptive. Population Sciences, 6, 97-105, 1985. \n37-Actinomyces in the vaginas of women with and without intrauterine contraceptive devices. Population Sciences, 6, 77-85, 1985. \n38-Comparative efficacy of ibuprofen and etamsylate in the treatment of I.U.D. menorrhagia. Population Sciences, 6, 63-77, 1985. \n39-Changes in cervical mucus copper and zinc in women using I.U.D.�s. Population Sciences, 6, 35-41, 1985. \n40-Histochemical study of the endometrium of infertile women. Egypt. J. Histol. 8(1) 63-66, 1985. \n41-Genital flora in pre- and post-menopausal women. Egypt. J. Med. Sci. 4(2), 165-172, 1983. \n42-Evaluation of the vaginal rugae and thickness in 8 different groups. Journal of the Egypt. Soc. of Ob./Gyn. 9:2, 101-114, May 1983. \n43-The effect of menopausal status and conjugated oestrogen therapy on serum cholesterol, triglycerides and electrophoretic lipoprotein patterns. Al-Azhar Medical Journal, 12:2, 113-119, April 1983. \n44-Laparoscopic ventrosuspension: A New Technique. Int. J. Gynaecol. Obstet., 20, 129-31, 1982. \n45-The laparoscope: A useful diagnostic tool in general surgery. Al-Azhar Medical Journal, 11:4, 397-401, Oct. 1982. \n46-The value of the laparoscope in the diagnosis of polycystic ovary. Al-Azhar Medical Journal, 11:2, 153-159, April 1982. \n47-An anaesthetic approach to the management of eclampsia. Ain Shams Medical Journal, accepted for publication 1981. \n48-Laparoscopy on patients with previous lower abdominal surgery. Fertility management edited by E. Osman and M. Wahba 1981. \n49-Heart diseases with pregnancy. Population Sciences, 11, 121-130, 1981. \n50-A study of the biosocial factors affecting perinatal mortality in an Egyptian maternity hospital. Population Sciences, 6, 71-90, 1981. \n51-Pregnancy Wastage. Journal of the Egypt. Soc. of Ob./Gyn. 11:3, 57-67, Sept. 1980. \n52-Analysis of maternal deaths in Egyptian maternity hospitals. Population Sciences, 1, 59-65, 1979. \nArticles published on OBGYN.net: \n1- Abdel Karim M. El Hemaly*, Ibrahim M. Kandil, Laila A. S. Mousa and Mohamad A.K.M.El Hemaly.\nUrethro-vaginoplasty, an innovated operation for the treatment of: Stress Urinary Incontinence (SUI), Detursor Overactivity (DO), Mixed Urinary Incontinence and Anterior Vaginal Wall Descent. \nhttp://www.obgyn.net/urogyn/urogyn.asp?page=/urogyn/articles/ urethro-vaginoplasty_01\n\n2- Abdel Karim M. El Hemaly, Ibrahim M Kandil, Mohamed M. Radwan.\n Urethro-raphy a new technique for surgical management of Stress Urinary Incontinence.\nhttp://www.obgyn.net/urogyn/urogyn.asp?page=/urogyn/articles/\nnew-tech-urethro\n\n3- Abdel Karim M. El Hemaly, Ibrahim M Kandil, Mohamad A. Rizk, Nabil Abdel Maksoud H., Mohamad M. Radwan, Khalid Z. El Shieka, Mohamad A. K. M. El Hemaly, and Ahmad T. El Saban.\nUrethro-raphy The New Operation for the treatment of stress urinary incontinence, SUI, detrusor instability, DI, and mixed-type of urinary incontinence; short and long term results. \nhttp://www.obgyn.net/urogyn/urogyn.asp?page=urogyn/articles/\nurethroraphy-09280\n\n4-Abdel Karim M. El Hemaly, Ibrahim M Kandil, and Bahaa E. El Mohamady. Menopause, and Voiding troubles. \nhttp://www.obgyn.net/displayppt.asp?page=/English/pubs/features/presentations/El-Hemaly03/el-hemaly03-ss\n\n5-El Hemaly AKMA, Mousa L.A. Micturition and Urinary\tContinence. Int J Gynecol Obstet 1996; 42: 291-2. \n\n6-Abdel Karim M. El Hemaly.\n Urinary incontinence in gynecology, a review article.\nhttp://www.obgyn.net/urogyn/urogyn.asp?page=/urogyn/articles/abs-urinary_incotinence_gyn_ehemaly \n\n7-El Hemaly AKMA. Nocturnal Enuresis: Pathogenesis and Treatment. \nInt Urogynecol J Pelvic Floor Dysfunct 1998;9: 129-31.\n \n8-El Hemaly AKMA, Mousa L.A.E. Stress Urinary Incontinence, a New Concept. Eur J Obstet Gynecol Reprod Biol 1996; 68: 129-35. \n\n9- El Hemaly AKMA, Kandil I. M. Stress Urinary Incontinence SUI facts and fiction. Is SUI a puzzle?! http://www.obgyn.net/displayppt.asp?page=/English/pubs/features/presentations/El-Hemaly/el-hemaly-ss\n\n10-Abdel Karim El Hemaly, Nabil Abdel Maksoud, Laila A. Mousa, Ibrahim M. Kandil, Asem Anwar, M.A.K El Hemaly and Bahaa E. El Mohamady. \nEvidence based Facts on the Pathogenesis and Management of SUI. http://www.obgyn.net/displayppt.asp?page=/English/pubs/features/presentations/El-Hemaly02/el-hemaly02-ss\n\n11- Abdel Karim M. El Hemaly*, Ibrahim M. Kandil, Mohamad A. Rizk and Mohamad A.K.M.El Hemaly.\n Urethro-plasty, a Novel Operation based on a New Concept, for the Treatment of Stress Urinary Incontinence, S.U.I., Detrusor Instability, D.I., and Mixed-type of Urinary Incontinence.\nhttp://www.obgyn.net/urogyn/urogyn.asp?page=/urogyn/articles/urethro-plasty_01\n\n12-Ibrahim M. Kandil, Abdel Karim M. El Hemaly, Mohamad M. Radwan: Ultrasonic Assessment of the Internal Urethral Sphincter in Stress Urinary Incontinence. The Internet Journal of Gynecology and Obstetrics. 2003. Volume 2 Number 1. \n\n13-Abdel Karim M. El Hemaly. Nocturnal Enureses: A Novel Concept on its pathogenesis and Treatment.\nhttp://www.obgyn.net/urogynecolgy/?page=articles/nocturnal_enuresis\n\n14- Abdel Karim M. El Hemaly. 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